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  • 1.
    Afghahi, Henri
    et al.
    Department of Medicine, Kärnsjukhuset, Sweden.
    Cederholm, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine.
    Eliasson, Björn
    Gothenburg University.
    Zethelius, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Gudbjörnsdottir, Soffia
    Gothenburg University.
    Hadimeri, Henrik
    Gothenburg University.
    Svensson, Maria K
    Gothenburg University.
    Risk factors for the development of albuminuria and renal impairment in type 2 diabetes—the Swedish National Diabetes Register (NDR)2010In: Nephrology, Dialysis and Transplantation, ISSN 0931-0509, E-ISSN 1460-2385, Vol. 26, no 4, p. 1236-1243Article in journal (Refereed)
    Abstract [en]

    Background. The aim of this study was to identify clinical risk factors associated with the development of albuminuria and renal impairment in patients with type 2 diabetes (T2D). In addition, we evaluated if different equations to estimate renal function had an impact on interpretation of data. This was done in a nationwide population-based study using data from the Swedish National Diabetes Register. Methods. Three thousand and six hundred sixty-seven patients with T2D aged 30-74 years with no signs of renal dysfunction at baseline (no albuminuria and eGFR >60 mL/min/1.73 m(2) according to MDRD) were followed up for 5 years (2002-2007). Renal outcomes, development of albuminuria and/or renal impairment [eGFR < 60 mL/min/1.73 m(2) by MDRD or eCrCl > 60 mL/min by Cockgroft-Gault (C-G)] were assessed at follow-up. Univariate regression analyses and stepwise regression models were used to identify significant clinical risk factors for renal outcomes. Results. Twenty percent of patients developed albuminuria, and 11% renal impairment; thus, ~6-7% of all patients developed non-albuminuric renal impairment. Development of albuminuria or renal impairment was independently associated with high age (all P < 0.001), high systolic BP (all P < 0.02) and elevated triglycerides (all P < 0.02). Additional independent risk factors for albuminuria were high BMI (P < 0.01), high HbA1c (P < 0.001), smoking (P < 0.001), HDL (P < 0.05) and male sex (P < 0.001), and for renal impairment elevated plasma creatinine at baseline and female sex (both P < 0.001). High BMI was an independent risk factor for renal impairment when defined by MDRD (P < 0.01), but low BMI was when defined by C-G (P < 0.001). Adverse effects of BMI on HbA1c, blood pressure and lipids accounted for ~50% of the increase risk for albuminuria, and for 41% of the increased risk for renal impairment (MDRD). Conclusions. Distinct sets of risk factors were associated with the development of albuminuria and renal impairment consistent with the concept that they are not entirely linked in patients with type 2 diabetes. Obesity and serum triglycerides are semi-novel risk factors for development of renal dysfunction and BMI accounted for a substantial proportion of the increased risk. The equations used to estimate renal function (MDRD vs. C-G) had an impact on interpretation of data, especially with regard to body composition and gender.

  • 2.
    Annuk, Margus
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Fellström, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Cyclooxygenase inhibition improves endothelium-dependent vasodilatation in patients with chronic renal failure2002In: Nephrology, Dialysis and Transplantation, ISSN 0931-0509, E-ISSN 1460-2385, Vol. 17, no 12, p. 2159-2163Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Some studies have demonstrated beneficial effects of L-arginine as a substrate for nitric oxide synthesis, and diclofenac as an inhibitor of cyclooxygenase (COX)-derived vasoconstrictive agents on vascular responses in humans during several pathological conditions. The aim of the present study was to investigate the acute effects of L-arginine and diclofenac on endothelium-dependent vasodilatation (EDV) and endothelium-independent vasodilatation (EIDV) in patients with chronic renal failure (CRF).

    METHODS: Effects of L-arginine and diclofenac on EDV and EIDV were measured in 15 patients with CRF and in 15 healthy controls by means of forearm blood flow measurements with venous occlusion plethysmography during local intra-arterial infusions of methacholine (2 and 4 micro g/min evaluating EDV) and sodium nitroprusside (5 and 10 micro g/min evaluating EIDV).

    RESULTS: L-Arginine infusion increased methacholine-induced vasodilatation both in patients with CRF and healthy controls. Diclofenac infusion increased methacholine-induced vasodilatation only in patients with CRF. There was no significant change in nitroprusside-induced vasodilatation after L-arginine and diclofenac infusions both in patients with CRF and healthy controls.

    CONCLUSIONS: These results suggest that COX inhibition reduces the levels of a prostanoid-derived vasoconstrictive agent contributing to the impaired EDV in patients with CRF, while in this age group L-arginine improves EDV regardless of renal function.

  • 3.
    Annuk, Margus
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Linde, Torbjörn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Fellström, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Impaired endothelium-dependent vasodilatation in renal failure in humans2001In: Nephrology, Dialysis and Transplantation, ISSN 0931-0509, E-ISSN 1460-2385, Vol. 16, no 2, p. 302-306Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The main causes of death in patients with chronic renal failure (CRF) are cardiovascular complications. The aim of the present study was to compare endothelium-dependent vasodilatation (EDV) in patients with chronic renal failure with a control population controlling for hypertension, diabetes mellitus and hypercholesterolaemia.

    METHODS: Fifty-six patients with moderate CRF (mean creatinine clearance 29.4 ml/min/1.73 m(2)) underwent evaluation of EDV and endothelium-independent vasodilatation (EIDV) by means of forearm blood flow (FBF) measurements with venous occlusion plethysmography during local intra-arterial infusions of methacholine (Mch, 2 and 4 microg/min evaluating EDV) and sodium nitroprusside (SNP, 5 and 10 microg/min evaluating EIDV). Fifty-six control subjects without renal impairment underwent the same investigation.

    RESULTS: Infusion of Mch increased FBF significantly less in patients with renal failure than in controls (198 vs 374%, P<0.001), whereas no significant difference was seen regarding the vasodilatation induced by SNP (278 vs 269%). The differences in EDV between the groups were still significant after controlling for hypertension, blood glucose, and serum cholesterol in multiple regression analysis (P<0.001). EDV was related to serum creatinine (r=-0.37, P<0.01), creatinine clearance (r=0.45, P<0.005) and to serum triglyceride levels (r=-0.29, P<0.005) in the CRF group.

    CONCLUSIONS: Patients with moderate CRF have an impaired EDV even after correction for traditional cardiovascular risk factors and this impairment is related to the degree of renal failure.

  • 4.
    Bhandari, Sunil
    et al.
    Hull & East Yorkshire Hosp NHS Trust, Nephrol, Kingston Upon Hull, N Humberside, England.
    Wikström, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Renal Medicine.
    Kalra, Philip
    Salford Royal Hosp, Nephrol, Salford, Lancs, England.
    Administration of high doses (> 1000 Mg) of iron isomaltoside in chronic kidney disease patients with iron deficiency anaemia gives an effective increase in haemoglobin without additional safety concerns2018In: Nephrology, Dialysis and Transplantation, ISSN 0931-0509, E-ISSN 1460-2385, Vol. 33, no Supplement: 1Article in journal (Other academic)
  • 5. Bruck, Katharina
    et al.
    Jager, Kitty J.
    Dounousi, Evangelia
    Kainz, Alexander
    Nitsch, Dorothea
    Ärnlov, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Rothenbacher, Dietrich
    Browne, Gemma
    Capuano, Vincenzo
    Ferraro, Pietro Manuel
    Ferrieres, Jean
    Gambaro, Giovanni
    Guessous, Idris
    Hallan, Stein
    Kastarinen, Mika
    Navis, Gerjan
    Otero Gonzalez, Alfonso
    Palmieri, Luigi
    Romundstad, Solfrid
    Spoto, Belinda
    Stengel, Benedicte
    Tomson, Charles
    Tripepi, Giovanni
    Voelzke, Henry
    Wiecek, Andrzej
    Gansevoort, Ron
    Schoettker, Ben
    Wanner, Christoph
    Vinhas, Jose
    Zoccali, Carmine
    Van Biesen, Wim
    Stel, Vianda S.
    Methodology used in studies reporting chronic kidney disease prevalence: a systematic literature review2015In: Nephrology, Dialysis and Transplantation, ISSN 0931-0509, E-ISSN 1460-2385, Vol. 30, no S4, p. 6-16Article, review/survey (Refereed)
    Abstract [en]

    Background. Many publications report the prevalence of chronic kidney disease (CKD) in the general population. Comparisons across studies are hampered as CKD prevalence estimations are influenced by study population characteristics and laboratory methods. Methods. For this systematic review, two researchers independently searched PubMed, MEDLINE and EMBASE to identify all original research articles that were published between 1 January 2003 and 1 November 2014 reporting the prevalence of CKD in the European adult general population. Data on study methodology and reporting of CKD prevalence results were independently extracted by two researchers. Results. We identified 82 eligible publications and included 48 publications of individual studies for the data extraction. There was considerable variation in population sample selection. The majority of studies did not report the sampling frame used, and the response ranged from 10 to 87%. With regard to the assessment of kidney function, 67% used a Jaffe assay, whereas 13% used the enzymatic assay for creatinine determination. Isotope dilution mass spectrometry calibration was used in 29%. The CKD-EPI (52%) and MDRD (75%) equations were most often used to estimate glomerular filtration rate (GFR). CKD was defined as estimated GFR (eGFR) <60 mL/min/1.73 m(2) in 92% of studies. Urinary markers of CKD were assessed in 60% of the studies. CKD prevalence was reported by sex and age strata in 54 and 50% of the studies, respectively. In publications with a primary objective of reporting CKD prevalence, 39% reported a 95% confidence interval. Conclusions. The findings from this systematic review showed considerable variation in methods for sampling the general population and assessment of kidney function across studies reporting CKD prevalence. These results are utilized to provide recommendations to help optimize both the design and the reporting of future CKD prevalence studies, which will enhance comparability of study results.

  • 6. Carrero, Juan J.
    et al.
    Huang, Xiaoyan
    Jimenez-Moleon, Jose
    Lindholm, Bengt
    Cederholm, Tommy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Arnlov, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Riserus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Sjögren, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Mediterranean Diet, Kidney Function, And Mortality In Men With Chronic Kidney Disease2013In: Nephrology, Dialysis and Transplantation, ISSN 0931-0509, E-ISSN 1460-2385, Vol. 28, no S1, p. 8-8Article in journal (Other academic)
  • 7.
    Carrero, Juan J.
    et al.
    Karolinska Inst, Renal Med, Stockholm, Sweden..
    Varenhorst, Christoph
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Jensevik, Karin
    Szummer, Karolina
    Karolinska Inst, Cardiol, Stockholm, Sweden..
    Lagerqvist, Bo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala Univ, Uppsala Clin Res Ctr, Uppsala, Sweden..
    Evans, Marie
    Karolinska Inst, Renal Med, Stockholm, Sweden..
    Spaak, Jonas
    Karolinska Inst, Clin Sci, Stockholm, Sweden..
    Held, Claes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Psychology in Healthcare.
    James, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Jernberg, Tomas
    Karolinska Inst, Cardiol, Stockholm, Sweden..
    Clinical Outcomes Associated With The Duration Of Dual Antiplatelet Therapy With Clopidogrel And Aspirin In Chronic Kidney Disease Patients With Acute Coronary Syndrome2016In: Nephrology, Dialysis and Transplantation, ISSN 0931-0509, E-ISSN 1460-2385, Vol. 31, p. 1441-1441Article in journal (Other academic)
  • 8. Coppo, Rosanna
    et al.
    D'Arrigo, Graziella
    Tripepi, Giovanni
    Russo, Maria Luisa
    Roberts, Ian S D
    Bellur, Shubha
    Cattran, Daniel
    Cook, Terence H
    Feehally, John
    Tesar, Vladimir
    Maixnerova, Dita
    Peruzzi, Licia
    Amore, Alessandro
    Lundberg, Sigrid
    Di Palma, Anna Maria
    Gesualdo, Loreto
    Emma, Francesco
    Rollino, Cristiana
    Praga, Manuel
    Biancone, Luigi
    Pani, Antonello
    Feriozzi, Sandro
    Polci, Rosaria
    Barratt, Jonathan
    Del Vecchio, Lucia
    Locatelli, Francesco
    Pierucci, Alessandro
    Caliskan, Yasar
    Perkowska-Ptasinska, Agnieszka
    Durlik, Magdalena
    Moggia, Elisabetta
    Ballarin, José C
    Wetzels, Jack F M
    Goumenos, Dimitris
    Papasotiriou, Marios
    Galesic, Kresimir
    Toric, Luka
    Papagianni, Aikaterini
    Stangou, Maria
    Benozzi, Luisa
    Cusinato, Stefano
    Berg, Ulla
    Topaloglu, Rezan
    Maggio, Milena
    Ots-Rosenberg, Mai
    D'Amico, Marco
    Geddes, Colin
    Balafa, Olga
    Quaglia, Marco
    Cravero, Raffaella
    Lino Cirami, Calogero
    Fellström, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Renal Medicine.
    Floege, Jürgen
    Egido, Jesus
    Mallamaci, Francesca
    Zoccali, Carmine
    Is there long-term value of pathology scoring in immunoglobulin A nephropathy?: A validation study of the Oxford Classification for IgA Nephropathy (VALIGA) update2018In: Nephrology, Dialysis and Transplantation, ISSN 0931-0509, E-ISSN 1460-2385Article in journal (Refereed)
    Abstract [en]

    Background: It is unknown whether renal pathology lesions in immunoglobulin A nephropathy (IgAN) correlate with renal outcomes over decades of follow-up.

