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  • 1.
    Annuk, Margus
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Soveri, Inga
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Zilmer, Mihkel
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Hulthe, Johannes
    Fellström, Bengt
    Endothelial function, CRP and oxidative stress in chronic kidney disease2005In: JN. Journal of Nephrology (Milano. 1992), ISSN 1121-8428, E-ISSN 1724-6059, Vol. 18, no 6, p. 721-726Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Chronic kidney disease (CKD) is associated with increased morbidity and mortality in cardiovascular disease (CVD). Apart from traditional risk factors, chronic inflammation, oxidative stress, malnutrition and endothelial dysfunction are important in CVD development in renal patients. Our aim was to investigate the relationship between high sensitivity C-reactive protein (CRP), endothelium dependent vasodilation (EDV) and oxidative stress markers in patients with CKD K/DOQI stage 3-5.

    METHODS: Measurements of CRP, conjugated dienes (CD), lipid hydroperoxide (LOOH), oxidized low density lipoprotein,glutathione and albumin were performed in 44 consecutive patients with CKD stage 3-5. EDV was measured by methacholine infusion in the brachial artery and venous occlusion plethysmography.

    RESULTS: Patients with high CRP had significantly lower glomerular filtration rates and albumin, but increased LOOH and CD. In multiple regression analysis, only LOOH and CD remained significant. Patients with poor EDV had increased urea and lower glutathione (GSH). In multiple regression analysis, GSH and urea were independently related to EDV. No correlation was found between CRP and endothelial function.

    CONCLUSION: CRP was related to lipid peroxidation, while endothelial function was related to intracellular oxidative stress in patients with CKD. CRP and EDV were unrelated to each other. Therefore, CRP and endothelial function could provide complementary prognostic information regarding future cardiovascular disorders in renal patients.

  • 2. Beshara, Soheir
    et al.
    Bàràny, Peter
    Gutierrez, Alberto
    Wikström, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Varying intervals of subcutaneous epoetin alfa in hemodialysis patients2004In: JN. Journal of Nephrology (Milano. 1992), ISSN 1121-8428, E-ISSN 1724-6059, Vol. 17, no 4, p. 525-530Article in journal (Other academic)
    Abstract [en]

    BACKGROUND: The optimal subcutaneous (SC) epoetin alfa strategy is unestablished. The individual variability in dose requirements needs consideration. In this study, prolonged intervals were assessed in relation to varying dose requirements. METHODS: The study included 153 hemodialysis (HD) patients on stable SC epoetin alfa. Based on dose requirements, the patients received either 4,000 U (group I, n=51) or 10,000 U (group II, n=102) as whole 1 mL vials at prolonged intervals. The study comprised three 8-week periods: an initial period maintaining the basal regimens, an adjustment period where the intervals were prolonged, and a maintenance period. Alterations in hemoglobin (Hb), weekly doses and intervals in each group were compared. RESULTS: One hundred and thirty-seven patients completed the study (48 in group I and 89 in group II). In group I, the mean interval was prolonged from 5.4 +/- 1.9 to 7.8 +/- 3.1 days (p=0,01) with stable Hb and EPO doses. In group II, prolonged intervals were associated with a reduction in mean Hb below target level and a significant increase in EPO doses (p=0,002). Iron deficiency and inflammation could explain the poor response in approximately one-third of the patients. CONCLUSIONS: In HD patients, the optimal injection frequency should be individually adjusted. Prolonged intervals can be applied to patients with low-dose requirements. Observing iron status and inflammation is necessary for optimal response.

  • 3.
    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.
    Englund, Anders
    Wikström, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Heart rate variability is decreased in chronic kidney disease but may improve with hemoglobin normalization2008In: JN. Journal of Nephrology (Milano. 1992), ISSN 1121-8428, E-ISSN 1724-6059, Vol. 21, no 1, p. 45-52Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Cardiac autonomic function can be measured by heart rate variability (HRV). Dialysis patients have an abnormally low HRV and are at increased risk for sudden death. A reduction in HRV is associated with anemia. HRV was therefore measured in patients with chronic kidney disease (CKD) after hemoglobin normalization.

    METHODS: Sixteen nondiabetic patients with CKD stage 4 (glomerular filtration rate 23.7 +/- 13.9 ml/min) and renal anemia received epoetin aiming at a hemoglobin level of 135-150 g/L. HRV was measured by 24-hour Holter electrocardiogram at baseline and after hemoglobin normalization and in a reference group consisting of 16 volunteers without impairment of renal function.

