uu.seUppsala universitets publikasjoner
Endre søk
Begrens søket
12 1 - 50 of 82
RefereraExporteraLink til resultatlisten
Permanent link
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Annet format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annet språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf
Treff pr side
  • 5
  • 10
  • 20
  • 50
  • 100
  • 250
Sortering
  • Standard (Relevans)
  • Forfatter A-Ø
  • Forfatter Ø-A
  • Tittel A-Ø
  • Tittel Ø-A
  • Type publikasjon A-Ø
  • Type publikasjon Ø-A
  • Eldste først
  • Nyeste først
  • Skapad (Eldste først)
  • Skapad (Nyeste først)
  • Senast uppdaterad (Eldste først)
  • Senast uppdaterad (Nyeste først)
  • Disputationsdatum (tidligste først)
  • Disputationsdatum (siste først)
  • Standard (Relevans)
  • Forfatter A-Ø
  • Forfatter Ø-A
  • Tittel A-Ø
  • Tittel Ø-A
  • Type publikasjon A-Ø
  • Type publikasjon Ø-A
  • Eldste først
  • Nyeste først
  • Skapad (Eldste først)
  • Skapad (Nyeste først)
  • Senast uppdaterad (Eldste først)
  • Senast uppdaterad (Nyeste først)
  • Disputationsdatum (tidligste først)
  • Disputationsdatum (siste først)
Merk
Maxantalet träffar du kan exportera från sökgränssnittet är 250. Vid större uttag använd dig av utsökningar.
  • 1.
    Acosta Ruiz, Vanessa
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Båtelsson, Sarah
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Onkamo, Elina
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Wernroth, Lisa
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi.
    Nilsson, Thomas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Njurmedicin.
    Lönnemark, Maria
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Dahlman, Pär
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Magnusson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Split Renal Function after Treatment of Small Renal Masses: Comparison between Radiofrequency Ablation and Laparoscopic Partial NephrectomyManuskript (preprint) (Annet vitenskapelig)
  • 2. Bakhai, Ameet
    et al.
    Palaka, Eirini
    Linde, Cecilia
    Bennett, Hayley
    Furuland, Hans
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Njurmedicin.
    Qin, Lei
    McEwan, Phil
    Ewans, Marc
    Development of a health economic model to evaluate the potential benefits of optimal serum potassium management in patients with heart failure.2018Inngår i: Journal of Medical Economics, ISSN 1369-6998, E-ISSN 1941-837X, Vol. 21, nr 12, s. 1172-1182Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Aims: Patients with heart failure are at increased risk of hyperkalemia, particularly when treated with renin-angiotensin-aldosterone system inhibitor (RAASi) agents. This study developed a model to quantify the potential health and economic value associated with sustained potassium management and optimal RAASi therapy in heart failure patients.

    Materials and methods: A patient-level, fixed-time increment stochastic simulation model was designed to characterize the progression of heart failure through New York Heart Association functional classes, and predict associations between serum potassium levels, RAASi use, and consequent long-term outcomes. Following internal and external validation exercises, model analyses sought to quantify the health and economic benefits of optimizing both serum potassium levels and RAASi therapy in heart failure patients. Analyses were conducted using a UK payer perspective, independent of costs and utilities related to pharmacological potassium management.

    Results: Validation against multiple datasets demonstrated the predictive capability of the model. Compared to those who discontinued RAASi to manage serum potassium, patients with normokalemia and ongoing RAASi therapy benefited from longer life expectancy (+1.38 years), per-patient quality-adjusted life year gains (+0.53 QALYs), cost savings (110) pound, and associated net monetary benefit (10,679 pound at 20,000 pound per QALY gained) over a lifetime horizon. The predicted value of sustained potassium management and ongoing RAASi treatment was largely driven by reduced mortality and hospitalization risks associated with optimal RAASi therapy.

    Limitations: Several modeling assumptions were made to account for a current paucity of published literature; however, ongoing refinement and validation of the model will ensure its continued accuracy as the clinical landscape of hyperkalemia evolves.

    Conclusions: Predictions generated by this novel modeling approach highlight the value of sustained potassium management to avoid hyperkalemia, enable RAASi therapy, and improve long-term health economic outcomes in patients with heart failure.