    Methods: In 1130 patients of the original Validation Study of the Oxford Classification for IgA Nephropathy (VALIGA) cohort, we studied the relationship between the MEST score (mesangial hypercellularity, M; endocapillary hypercellularity, E; segmental glomerulosclerosis, S; tubular atrophy/interstitial fibrosis, T), crescents (C) and other histological lesions with both a combined renal endpoint [50% estimated glomerular filtration rate (eGFR) loss or kidney failure] and the rate of eGFR decline over a follow-up period extending to 35 years [median 7 years (interquartile range 4.1-10.8)].

    Results: In this extended analysis, M1, S1 and T1-T2 lesions as well as the whole MEST score were independently related with the combined endpoint (P < 0.01), and there was no effect modification by age for these associations, suggesting that they may be valid in children and in adults as well. Only T lesions were associated with the rate of eGFR loss in the whole cohort, whereas C showed this association only in patients not treated with immunosuppression. In separate prognostic analyses, the whole set of pathology lesions provided a gain in discrimination power over the clinical variables alone, which was similar at 5 years (+2.0%) and for the whole follow-up (+1.8%). A similar benefit was observed for risk reclassification analyses (+2.7% and +2.4%).

    Conclusion: Long-term follow-up analyses of the VALIGA cohort showed that the independent relationship between kidney biopsy findings and the risk of progression towards kidney failure in IgAN remains unchanged across all age groups and decades after the renal biopsy.

  • 9. Dahle, Dag Olav
    et al.
    Mjoen, Geir
    Oqvist, Bjorn
    Scharnagl, Hubert
    Weihrauch, Gisela
    Grammer, Tanja
    Maerz, Winfried
    Abedini, Sadollah
    Norby, Gudrun E.
    Holme, Ingar
    Fellström, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Jardine, Alan
    Holdaas, Hallvard
    Inflammation-associated graft loss in renal transplant recipients2011In: Nephrology, Dialysis and Transplantation, ISSN 0931-0509, E-ISSN 1460-2385, Vol. 26, no 11, p. 3756-3761Article in journal (Refereed)
    Abstract [en]

    Background. Although short-term graft survival has improved substantially in renal transplant recipients, long-term graft survival has not improved over the last decades. The lack of knowledge of specific causes and risk factors has hampered improvements in long-term allograft survival. There is an uncertainty if inflammation is associated with late graft loss.

    Methods. We examined, in a large prospective trial, the inflammation markers high-sensitivity C-reactive protein (hsCRP) and interleukin-6 (IL-6) and their association with chronic graft dysfunction. We collected data from the Assessment of Lescol in Renal Transplant trial, which recruited 2102 maintenance renal transplant recipients.

    Results. Baseline values were hsCRP 3.8 +/- 6.7 mg/L and IL-6 2.9 +/- 1.9 pg/mL. Adjusted for traditional risk factors, hsCRP and IL-6 were independently associated with death-censored graft loss, the composite end points graft loss or death and doubling of serum creatinine, graft loss or death.

    Conclusion. The inflammation markers hsCRP and IL-6 are associated with long-term graft outcomes in renal transplant recipients.

  • 10. Drechsler, Christiane
    et al.
    Philstrom, Hege
    Meinitzer, Andreas
    Pilz, Stefan
    Tomaschitz, Andreas
    Abedini, Sadollah
    Fellström, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Renal Medicine.
    Jardine, Alan
    Wanner, Christoph
    Maerz, Winfried
    Holdaas, Hallvard
    Homoarginine and Clinical Outcomes in Renal Transplant Recipients: Results from the Alert Study2014In: Nephrology, Dialysis and Transplantation, ISSN 0931-0509, E-ISSN 1460-2385, Vol. 29, p. 539-539Article in journal (Other academic)
  • 11.
    Eriksson, Daniel
    et al.
    Quantify Research, Stockholm, Sweden.
    Karlsson, Linda
    Quantify Research, Stockholm, Sweden.
    Eklund, Oskar
    Quantify Research, Stockholm, Sweden.
    Dieperink, Hans
    Department of Nephrology, Odense University Hospital, Odense C, Denmark.
    Honkanen, Eero
    Division of Nephrology, Department of Medicine , Helsinki University Central Hospital, Helsinki, Finland.
    Melin, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Renal Medicine.
    Selvig, Kristian
    Department of Nephrology, Vestre Viken Hospital Trust, Drammen, Norway.
    Lundberg, Johan
    Otsuka Pharma Scandinavia, Stockholm, Sweden.
    Health-related quality of life across all stages of autosomal dominant polycystic kidney disease2017In: Nephrology, Dialysis and Transplantation, ISSN 0931-0509, E-ISSN 1460-2385, Vol. 32, no 12, p. 2106-2111Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: A limited number of studies have assessed health-related quality of life (HRQoL) in autosomal dominant polycystic kidney disease (ADPKD). Results to date have been conflicting and studies have generally focused on patients with later stages of the disease. This study aimed to assess HRQoL in ADPKD across all stages of the disease, from patients with early chronic kidney disease (CKD) to patients with end-stage renal disease.

    METHODS: A study involving cross-sectional patient-reported outcomes and retrospective clinical data was undertaken April-December 2014 in Denmark, Finland, Norway and Sweden. Patients were enrolled into four mutually exclusive stages of the disease: CKD stages 1-3; CKD stages 4-5; transplant recipients; and dialysis patients.

    RESULTS: Overall HRQoL was generally highest in patients with CKD stages 1-3, followed by transplant recipients, patients with CKD stages 4-5 and patients on dialysis. Progressive disease predominately had an impact on physical health, whereas mental health showed less variation between stages of the disease. A substantial loss in quality of life was observed as patients progressed to CKD stages 4-5.

    CONCLUSIONS: Later stages of ADPKD are associated with reduced physical health. The value of early treatment interventions that can delay progression of the disease should be considered.

  • 12.
    Furuland, Hans
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Linde, Torbjörn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Ahlmén, Jarl
    Christensson, Anders
    Strömbom, Ulf
    Danielson, Bo G.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    A randomized controlled trial of haemoglobin normalization with epoetin alfa in pre-dialysis and dialysis patients2003In: Nephrology, Dialysis and Transplantation, ISSN 0931-0509, E-ISSN 1460-2385, Vol. 18, no 2, p. 353-361Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Partial correction of renal anaemia with erythropoietin improves quality of life (QoL). We aimed to examine if normalization of haemoglobin with epoetin alfa in pre-dialysis and dialysis patients further improves QoL and is safe.

    METHODS: 416 Scandinavian patients with renal anaemia [pre-dialysis, haemodialysis (HD) and peritoneal dialysis patients] were randomized to reach a normal haemoglobin of 135-160 g/l (n=216) or a subnormal haemoglobin of 90-120 g/l (n=200) with or without epoetin alfa. Study duration was 48-76 weeks. QoL was measured using Kidney Disease Questionnaires in 253 Swedish dialysis patients. Safety was examined in all patients.

    RESULTS: QoL improved, measured as a decrease in physical symptoms (P=0.02), fatigue (P=0.05), depression (P=0.01) and frustration (P=0.05) in the Swedish dialysis patients when haemoglobin was normalized. In pre-dialysis patients, diastolic blood pressure was higher in the normal compared with the subnormal haemoglobin group after 48 weeks. However, the progression rate of chronic renal failure was comparable. In the normal haemoglobin group (N-Hb), 51% had at least one serious adverse event compared with 49% in the subnormal haemoglobin group (S-Hb) (P=0.32). The incidence of thrombovascular events and vascular access thrombosis in HD patients did not differ. The mortality rate was 13.4% in the N-Hb group and 13.5% in the S-Hb group (P=0.98). Mortality decreased with increasing mean haemoglobin in both groups.

    CONCLUSIONS: Normalization of haemoglobin improved QoL in the subgroup of dialysis patients, appears to be safe and can be considered in many patients with end-stage renal disease.

  • 13.
    Furuland, Hans
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Renal Medicine.
    McEwan, Phil
    HEOR Ltd, Hlth Econ & Outcomes Res, Cardiff, S Glam, Wales; Swansea Univ, Sch Human & Hlth Sci, Swansea, W Glam, Wales.
    Evans, Marc
    Llandough Hosp, Diabet Resource Ctr, Cardiff, S Glam, Wales.
    Linde, Cecilia
    Karolinska Univ Hosp, Heart & Vasc Theme, Stockholm, Sweden.;Karolinska Inst, Stockholm, Sweden.
    Ayoubkhani, Daniel
    HEOR Ltd, Hlth Econ & Outcomes Res, Cardiff, S Glam, Wales.
    Bakhai, Ameet
    Royal Free Hosp, Dept Cardiol, London, England.
    Grandy, Susan
    AstraZeneca, Global Hlth Econ, Gaithersburg, MD USA.
    Palaka, Eirini
    AstraZeneca, Global Hlth Econ, Cambridge, England.
    Qin, Lei
    AstraZeneca, Global Hlth Econ, Gaithersburg, MD USA.
    RECURRENT HYPERKALAEMIA AND ASSOCIATION WITH LENGTH-OF-STAY AND MORTALITY FOLLOWING HOSPITALISATION: REAL-WORLD EVIDENCE FROM UK PATIENTS WITH CKD2018In: Nephrology, Dialysis and Transplantation, ISSN 0931-0509, E-ISSN 1460-2385, Vol. 33, no Supplement: 1, p. 157-157Article in journal (Other academic)
  • 14.
    Gasparini, Alessandro
    et al.
    Karolinska Inst, Dept Clin Sci Technol & Intervent, Div Renal Med & Baxter Novum, Stockholm, Sweden..
    Evans, Marie
    Karolinska Inst, Dept Clin Sci Technol & Intervent, Div Renal Med & Baxter Novum, Stockholm, Sweden..
    Coresh, Josef
    Johns Hopkins Univ, Welch Ctr Prevent Epidemiol & Clin Res, Baltimore, MD USA..
    Grams, Morgan E.
    Johns Hopkins Univ, Welch Ctr Prevent Epidemiol & Clin Res, Baltimore, MD USA.;Johns Hopkins Univ, Dept Med, Div Nephrol, Baltimore, MD USA..
    Norin, Olof
    Karolinska Inst, Dept Learning Informat Management & Eth, Med Management Ctr, Stockholm, Sweden..
    Qureshi, Abdul R.
    Karolinska Inst, Dept Clin Sci Technol & Intervent, Div Renal Med & Baxter Novum, Stockholm, Sweden..
    Runesson, Bjorn
    Karolinska Inst, Dept Clin Sci Technol & Intervent, Div Renal Med & Baxter Novum, Stockholm, Sweden..
    Barany, Peter
    Karolinska Inst, Dept Clin Sci Technol & Intervent, Div Renal Med & Baxter Novum, Stockholm, Sweden..
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Dalarna Univ, Sch Hlth & Social Studies, Falun, Sweden.
    Jernberg, Tomas
    Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.;Karolinska Univ Hosp, Dept Cardiol, Stockholm, Sweden..
    Wettermark, Bjorn
    Stockholm Cty Council, Publ Healthcare Serv Comm, Stockholm, Sweden.;Karolinska Inst, Dept Med, Ctr Pharmacoepidemiol, Stockholm, Sweden..
    Elinder, Carl G.
    Karolinska Inst, Dept Clin Sci Technol & Intervent, Div Renal Med & Baxter Novum, Stockholm, Sweden.;Stockholm Cty Council, Publ Healthcare Serv Comm, Stockholm, Sweden..
    Carrero, Juan-Jesus
    Karolinska Inst, Dept Clin Sci Technol & Intervent, Div Renal Med & Baxter Novum, Stockholm, Sweden.;Karolinska Inst, Ctr Mol Med, Stockholm, Sweden..
    Prevalence and recognition of chronic kidney disease in Stockholm healthcare2016In: Nephrology, Dialysis and Transplantation, ISSN 0931-0509, E-ISSN 1460-2385, Vol. 31, no 12, p. 2086-2094Article in journal (Refereed)
    Abstract [en]

    Background. Chronic kidney disease (CKD) is common, but the frequency of albuminuria testing and referral to nephrology care has been difficult to measure. We here characterize CKD prevalence and recognition in a complete healthcare utilization cohort of the Stockholm region, in Sweden. Methods. We included all adult individuals (n = 1 128 058) with at least one outpatient measurement of IDMS-calibrated serum creatinine during 2006-11. Estimated glomerular filtration rate (eGFR) was calculated via the CKD-EPI equation and CKD was solely defined as eGFR <60 mL/min/1.73 m(2). We also assessed the performance of diagnostic testing (albuminuria), nephrology consultations, and utilization of ICD-10 diagnoses. Results. A total of 68 894 individuals had CKD, with a crude CKD prevalence of 6.11% [95% confidence interval (CI): 6.07-6.16%] and a prevalence standardized to the European population of 5.38% (5.33-5.42%). CKD was more prevalent among the elderly (28% prevalence >75 years old), women (6.85 versus 5.24% in men), and individuals with diabetes (17%), hypertension (17%) or cardiovascular disease (31%). The frequency of albuminuria monitoring was low, with 38% of diabetics and 27% of CKD individuals undergoing albuminuria testing over 2 years. Twenty-three per cent of the 16 383 individuals satisfying selected KDIGO criteria for nephrology referral visited a nephrologist. Twelve per cent of CKD patients carried an ICD-10 diagnostic code of CKD. Conclusions. An estimated 6% of the adult Stockholm population accessing healthcare has CKD, but the frequency of albuminuria testing, nephrology consultations and registration of CKD diagnoses was suboptimal despite universal care. Improving provider awareness and treatment of CKD could have a significant public health impact.