    RESULTS: Hemoglobin level increased from 100.7 +/- 12.6 g/L to 142.4 +/- 7.2 g/L during the study. At baseline, HRV measured in the time domain as the standard deviation of all normal RR intervals in the entire 24-hour electrocardiogram (SDNN) was 116.3 +/- 39.2 ms compared with 147.5 +/- 27.2 ms in the reference group (p<0.05). The frequency domain measures low-frequency power and total power were 367.7 +/- 350.2 ms2 and 1,368.9 +/- 957.4 ms2 compared with 717.3 +/- 484.5 ms2 and 2,228.3 +/- 1142.4 ms2 (p<0.05) in the reference group. After hemoglobin normalization there was an increase in low-frequency power to 498.3 +/- 432.7 ms2 (p<0.05) and in total power to 1,731.0 +/- 1,069.4 ms2 (p<0.05) while SDNN remained at 120.9 +/- 33.8 ms (p=ns).

    CONCLUSIONS: CKD patients not yet on dialysis had a reduced HRV, indicating impaired autonomic function, compared with a reference group without impaired renal function. Hemoglobin normalization improved but did not fully normalize HRV. The clinical significance of this deserves further investigation.

  • 4.
    Furuland, Hans
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Linde, Torbjörn
    Wikström, Björn
    Danielson, Bo G.
    Reduced hemodialysis adequacy after hemoglobin normalization with epoetin2005In: JN. Journal of Nephrology (Milano. 1992), ISSN 1121-8428, E-ISSN 1724-6059, Vol. 18, no 1, p. 80-85Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Increased hemoglobin (Hb) levels and higher blood viscosity could reduce hemodialyzer clearance. We examined hemodialysis (HD) adequacy after treatment with epoetin alfa aimed at normalizing Hb levels.

    METHODS: Thirty-three HD patients were randomly allocated to achieve a normal Hb level (135-160 g/L) or a subnormal (control) Hb level of 90-120 g/L. HD adequacy was assessed by Kt/V measurement.

    RESULTS: In the 24 evaluable patients, Hb levels reached 144 +/- 11 g/L in the normal Hb group (n=10) and 109 +/- 10 g/L in the subnormal group (n=14). Single-pool Kt/V decreased from 1.25 +/- 0.19 to 1.15 +/- 0.13 (p<0.01) in the normal Hb group, but remained constant in the subnormal group (1.26 +/- 0.26 and 1.26 +/- 0.28).

    CONCLUSIONS: Normalization of Hb with epoetin alfa in HD patients resulted in a slight but statistically significant reduction in Kt/V. Therefore, when Hb is normalized, an increased dialysis dose could be necessary to maintain dialysis adequacy

  • 5. Laux, Timothy S
    et al.
    Bert, Philip J
    Barreto Ruiz, Gerardo M
    González, Marvin
    Unruh, Mark
    Aragon, Aurora
    Torres Lacourt, Cecilia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Occupational and Environmental Medicine.
    Nicaragua revisited: evidence of lower prevalence of chronic kidney disease in a high-altitude, coffee-growing village2012In: JN. Journal of Nephrology (Milano. 1992), ISSN 1121-8428, E-ISSN 1724-6059, Vol. 25, no 4, p. 533-540Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Chronic kidney disease (CKD) is found at epidemic levels in certain populations of the Pacific Coast in northwestern Nicaragua especially in younger men. There are knowledge gaps concerning CKD's prevalence in regions at higher altitudes.

    METHODS: A cross-sectional study of adults between the ages of 20 and 60 years in 1 coffee-growing village in Nicaragua located at 1,000 m above sea level (MASL) altitude was performed. Predictors included participant sex, age, occupation, conventional CKD risk factors and other factors associated with CKD suggested by previous surveys in Central America. Outcomes included serum creatinine (SCr) values >1.2 mg/dL for men and >0.9 mg/dL for women, estimated glomerular filtration rate (GFR) <60 ml/min per 1.73 m2, dipstick proteinuria stratified as microalbuminuria (30-300 mg/dL) and macroalbuminuria (>300 mg/dL), hypertension and body mass index.

    RESULTS: Of 324 eligible participants, 293 were interviewed (90.4%), and 267 of those received the physical exam (82.4% overall). Of the sample, 45% were men. Prevalence rate of estimated GFR <60 ml/min per 1.73 m2 was 0 for men (0%) and 2 for women (1.4%). The prevalence of at least microalbuminuria was significantly higher among men compared with women (27.5% vs. 21.4%, respectively; p=0.02).