  • 3.
    Barbour, Sean J.
    et al.
    Univ British Columbia, Div Nephrol, 2775 Laurel St,Fifth Floor, Vancouver, BC V5Z 1M9, Canada;BC Renal, Vancouver, BC, Canada.
    Coppo, Rosanna
    Regina Margherita Childrens Univ Hosp, Turin, Italy.
    Zhang, Hong
    Peking Univ, Inst Nephrol, Beijing, Peoples R China.
    Liu, Zhi-Hong
    Nanjing Univ, Sch Med, Nanjing, Jiangsu, Peoples R China.
    Suzuki, Yusuke
    Juntendo Univ, Fac Med, Tokyo, Japan.
    Matsuzaki, Keiichi
    Juntendo Univ, Fac Med, Tokyo, Japan.
    Katafuchi, Ritsuko
    Natl Fukuoka Higashi Med Ctr, Fukuoka, Fukuoka, Japan.
    Er, Lee
    BC Renal, Vancouver, BC, Canada.
    Espino-Hernandez, Gabriela
    BC Renal, Vancouver, BC, Canada.
    Kim, S. Joseph
    Univ Toronto, Div Nephrol, Toronto, ON, Canada.
    Reich, Heather N.
    Univ Toronto, Div Nephrol, Toronto, ON, Canada.
    Feehally, John
    Leicester Gen Hosp, John Walls Renal Unit, Leicester, Leics, England.
    Cattran, Daniel C.
    Univ Toronto, Div Nephrol, Toronto, ON, Canada.
    Russo, M. L.
    Fdn Ric Molinette, Turin, Italy.
    Troyanov, S.
    Hop Sacre Coeur Montreal, Dept Med, Div Nephrol, Montreal, PQ, Canada;Hop Sacre Coeur Montreal, Dept Med, Div Nephrol, Montreal, PQ, Canada.
    Cook, H. T.
    Imperial Coll, Dept Med, Ctr Complement & Inflammat Res, London, England.
    Roberts, I.
    Oxford Univ Hosp NHS Fdn Trust, John Radcliffe Hosp, Dept Cellular Pathol, Oxford, England.
    Tesar, V.
    Charles Univ Prague, Fac Med 1, Dept Nephrol, Prague, Czech Republic;Charles Univ Prague, Gen Univ Hosp, Prague, Czech Republic.
    Maixnerova, D.
    Charles Univ Prague, Fac Med 1, Dept Nephrol, Prague, Czech Republic;Charles Univ Prague, Gen Univ Hosp, Prague, Czech Republic.
    Lundberg, S.
    Karolinska Inst, Dept Clin Sci, Nephrol Unit, Stockholm, Sweden.
    Gesualdo, L.
    Univ Bah Aldo Moro, Dept Nephrol Emergency & Organ Transplantat, Foggia, Italy.
    Emma, F.
    Bambino Gesu Pediat Hosp, IRCCS, Dept Pediat Subspecialties, Div Nephrol, Rome, Italy.
    Fuiano, L.
    Bambino Gesu Pediat Hosp, IRCCS, Dept Pediat Subspecialties, Div Nephrol, Rome, Italy.
    Beltrame, G.
    San Giovanni Bosco Hosp, Nephrol & Dialysis Unit, Turin, Italy;Univ Turin, Turin, Italy.
    Rollino, C.
    San Giovanni Bosco Hosp, Nephrol & Dialysis Unit, Turin, Italy;Univ Turin, Turin, Italy.
    Amore, A.
    Regina Margherita Childrens Hosp, Nephrol Unit, Turin, Italy;Univ Turin, Regina Margherita Childrens Hosp, Nephrol Dialysis & Transplantat Unit, Turin, Italy.
    Camilla, R.
    Regina Margherita Childrens Hosp, Nephrol Unit, Turin, Italy.
    Peruzzi, L.
    Regina Margherita Childrens Hosp, Nephrol Unit, Turin, Italy.
    Praga, M.
    Hosp 12 Octubre, Nephrol Unit, Madrid, Spain.
    Feriozzi, S.
    Belcolle Hosp, Nephrol Unit, Viterbo, Italy.
    Polci, R.
    Belcolle Hosp, Nephrol Unit, Viterbo, Italy.
    Segoloni, G.
    Univ Turin, Turin, Italy;Citta Salute & Sci Hosp, Dept Med Sci, Div Nephrol Dialysis & Transplantat, Turin, Italy.
    Colla, L.
    Univ Turin, Turin, Italy;Citta Salute & Sci Hosp, Dept Med Sci, Div Nephrol Dialysis & Transplantat, Turin, Italy.
    Pani, A.
    G Brotzu Hosp, Nephrol Unit, Cagliari, Italy.
    Piras, D.
    G Brotzu Hosp, Nephrol Unit, Cagliari, Italy.
    Angioi, A.
    G Brotzu Hosp, Nephrol Unit, Cagliari, Italy.
    Cancarini, G.
    Spedali Civili Univ Hosp, Nephrol Unit, Brescia, Italy.
    Ravera, S.
    Spedali Civili Univ Hosp, Nephrol Unit, Brescia, Italy.
    Durlik, M.
    Med Univ Warsaw, Dept Transplantat Med Nephrol & Internal Med, Warsaw, Poland.
    Moggia, E.
    Santa Croce Hosp, Nephrol Unit, Cuneo, Italy.
    Ballarin, J.
    Fdn Puigvert, Dept Nephrol, Barcelona, Spain.
    Di Giulio, S.
    San Camillo Forlanini Hosp, Nephrol Unit, Rome, Italy.
    Pugliese, F.
    Policlin Umberto Univ Hosp, Dept Nephrol, Rome, Italy.
    Serriello, I.
    Policlin Umberto Univ Hosp, Dept Nephrol, Rome, Italy.
    Caliskan, Y.
    Istanbul Univ, Istanbul Fac Med, Dept Internal Med, Div Nephrol, Istanbul, Turkey.
    Sever, M.
    Istanbul Univ, Istanbul Fac Med, Dept Internal Med, Div Nephrol, Istanbul, Turkey.
    Kilicaslan, I.
    Istanbul Univ, Istanbul Fac Med, Dept Pathol, Istanbul, Turkey.
    Locatelli, F.
    ASST Lecco, Alessandro Manzoni Hosp, Dept Nephrol & Dialysis, Lecce, Italy.
    Del Vecchio, L.
    ASST Lecco, Alessandro Manzoni Hosp, Dept Nephrol & Dialysis, Lecce, Italy.
    Wetzels, J. F. M.
    Radboud Univ Nijmegen, Med Ctr, Dept Nephrol, Nijmegen, Netherlands.
    Peters, H.
    Radboud Univ Nijmegen, Med Ctr, Dept Nephrol, Nijmegen, Netherlands.
    Berg, U.
    Dept Clin Sci Intervent & Technol, Div Pediat, Huddinge, Sweden.
    Carvalho, F.
    Hosp Curry Cabral, Nephrol Unit, Lisbon, Portugal.
    da Costa Ferreira, A. C.
    Hosp Curry Cabral, Nephrol Unit, Lisbon, Portugal.
    Maggio, M.
    Hosp Maggiore Lodi, Nephrol Unit, Lodi, Italy.
    Wiecek, A.
    Silesian Univ Med, Dept Nephrol Endocrinol & Metab Dis, Katowice, Poland.
    Ots-Rosenberg, M.
    Tartu Univ Clin, Nephrol Unit, Tartu, Estonia.
    Magistroni, R.
    Policlin Modena & Reggio Emilia, Dept Nephrol, Modena, Italy.
    Topaloglu, R.
    Hacettepe Univ, Dept Pediat Nephrol & Rheumatol, Ankara, Turkey.
    Bilginer, Y.
    Hacettepe Univ, Dept Pediat Nephrol & Rheumatol, Ankara, Turkey.
    D'Amico, M.
    St Anna Hosp, Nephrol Unit, Como, Italy.
    Stangou, M.
    Aristotle Univ Thessaloniki, Hippokrat Gen Hosp, Dept Nephrol, Thessaloniki, Greece.
    Giacchino, F.
    Ivrea Hosp, Nephrol Unit, Ivrea, Italy.
    Goumenos, D.
    Univ Hosp Patras, Dept Nephrol, Patras, Greece.
    Kalliakmani, P.
    Univ Hosp Patras, Dept Nephrol, Patras, Greece.
    Gerolymos, M.
    Univ Hosp Patras, Dept Nephrol, Patras, Greece.
    Galesic, K.
    Univ Hosp Dubrava, Dept Nephrol, Zagreb, Croatia.
    Geddes, C.
    Western Infirm Glasgow, Renal Unit, Glasgow, Lanark, Scotland;Western Infirm & Associated Hosp, Renal Unit, Glasgow, Lanark, Scotland.
    Siamopoulos, K.
    Univ Ioannina, Med Sch, Nephrol Unit, Ioannina, Greece.
    Balafa, O.
    Univ Ioannina, Med Sch, Nephrol Unit, Ioannina, Greece.
    Galliani, M.
    S Pertini Hosp, Nephrol Unit, Rome, Italy.
    Stratta, P.
    Piemonte Orientale Univ, Maggiore Carita Hosp, Dept Nephrol, Novara, Italy.
    Quaglia, M.
    Piemonte Orientale Univ, Maggiore Carita Hosp, Dept Nephrol, Novara, Italy.
    Bergia, R.
    Infermi Hosp, Nephrol Unit, Biella, Italy.
    Cravero, R.
    Infermi Hosp, Nephrol Unit, Biella, Italy.
    Salvadori, M.
    Careggi Hosp, Dept Nephrol, Florence, Italy.
    Cirami, L.
    Careggi Hosp, Dept Nephrol, Florence, Italy.
    Fellström, Bengt
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Njurmedicin.
    Smerud, Hilde Kloster
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Njurmedicin.
    Ferrario, F.
    San Gerardo Hosp, Nephropathol Unit, Monza, Italy;San Gerardo Hosp, Nephropathol Unit, Monza, Italy;San Carlo Borromeo Hosp, Renal Immunopathol Ctr, Milan, Italy.
    Stellato, T.
    San Gerardo Hosp, Nephropathol Unit, Monza, Italy.
    Egido, J.
    Fdn Jimenez Diaz, Dept Nephrol, Madrid, Spain.
    Martin, C.
    Fdn Jimenez Diaz, Dept Nephrol, Madrid, Spain.
    Floege, J.
    Univ Aachen, Med Klin 2, Nephrol & Immunol, Aachen, Germany.
    Eitner, F.
    Univ Aachen, Med Klin 2, Nephrol & Immunol, Aachen, Germany.
    Lupo, A.
    Univ Verona, Dept Nephrol, Verona, Italy.
    Bernich, P.
    Univ Verona, Dept Nephrol, Verona, Italy.
    Mene, R.
    S Andrea Hosp, Dept Nephrol, Rome, Italy.
    Morosetti, M.
    Grassi Hosp, Nephrol Unit, Ostia, Italy.
    van Kooten, C.
    Leiden Univ, Med Ctr, Dept Nephrol, Leiden, Netherlands.
    Rabelink, T.
    Leiden Univ, Med Ctr, Dept Nephrol, Leiden, Netherlands.
    Reinders, M. E. J.
    Leiden Univ, Med Ctr, Dept Nephrol, Leiden, Netherlands.
    Boria Grinyo, J. M.
    Bellvitge Hosp, Dept Nephrol, Barcelona, Spain.
    Cusinato, S.
    Borgomanero Hosp, Nephrol Unit, Borgomanero, Italy.
    Benozzi, L.
    Borgomanero Hosp, Nephrol Unit, Borgomanero, Italy.
    Savoldi, S.
    Civile Hosp, Nephrol Unit, Cirie, Italy.
    Licata, C.
    Civile Hosp, Nephrol Unit, Cirie, Italy.
    Mizerska-Wasiak, M.
    Med Univ Warsaw, Dept Pediat, Warsaw, Poland.
    Martina, G.
    Chivasso Hosp, Nephrol Unit, Chivasso, Italy.
    Messuerotti, A.
    Chivasso Hosp, Nephrol Unit, Chivasso, Italy.
    Dal Canton, A.
    San Matteo Hosp, Nephrol Unit, Pavia, Italy.
    Esposito, C.
    Maugeri Fdn, Nephrol Unit, Pavia, Italy.
    Migotto, C.