  • 15.
    Gasparini, Alessandro
    et al.
    Karolinska Inst, Div Renal Med, Stockholm, Sweden.;Baxter Novum, CLINTEC, Stockholm, Sweden..
    Evans, Marie
    Karolinska Inst, Div Renal Med, Stockholm, Sweden.;Baxter Novum, CLINTEC, Stockholm, Sweden..
    Qureshi, Abdul Rashid
    Karolinska Inst, Div Renal Med, Stockholm, Sweden.;Baxter Novum, CLINTEC, Stockholm, Sweden..
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Barany, Peter
    Karolinska Inst, Div Renal Med, Stockholm, Sweden.;Baxter Novum, CLINTEC, Stockholm, Sweden..
    Coresh, Josef
    Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA..
    Wettermark, Bjorn
    Stockholm Cty Council, Publ Healthcare Serv Comm, Stockholm, Sweden.;Karolinska Inst, Dept Med, Ctr Pharmacoepidemiol, Stockholm, Sweden..
    Elinder, Carl-Gustaf
    Karolinska Inst, Div Renal Med, Stockholm, Sweden.;Baxter Novum, CLINTEC, Stockholm, Sweden.;Stockholm Cty Council, Publ Healthcare Serv Comm, Stockholm, Sweden..
    Carrero, Juan-Jesus
    Karolinska Inst, Div Renal Med, Stockholm, Sweden.;Baxter Novum, CLINTEC, Stockholm, Sweden..
    Prevalence, Diagnosis And Nephrology Care Of CKD In The Region Of Stockholm2016In: Nephrology, Dialysis and Transplantation, ISSN 0931-0509, E-ISSN 1460-2385, Vol. 31, p. 191-192Article in journal (Other academic)
  • 16. Holdaas, Hallvard
    et al.
    Fellström, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Jardine, Alan G.
    Nyberg, Gudrun
    Grönhagen-Riska, Carola
    Madsen, Sören
    Heumayer, Hans-Hellmut
    Cole, Edward
    Maes, Bart
    Ambühl, Patrice
    Logan, John O.
    Staffler, Beatrix
    Gimpelewicz, Claudio
    Beneficial effect of early initiation of lipid-lowering therapy following renal transplantation2005In: Nephrology, Dialysis and Transplantation, ISSN 0931-0509, E-ISSN 1460-2385, Vol. 20, no 5, p. 974-980Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Renal transplant recipients have a significantly reduced life expectancy, largely due to premature cardiovascular disease. The aim of the current analysis was to investigate the importance of time of initiation of therapy after transplantation, on the benefits of statin therapy. METHODS: 2102 renal transplant recipients with total cholesterol levels of 4.0-9.0 mmol/l were randomly assigned to treatment with fluvastatin (n = 1050) or placebo (n = 1052) and followed for a mean time of 5.1 years. The end-points were major cardiac events. The average median time from transplantation to randomization was 4.5 years (range: 0.5-29 years). RESULTS: In patients starting treatment with fluvastatin <4.5 years after renal transplantation, the incidence of cardiac events was 4.6% over 5.1 years vs 9.2% in those on placebo (P = 0.007). Fluvastatin significantly reduced the risk of cardiac death and non-fatal myocardial infarction by 56% [risk ratio (RR): 0.44; 95% confidence interval (95% CI): 0.26-0.74; P = 0.002]. In a more detailed analysis patients were grouped into 2-year intervals (since the last transplantation). The frequency of cardiac death and non-fatal myocardial infarction was reduced by 3.2%, 5.1%, 9.6% and 8.2% with fluvastatin treatment as compared to 6%, 10.4%, 13.4% and 9.6% with placebo when treatment was initiated at 0-2, 2-4, 4-6 and >6 years, respectively. The risk reduction for patients initiating therapy with fluvastatin at years 0-2 (compared with >6 years) following transplantation was 59% (RR: 0.41; 95% CI: 0.18-0.92; P = 0.0328). This is also reflected in total time on renal replacement therapy: in patients in the first quartile (<47 months) fluvastatin use was associated with a risk reduction of 64% compared with 19% for patients in the fourth quartile (>120 months) (P = 0.033). CONCLUSIONS: Our data support an early introduction of fluvastatin therapy in a population of transplant recipients at high risk of premature coronary heart disease.

  • 17. Honkanen, Eero
    et al.
    Kauppila, Leena
    Wikström, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Rensma, Pieter L.
    Krzesinski, Jean-Marie
    Aasarod, Knut
    Verbeke, Francis
    Jensen, Per Bruno
    Mattelaer, Pierre
    Volck, Birgitte
    Abdominal aortic calcification in dialysis patients: results of the CORD study2008In: Nephrology, Dialysis and Transplantation, ISSN 0931-0509, E-ISSN 1460-2385, Vol. 23, no 12, p. 4009-4015Article in journal (Refereed)
    Abstract [en]

    Background. Patients with chronic kidney disease stage 5 have a high prevalence of vascular calcification, but the specific anatomical distribution and severity of abdominal aortic calcification (AAC), in contrast to coronary calcification, is less well documented. AAC may be recorded using plain radiographs. The present report is an analysis of baseline data on AAC in patients enrolled in the CORD (Calcification Outcome in Renal Disease) study. Methods. A total of 47 centres in six European countries participated in this cross-sectional study. Inclusion criteria were age >= 18 years and duration of dialysis >= 3 months. Lateral lumbar radiography of the abdominal aorta was used to determine the overall AAC score, which is related to the severity of calcific deposits at lumbar vertebral segments L1-L4. The reliability of the method was tested by double reading of 64 radiographs (coefficient of correlation 0.9). Results. A lateral lumbar radiograph was obtained in 933 patients. Calcification (AAC score >= 1) was present in 81% of the patients; its severity increased significantly from L1 to L4 (P < 0.0001) and affected all of these segments in 51% of patients. Independent predictors for the presence and severity of calcification were age (odds ratio [OR] 1.103/year; P < 0.0001), duration of dialysis (OR 1.110/year; P = 0.002) and history of cardiovascular disease (OR 3.247; P < 0.0001). Conclusions. AAC detected by lateral lumbar radiograph is associated with several risk factors of uraemic calcification. This semi-quantitative method is more widely available and less expensive than the current procedures for studying calcification and could form part of a pre-transplant workup and cardiovascular risk stratification.

  • 18. Huang, Xiaoyan
    et al.
    Sjögren, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Cederholm, Tommy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Lindholm, Bengt
    Risérus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Carrero, Juan Jesús
    Serum and adipose tissue fatty acid composition as biomarkers of habitual dietary fat intake in elderly men with chronic kidney disease2014In: Nephrology, Dialysis and Transplantation, ISSN 0931-0509, E-ISSN 1460-2385, Vol. 29, no 1, p. 128-136Article in journal (Refereed)
    Abstract [en]

    Background

    Fatty acid (FA) composition in serum cholesterol esters (CE) and adipose tissue (AT) reflect the long-term FA intake in the general population. Because both dietary intake and FA biomarkers associate with renal function, our aim was to identify which CE and AT FAs are useful biomarkers of habitual FA intake in individuals with chronic kidney disease (CKD).

    Methods

    Cross-sectional analysis was performed in 506 men (aged 70 years) with a glomerular filtration rate (GFR) of <60 mL/min per 1.73 m(2) from the Uppsala Longitudinal Study of Adult Men cohort. Dietary habits were evaluated with a 7-day dietary record. FA compositions in CE and AT were analyzed by gas-liquid chromatography in two random subsamples of 248 and 318 individuals, respectively.

    Results

    Both CE and AT linoleic acid and docosahexaenoic acid (DHA) were strongly associated with their corresponding intake, after adjustments for non-dietary factors. The proportions of eicosapentaenoic acid (EPA) and palmitic acid in CE and AT moderately correlated with dietary intake, whereas correlations of other FAs were weaker or absent. Proportions of EPA and DHA in CE and AT were positively associated with the total energy-adjusted fish intake. Results were confirmed in adequate reporters as identified by the Goldberg cutoff method. These relationships held constant, regardless of a GFR above or below 45 mL/min per 1.73 m(2) or the prevalence of microalbuminuria.

    Conclusions

    Proportions of EPA, DHA, palmitic and linoleic acid in serum CE and AT are good indicators of their dietary intake in men with CKD. They can be considered valid biomarkers for epidemiological studies and assessment of compliance.

  • 19. Huang, Xiaoyan
    et al.
    Stenvinkel, Peter
    Qureshi, Abdul Rashid
    Riserus, Ulf
    Cederholm, Tommy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Barany, Peter
    Heimburger, Olof
    Lindholm, Bengt
    Carrero, Juan Jesus
    Essential polyunsaturated fatty acids, inflammation and mortality in dialysis patients2012In: Nephrology, Dialysis and Transplantation, ISSN 0931-0509, E-ISSN 1460-2385, Vol. 27, no S2, p. 287-287Article in journal (Other academic)
  • 20. Huang, Xiaoyan
    et al.
    Stenvinkel, Peter
    Qureshi, Abdul Rashid
    Riserus, Ulf
    Cederholm, Tommy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Barany, Peter
    Heimburger, Olof
    Lindholm, Bengt
    Carrero, Juan Jesus
    Estimated hepatic and adipose tissue stearoyl-coa desaturase-1 activities are associated with inflammation and all-cause mortality in dialysis patients2012In: Nephrology, Dialysis and Transplantation, ISSN 0931-0509, E-ISSN 1460-2385, Vol. 27, no S2, p. 272-272Article in journal (Other academic)
  • 21. Huang, Xiaoyan
    et al.
    Stenvinkel, Peter
    Qureshi, Abdul Rashid
    Risérus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Cederholm, Tommy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Barany, Peter
    Heimburger, Olof
    Lindholm, Bengt
    Carrero, Juan Jesus
    Essential polyunsaturated fatty acids, inflammation and mortality in dialysis patients2012In: Nephrology, Dialysis and Transplantation, ISSN 0931-0509, E-ISSN 1460-2385, Vol. 27, no 9, p. 3615-3620Article in journal (Refereed)
    Abstract [en]

    Background. Polyunsaturated fatty acids (PUFA) are essential nutrients with anti-inflammatory and cardioprotective properties. We investigated the association of essential dietary PUFA intake, reflected by plasma fatty acid composition, with inflammation and mortality in dialysis patients.

    Methods. We recruited 222 Swedish dialysis subjects (39% women) with median age of 57 years and average 12 months of dialysis vintage. Plasma phospholipid PUFA were assessed by gas-liquid chromatography. Overall mortality was assessed after 18.4 (10th-90th percentiles: 2.3-60) months of follow-up.

    Results. Linoleic acid (LA), Mead acid (MA), alpha-linolenic acid (ALA) and long-chain n-3 PUFA (LC n-3; the sum of eicosapentaenoic, docosapentaenoic and docosahexaenoic acids) represented 19.7, 0.26, 0.26 and 7.64% of all fatty acids in plasma, respectively. This may reflect an adequate n-3 PUFA intake. LA was negatively (beta = -0.21, P = 0.004) but MA positively (beta = 0.25, P < 0.001) associated with interleukin (IL)-6 in multivariate analyses. Neither ALA nor LC n-3 were independently associated with IL-6. During follow-up, 61 deaths and 115 kidney transplants occurred. Fully adjusted competing risk models showed that every percent increase in the proportion of plasma LA was associated with 12% reduction in mortality risk before transplantation (hazard ratio 0.88, 95% confidence interval 0.79-0.99). MA was directly associated with mortality. Neither ALA nor LC n-3 predicted outcome.