    CONCLUSIONS: The CKD prevalence in this village is comparable to a previously studied Nicaraguan coffee-farming region and much lower than previously screened portions of northwestern Nicaragua. There is heterogeneity in CKD prevalence across Nicaragua. At this time, screenings should target individuals living in previously identified, higher risk regions. More work is needed to understand determinants of CKD in this resource-poor nation.

  • 6.
    Soveri, Inga
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Abedini, Sadollah
    Holdaas, Halvard
    Jardine, Alan
    Eriksson, Niclas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Fellström, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Graft Loss Risk in Renal Transplant Recipients with Metabolic Syndrome: Subgroup Analyses of the ALERT Trial2012In: JN. Journal of Nephrology (Milano. 1992), ISSN 1121-8428, E-ISSN 1724-6059, Vol. 25, no 2, p. 245-254Article in journal (Refereed)
    Abstract [en]

    Background: Several nonimmunologic risk factors for late renal graft loss (RGL) are also known components of metabolic syndrome (MS). We aimed to study MS as a risk factor for RGL. Also, the effect of statin treatment in reducing renal risk in renal transplant recipients (RTRs) with MS was studied. Methods: Nondiabetic RTRs (n=1,706) from the ALERT trial were followed for 7-8 years. MS was defined according to National Cholesterol Education Program Adult Treatment Panel III definition with waist girth replaced by BMI =30 (calculated as kg/m2). Renal end points included death-censored RGL and graft loss or doubling of serum creatinine. Results: During the follow-up, 284 patients experienced RGL, and there were 343 cases of graft loss or doubling of serum creatinine. Those with MS had increased risk for RGL (relative risk = 1.28, 95% confidence interval, 1.00-1.63; p=0.047), but not for the combined end point. After adjustment for other known and potential risk factors, MS was no longer associated with increased risk for RGL. The association between MS and RGL risk was attenuated once adjustment for creatinine was made. Statin treatment did not reduce the risk for renal end points in RTRs with or without MS. Conclusion: MS had no independent association with RGL risk. Adjustment for renal function attenuated the association between MS and RGL.

  • 7.
    Wikström, Björn
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Bhandari, Sunil
    Barany, Peter
    Kalra, Philip A.
    Ladefoged, Soren
    Wilske, Jan
    Thomsen, Lars L.
    Iron isomaltoside 1000: a new intravenous iron for treating iron deficiency in chronic kidney disease2011In: JN. Journal of Nephrology (Milano. 1992), ISSN 1121-8428, E-ISSN 1724-6059, Vol. 24, no 5, p. 589-596Article in journal (Refereed)
    Abstract [en]

    Background: Patients with chronic kidney disease (CKD) often suffer from iron deficiency anemia necessitating treatment with intravenous iron. This study was designed to assess the safety of iron isomaltoside 1000 (Monofer) in CKD patients. The secondary objective was to assess its effect on iron deficiency anemia. Methods: This open-label, noncomparative, multi-center trial assigned 182 patients with CKD (n=161 in dialysis and n=21 in predialysis) to iron isomaltoside 1000 either as 4 intravenous bolus injections of 100-200 mg iron per dose or as a fast high-dose infusion at baseline. Patients were generally undergoing erythropoiesis-stimulating agent (ESA) treatment (82%), and the dosage was to be kept constant during the trial. They were either switched from an existing parenteral maintenance therapy (n=144) or were not currently being treated with parenteral iron (n=38). Frequency of adverse events (AEs) and changes in markers of iron deficiency anemia were measured during 8 weeks from baseline. Results: Nineteen treatment-related AEs occurred in 13 patients (7.1%) and after 584 treatments (3.3%). No anaphylactic or delayed allergic reactions were observed. There were no clinically significant changes in routine clinical laboratory tests or vital signs. Hemoglobin increased from 99.2 g/L (SD=9.0) at baseline to 111.2 g/L (SD=14.7) at week 8 in patients not currently treated with parenteral iron (p<0.001) and increased slightly or stabilized in patients in maintenance therapy. S-Ferritin, s-iron and transferrin saturation increased significantly at all visits. Conclusions: Iron isomaltoside 1000 was clinically well tolerated, safe and effective. This new intravenous iron may offer a further valuable choice in treating the anemia of CKD.

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