    Maugeri Fdn, Nephrol Unit, Pavia, Italy.
    Triolo, G.
    Nephrol Unit CTO, Turin, Italy.
    Mariano, F.
    Nephrol Unit CTO, Turin, Italy.
    Pozzi, C.
    Bassini Hosp, Nephrol Unit, Cinisello Balsamo, Italy.
    Boero, R.
    Martini Hosp, Nephrol Unit, Turin, Italy.
    Bellur, S.
    Oxford Univ Hosp NHS Fdn Trust, John Radcliffe Hosp, Dept Cellular Pathol, Oxford, England.
    Mazzucco, G.
    Univ Turin, Pathol Dept, Turin, Italy.
    Giannakakis, C.
    Sapienza Univ, Pathol Dept, Rome, Italy.
    Honsova, E.
    Inst Clin & Expt Med, Dept Clin & Transplant Pathol, Prague, Czech Republic.
    Sundelin, B.
    Karolinska Univ Hosp, Karolinska Inst, Dept Pathol & Cytol, Stockholm, Sweden.
    Di Palma, A. M.
    Aldo Moro Univ, Nephrol Unit, Foggia, Italy.
    Gutierrez, E.
    Univ Autonoma Madrid, Fdn Jimenez Diaz, Fdn Inst Invest Sanitarias, Renal Vasc & Diabet Res Lab, Madrid, Spain.
    Asunis, A. M.
    Brotzu Hosp, Dept Pathol, Cagliari, Italy.
    Barratt, J.
    Leicester Gen Hosp, John Walls Renal Unit, Leicester, Leics, England;Leicester Gen Hosp, John Walls Renal Unit, Leicester, Leics, England.
    Tardanico, R.
    Univ Brescia, Spedali Civili Hosp, Dept Pathol, Brescia, Italy.
    Perkowska-Ptasinska, A.
    Med Univ Warsaw, Dept Transplantat Med Nephrol & Internal Med, Warsaw, Poland.
    Arce Terroba, J.
    Fundacio Puigvert, Pathol Dept, Barcelona, Spain.
    Fortunato, M.
    S Croce Hosp, Pathol Dept, Cuneo, Italy.
    Pantzaki, A.
    Hippokrateion Hosp, Dept Pathol, Thessaloniki, Greece.
    Ozluk, Y.
    Istanbul Univ, Istanbul Fac Med, Dept Pathol, Istanbul, Turkey.
    Steenbergen, E.
    Radboud Univ Nijmegen, Med Ctr, Dept Pathol, Nijmegen, Netherlands.
    Soderberg, M.
    Dept Pathol Drug Safety & Metab, Huddinge, Sweden.
    Riispere, Z.
    Univ Tartu, Dept Pathol, Tartu, Estonia.
    Furci, L.
    Univ Modena, Pathol Dept, Modena, Italy.
    Orhan, D.
    Hacettepe Univ, Fac Med, Div Rheumatol, Dept Pediat, Ankara, Turkey.
    Kipgen, D.
    Queen Elizabeth Univ Hosp, Pathol Dept, Glasgow, Lanark, Scotland.
    Casartelli, D.
    Manzoni Hosp, Pathol Dept, Lecce, Italy.
    Ljubanovic, D. Galesic
    Univ Hosp Zagreb, Nephrol Dept, Zagreb, Croatia.
    Gakiopoulou, H.
    Univ Athens, Dept Pathol, Athens, Greece.
    Bertoni, E.
    Careggi Hosp, Nephrol Dept, Florence, Italy.
    Cannata Ortiz, P.
    UAM, IIS Fdn Jimenez Diaz, Pathol Dept, Madrid, Spain.
    Karkoszka, H.
    Med Univ Silesia, Nephrol Endocrinol & Metab Dis, Katowice, Poland.
    Groene, H. J.
    German Canc Res Ctr, Cellular & Mol Pathol, Heidelberg, Germany.
    Stoppacciaro, A.
    Sapienza Univ Rome, Osped St Andrea, Dept Clin & Mol Med, Surg Pathol Unit, Rome, Italy.
    Bajema, I.
    Leiden Univ, Med Ctr, Dept Pathol, Leiden, Netherlands.
    Bruijn, J.
    Leiden Univ, Med Ctr, Dept Pathol, Leiden, Netherlands;Leiden Univ, Med Ctr, Dept Pathol, Leiden, Netherlands.
    Fulladosa Oliveras, X.
    Bellvitge Univ Hosp, Nephrol Unit, Barcelona, Spain.
    Maldyk, J.
    Med Univ Warsaw, Childrens Clin Hosp, Div Pathomorphol, Warsaw, Poland.
    Loachim, E.
    Univ Ioannina, Med Sch, Dept Pathol, Ioannina, Greece.
    Bavbek, N.
    Vanderbilt Univ, Dept Pathol, Nashville, TN USA.
    Cook, T.
    Imperial Coll, London, England.
    Alpers, C.
    Univ Washington, Med Ctr, Dept Pathol, Seattle, WA 98195 USA.
    Berthoux, F.
    CHU St Etienne, Hop Nord, Dept Nephrol Dialysis & Renal Transplantat, St Etienne, France.
    Bonsib, S.
    LSU Hlth Sci Ctr, Dept Pathol, Shreveport, LA USA.
    D'Agati, V
    Columbia Univ, Coll Phys & Surg, Dept Pathol, New York, NY USA.
    D'Amico, G.
    Fdn DAmico Ric Malattie Renali, Milan, Italy.
    Emancipator, S.
    Case Western Reserve Univ, Dept Pathol, Cleveland, OH 44106 USA.
    Emmal, F.
    Bambino Gesu Childrens Hosp & Res Inst, Dept Nephrol & Urol, Div Nephrol & Dialysis, Rome, Italy.
    Fervenza, F.
    Mayo Clin, Div Nephrol & Hypertens, Rochester, MN USA.
    Florquin, S.
    Univ Amsterdam, Acad Med Ctr, Dept Pathol, Amsterdam, Netherlands.
    Fogo, A.
    Vanderbilt Univ, Dept Pathol, Nashville, TN USA.
    Groene, H.
    German Canc Res Ctr, Dept Cellular & Mol Pathol, Heidelberg, Germany.
    Haas, M.
    Cedars Sinai Med Ctr, Dept Pathol & Lab Med, Los Angeles, CA 90048 USA.
    Hill, P.
    St Vincents Hosp, Melbourne, Vic, Australia.
    Hogg, R.
    Scott & White Med Ctr, Temple, TX USA.
    Hsu, S.
    Univ Florida, Coll Med, Div Nephrol Hypertens & Renal Transplantat, Gainesville, FL USA.
    Hunley, T.
    Vanderbilt Univ, Dept Pathol, Nashville, TN USA.
    Hladunewich, M.
    Jennette, C.
    Univ N Carolina, Dept Pathol & Lab Med, Chapel Hill, NC 27515 USA.
    Joh, K.
    East Natl Hosp, Clin Res Ctr Chiba, Div Immunopathol, Chiba, Japan.
    Julian, B.
    Univ Alabama Birmingham, Dept Med, Birmingham, AL 35294 USA.
    Kawamura, T.
    Jikei Univ, Sch Med, Div Nephrol & Hypertens, Tokyo, Japan;Jikei Univ, Sch Med, Dept Internal Med, Div Nephrol & Hypertens, Tokyo, Japan.
    Lai, F.
    Chinese Univ Hong Kong, Hong Kong, Peoples R China.
    Leung, C.
    Chinese Univ Hong Kong, Prince Wales Hosp, Dept Med, Hong Kong, Peoples R China.
    Li, L.
    Nanjing Univ, Sch Med, Jinling Hosp, Res Inst Nephrol, Nanjing, Jiangsu, Peoples R China.
    Li, P.
    Chinese Univ Hong Kong, Prince Wales Hosp, Dept Med, Hong Kong, Peoples R China.
    Liu, Z.
    Nanjing Univ, Sch Med, Nanjing, Jiangsu, Peoples R China;Nanjing Univ, Sch Med, Jinling Hosp, Res Inst Nephrol, Nanjing, Jiangsu, Peoples R China.
    Massat, A.
    Mayo Clin, Div Nephrol & Hypertens, Rochester, MN USA.
    Mackinnon, B.
    Western Infirm & Associated Hosp, Renal Unit, Glasgow, Lanark, Scotland.
    Mezzano, S.
    Univ Austral Chile, Escuela Med, Dept Nefrol, Valdivia, Chile.
    Schena, F.
    Policlinico, Renal Dialysis & Transplant Unit, Bari, Italy.
    Tomino, Y.
    Juntendo Univ, Sch Med, Dept Internal Med, Div Nephrol, Tokyo, Japan.
    Walker, P.
    Nephropathol Associates, Little Rock, AR USA.
    Wang, H.
    Peking Univ, Inst Nephrol, Hosp 1, Renal Div, Beijing, Peoples R China.
    Weening, J.
    Erasmus MC, Rotterdam, Netherlands.
    Yoshikawa, N.
    Wakayama Med Univ, Dept Pediat, Wakayama, Japan.
    Zeng, Cai-Hong
    Nanjing Univ, Sch Med, Nanjing, Jiangsu, Peoples R China.
    Shi, Sufang
    Peking Univ, Inst Nephrol, Beijing, Peoples R China.
    Nogi, C.
    Juntendo Univ, Fac Med, Tokyo, Japan.
    Suzuki, H.
    Juntendo Univ, Fac Med, Tokyo, Japan;Juntendo Univ, Fac Med, Tokyo, Japan.
    Koike, K.
    Jikei Univ, Sch Med, Dept Internal Med, Div Nephrol & Hypertens, Tokyo, Japan.
    Hirano, K.
    Jikei Univ, Sch Med, Dept Internal Med, Div Nephrol & Hypertens, Tokyo, Japan.
    Yokoo, T.
    Jikei Univ, Sch Med, Dept Internal Med, Div Nephrol & Hypertens, Tokyo, Japan.
    Hanai, M.
    Kurume Univ, Sch Med, Dept Med, Div Nephrol, Fukuoka, Fukuoka, Japan.
    Fukami, K.
    Kurume Univ, Sch Med, Dept Med, Div Nephrol, Fukuoka, Fukuoka, Japan.
    Takahashi, K.
    Fujita Hlth Univ, Sch Med, Dept Nephrol, Toyoake, Aichi, Japan.
    Yuzawa, Y.
    Fujita Hlth Univ, Sch Med, Dept Nephrol, Toyoake, Aichi, Japan.
    Niwa, M.
    Nagoya Univ, Grad Sch Med, Dept Nephrol, Nagoya, Aichi, Japan.
    Yasuda, Y.
    Nagoya Univ, Grad Sch Med, Dept Nephrol, Nagoya, Aichi, Japan.
    Maruyama, S.
    Nagoya Univ, Grad Sch Med, Dept Nephrol, Nagoya, Aichi, Japan.
    Ichikawa, D.
    St Marianna Univ, Sch Med, Dept Internal Med, Div Nephrol & Hypertens, Kawasaki, Kanagawa, Japan.
    Suzuki, T.
    Juntendo Univ, Fac Med, Tokyo, Japan;St Marianna Univ, Sch Med, Dept Internal Med, Div Nephrol & Hypertens, Kawasaki, Kanagawa, Japan.
    Shirai, S.
    St Marianna Univ, Sch Med, Dept Internal Med, Div Nephrol & Hypertens, Kawasaki, Kanagawa, Japan.
    Fukuda, A.
    Miyazaki Univ, Fac Med, Dept Internal Med 1, Miyazaki, Japan.
    Fujimoto, S.
    Univ Miyazaki, Fac Med, Dept Hemovasc Med & Artificial Organs, Miyazaki, Japan.
    Trimarchi, H.
    Hosp Britanico, Div Nephrol, Buenos Aires, DF, Argentina.
    Evaluating a New International Risk-Prediction Tool in IgA Nephropathy2019Inngår i: JAMA Internal Medicine, ISSN 2168-6106, E-ISSN 2168-6114, Vol. 179, nr 7, s. 942-952Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Importance  Although IgA nephropathy (IgAN) is the most common glomerulonephritis in the world, there is no validated tool to predict disease progression. This limits patient-specific risk stratification and treatment decisions, clinical trial recruitment, and biomarker validation.