    Conclusions. The proportion of plasma phospholipid LA is inversely associated with IL-6 and all-cause mortality in Swedish dialysis patients. We raise the hypothesis that dialysis patients could benefit from increased intake of vegetable oils, the primary source of LA in the Western-type diet.

  • 22. Hultström, Michael
    et al.
    Leh, Sabine
    Skogstrand, Trude
    Iversen, Bjarne M
    Upregulation of tissue inhibitor of metalloproteases-1 (TIMP-1) and procollagen-N-peptidase in hypertension-induced renal damage.2008In: Nephrology, Dialysis and Transplantation, ISSN 0931-0509, E-ISSN 1460-2385, Vol. 23, no 3, p. 896-903Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Hypertensive renal damage starts in the juxtamedullary cortex (JMC) and gradually extends towards the outer cortex (OC). The intention of the study was to examine if the increase of fibrous tissue in the JMC of the spontaneously hypertensive rat (SHR) is dependent on an increase of collagen synthesis or a decreased collagen breakdown compared to the normotensive control (WKY).

    METHODS AND RESULTS: The renal damage was evaluated by light microscopy, and the amount of fibrosis was quantified using Sirius red staining. Real-time RT-PCR was used to quantify mRNA for: collagen-type-1-alpha-1 (col1a1), procollagen-n- and -c-proteinase, matrix metalloproteases, MMP-2 and MMP-9, tissue inhibitor of metalloproteases, TIMP-1 and TIMP-2. Western blot was used to quantify the proteins of MMP-2, MMP-9, TIMP-1 and TIMP-2. The relative activities of MMP-2 and MMP-9 were assayed by zymography. The JMC in SHR had an increased amount of collagen as measured by Sirius red, and a 15-fold increase in the mRNA for col1a1. The gene expression of procollagen-c-proteinase was unchanged while procollagen-n-proteinase was increased in SHR and had the highest expression in the JMC. The mRNA for MMP-2 and MMP-9 showed increased expression in SHR, but not specifically in the JMC. Protein analysis showed increased expression for MMP-2 in SHR and in the JMC. MMP-9 protein was lower in SHR. TIMP-1 was increased in SHR at both mRNA and protein level and more so in the JMC. The mRNA and protein analysis of TIMP-2 showed small differences between SHR and WKY.

    CONCLUSION: An imbalance of collagen metabolism featuring increased synthesis and inhibition of breakdown favours renal interstitial fibrosis in SHR.

  • 23. Ingvar, Åsa
    et al.
    Smedby, Karin Ekström
    Lindelöf, Bernt
    Fernberg, Pia
    Bellocco, Rino
    Tufveson, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Höglund, Petter
    Adami, Johanna
    Immunosuppressive treatment after solid organ transplantation and risk of post-transplant cutaneous squamous cell carcinoma2010In: Nephrology, Dialysis and Transplantation, ISSN 0931-0509, E-ISSN 1460-2385, Vol. 25, no 8, p. 2764-2771Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The risk of cutaneous squamous cell carcinoma (CSCC) is found to be substantially increased after organ transplantation. The association with specific immunosuppressive regimens has been previously investigated, but results are not concordant. We aimed to clarify the relationship between separate immunosuppressive drugs, drug load, timing and risk of post-transplant CSCC. METHODS: A population-based nested case-control study was performed in the Swedish organ transplantation cohort (n = 5931). All patients who developed CSCC during the follow-up (1970-97) were eligible as cases (n = 207). Controls (n = 189) were randomly selected from the cohort and individually matched to the cases on follow-up time, age at and calendar period of transplantation. Exposure information was collected through extensive and standardized review of medical records. RESULTS: The median time to CSCC was 6.7 years. Post-transplant azathioprine (Aza) treatment considerably increased the risk of CSCC during all time periods analysed, and the risk augmented with increasing dose and duration. Patients who after the entire follow-up period had received a high accumulated dose of Aza had an 8.8-fold increased risk of CSCC in multivariate analysis (P < 0.0001), compared to patients never treated with Aza. Additionally, a high accumulated dose of corticosteroids during the same period conferred a 3.9-fold elevated risk of CSCC (P = 0.09), compared to the lowest accumulated dose of corticosteroids. Cyclosporine treatment was not associated with the risk of CSCC post-transplantation. CONCLUSIONS: This study provides evidence that Aza treatment, but not cyclosporine treatment, is strongly associated with post-transplant CSCC risk. The results suggest that the risk of CSCC after organ transplantation is not only an effect of the immunosuppressive load per se.

  • 24.
    Kloster Smerud, Hilde
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Bárány, Peter
    Lindström, Karin
    Fernström, Anders
    Sandell, Anna
    Påhlsson, Peter
    Fellström, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    New Treatment of IgA nephropathy: Enteric Budesonide Targeted to the Ileocaecal Region Ameliorates Proteinuria2011In: Nephrology, Dialysis and Transplantation, ISSN 0931-0509, E-ISSN 1460-2385, Vol. 26, no 10, p. 3237-3242Article in journal (Refereed)
    Abstract [en]

    Background. Systemic corticosteroid treatment has been shown to exert some protection against renal deterioration in IgA nephropathy (IgAN) but is not commonly recommended for long-term use due to the well-known systemic side effects. In this study, we investigated the efficacy and safety of a new enteric formulation of the locally acting glucocorticoid budesonide (Nefecon (R)), designed to release the active compound in the ileocecal region. The primary objective was to evaluate the efficacy of targeted release budesonide on albuminuria.

    Methods. Budesonide 8 mg/day was given to 16 patients with IgAN for 6 months, followed by a 3-month follow-up period. The efficacy was measured as change in 24-h urine albumin excretion, serum creatinine and estimated glomerular filtration rate (eGFR).

    Results. The median relative reduction in urinary albumin excretion was 23% during the treatment period (interquartile range: -0.36 to -0.04, P = 0.04) with pretreatment values ranging from 0.3 to 6 g/24 h (median: 1.5 g/24 h). The median reduction in urine albumin peaked at 40% (interquartile range: -0.58 to -0.15) 2 months after treatment discontinuation. Serum creatinine was reduced by 6% (interquartile range: -0.12 to -0.02; P = 0.003), and eGFR [Modification of Diet in Renal Disease (MDRD)] increased similar to 8% (interquartile range: 0.02-0.16, P = 0.003) during treatment. No major corticosteroid-related side effects were observed.

    Conclusions. In the present pilot study, enteric budesonide targeted to the ileocecal region had a significant effect on urine albumin excretion, accompanied by a minor reduction of serum creatinine and a modest increase of eGFR calculated by the MDRD equation, while eGFR calculated from Cockcroft-Gault equation and cystatin C was not changed. Enteric budesonide may represent a new treatment of IgAN warranting further investigation.

  • 25.
    Kuppe, Christoph
    et al.
    Rhein Westfal TH Aachen, Div Nephrol & Immunol, Aachen, Germany.
    Rohlfs, Wilko
    Rhein Westfal TH Aachen, Inst Heat & Mass Transfer, Aachen, Germany.
    Grepl, Martin
    Rhein Westfal TH Aachen, Fac Math Informat & Nat Sci, Numer Math, Aachen, Germany.
    Schulte, Kevin
    Rhein Westfal TH Aachen, Div Nephrol & Immunol, Aachen, Germany;Univ Kiel, Dept Nephrol, Kiel, Germany.
    Veron, Delma
    Yale Univ, Sch Med, Dept Pediat, New Haven, CT 06510 USA.
    Elger, Marlies
    Heidelberg Univ, Med Fac Mannheim, Dept Anat & Dev Biol, Mannheim, Germany.
    Sanden, Silja Kerstin
    Rhein Westfal TH Aachen, Div Nephrol & Immunol, Aachen, Germany.
    Saritas, Turgay
    Rhein Westfal TH Aachen, Div Nephrol & Immunol, Aachen, Germany.
    Andrae, Johanna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Vascular Biology.
    Betsholtz, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Vascular Biology.
    Trautwein, Christian
    RWTH Aachen Univ Hosp, Div Gastroenterol & Endocrinol, Aachen, Germany.
    Hausmann, Ralf
    RWTH Aachen Univ Hosp, Inst Mol Pharmacol, Aachen, Germany.
    Quaggin, Susan
    Northwestern Univ, Div Med Nephrol, Feinberg Cardiovasc Res Inst, Chicago, IL 60611 USA.
    Bachmann, Sebastian
    Charite, Dept Anat, Berlin, Germany.
    Kriz, Wilhelm
    Heidelberg Univ, Med Fac Mannheim, Dept Anat & Dev Biol, Mannheim, Germany.
    Tufro, Alda
    Yale Univ, Sch Med, Dept Pediat, New Haven, CT 06510 USA.
    Floege, Jürgen
    Rhein Westfal TH Aachen, Div Nephrol & Immunol, Aachen, Germany.
    Moeller, Marcus J.
    Rhein Westfal TH Aachen, Div Nephrol & Immunol, Aachen, Germany;RWTH Aachen Univ Hosp, Interdisciplinary Ctr Clin Res IZKF Aachen, Aachen, Germany;Rhein Westfal TH Aachen, Heisenberg Chair Prevent & Translat Nephrol, Div Nephrol, Aachen, Germany.
    Inverse correlation between vascular endothelial growth factor back-filtration and capillary filtration pressures2018In: Nephrology, Dialysis and Transplantation, ISSN 0931-0509, E-ISSN 1460-2385, Vol. 33, no 9, p. 1514-1525Article in journal (Refereed)
    Abstract [en]

    Background: Vascular endothelial growth factor A (VEGF) is an essential growth factor during glomerular development and postnatal homeostasis. VEGF is secreted in high amounts by podocytes into the primary urine, back-filtered across the glomerular capillary wall to act on endothelial cells. So far it has been assumed that VEGF back-filtration is driven at a constant rate exclusively by diffusion.

    Methods: In the present work, glomerular VEGF back-filtration was investigated in vivo using a novel extended model based on endothelial fenestrations as surrogate marker for local VEGF concentrations. Single nephron glomerular filtration rate (SNGFR) and/or local filtration flux were manipulated by partial renal mass ablation, tubular ablation, and in transgenic mouse models of systemic or podocytic VEGF overexpression or reduction.

    Results: Our study shows positive correlations between VEGF back-filtration and SNGFR as well as effective filtration rate under physiological conditions along individual glomerular capillaries in rodents and humans.

    Conclusion: Our results suggest that an additional force drives VEGF back-filtration, potentially regulated by SNGFR.

  • 26.
    Linde, Cecilia
    et al.
    Karolinska Univ Hosp, Heart & Vasc Theme, Stockholm, Sweden; Karolinska Inst, Heart & Vasc Theme, Stockholm, Sweden.
    McEwan, Phil
    HEOR Ltd, Hlth Econ & Outcomes Res, Cardiff, S Glam, Wales; Swansea Univ, Sch Human & Hlth Sci, Swansea, W Glam, Wales.
    Bakhai, Ameet
    Royal Free Hosp, Dept Cardiol, London, England.
    Furuland, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Renal Medicine.
    Evans, Marc
    Llandough Hosp, Diabet Resource Ctr, Cardiff, S Glam, Wales.
    Ayoubkhani, Daniel
    HEOR Ltd, Hlth Econ & Outcomes Res, Cardiff, S Glam, Wales.
    Grandy, Susan
    AstraZeneca, Global Hlth Econ, Gaithersburg, MD USA.
    Palaka, Eirini
    AstraZeneca, Global Hlth Econ, Cambridge, England.
    Qin, Lei
    AstraZeneca, Global Hlth Econ, Gaithersburg, MD USA.
    RELATIONSHIP BETWEEN HYPERKALAEMIA AND DOWN-TITRATION OR DISCONTINUATION OF RENIN-ANGIOTENSIN-ALDOSTERONE SYSTEM INHIBITORS IN UK PATIENTS WITH CKD2018In: Nephrology, Dialysis and Transplantation, ISSN 0931-0509, E-ISSN 1460-2385, Vol. 33, no Supplement: 1, p. 145-145Article in journal (Other academic)
  • 27.
    Linde, Torbjörn
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Sandhagen, B.
    Bratteby, L. E.
    de Verdier, C. H.
    Danielson, Bo G.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Wikström, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Reduced oxygen affinity contributes to improved oxygen releasing capacityduring erythropoietin treatment of renal anaemia1993In: Nephrology, Dialysis and Transplantation, ISSN 0931-0509, E-ISSN 1460-2385, Vol. 8, no 6, p. 524-529Article in journal (Refereed)
    Abstract [en]

    In addition to haemoglobin concentration, haemoglobin oxygen affinity plays a major role in the oxygen releasing capacity of the blood. In this study we have measured oxygen affinity as P50 and calculated the oxygen releasing capacity of blood from 10 haemodialysis patients treated with erythropoietin (rHuEpo). The patients were examined with different assays before start of treatment, after 11 weeks, and after 27 weeks. During the first phase of treatment the oxygen releasing capacity improved because of an increase in the haemoglobin concentration and P50. During the second phase there was a further significant increase in haemoglobin concentration, but due to a decrease in the P50 value the oxygen releasing capacity remained unchanged. Despite an unchanged oxygen releasing capacity and total blood volume, the antihypertensive treatment had to be increased during that phase of treatment. An increase in whole-blood viscosity may explain the increased need of antihypertensive drugs. The increase in P50 during the first phase of rHuEpo treatment can probably be explained by decreased mean age of the erythrocyte population and implies that the beneficial effect is greater than could be concluded from the increase in haemoglobin concentration.

  • 28.
    Linde, Torbjörn
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Sandhagen, Bo
    Backman, Ulla
    Fellström, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Altered flow properties of blood and increased plasma fibrinogen in cyclosporin treated renal allograft recipients1999In: Nephrology, Dialysis and Transplantation, ISSN 0931-0509, E-ISSN 1460-2385, Vol. 14, no 6, p. 1525-1529Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Abnormalities in blood rheology may be factors contributing to cardiovascular complications and the progression of renal failure in kidney allograft recipients. The haemorheological variables haematocrit, fibrinogen, whole blood viscosity, plasma viscosity, erythrocyte aggregation tendency and fluidity were measured in 27 cyclosporin A (CyA)-treated patients who had received a renal graft at least 6 months previously. Their creatinine clearance was in the range of 12-92 ml/min/1.73 m2 (mean 55+/-19). The values were compared with those obtained from a control group comprising 20 healthy subjects matched according to age, sex and smoking habits.

    RESULTS: The haematocrit, plasma fibrinogen, whole blood viscosity, plasma viscosity, erythrocyte aggregation tendency, body mass index (BMI), mean arterial pressure (MAP) and serum triglycerides were increased in the transplanted patients, and the serum high density lipoprotein (HDL)-cholesterol and erythrocyte fluidity decreased. The haemorheological variables were used as dependent variables in a stepwise regression analysis with age, MAP, BMI, urinary albumin excretion rate, blood CyA concentration, creatinine clearance, and serum triglycerides, cholesterol and HDL-cholesterol as independent variables. Plasma fibrinogen was positively correlated with BMI and blood CyA. The whole blood viscosity was positively correlated with blood CyA and negatively with serum HDL-cholesterol. Only serum triglycerides remained correlated with erythrocyte aggregation tendency.

    CONCLUSIONS: All variables with a known impact on blood viscosity were altered in the present group of renal transplant recipients. Inappropriate regulation of erythrocyte formation, overweight, the use of CyA, high triglycerides and low HDL-cholesterol levels may be factors contributing to this. The importance of impaired flow properties of blood for the development of cardiovascular diseases and transplant glomerulosclerosis needs to be examined.

  • 29.
    Linde, Torbjörn
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Sandhagen, Bo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Wikström, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Danielson, Bo G.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    The required dose of erythropoietin during renal anaemia treatment is related to the degree of impairment in erythrocyte deformability1997In: Nephrology, Dialysis and Transplantation, ISSN 0931-0509, E-ISSN 1460-2385, Vol. 12, no 11, p. 2375-2379Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Renal anaemia is rapidly corrected by recombinant human erythropoietin (rHuEpo) therapy, but the dose required varies greatly. Since impaired erythrocyte deformability may be one factor contributing to the development of renal anaemia, the interrelationship between that variable and the rHuEpo requirement was examined.

    METHODS: Twenty-five patients treated with hemodialysis and rHuEpo for at least 6 months were included in the study. The Hb value had been stable and the rHuEpo dose unchanged the last two months. Using a rotational viscometer, the fluidity of erythrocytes, separated from plasma and re-suspended in isotonic buffered saline to a standardized haematocrit, was taken as a measure of erythrocyte deformability.

    RESULTS: The average weekly dose of s.c. epoetin alpha was 186 +/- 93 U/kg body weight (range 56-370). The dose was correlated to the reticulocyte fraction (R = 0.69, P = 0.0001). When the rHuEpo dose was used as dependent variable and blood haemoglobin concentration, serum (S) albumin, S ferritin, S aluminium, S PTH, S urea, Kt/V/week, erythrocyte fluidity, and plasma viscosity were used as independent variables in a stepwise multiple regression analysis, only erythrocyte fluidity remained significantly negatively correlated to the rHuEpo dose (R = 0.5, P = 0.01). Despite a tendency towards higher doses of rHuEpo in patients with a C-reactive protein concentration exceeding 20 mg/l, the Hb was lower in these patients.

    CONCLUSIONS: We conclude that the interindividual differences in bone marrow response to rHuEpo were small in these patients. Impaired erythrocyte deformability and inflammation seem to be factors associated with increased rHuEpo requirement.

  • 30.
    Luis, Desiree
    et al.
    Karolinska Inst, Div Renal Med & Baxter Novum, Stockholm, Sweden..
    Huang, Xiaoyan
    Karolinska Inst, Div Renal Med & Baxter Novum, Stockholm, Sweden..
    Risérus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Sjögren, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Lindholm, Bengt
    Karolinska Inst, Div Renal Med & Baxter Novum, Stockholm, Sweden..
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Cederholm, Tommy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Carrero, Juan Jesus
    Karolinska Inst, Div Renal Med & Baxter Novum, Stockholm, Sweden..
    Dietary Acid Load, Kidney Function, Changes in Blood Pressure and Hypertension Incidence in Community Dwelling Elderly Men2015In: Nephrology, Dialysis and Transplantation, ISSN 0931-0509, E-ISSN 1460-2385, Vol. 30Article in journal (Other academic)
  • 31. Mafham, Marion M
    et al.
    Staplin, Natalie
    Emberson, Jonathan
    Haynes, Richard
    Herrington, William
    Reith, Christina
    Wanner, Christoph
    Walker, Robert
    Cass, Alan
    Levin, Adeera
    Fellström, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Renal Medicine.
    Jiang, Lixin
    Holdaas, Hallvard
    Kasiske, Bertram
    Wheeler, David C
    Landray, Martin J
    Baigent, Colin
    Prognostic utility of estimated albumin excretion rate in chronic kidney disease: results from the Study of Heart and Renal Protection2018In: Nephrology, Dialysis and Transplantation, ISSN 0931-0509, E-ISSN 1460-2385, Vol. 33, no 2, p. 257-264Article in journal (Refereed)
    Abstract [en]

    Background: Estimated albumin excretion rate (eAER) provides a better estimate of 24-h albuminuria than albumin:creatinine ratio (ACR). However, whether eAER is superior to ACR in predicting end-stage renal disease (ESRD), vascular events (VEs) or death is uncertain.

    Methods: The prognostic utility of ACR and eAER (estimated from ACR, sex, age and race) to predict mortality, ESRD and VEs was compared using Cox proportional hazards regression among 5552 participants with chronic kidney disease in the Study of Heart and Renal Protection, who were not on dialysis at baseline.

    Results: During a median follow-up of 4.8 years, 1959 participants developed ESRD, 1204 had a VE and 1130 died (641 from a non-vascular, 369 from a vascular and 120 from an unknown cause). After adjustment for age, sex and eGFR, both ACR and eAER were strongly and similarly associated with ESRD risk. The average relative risk (RR) per 10-fold higher level was 2.70 (95% confidence interval 2.45-2.98) for ACR and 2.67 (2.43-2.94) for eAER. Neither ACR nor eAER provided any additional prognostic information for ESRD risk over and above the other. For VEs, there were modest positive associations between both ACR and eAER and risk [adjusted RR per 10-fold higher level 1.37 (1.22-1.53) for ACR and 1.36 (1.22-1.52) for eAER]. Again, neither measure added prognostic information over and above the other. Similar results were observed when ACR and eAER were related to vascular mortality [RR per 10-fold higher level: 1.64 (1.33-2.03) and 1.62 (1.32-2.00), respectively] or to non-vascular mortality [1.53 (1.31-1.79) and 1.50 (1.29-1.76), respectively].

    Conclusions: In this study, eAER did not improve risk prediction of ESRD, VEs or mortality.

  • 32.
    Makela, Satu
    et al.
    Tampere Univ Hosp, Internal Med, Tampere, Finland..
    Asola, Markku
    Baxter Oy, Helsinki, Finland..
    Hadimeri, Henrik
    Karnsjukhuset Skovde, Dept Med & Nephrol, Skovde, Sweden..
    Heaf, James
    Univ Copenhagen, Roskilde Hosp, Dept Med, Roskilde, Denmark..
    Heiro, Maija
    Turku Univ Hosp, Dept Med, FIN-20520 Turku, Finland..
    Kauppila, Leena
    Terveystalo Healthcare, Terveystalo, Helsinki, Finland..
    Ljungman, Susanne
    Sahlgrens Univ Hosp, Dept Nephrol, Gothenburg, Sweden..
    Ots-Rosenberg, Mai
    Tartu Univ Hosp, Dept Nephrol, Tartu, Estonia..
    Povlsen, Johan
    Aarhus Univ Hosp, Dept Nephrol, DK-8000 Aarhus, Denmark..
    Rogland, Björn
    Hassleholm Hosp, Dept Med, Kristianstad, Sweden..
    Rossel, Petra
    Aalborg Univ Hosp, Dept Med, Aalborg, Denmark..
    Svensson, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Vainiotalo, Maarit
    Satakunta Cent Hosp, Internal Med, Pori, Finland..
    Saha, Heikki
    Tampere Univ Hosp, Internal Med, Tampere, Finland..
    Abdominal Aortic Calcifications Predict All-Cause Mortality In Peritoneal Dialysis Patients2016In: Nephrology, Dialysis and Transplantation, ISSN 0931-0509, E-ISSN 1460-2385, Vol. 31, p. 241-241Article in journal (Other academic)
  • 33. Mann, Johannes F. E.
    et al.
    Sheridan, Patrick
    McQueen, Matthew J.
    Held, Claes
    Munich Gen Hosp, Dept Med, Munich, Germany .
    Arnold, J. Malcolm O.
    Fodor, George
    Yusuf, Salim
    Lonn, Eva M.
    Homocysteine lowering with folic acid and B vitamins in people with chronic kidney disease: results of the renal Hope-2 study2008In: Nephrology, Dialysis and Transplantation, ISSN 0931-0509, E-ISSN 1460-2385, Vol. 23, no 2, p. 645-653Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Elevated plasma homocysteine levels are reported to be associated with higher rates of vascular diseases. Plasma homocysteine increases in chronic kidney disease (CKD) and could contribute to the increased cardiovascular risk in CKD. METHODS: Participants aged 55 years or older with CKD, defined as estimated GFR<60 ml/min and at high cardiovascular risk, were randomly assigned to the combination of folic acid, 2.5 mg, vitamin B6, 50 mg and vitamin B12, 1 mg (n = 307) or placebo (n = 312) daily for 5 years. The primary outcome was a composite of death from cardiovascular causes, myocardial infarction and stroke. RESULTS: Mean baseline plasma homocysteine was 15.9 +/- 7.3 micromol/l in the active treatment group and 15.7 +/- 5.7 micromol/l in placebo group and decreased to 11.9 +/- 3.3 micromol/l (P < 0.001) on active treatment (15.5 +/- 4.5 on placebo). Primary outcome events occurred in 90 participants (29.3%) on active therapy and in 80 (25.6%) on placebo (relative risk, 1.19; 95% confidence interval, 0.88-1.61; P = 0.25). There were no significant treatment benefits on death from cardiovascular causes (1.24; 0.84-1.83), myocardial infarction (1.10; 0.76-1.61) and stroke (1.00; 0.54-1.85). More participants in the active treatment group were hospitalized for heart failure (1.98; 1.21-3.26; P = 0.007) and for unstable angina (1.70; 1.02-2.83; P = 0.04). Incidence of primary outcome increased with decreasing GFR. CONCLUSIONS: Active treatment with B vitamins lowered homocysteine levels in participants with CKD but did not reduce cardiovascular risk.