    Objective  To derive and externally validate a prediction model for disease progression in IgAN that can be applied at the time of kidney biopsy in multiple ethnic groups worldwide.

    Design, Setting, and Participants  We derived and externally validated a prediction model using clinical and histologic risk factors that are readily available in clinical practice. Large, multi-ethnic cohorts of adults with biopsy-proven IgAN were included from Europe, North America, China, and Japan.

    Main Outcomes and Measures  Cox proportional hazards models were used to analyze the risk of a 50% decline in estimated glomerular filtration rate (eGFR) or end-stage kidney disease, and were evaluated using the R2D measure, Akaike information criterion (AIC), C statistic, continuous net reclassification improvement (NRI), integrated discrimination improvement (IDI), and calibration plots.

    Results  The study included 3927 patients; mean age, 35.4 (interquartile range, 28.0-45.4) years; and 2173 (55.3%) were men. The following prediction models were created in a derivation cohort of 2781 patients: a clinical model that included eGFR, blood pressure, and proteinuria at biopsy; and 2 full models that also contained the MEST histologic score, age, medication use, and either racial/ethnic characteristics (white, Japanese, or Chinese) or no racial/ethnic characteristics, to allow application in other ethnic groups. Compared with the clinical model, the full models with and without race/ethnicity had better R2D (26.3% and 25.3%, respectively, vs 20.3%) and AIC (6338 and 6379, respectively, vs 6485), significant increases in C statistic from 0.78 to 0.82 and 0.81, respectively (ΔC, 0.04; 95% CI, 0.03-0.04 and ΔC, 0.03; 95% CI, 0.02-0.03, respectively), and significant improvement in reclassification as assessed by the NRI (0.18; 95% CI, 0.07-0.29 and 0.51; 95% CI, 0.39-0.62, respectively) and IDI (0.07; 95% CI, 0.06-0.08 and 0.06; 95% CI, 0.05-0.06, respectively). External validation was performed in a cohort of 1146 patients. For both full models, the C statistics (0.82; 95% CI, 0.81-0.83 with race/ethnicity; 0.81; 95% CI, 0.80-0.82 without race/ethnicity) and R2D (both 35.3%) were similar or better than in the validation cohort, with excellent calibration.

    Conclusions and Relevance  In this study, the 2 full prediction models were shown to be accurate and validated methods for predicting disease progression and patient risk stratification in IgAN in multi-ethnic cohorts, with additional applications to clinical trial design and biomarker research.

  • 4.
    Bergström, Marcus
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Joly, A. -L
    Seiron, P.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Isringhausen, S.
    Modig, E.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Fellström, Bengt
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Njurmedicin.
    Andersson, J.
    Berglund, David
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Transplantationskirurgi.
    Immunological Profiling of Haemodialysis Patients and Young Healthy Individuals with Implications for Clinical Regulatory T Cell Sorting2015Inngår i: Scandinavian Journal of Immunology, ISSN 0300-9475, E-ISSN 1365-3083, Vol. 81, nr 5, s. 318-324Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    With the increasing interest in clinical trials with regulatory T cells (Tregs), immunological profiling of prospective target groups and standardized procedures for Treg isolation are needed. In this study, flow cytometry was used to assess peripheral blood lymphocyte profiles of young healthy individuals and patients undergoing haemodialysis treatment. Tregs obtained from the former may be used in haematopoietic stem cell transplantation and Tregs from the latter in the prevention of kidney transplant rejection. FOXP3 mRNA expression with accompanying isoform distribution was also assessed by the quantitative reverse transcriptase polymerase chain reaction. Flow-cytometric gating strategies were systematically analysed to optimize the isolation of Tregs. Our findings showed an overall similar immunological profile of both cohorts in spite of great differences in both age and health. Analysis of flow-cytometric gating techniques highlighted the importance of gating for both CD25high and CD127low expression in the isolation of FOXP3-positive cells. This study provides additional insight into the immunological profile of young healthy individuals and uraemic patients as well as in-depth analysis of flow-cytometric gating strategies for Treg isolation, supporting the development of Treg therapy using cells from healthy donors and uraemic patients.

  • 5.
    Bhandari, Sunil
    et al.
    Hull & East Yorkshire Hosp NHS Trust, Nephrol, Kingston Upon Hull, N Humberside, England.
    Wikström, Björn
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Njurmedicin.
    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 concerns2018Inngår i: Nephrology, Dialysis and Transplantation, ISSN 0931-0509, E-ISSN 1460-2385, Vol. 33, nr Supplement: 1Artikkel i tidsskrift (Annet vitenskapelig)
  • 6.
    Cameron-Christie, Sophia
    et al.
    AstraZeneca, R&D BioPharmaceut, Discovery Sci, AstraZeneca Ctr Genom Res, Cambridge, England.
    Wolock, Charles J.
    Columbia Univ, Dept Genet & Dev, New York, NY USA.
    Groopman, Emily
    Columbia Univ, Dept Med, Div Nephrol, New York, NY USA.
    Petrovski, Slave
    AstraZeneca, R&D BioPharmaceut, Discovery Sci, AstraZeneca Ctr Genom Res, Cambridge, England.
    Kamalakaran, Sitharthan
    Columbia Univ, Dept Genet & Dev, New York, NY USA.
    Povysil, Gundula
    AstraZeneca, R&D BioPharmaceut, Discovery Sci, AstraZeneca Ctr Genom Res, Cambridge, England;Columbia Univ, Med Ctr, Inst Genom Med, New York, NY USA.
    Vitsios, Dimitrios
    AstraZeneca, R&D BioPharmaceut, Discovery Sci, AstraZeneca Ctr Genom Res, Cambridge, England.
    Zhang, Mengqi
    Columbia Univ, Med Ctr, Inst Genom Med, New York, NY USA;Duke Univ, Dept Biostatist & Bioinformat, Durham, NC USA.
    Fleckner, Jan
    AstraZeneca, R&D BioPharmaceut, Discovery Sci, AstraZeneca Ctr Genom Res, Cambridge, England.
    March, Ruth E.
    AstraZeneca, R&D Oncol, Precis Med, Cambridge, England.
    Gelfman, Sahar
    Columbia Univ, Dept Genet & Dev, New York, NY USA.
    Marasa, Maddalena
    Columbia Univ, Dept Med, Div Nephrol, New York, NY USA.
    Li, Yifu
    Columbia Univ, Dept Med, Div Nephrol, New York, NY USA.
    Sanna-Cherchi, Simone
    Columbia Univ, Dept Med, Div Nephrol, New York, NY USA.
    Kiryluk, Krzysztof
    Columbia Univ, Dept Med, Div Nephrol, New York, NY USA.
    Allen, Andrew S.
    Columbia Univ, Med Ctr, Inst Genom Med, New York, NY USA;Duke Univ, Dept Biostatist & Bioinformat, Durham, NC USA.
    Fellström, Bengt
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Njurmedicin.
    Haefliger, Carolina
    AstraZeneca, R&D BioPharmaceut, Discovery Sci, AstraZeneca Ctr Genom Res, Cambridge, England.
    Platt, Adam
    AstraZeneca, R&D BioPharmaceut, Discovery Sci, AstraZeneca Ctr Genom Res, Cambridge, England.
    Goldstein, David B.
    AstraZeneca, R&D BioPharmaceut, Discovery Sci, AstraZeneca Ctr Genom Res, Cambridge, England;Columbia Univ, Dept Genet & Dev, New York, NY USA;Columbia Univ, Med Ctr, Inst Genom Med, New York, NY USA.
    Gharavi, Ali G.
    Columbia Univ, Dept Med, Div Nephrol, New York, NY USA;Columbia Univ, Med Ctr, Inst Genom Med, New York, NY USA.
    Exome-Based Rare-Variant Analyses in CKD2019Inngår i: Journal of the American Society of Nephrology, ISSN 1046-6673, E-ISSN 1533-3450, Vol. 30, nr 6, s. 1109-1122Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background Studies have identified many common genetic associations that influence renal function and all-cause CKD, but these explain only a small fraction of variance in these traits. The contribution of rare variants has not been systematically examined. Methods We performed exome sequencing of 3150 individuals, who collectively encompassed diverse CKD subtypes, and 9563 controls. To detect causal genes and evaluate the contribution of rare variants we used collapsing analysis, in which we compared the proportion of cases and controls carrying rare variants per gene. Results The analyses captured five established monogenic causes of CKD: variants in PKD1, PKD2, and COL4A5 achieved study-wide significance, and we observed suggestive case enrichment for COL4A4 and COL4A3. Beyond known disease-associated genes, collapsing analyses incorporating regional variant intolerance identified suggestive dominant signals in CPT2 and several other candidate genes. Biallelic mutations in CPT2 cause carnitine palmitoyltransferase II deficiency, sometimes associated with rhabdomyolysis and acute renal injury. Genetic modifier analysis among cases with APOL1 risk genotypes identified a suggestive signal in AHDC1, implicated in Xia-Gibbs syndrome, which involves intellectual disability and other features. On the basis of the observed distribution of rare variants, we estimate that a two-to three-fold larger cohort would provide 80% power to implicate new genes for all-cause CKD. Conclusions This study demonstrates that rare-variant collapsing analyses can validate known genes and identify candidate genes and modifiers for kidney disease. In so doing, these findings provide a motivation for larger-scale investigation of rare-variant risk contributions across major clinical CKD categories.