  • 34.
    Marsell, Richard
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Krajisnik, Tijana
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Göransson, Hanna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Ohlsson, Claes
    Ljunggren, Osten
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Larsson, Tobias E.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Jonsson, Kennet B
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Gene Expression Analysis of Kidneys From Transgenic Mice Expressing Fibroblast Growth Factor-232008In: Nephrology, Dialysis and Transplantation, ISSN 0931-0509, E-ISSN 1460-2385, Vol. 23, no 3, p. 827-833Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Fibroblast growth factor-23 (FGF23), a circulating protein produced in bone, causes decreased renal inorganic phosphate (Pi) reabsorption by reducing the expression of the sodium phosphate cotransporter type 2a (Npt2a). We have previously generated transgenic mice expressing human wild-type (WT) FGF23 under the control of the alpha1 (I) collagen promoter. METHODS: In this study, we performed a large-scale gene expression study of kidneys from FGF23 transgenic mice and WT littermates. Microarray expression data of key transcripts were verified by real-time RT-PCR analysis. RESULTS: Several genes that play a role in Pi regulation revealed decreased expression levels in the transgenic mice, such as Npt2a and Pdzk1, a scaffolding protein known to interact with Npt2a. Importantly, Klotho, a suggested FGF23 receptor cofactor, was the most significantly decreased transcript and alpha2-Na(+)/K(+)-ATPase (Atp1a2), a gene isoform of alpha1-Na(+)/K(+)-ATPase (Atp1a1) which has recently been shown to interact with Klotho and regulate calcium metabolism, was the most increased transcript. In contrast, other genes proposed to regulate Pi levels, such as secreted frizzled-related protein-4 (sFrp4) and Na(+)/H(+) exchanger regulatory factor-1 (Nherf1) revealed no changes. CONCLUSIONS: FGF23 transgenic mice display differentially expressed transcript levels of several genes essential in renal Pi regulation. These findings may lead to further understanding of how FGF23 mediates its actions on renal Pi regulation.

  • 35.
    Massart, Annick
    et al.
    Univ Libre Bruxelles, Renal Unit, CUB Hop Erasme, Brussels, Belgium.;ULB, Med Genet Dept, Brussels, Belgium..
    Pallier, Annaick
    French Inst Hlth & Med Res, Joint Res Unit 1064, Nantes, France..
    Pascual, Julio
    Hosp del Mar, Nephrol, Barcelona, Spain..
    Viklicky, Ondrej
    Inst Clin & Expt Med, Dept Nephrol, Prague, Czech Republic..
    Budde, Klemens
    Charite Campus Mitte, Nephrol, Berlin, Germany..
    Spasovski, Goce
    Univ Dept Nephrol, Skopje, Macedonia..
    Klinger, Marian
    Nephrol & Transplantat Med, Wroclaw, Poland..
    Sever, Mehmet Sukru
    Istanbul Sch Med, Internal Med, Nephrol, Istanbul, Turkey..
    Sorensen, Soren Schwartz
    Rigshosp, Nephrol P, Copenhagen, Denmark..
    Hadaya, Karine
    Univ Hosp Geneva, Nephrol & Transplantat, Geneva, Switzerland..
    Oberbauer, Rainer
    Krankenhaus Elisabethinen Linz, Dept Med Nephrol Hypertens & Renal Transp 3, Linz, Austria..
    Dudley, Christopher
    North Bristol NHS Trust, Richard Bright Renal Ctr, Southmead Hosp, Bristol, Avon, England..
    De Fijter, Johan W.
    Leiden Univ, Med Ctr, Dept Med, Div Nephrol, Leiden, Netherlands..
    Yussim, Alexander
    Tel Aviv Univ, Sackler Sch Med, Dept Transplantat, Rabin Med Ctr, Tel Aviv, Israel..
    Hazzan, Marc
    CHU Lille, Nephrol Dept, Lille, France..
    Wekerle, Thomas
    Med Univ Vienna, Dept Surg, Sect Transplantat Immunol, Vienna, Austria..
    Berglund, David
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    De Biase, Consuelo
    Az Osped Univ Parma, UOS Trapianti Rene Pancreas, Ctr Trapianti Parma, Parma, Italy..
    Jose Perez-Saez, Maria
    Hosp del Mar, Nephrol, Barcelona, Spain..
    Muehlfeld, Anja
    Univ Hosp Aachen, Dept Nephrol, Aachen, Germany..
    Orlando, Giuseppe
    Wake Forest Sch Med, Dept Surg, Sect Transplantat, Winston Salem, NC USA..
    Clemente, Katia
    UOC Trapianti Organo, Laquila, Italy..
    Lai, Quirino
    UOC Trapianti Organo, Laquila, Italy..
    Pisani, Francesco
    UOC Trapianti Organo, Laquila, Italy..
    Kandus, Aljosa
    Univ Med Ctr Ljubljana, Renal Transplantat Ctr Ljubljana, Dept Nephrol, Ljubljana, Slovenia..
    Baas, Marije
    Radboudumc Nijmegen, Kidney Dis, Nijmegen, Netherlands..
    Bemelman, Frederike
    Acad Med Ctr, Dept Nephrol, Renal Transplant Unit, Amsterdam, Netherlands..
    Ponikvar, Jadranka Buturovic
    Univ Med Ctr Ljubljana, Renal Transplantat Ctr Ljubljana, Dept Nephrol, Ljubljana, Slovenia..
    Mazouz, Hakim
    CHU Sud, Serv Nephrol, Unite Transplantat Renale & Pancreat, Amiens, France..
    Stratta, Piero
    Amedeo Avogadro Univ, Dept Translat Med, AOU Maggiore Carita Novara, Novara, Italy..
    Subra, Jean-Francois
    CHU Angers, Serv Nephrol Dialyse Transplantat, Angers, France..
    Villemain, Florence
    CHU Angers, Serv Nephrol Dialyse Transplantat, Angers, France..
    Hoitsma, Andries
    Radboudumc Nijmegen, Kidney Dis, Nijmegen, Netherlands..
    Braun, Laura
    CHU Strasbourg, Hop Jour Nephrol, Serv Nephrol & Transplantat Renale, Nouvel Hop Civil, Strasbourg, France..
    Carmen Cantarell, Maria
    Hosp Univ Val dHebron, Nephrol, Barcelona, Spain..
    Colak, Hulya
    Tepecik Training & Res Hosp, Nephrol, Izmir, Turkey..
    Courtney, Aisling
    Belfast City Hosp, Reg Nephrol Unit, Belfast, Antrim, North Ireland..
    Frasca, Giovanni Maria
    AO Torrette Umberto I, Nefrol Dialisi & Trapianto Rene, Ancona, Italy..
    Howse, Matthew
    Royal Liverpool Univ Hosp, Nephrol Transplantat, Liverpool, Merseyside, England..
    Naesens, Maarten
    Univ Hosp Leuven, Dept Nephrol & Renal Transplantat, Leuven, Belgium..
    Reischig, Tomas
    Univ Hosp Plzen, Dept Internal Med, Nephrol Ward, Plzen, Czech Republic..
    Seron, Daniel
    Hosp Univ Val dHebron, Nephrol, Barcelona, Spain..
    Seyahi, Nurhan
    Istanbul Univ, Cerrahpasa Med Fac, Nephrol, Istanbul, Turkey..
    Tugmen, Cem
    Tepecik Training & Res Hosp, Gen Surg, Izmir, Turkey..
    Alonso Hernandez, Angel
    Univ Hosp, Serv Nefrol, La Coruna, Spain..
    Bena, Luboslav
    Univ Hosp Louis Pasteur Kosice, Transplant Ctr, Kosice, Slovakia..
    Biancone, Luigi
    Univ Turin, Dept Med Sci, Turin, Italy..
    Cuna, Vania
    Univ Bologna, St Orsola Univ Hosp, Dept Specialized Expt & Diagnost Med, Sect Nephrol,Nephrol Dialysis & Renal Transplant, Bologna, Italy..
    Diaz-Corte, Carmen
    HUCA, Nephrol, Oviedo, Spain..
    Dufay, Alexandre
    Hop Victor Provo, Serv Nephrol, Roubaix, France..
    Gaasbeek, Andre
    LUMC, Nierziekten, Leiden, Netherlands..
    Garnier, Arnaud
    Hop Enfants, Nephrol Med Interne Hypertens Pediat, Toulouse, France..
    Gatault, Philippe
    CHRU, Serv Nephrol Immunoclin, Hop Bretonneau, Tours, France..
    Gentil Govantes, Miguel Angel
    Hosp Univ Virgen del Rocio, Unidad Gest Clin Urol & Nefrol, Seville, Spain..
    Glowacki, Francois
    Univ Hosp Lille, Dept Nephrol, Lille, France..
    Gross, Oliver
    Univ Med Gottingen, Dept Nephrol & Rheumatol, Gottingen, Germany..
    de Ligny, Bruno Hurault
    CHRU Ave Georges Clemenceau, Serv Nephrol, Caen, France..
    Huynh-Do, Uyen
    Univ Hosp Bern, Inselspital, Div Nephrol Hypertens & Clin Pharmacol, Bern, Switzerland..
    Janbon, Benedicte
    CHU Grenoble, Transplantat Renale, Grenoble, France..
    Antonio Jimenez del Cerro, Luis
    Hosp Gen Univ Alicante, Serv Nefrol, Alicante, Spain..
    Keller, Frieder
    Univ Hosp Ulm, Internal Med 1, Nephrol, Ulm, Germany..
    La Manna, Gaetano
    Univ Bologna, St Orsola Univ Hosp, Dept Specialized Expt & Diagnost Med, Sect Nephrol,Nephrol Dialysis & Renal Transplant, Bologna, Italy..
    Lauzurica, Ricardo
    Hosp Badalona Germans Trias & Pujol, Nephrol, Badalona, Barcelona, Spain..
    De Sagazan, Herve Le Monies
    Hop Victor Provo, Serv Nephrol, Roubaix, France..
    Thaiss, Friedrich
    Univ Hosp Hamburg Eppendorf UKE, Hamburg, Germany..
    Legendre, Christophe
    Univ Paris 05, Paris, France.;Hop Necker Enfants Malad, Paris, France..
    Martin, Severine
    Hop Robert Boulin, Serv Hemodialyse & Nephrol, Libourne, France..
    Moal, Marie-Christine
    CHRU Brest, Serv Nephrol, Brest, France..
    Noel, Christian
    Univ Hosp Lille, Dept Nephrol, Lille, France..
    Pillebout, Evangeline
    Hop St Louis, Nephrol Unit, Paris, France..
    Piredda, Gian Benedetto
    Kidney Transplant Az Osp G Brotzu, Kidney Dis, Cagliari, Italy..
    Ramirez Puga, Ana
    Hosp Univ Insular Gran Canaria, Serv Nefrol, Las Palmas Gran Canaria, Spain..
    Sulowicz, Wladyslaw
    Univ Hosp Krakow, Dept Nephrol, Krakow, Poland..
    Tuglular, Serhan
    Marmara Sch Med Hastanesi, Nephrol, Istanbul, Turkey..
    Prokopova, Michaela
    Inst Clin & Expt Med, Dept Nephrol, Prague, Czech Republic..
    Chesneau, Melanie
    Nantes Univ Hosp, Inst Transplantat Urol & Nephrol, Nantes, France..
    Le Moine, Alain
    Univ Libre Bruxelles, Renal Unit, CUB Hop Erasme, Brussels, Belgium..
    Guerif, Pierrick
    Nantes Univ Hosp, Inst Transplantat Urol & Nephrol, Nantes, France..
    Soulillou, Jean-Paul
    French Inst Hlth & Med Res, Joint Res Unit 1064, Nantes, France.;Nantes Univ Hosp, Inst Transplantat Urol & Nephrol, Nantes, France.;Univ Nantes, Fac Med, Nantes, France..
    Abramowicz, Marc
    ULB, Med Genet Dept, Brussels, Belgium.;ULB, IRIBHM, Brussels, Belgium..
    Giral, Magali
    French Inst Hlth & Med Res, Joint Res Unit 1064, Nantes, France.;Nantes Univ Hosp, Inst Transplantat Urol & Nephrol, Nantes, France.;Univ Nantes, Fac Med, Nantes, France..
    Racape, Judith
    ULB, Res Ctr Epidemiol Biostat & Clin Res, Sch Publ Hlth, Brussels, Belgium..
    Maggiore, Umberto
    Az Osped Univ Parma, UOS Trapianti Rene Pancreas, Ctr Trapianti Parma, Parma, Italy..
    Brouard, Sophie
    French Inst Hlth & Med Res, Joint Res Unit 1064, Nantes, France.;Nantes Univ Hosp, Inst Transplantat Urol & Nephrol, Nantes, France.;Univ Nantes, Fac Med, Nantes, France..
    Abramowicz, Daniel
    Univ Ziekenhuis Antwerp, Nephrol Renal Transplantat Dept, Antwerp, Belgium.;Univ Libre Bruxelles, Brussels, Belgium..
    The DESCARTES-Nantes survey of kidney transplant recipients displaying clinical operational tolerance identifies 35 new tolerant patients and 34 almost tolerant patients2016In: Nephrology, Dialysis and Transplantation, ISSN 0931-0509, E-ISSN 1460-2385, Vol. 31, no 6, p. 1002-1013Article in journal (Refereed)
    Abstract [en]

    Background. Kidney recipients maintaining a prolonged allograft survival in the absence of immunosuppressive drugs and without evidence of rejection are supposed to be exceptional. The ERA-EDTA-DESCARTES working group together with Nantes University launched a European-wide survey to identify new patients, describe them and estimate their frequency for the first time. Methods. Seventeen coordinators distributed a questionnaire in 256 transplant centres and 28 countries in order to report as many 'operationally tolerant' patients (TOL; defined as having a serum creatinine <1.7 mg/dL and proteinuria <1 g/day or g/g creatinine despite at least 1 year without any immunosuppressive drug) and 'almost tolerant' patients (minimally immunosuppressed patients (MIS) receiving low-dose steroids) as possible. We reported their number and the total number of kidney transplants performed at each centre to calculate their frequency. Results. One hundred and forty-seven questionnaires were returned and we identified 66 TOL (61 with complete data) and 34 MIS patients. Of the 61 TOL patients, 26 were previously described by the Nantes group and 35 new patients are presented here. Most of them were noncompliant patients. At data collection, 31/35 patients were alive and 22/31 still operationally tolerant. For the remaining 9/31, 2 were restarted on immunosuppressive drugs and 7 had rising creatinine of whom 3 resumed dialysis. Considering all patients, 10-year death-censored graft survival post-immunosuppression weaning reached 85% in TOL patients and 100% in MIS patients. With 218 913 kidney recipients surveyed, cumulative incidences of operational tolerance and almost tolerance were estimated at 3 and 1.5 per 10 000 kidney recipients, respectively. Conclusions. In kidney transplantation, operational tolerance and almost tolerance are infrequent findings associated with excellent long-term death-censored graft survival.