  • 7.
    Carlsson, Daniel O
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Nanoteknologi och funktionella material.
    Ferraz, Natalia
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Nanoteknologi och funktionella material.
    Fellström, Bengt
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Njurmedicin.
    Nyholm, Leif
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Oorganisk kemi.
    Mihranyan, Albert
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Nanoteknologi och funktionella material.
    Strømme, Maria
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Nanoteknologi och funktionella material.
    Towards blood purification applications of polypyrrole and cellulose nanocomposites2013Konferansepaper (Fagfellevurdert)
  • 8.
    Carlsson, Daniel O
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Nanoteknologi och funktionella material.
    Ferraz, Natalie
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Nanoteknologi och funktionella material.
    Hong, J
    Larsson, R
    Fellström, Bengt
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Njurmedicin.
    Nyholm, Leif
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Oorganisk kemi.
    Strömme, Maria
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Nanoteknologi och funktionella material.
    Mihranyan, Albert
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Nanoteknologi och funktionella material.
    Conduting nanocellulose polypyrrole membranes intended for hemodialysis2012Konferansepaper (Fagfellevurdert)
  • 9. 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 universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Njurmedicin.
    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) update2018Inngår i: Nephrology, Dialysis and Transplantation, ISSN 0931-0509, E-ISSN 1460-2385Artikkel i tidsskrift (Fagfellevurdert)
    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.

  • 10. Dahle, Dag Olav
    et al.
    Jenssen, Trond
    Holdaas, Hallvard
    Åsberg, Anders
    Soveri, Inga
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Njurmedicin.
    Holme, Ingar
    Mjøen, Geir
    Eide, Ivar A
    Pihlstrøm, Hege
    Dörje, Christina
    Halden, Thea A S
    Hartmann, Anders
    Uric acid and clinical correlates of endothelial function in kidney transplant recipients2014Inngår i: Clinical Transplantation, ISSN 0902-0063, E-ISSN 1399-0012, Vol. 28, nr 10, s. 1167-1176Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Uric acid is associated with increased mortality in kidney transplant recipients (KTRs), but it is uncertain if this involves endothelial dysfunction. We hypothesized, first, that there was an association between uric acid and endothelial function, and second, that there were associations between endothelial function and cardiac and mortality risk scores.

    METHODS: One hundred and fifty-two patients were examined 10 wk after kidney transplantation by two measures of endothelial function, the brachial artery flow-mediated dilatation (FMD) expressed as percent dilatation (FMD%), and fingertip peripheral arterial tone (PAT) expressed as log-reactive hyperemia index (LnRHI). Risk scores were calculated from a recently validated formula. Other clinical correlates of endothelial function were described in stepwise linear regression models.

    RESULTS: Uric acid was associated negatively with FMD% in an age- and gender-adjusted model, while not in the multivariable model. No association was shown between uric acid and LnRHI. FMD% was associated negatively with risk scores in both crude and age- and gender-adjusted models (p < 0.01). LnRHI was associated negatively with risk scores in the latter model only (p < 0.05).

    CONCLUSIONS: Uric acid was neither associated with FMD% nor LnRHI in KTRs. There were significant associations between endothelial function indices and cardiac and mortality risk scores.

  • 11. Delanaye, Pierre
    et al.
    Ebert, Natalie
    Melsom, Toralf
    Gaspari, Flavio
    Mariat, Christophe
    Cavalier, Etienne
    Björk, Jonas
    Christensson, Anders
    Nyman, Ulf
    Porrini, Esteban
    Remuzzi, Giuseppe
    Ruggenenti, Piero
    Schaeffner, Elke
    Soveri, Inga
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Njurmedicin.
    Sterner, Gunnar
    Eriksen, Bjørn Odvar
    Bäck, Sten-Erik
    Iohexol plasma clearance for measuring glomerular filtration rate in clinical practice and research: a review. Part 1 How to measure glomerular filtration rate with iohexol?2016Inngår i: Clinical Kidney Journal, ISSN 2048-8505, E-ISSN 2048-8513, Vol. 9, nr 5, s. 682-699Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    While there is general agreement on the necessity to measure glomerular filtration rate (GFR) in many clinical situations, there is less agreement on the best method to achieve this purpose. As the gold standard method for GFR determination, urinary (or renal) clearance of inulin, fades into the background due to inconvenience and high cost, a diversity of filtration markers and protocols compete to replace it. In this review, we suggest that iohexol, a non-ionic contrast agent, is most suited to replace inulin as the marker of choice for GFR determination. Iohexol comes very close to fulfilling all requirements for an ideal GFR marker in terms of low extra-renal excretion, low protein binding and in being neither secreted nor reabsorbed by the kidney. In addition, iohexol is virtually non-toxic and carries a low cost. As iohexol is stable in plasma, administration and sample analysis can be separated in both space and time, allowing access to GFR determination across different settings. An external proficiency programme operated by Equalis AB, Sweden, exists for iohexol, facilitating interlaboratory comparison of results. Plasma clearance measurement is the protocol of choice as it combines a reliable GFR determination with convenience for the patient. Single-sample protocols dominate, but multiple-sample protocols may be more accurate in specific situations. In low GFRs one or more late samples should be included to improve accuracy. In patients with large oedema or ascites, urinary clearance protocols should be employed. In conclusion, plasma clearance of iohexol may well be the best candidate for a common GFR determination method.

  • 12. Delanaye, Pierre
    et al.
    Melsom, Toralf
    Ebert, Natalie
    Bäck, Sten-Erik
    Mariat, Christophe
    Cavalier, Etienne
    Björk, Jonas
    Christensson, Anders
    Nyman, Ulf
    Porrini, Esteban
    Remuzzi, Giuseppe
    Ruggenenti, Piero
    Schaeffner, Elke
    Soveri, Inga
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Njurmedicin.
    Sterner, Gunnar
    Eriksen, Bjørn Odvar
    Gaspari, Flavio
    Iohexol plasma clearance for measuring glomerular filtration rate in clinical practice and research: a review. Part 2 Why to measure glomerular filtration rate with iohexol?2016Inngår i: Clinical Kidney Journal, ISSN 2048-8505, E-ISSN 2048-8513, Vol. 9, nr 5, s. 700-704Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    A reliable assessment of glomerular filtration rate (GFR) is of paramount importance in clinical practice as well as epidemiological and clinical research settings. It is recommended by Kidney Disease: Improving Global Outcomes guidelines in specific populations (anorectic, cirrhotic, obese, renal and non-renal transplant patients) where estimation equations are unreliable. Measured GFR is the only valuable test to confirm or confute the status of chronic kidney disease (CKD), to evaluate the slope of renal function decay over time, to assess the suitability of living kidney donors and for dosing of potentially toxic medication with a narrow therapeutic index. Abnormally elevated GFR or hyperfiltration in patients with diabetes or obesity can be correctly diagnosed only by measuring GFR. GFR measurement contributes to assessing the true CKD prevalence rate, avoiding discrepancies due to GFR estimation with different equations. Using measured GFR, successfully accomplished in large epidemiological studies, is the only way to study the potential link between decreased renal function and cardiovascular or total mortality, being sure that this association is not due to confounders, i.e. non-GFR determinants of biomarkers. In clinical research, it has been shown that measured GFR (or measured GFR slope) as a secondary endpoint as compared with estimated GFR detected subtle treatment effects and obtained these results with a comparatively smaller sample size than trials choosing estimated GFR. Measuring GFR by iohexol has several advantages: simplicity, low cost, stability and low interlaboratory variation. Iohexol plasma clearance represents the best chance for implementing a standardized GFR measurement protocol applicable worldwide both in clinical practice and in research.