  • 36.
    Mirza, Majd A I
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Hansen, Tomas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Johansson, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Larsson, Tobias E
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Relationship between circulating FGF23 and total body atherosclerosis in the community2009In: Nephrology, Dialysis and Transplantation, ISSN 0931-0509, E-ISSN 1460-2385, Vol. 24, no 10, p. 3125-3131Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Fibroblast growth factor-23 (FGF23) is a regulator of mineral metabolism and has been suggested to play a role in vascular calcification in chronic kidney disease (CKD). Data on the association between FGF23 and atherosclerosis, both in CKD and in the community, is limited. METHODS: The total body atherosclerosis score (AS) was determined by a magnetic resonance imaging-based angiography in 306 elderly men and women, representing a subsample of the community-based PIVUS cohort. Subjects were divided into three categories based on AS: AS = 0, low AS and high AS. Serum FGF23 was measured using a two-site monoclonal antibody ELISA. RESULTS: In continuous and multi-category regression models, higher FGF23 was associated with a significant increase in the odds of having a high AS (OR 1.43, CI 1.06-1.92 to OR 3.01, CI 1.52-5.99). This association was stronger in individuals with eGFR <60 mL/min/1.73 m(2) (n = 27), reaching a nearly 6-fold increase in the odds for a high AS in the upper FGF23 tertile (OR 5.64, CI 2.78-11.5). We found weaker support for a relationship between FGF23 and the presence of atherosclerosis as subjects in the highest FGF23 tertile had an increased risk for an AS > 0 in crude models (OR 1.93, CI 1.05-3.55), but this was not statistically significant in adjusted (OR 1.42, CI 0.74-1.72) models. CONCLUSIONS: We provide novel evidence supporting an association between serum FGF23 and total body atherosclerosis in the community. Additional studies are warranted to determine the prospective relationship between FGF23 and atherosclerosis, and whether FGF23 is a modifiable cardiovascular risk factor.

  • 37. Mjoen, Geir
    et al.
    Zannad, Faiez
    Jardine, Alan
    Schmieder, Roland
    Fellström, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Renal Medicine.
    Holdaas, Hallvard
    Pulse Pressure Superior to Systolic or Diastolic Blood Pressure in Predicting Mortality in Hemodialysis Patients2014In: Nephrology, Dialysis and Transplantation, ISSN 0931-0509, E-ISSN 1460-2385, Vol. 29, p. 79-79Article in journal (Other academic)
  • 38. Naess, Hege
    et al.
    Fellström, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Renal Medicine.
    Jardine, Alan G.
    Schmieder, Roland E.
    Zannad, Faiez
    Holdaas, Hallvard
    Mjoen, Geir
    Risk Factors for Cardiovascular Events and All-Cause Mortality in Diabetic Hemodialysis Patients2014In: Nephrology, Dialysis and Transplantation, ISSN 0931-0509, E-ISSN 1460-2385, Vol. 29, p. 487-487Article in journal (Other academic)
  • 39.
    Naess, Hege
    et al.
    Ringerike Hosp, Med, Honefoss, Norway..
    Zannad, Faiez
    Nancy Univ, Dept Cardiol, Nancy, France..
    Jardine, Alan G.
    Univ Glasgow, Renal Res Grou, Glasgow, Lanark, Scotland..
    Schmieder, Roland E.
    Univ Hosp Erlangen, Dept Hypertens & Nephrol, Erlangen, Germany..
    Fellström, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Renal Medicine.
    Holdaas, Hallvard
    Oslo Univ Hosp, Dept Transplant Med, Oslo, Norway..
    Mjoen, Geir
    Oslo Univ Hosp, Dept Nephrol, Oslo, Norway..
    NON-TRADITIONAL CARDIOVASCULAR RISK FACTORS PREDOMINATE IN HEMODIALYSIS PATIENTS WITH PRE-EXISTIN CARDIOVASCULAR DISEASE2015In: Nephrology, Dialysis and Transplantation, ISSN 0931-0509, E-ISSN 1460-2385, Vol. 30Article in journal (Other academic)
  • 40.
    Nerpin, Elisabet
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics. Högskolan Dalarna-Medicinsk vetenskap.
    Ingelsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Risérus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Andrén, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Jobs, Elisabet
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics. Högskolan Dalarna Medicinsk vetenskap.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics. Högskolan Dalarna Medicinsk vetenskap.
    The association between glomerular filtration rate and left ventricular function in two independent community-based cohorts of elderly2014In: Nephrology, Dialysis and Transplantation, ISSN 0931-0509, E-ISSN 1460-2385, Vol. 29, no 11, p. 2069-2074Article in journal (Refereed)
    Abstract [en]

    The cardiorenal syndrome, the detrimental bi-directional interplay between symptomatic heart failure and chronic kidney disease, is a major clinical challenge. Nonetheless, it is unknown if this interplay begins already at an asymptomatic stage. Therefore we investigated whether the glomerular filtration rate (GFR) is associated with left ventricular function in participants free from clinical heart failure and with a left ventricular ejection fraction (LVEF) > 40% and with pre-specified sub-group analyses in individuals with a GFR > 60 mL/min/m(2). Two independent community-based cohorts were used; the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS; n = 911; 50% women; mean age: 70 years) and the Uppsala Longitudinal Study of Adult Men (ULSAM; n = 538; mean age: 71 years). We investigated cross-sectional association between cystatin C-based GFR (estimated glomerular function [eGFR]) and systolic (LVEF), diastolic- (isovolumic relaxation time [IVRT]) and global left ventricular function (myocardial performance index [MPI]) determined by echocardiography. In both PIVUS and ULSAM, higher eGFR was significantly associated with higher LVEF (P = 0.004 [PIVUS] and P = 0.005 [ULSAM]). In PIVUS, higher eGFR was significantly associated with lower IVRT (P = 0.001) and MPI (P = 0.006), in age- and sex-adjusted models. After further adjustment for cardiovascular risk factors, the association between higher eGFR and higher LVEF was still statistically significant (P = 0.008 [PIVUS] and P = 0.02 [ULSAM]). In PIVUS, the age- and sex-adjusted association between eGFR and left ventricular function was similar in participants with eGFR > 60 mL/min/m(2). Our data suggest that the interplay between kidney and heart function begins prior to the development of symptomatic heart failure and kidney disease.

  • 41.
    Nerpin, Elisabet
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Ingelsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Risérus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Jobs, Elisabeth
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Jobs, Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Virology.
    Hallan, Stein
    Zethelius, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Berglund, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Basu, Samar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Arnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    The combined contribution of albuminuria and glomerular filtration rate to the prediction of cardiovascular mortality in elderly men2011In: Nephrology, Dialysis and Transplantation, ISSN 0931-0509, E-ISSN 1460-2385, Vol. 26, no 9, p. 2820-2827Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Cardiovascular risk prediction is particularly important in the primary prevention of cardiovascular disease (CVD). Yet, data on whether the combined addition of albuminuria and estimated glomerular filtration rate (eGFR) improves cardiovascular risk prediction in individuals without CVD in the community is scarce.

    METHODS: We investigated associations between urinary albumin excretion rate (UAER), cystatin C-based eGFR and cardiovascular mortality in a community-based cohort of elderly men (ULSAM study; n = 1113, mean age 71 years, 208 cardiovascular deaths, median follow-up 12.9 years) with prespecified analyses in participants without CVD (n = 649, 86 cardiovascular deaths).

    RESULTS: Using multivariable Cox regression, higher UAER and lower eGFR were associated with increased risk for cardiovascular mortality independently of established cardiovascular risk factors in the whole sample and in men without CVD at baseline [subsample without CVD: UAER; hazard ratio (HR) per 1 SD 1.26, 95% confidence interval (CI) 1.05-1.51, P = 0.01; eGFR: HR per 1 SD 0.74, 95% CI 0.59-0.92, P = 0.007]. Analyses of model discrimination, calibration, reclassification and global fit suggested that UAER and eGFR also add relevant prognostic information beyond established cardiovascular risk factors in participants without prevalent CVD. Interestingly, established cutoffs used to diagnose microalbuminuria (UAER > 20 μg/min) and chronic kidney disease Stage 3 (eGFR < 60 mL/min/1.73m(2)), appeared less suitable for cardiovascular risk prediction [integrated discrimination improvement (IDI) 0.006, P = 0.11], while cutoffs UAER > 6 μg/min and eGFR < 45 mL/min/1.73m(2) significantly improved IDI (0.047, P < 0.001).

    CONCLUSIONS: UAER and eGFR improved cardiovascular risk prediction beyond established cardiovascular risk factors, suggesting that these kidney biomarkers may be useful in predicting cardiovascular death in elderly men.

  • 42. Nilssen, Camilla
    et al.
    Zannad, Faiez
    Jardine, Alan
    Schmieder, Roland
    Fellström, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Renal Medicine.
    Holdaas, Hallvard
    Mjoen, Geir
    Risk Factors for Stroke in Hemodialysis Patients2014In: Nephrology, Dialysis and Transplantation, ISSN 0931-0509, E-ISSN 1460-2385, Vol. 29, p. 484-484Article in journal (Other academic)
  • 43. Papazova, Diana A.
    et al.
    Friederich-Persson, Malou
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Koeners, Maarten P.
    Joles, Jaap A.
    Verhaar, Marianne C.
    Donor Pretreatment with Mitotempo Decreases Mitochondrial Uncoupling after Experimental Renal Transplantation2014In: Nephrology, Dialysis and Transplantation, ISSN 0931-0509, E-ISSN 1460-2385, Vol. 29, p. 533-533Article in journal (Other academic)
  • 44. Perl, Jeffrey
    et al.
    Zhang, Jinyao
    Gillespie, Brenda
    Wikström, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Renal Medicine.
    Fort, Joan
    Hasegawa, Takeshi
    Fuller, Douglas S.
    Pisoni, Ronald L.
    Robinson, Bruce M.
    Tentori, Francesca
    Reduced survival and quality of life following return to dialysis after transplant failure: the Dialysis Outcomes and Practice Patterns Study2012In: Nephrology, Dialysis and Transplantation, ISSN 0931-0509, E-ISSN 1460-2385, Vol. 27, no 12, p. 4464-4472Article in journal (Refereed)
    Abstract [en]

    Although dialysis after kidney transplant failure (TF) is common, the outcomes of these patients remain unclear. We compared outcomes of TF patients with transplant-nave (TN) patients wait-listed for kidney transplantation. We used data from the Dialysis Outcomes and Practice Patterns Study (DOPPS), including laboratory markers and health-related quality of life (HR-QOL). Mortality and hospitalization of participants with one prior TF versus TN patients were compared using the Cox regression analysis. HR-QOL physical and mental component summary scores (PCS and MCS) were examined using linear mixed models, and clinical practices were compared using logistic regression. Compared with TN patients (n 2806), TF patients (n 1856) were younger (48 versus 51 years, P 0.003), less likely to be diabetic (18 versus 27, P 0.0001) and to use a permanent surgical vascular access {adjusted odds ratio (AOR): 0.85 [95 confidence interval (CI): 0.701.03], P 0.10}, particularly within the first 3 months after TF [AOR 0.45 (0.320.62), P 0.0001]. TF patients also had lower PCS [mean difference 2.56 (3.36, 1.75), P 0.0001] but not MCS [0.42 (1.34, 0.50), P 0.37]. All-cause mortality [adjusted hazard ratio (AHR): 1.32 (95 CI: 1.051.66), P 0.02], especially infection-related [AHR 2.45 (95 CI: 1.364.41), P 0.01], was higher among TF patients. TF patients have reduced QOL and higher mortality, particularly due to infections, than TN patients. Interventions to optimize care before and after starting dialysis remain to be identified and applied in clinical practice.

  • 45. Pisoni, Ronald L.
    et al.
    Wikström, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Elder, Stacey J.
    Akizawa, Tadao
    Asano, Yashushi
    Keen, Marcia L.
    Saran, Rajiv
    Mendelssohn, David C.
    Young, Eric W.
    Port, Friedrich K.
    Pruritus in haemodialysis patients: international results from the Dialysis Outcomes and Practice Patterns Study (DOPPS)2006In: Nephrology, Dialysis and Transplantation, ISSN 0931-0509, E-ISSN 1460-2385, Vol. 21, no 12, p. 3495-3505Article in journal (Refereed)
    Abstract [en]

    Background. Pruritus affects many haemodialysis (HD) patients. In this study, pruritus and its relationship to morbidity, mortality, quality of life (QoL), sleep quality and patient laboratory measures were analysed in > 300 dialysis units in 12 countries. Methods. Pruritus data were collected from 18 801 HD patients in the Dialysis Outcomes and Practice Patterns Study (DOPPS) (1996-2004). Analyses were adjusted for age, gender, black race, Kt/V, haemoglobin, serum albumin, albumin-corrected serum calcium, serum phosphorus, 13 comorbidities, depression, years on dialysis, country and facility clustering effects. Results. Moderate to extreme pruritus was experienced by 42% of prevalent HD patients in DOPPS during 2002/2003. Many patient characteristics were significantly associated with pruritus, but this did not explain the large differences in pruritus between countries (ranging from 36% in France to 50% in the UK) and between facilities (5-75%). Pruritus was slightly less common in patients starting HD than in patients on dialysis > 3 months. Pruritus in new end-stage renal disease (ESRD) patients likely results from pre-existing conditions and not haemodialysis per se, indicating the need to understand development of pruritus before ESRD. Patients with moderate to extreme pruritus were more likely to feel drained [adjusted odds ratio (AOR) = 2.3-5.2, P < 0.0001] and to have poor sleep quality (AOR = 1.9-4.1, P <= 0.0002), physician-diagnosed depression (AOR = 1.3-1.7, P <= 0.004), and QoL mental and physical composite scores 3.1-8.6 points lower (P < 0.0001) than patients with no/mild pruritus. Pruritus in HD patients was associated with a 17% higher mortality risk (P < 0.0001), which was no longer significant after adjusting for sleep quality measures. Conclusions. The pruritus/mortality relationship may be substantially attributed to poor sleep quality. The many poor outcomes associated with pruritus underscore the need for better therapeutic agents to provide relief for the 40-50% of HD patients affected by pruritus.

  • 46.
    Pruijm, Menno
    et al.
    Univ Hosp Lausanne CHUV, Dept Med, Serv Nephrol & Hypertens, Lausanne, Switzerland.
    Mendichovszky, Iosif A.
    Cambridge Univ Hosp NHS Fdn Trust, Addenbrookes Hosp, Dept Radiol, Cambridge, England.
    Liss, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Van der Niepen, Patricia
    Univ Ziekenhuis Brussel VUB, Dept Nephrol & Hypertens, Brussels, Belgium.
    Textor, Stephen C.
    Mayo Clin, Div Nephrol & Hypertens, Rochester, MN USA.
    Lerman, Lilach O.
    Mayo Clin, Div Nephrol & Hypertens, Rochester, MN USA.
    Krediet, C. T. Paul
    Univ Amsterdam, Acad Med Ctr, Div Nephrol, Dept Internal Med, Amsterdam, Netherlands.
    Caroli, Anna
    Ist Ric Farmacol Mario Negri, IRCCS, Dept Bioengn, Med Imaging Unit, Bergamo, Italy.
    Burnier, Michel
    Univ Hosp Lausanne CHUV, Dept Med, Serv Nephrol & Hypertens, Lausanne, Switzerland.
    Prasad, Pottumarthi Vara
    NorthShore Univ HealthSyst, Dept Radiol, Evanston, IL USA.
    Renal blood oxygenation level-dependent magnetic resonance imaging to measure renal tissue oxygenation: a statement paper and systematic review2018In: Nephrology, Dialysis and Transplantation, ISSN 0931-0509, E-ISSN 1460-2385, Vol. 33, p. II22-II28Article, review/survey (Refereed)
    Abstract [en]

    Tissue hypoxia plays a key role in the development and progression of many kidney diseases. Blood oxygenation level-dependent magnetic resonance imaging (BOLD-MRI) is the most promising imaging technique to monitor renal tissue oxygenation in humans. BOLD-MRI measures renal tissue deoxyhaemoglobin levels voxel by voxel. Increases in its outcome measure R2* (transverse relaxation rate expressed as per second) correspond to higher deoxyhaemoglobin concentrations and suggest lower oxygenation, whereas decreases in R2* indicate higher oxygenation. BOLD-MRI has been validated against micropuncture techniques in animals. Its reproducibility has been demonstrated in humans, provided that physiological and technical conditions are standardized. BOLD-MRI has shown that patients suffering from chronic kidney disease (CKD) or kidneys with severe renal artery stenosis have lower tissue oxygenation than controls. Additionally, CKD patients with the lowest cortical oxygenation have the worst renal outcome. Finally, BOLD-MRI has been used to assess the influence of drugs on renal tissue oxygenation, and may offer the possibility to identify drugs with nephroprotective or nephrotoxic effects at an early stage. Unfortunately, different methods are used to prepare patients, acquire MRI data and analyse the BOLD images. International efforts such as the European Cooperation in Science and Technology (COST) action 'Magnetic Resonance Imaging Biomarkers for Chronic Kidney Disease' (PARENCHIMA) are aiming to harmonize this process, to facilitate the introduction of this technique in clinical practice in the near future. This article represents an extensive overview of the studies performed in this field, summarizes the strengths and weaknesses of the technique, provides recommendations about patient preparation, image acquisition and analysis, and suggests clinical applications and future developments.

  • 47. Robinson, Bm
    et al.
    Wang, Mia
    Bieber, Brian
    Fluck, Richard
    Kerr, Peter G.
    Wikström, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Renal Medicine.
    Krishnan, Mahesh
    Nissenson, Allen
    Pisoni, Ronald L.
    International variation in influenza vaccination practices and coverage rates among hemodialysis patients: an opportunity to improve care2012In: Nephrology, Dialysis and Transplantation, ISSN 0931-0509, E-ISSN 1460-2385, Vol. 27, p. 397-397Article in journal (Other academic)
  • 48.
    Sanner, Margareta A.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Health Services Research.
    The donation process of living kidney donors2005In: Nephrology, Dialysis and Transplantation, ISSN 0931-0509, E-ISSN 1460-2385, Vol. 20, no 8, p. 1707-13Article in journal (Refereed)
    Abstract [en]

    Background. The rates of both genetic and non-genetic living donors are increasing. However, previous research has almost exclusively explored the decision-making of genetic donors. Therefore, in this study both genetic and non-genetic donors are investigated with focus on their whole donation process.

    Methods. Thirty-nine donors were interviewed the day before nephrectomy and 3 weeks afterwards. Twenty-three donors were genetic relatives, 16 were not. The interviews were analysed qualitatively, mainly by narrative structuring.

    Results. All donors but one passed seven steps in the donation process. They included: (i) awareness of suffering; compassion and empathy; (ii) imminence of transplantation; recognition of oneself as potential donor; (iii) information acquisition and deliberation; (iv) attribution of responsibility to oneself; announcement of decision to donate; (v) examination; maintaining the decision; (vi) facing nephrectomy; and (vii) postoperative experiences. Two types of decision-making were displayed: immediate and later announcement of decision. Half the donors belonged to each type. Various relationship groups displayed different types. The examination period was the most stressful time, partly due to imperfect coordination and excessive time-wasting. One-third found postoperative pain the most painful experience ever. There was a lack of attention to regressive needs and to recognition of the deed.

    Conclusions. The two types of decision-making seem similar in ethical requirements. It is not a genetic or non-genetic relationship per se that determines what kind of decision the donors make. Psychological support, especially during Steps 5 and 7, should be improved and the donors included in a structured donation programme. Possible health care ambivalence toward living donation should not affect the donors.

  • 49.
    Sanner, Margareta
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Health Services Research.
    Lagging, Eva
    Tibell, Annika
    Karolinska Institutet, Institutionen för klinisk vetenskap, intervention och teknik.
    The kidney recipients' path to transplantation: A comparison between living and deceased kidney donor recipients in Stockholm, Sweden2011In: Nephrology, Dialysis and Transplantation, ISSN 0931-0509, E-ISSN 1460-2385, Vol. 26, no 3, p. 1053-1057Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Much remains to be done to facilitate the transplantation process for patients with end-stage renal disease. The aim here was to explore these patients' experiences of the donation process and factors related to whether the actual donors of the recipients were living or deceased and describe which issues needed attention in a quality development project. Method. A specially constructed questionnaire was sent to 246 recipients of living and deceased kidney transplants who had been transplanted at the Karolinska University Hospital in Stockholm, Sweden. The response rate was 87%.

    RESULTS: Six conditions were identified as problematic:- Most living-donor kidney recipients perceived the evaluation period for the donors as too long. - Although a living donor was available, most living-donor kidney recipients had to undergo dialysis for a relatively long period. - A majority of the patients perceived it difficult to ask for a donation. Deceased-donor kidney recipients were least satisfied with the offered support in finding a living donor. - Patients perceived fear as the main reason for potential living donors to refuse donation. - About one-fourth of living-donor kidney recipients thought that the donors were abandoned by healthcare after nephrectomy. - Older patients and singles were least likely to receive a living-donor kidney.

    CONCLUSIONS: The problem issues outlined above should be scrutinized and improved. Checking these issues can be used in quality control when analysing living kidney donation at local and national levels.

  • 50. Schildroth, Janice
    et al.
    Rettig-Zimmermann, Juliane
    Kalk, Philipp
    Steege, Andreas
    Faehling, Michael
    Sendeski, Mauricio
    Paliege, Alexander
    Lai, En Yin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Bachmann, Sebastian
    Persson, Pontus B.
    Hocher, Berthold
    Patzak, Andreas
    Endothelin type A and B receptors in the control of afferent and efferent arterioles in mice2011In: Nephrology, Dialysis and Transplantation, ISSN 0931-0509, E-ISSN 1460-2385, Vol. 26, no 3, p. 779-789Article in journal (Refereed)
    Abstract [en]

    Background. Endothelin 1 contributes to renal blood flow control and pathogenesis of kidney diseases. The differential effects, however, of endothelin 1 (ET-1) on afferent (AA) and efferent arterioles (EA) remain to be established. Methods. We investigated endothelin type A and B receptor (ETA-R, ETB-R) functions in the control of AA and EA. Arterioles of ETB-R deficient, rescued mice [ETB (-/-)] and wild types [ETB(+/+)] were microperfused. Results. ET-1 constricted AA stronger than EA in ETB (-/-) and ETB(+/+) mice. Results in AA: ET-1 induced similar constrictions in ETB(-/-) and ETB(+/+) mice. BQ-123 (ETA-R antagonist) inhibited this response in both groups. ALA-ET-1 and IRL1620 (ETB-R agonists) had no effect on arteriolar diameter. L-NAME did neither affect basal diameters nor ET-1 responses. Results in EA: ET-1 constricted EA stronger in ETB(+/+) compared to ETB(-/-). BQ-123 inhibited the constriction completely only in ETB(-/-). ALA-ET-1 and IRL1620 constricted only arterioles of ETB(+/+) mice. L-NAME decreased basal diameter in ETB(+/+), but not in ETB(-/-) mice and increased the ET-1 response similarly in both groups. The L-NAME actions indicate a contribution of ETB-R in basal nitric oxide (NO) release in EA and suggest dilatory action of ETA-R in EA. Conclusions. ETA-R mediates vasoconstriction in AA and contributes to vasoconstriction in EA in this mouse model. ETB-R has no effect in AA but mediates basal NO release and constriction in EA. The stronger effect of ET-1 on AA supports observations of decreased glomerular filtration rate to ET-1 and indicates a potential contribution of ET-1 to the pathogenesis of kidney diseases.

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