  • 13. Drechsler, Christiane
    et al.
    Philstrom, Hege
    Meinitzer, Andreas
    Pilz, Stefan
    Tomaschitz, Andreas
    Abedini, Sadollah
    Fellström, Bengt
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Njurmedicin.
    Jardine, Alan
    Wanner, Christoph
    Maerz, Winfried
    Holdaas, Hallvard
    Homoarginine and Clinical Outcomes in Renal Transplant Recipients: Results from the Alert Study2014Inngår i: Nephrology, Dialysis and Transplantation, ISSN 0931-0509, E-ISSN 1460-2385, Vol. 29, s. 539-539Artikkel i tidsskrift (Annet vitenskapelig)
  • 14. Drechsler, Christiane
    et al.
    Pihlström, Hege
    Meinitzer, Andreas
    Pilz, Stefan
    Tomaschitz, Andreas
    Abedini, Sadollah
    Fellström, Bengt
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Njurmedicin.
    Jardine, Alan G
    Wanner, Christoph
    März, Winifred
    Holdaas, Hallvard
    Homoarginine and Clinical Outcomes in Renal Transplant Recipients: Results From the Assessment of Lescol in Renal Transplantation Study2015Inngår i: Transplantation, ISSN 0041-1337, E-ISSN 1534-6080, Vol. 99, nr 7, s. 1470-1476Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Despite improvements in kidney transplantation, complications, including cardiovascular morbidity and graft loss, contribute to reduced graft and patient survival. The amino acid homoarginine exerts a variety of beneficial effects that may be relevant for cardiovascular and graft outcomes, which is investigated in the present study.

    Methods: Homoarginine was measured in 829 renal transplant recipients participating in the placebo group of the Assessment of Lescol in Renal Transplantation study. Mean follow-up was 6.7 years. By Cox regression analyses, we determined hazard ratios (HRs) to reach prespecified, adjudicated endpoints according to baseline homoarginine levels: major adverse cardiovascular events (n = 103), cerebrovascular events (n = 53), graft failure or doubling of serum creatinine (n = 140), noncardiovascular mortality (n = 51), and all-cause mortality (n = 107).

    Results: Patients mean age was 50 ± 11 years, homoarginine concentration was 1.96 ± 0.76 µmol/L, and 65% were men. Patients in the lowest homoarginine quartile (<1.40 µmol/L) had an adjusted 2.6-fold higher risk of cerebrovascular events compared to those in the highest quartile (>2.34 µmol/L) (HR, 2.56; 95% confidence interval [95% CI], 1.13–5.82). Similarly, the renal endpoint occurred at a significantly increased rate in the lowest homoarginine quartile (HR, 2.34; 95% CI, 1.36–4.02). For noncardiovascular and all-cause mortality, there was also increased risk associated with the lowest levels of homoarginine, with HRs of 4.34 (95% CI, 1.63–10.69) and 2.50 (95% CI, 1.38–4.55), respectively.

    Conclusions: Low homoarginine is strongly associated with cerebrovascular events, graft loss and progression of kidney failure and mortality in renal transplant recipients. Whether interventions with homoarginine supplementation improve clinical outcomes requires further evaluation.

  • 15.
    Ekdahl, Kristina N
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi. Linnaeus Univ, Linnaeus Ctr Biomat Chem, SE-39182 Kalmar, Sweden.
    Soveri, Inga
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Njurmedicin.
    Hilborn, Jöns
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Polymerkemi.
    Fellström, Bengt
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Njurmedicin.
    Nilsson, Bo
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Cardiovascular disease in haemodialysis: role of the intravascular innate immune system.2017Inngår i: Nature Reviews Nephrology, ISSN 1759-5061, E-ISSN 1759-507X, Vol. 13, nr 5, s. 285-296Artikkel, forskningsoversikt (Fagfellevurdert)
    Abstract [en]

    Haemodialysis is a life-saving renal replacement modality for end-stage renal disease, but this therapy also represents a major challenge to the intravascular innate immune system, which is comprised of the complement, contact and coagulation systems. Chronic inflammation is strongly associated with cardiovascular disease (CVD) in patients on haemodialysis. Biomaterial-induced contact activation of proteins within the plasma cascade systems occurs during haemodialysis and initially leads to local generation of inflammatory mediators on the biomaterial surface. The inflammation is spread by soluble activation products and mediators that are generated during haemodialysis and transported in the extracorporeal circuit back into the patient together with activated leukocytes and platelets. The combined effect is activation of the endothelium of the cardiovascular system, which loses its anti-thrombotic and anti-inflammatory properties, leading to atherogenesis and arteriosclerosis. This concept suggests that maximum suppression of the intravascular innate immune system is needed to minimize the risk of CVD in patients on haemodialysis. A potential approach to achieve this goal is to treat patients with broad-specificity systemic drugs that target more than one of the intravascular cascade systems. Alternatively, 'stealth' biomaterials that cause minimal cascade system activation could be used in haemodialysis circuits.

  • 16.
    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 universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Njurmedicin.
    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 disease2017Inngår i: Nephrology, Dialysis and Transplantation, ISSN 0931-0509, E-ISSN 1460-2385, Vol. 32, nr 12, s. 2106-2111Artikkel i tidsskrift (Fagfellevurdert)
    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.

  • 17.
    Eriksson, Daniel
    et al.
    Quantify Res, Hantverkargatan 8, S-11221 Stockholm, Sweden..
    Karlsson, Linda
    Quantify Res, Hantverkargatan 8, S-11221 Stockholm, Sweden..
    Eklund, Oskar
    Quantify Res, Hantverkargatan 8, S-11221 Stockholm, Sweden..
    Dieperink, Hans
    Odense Univ Hosp, Dept Nephrol, Sdr Blvd 29, DK-5000 Odense C, Denmark..
    Honkanen, Eero
    Univ Helsinki, Cent Hosp, Dept Med, Div Nephrol, Haartmaninkatu 4,POB 372, FIN-00029 Hus Helsinki, Finland..
    Melin, Jan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Njurmedicin.
    Selvig, Kristian
    Vestre Viken Hosp Trust, Dept Nephrol, Postboks 800 3004, Drammen, Norway..
    Lundberg, Johan
    Otsuka Pharma Scandinavia, Birger Jarlsgatan 27, S-11145 Stockholm, Sweden..
    Real-world costs of autosomal dominant polycystic kidney disease in the Nordics2017Inngår i: BMC Health Services Research, ISSN 1472-6963, E-ISSN 1472-6963, Vol. 17, artikkel-id 560Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: There is limited real-world data on the economic burden of patients with autosomal dominant polycystic kidney disease (ADPKD). The objective of this study was to estimate the annual direct and indirect costs of patients with ADPKD by severity of the disease: chronic kidney disease (CKD) stages 1-3; CKD stages 4-5; transplant recipients; and maintenance dialysis patients. Methods: A retrospective study of ADPKD patients was undertaken April-December 2014 in Denmark, Finland, Norway and Sweden. Data on medical resource utilisation were extracted from medical charts and patients were asked to complete a self-administered questionnaire. Results: A total of 266 patients were contacted, 243 (91%) of whom provided consent to participate in the study. Results showed that the economic burden of ADPKD was substantial at all levels of the disease. Lost wages due to reduced productivity were large in absolute terms across all disease strata. Mean total annual costs were highest in dialysis patients, driven by maintenance dialysis care, while the use of immunosuppressants was the main cost component for transplant care. Costs were twice as high in patients with CKD stages 4-5 compared to CKD stages 1-3. Conclusions: Costs associated with ADPKD are significant and the progression of the disease is associated with an increased frequency and intensity of medical resource utilisation. Interventions that can slow the progression of the disease have the potential to lead to substantial reductions in costs for the treatment of ADPKD.

  • 18.
    Evans, Marc
    et al.
    Llandough Hosp, Diabet Resource Ctr, Cardiff, S Glam, Wales.
    Palaka, Eirini
    AstraZeneca, Global Hlth Econ, Cambridge, England.
    Furuland, Hans
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Njurmedicin.
    Bennett, Hayley
    Hlth Econ & Outcomes Res Ltd, Cardiff, S Glam, Wales.
    Linde, Cecilia
    Karolinska Univ Hosp, Heart & Vasc Theme, Stockholm, Sweden;Karolinska Inst, Stockholm, Sweden.
    Qin, Lei
    AstraZeneca, Global Hlth Econ, Gaithersburg, MD USA.
    McEwan, Phil
    Hlth Econ & Outcomes Res Ltd, Cardiff, S Glam, Wales;Swansea Univ, Sch Human & Hlth Sci, Swansea, W Glam, Wales.
    Bakhai, Ameet
    Royal Free Hosp, Dept Cardiol, London, England.
    The value of maintaining normokalaemia and enabling RAASi therapy in chronic kidney disease2019Inngår i: BMC Nephrology, ISSN 1471-2369, E-ISSN 1471-2369, Vol. 20, artikkel-id 31Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background

    People with chronic kidney disease (CKD) are at an increased risk of developing hyperkalaemia due to their declining kidney function. In addition, these patients are often required to reduce or discontinue guideline-recommended renin-angiotensin-aldosterone system inhibitor (RAASi) therapy due to increased risk of hyperkalaemia. This original research developed a model to quantify the health and economic benefits of maintaining normokalaemia and enabling optimal RAASi therapy in patients with CKD.

    Methods

    A patient-level simulation model was designed to fully characterise the natural history of CKD over a lifetime horizon, and predict the associations between serum potassium levels, RAASi use and long-term outcomes based on published literature. The clinical and economic benefits of maintaining sustained potassium levels and therefore avoiding RAASi discontinuation in CKD patients were demonstrated using illustrative, sensitivity and scenario analyses.

    Results

    Internal and external validation exercises confirmed the predictive capability of the model. Sustained potassium management and ongoing RAASi therapy were associated with longer life expectancy (+ 2.36 years), delayed onset of end stage renal disease (+ 5.4 years), quality-adjusted life-year gains (+ 1.02 QALYs), cost savings (£3135) and associated net monetary benefit (£23,446 at £20,000 per QALY gained) compared to an absence of RAASi to prevent hyperkalaemia.

    Conclusion

    This model represents a novel approach to predicting the long-term benefits of maintaining normokalaemia and enabling optimal RAASi therapy in patients with CKD, irrespective of the strategy used to achieve this target, which may support decision making in healthcare.

  • 19.
    Fellström, Bengt
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Njurmedicin.
    Risk Factors and Management Options for Cardiovascular Disease (CVD) in Kidney Transplantation2013Inngår i: Annals of Saudi Medicine, ISSN 0256-4947, E-ISSN 0975-4466, Vol. 33, nr 2, s. S15-S16Artikkel i tidsskrift (Fagfellevurdert)
  • 20.
    Fellström, Bengt
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Njurmedicin.
    Barratt, Jonathan
    Univ Leicester, Dept Infect Immun & Inflammat, Leicester, Leics, England; Leicester Gen Hosp, John Walls Renal Unit, Leicester, Leics, England; Hlth Educ East Midlands, Postgrad Specialty Sch Clin Acad Training, Leicester, Leics, England.
    Flöge, Jürgen
    Rhein Westfal TH Aachen, Med Klin 2, Aachen, Germany.
    Jardine, Alan
    Univ Glasgow, Inst Cardiovasc & Med Sci, Glasgow, Lanark, Scotland; Queen Elizabeth Hosp, Glasgow Renal Transplant Unit, Glasgow, Lanark, Scotland.
    Targeted-release budesonide therapy for IgA nephropathy - Authors' reply.2017Inngår i: The Lancet, ISSN 0140-6736, E-ISSN 1474-547X, Vol. 390, nr 10113, s. 2625-2626Artikkel i tidsskrift (Fagfellevurdert)
  • 21.
    Fellström, Bengt C.
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Njurmedicin.
    Barratt, Jonathan
    Univ Leicester, Leicester, Leics, England..
    Cook, Heather
    PharmaL Consulting AB, Stockholm, Sweden..
    Coppo, Rosanna
    Regina Margherita Hosp, Fdn Ric Molinette, Turin, Italy..
    Feehally, John
    Univ Leicester, Leicester, Leics, England..
    de Fijter, Johan W.
    Leiden Univ, Med Ctr, Leiden, Netherlands..
    Floege, Jürgen
    Rhein Westfal TH Aachen, Aachen, Germany..
    Hetzel, Gerd
    HeinrichHeine Univ, DaVita Renal Ctr, Dusseldorf, Germany..
    Jardine, Alan G.
    Univ Glasgow, Glasgow, Lanark, Scotland..
    Locatelli, Francesco
    Osped A Manzoni, Lecce, Italy..
    Maes, Bart D.
    AZ Delta, Roeselare, Belgium..
    Mercer, Alex
    Pharmalink AB, Stockholm, Sweden..
    Ortiz, Fernanda
    Helsinki Univ Hosp, Helsinki, Finland..
    Praga, Manuel
    Univ Complutense Madrid, Investigat Inst Hosp Octubre 12, Madrid, Spain..
    Sorensen, Soren S.
    Copenhagen Univ Hosp, Rigshosp, Copenhagen, Denmark..
    Tesar, Vladimir
    Charles Univ Prague, Prague, Czech Republic..
    Del Vecchio, Lucia
    Osped A Manzoni, Lecce, Italy..
    Targeted-release budesonide versus placebo in patients with IgA nephropathy (NEFIGAN): a double-blind, randomised, placebo-controlled phase 2b trial2017Inngår i: The Lancet, ISSN 0140-6736, E-ISSN 1474-547X, Vol. 389, nr 10084, s. 2117-2127Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: IgA nephropathy is thought to be associated with mucosal immune system dysfunction, which manifests as renal IgA deposition that leads to impairment and end-stage renal disease in 20-40% of patients within 10-20 years. In this trial (NEFIGAN) we aimed to assess safety and efficacy of a novel targeted-release formulation of budesonide (TRF-budesonide), designed to deliver the drug to the distal ileum in patients with IgA nephropathy.

    Methods: We did a randomised, double-blind, placebo-controlled phase 2b trial, comprised of 6-month run-in, 9-month treatment, and 3-month follow-up phases at 62 nephrology clinics across ten European countries. We recruited patients aged at least 18 years with biopsy-confirmed primary IgA nephropathy and persistent proteinuria despite optimised renin-angiotensin system (RAS) blockade. We randomly allocated patients with a computer algorithm, with a fixed block size of three, in a 1:1:1 ratio to 16 mg/day TRF-budesonide, 8 mg/day TRF-budesonide, or placebo, stratified by baseline urine protein creatinine ratio (UPCR). Patients self-administered masked capsules, once daily, 1 h before breakfast during the treatment phase. All patients continued optimised RAS blockade treatment throughout the trial. Our primary outcome was mean change from baseline in UPCR for the 9-month treatment phase, which was assessed in the full analysis set, defined as all randomised patients who took at least one dose of trial medication and had at least one post-dose efficacy measurement. Safety was assessed in all patients who received the intervention. This trial is registered with ClinicalTrials.gov, number NCT01738035.

    Findings: Between Dec 11, 2012, and June 25, 2015, 150 randomised patients were treated (safety set) and 149 patients were eligible for the full analysis set. Overall, at 9 months TRF-budesonide (16 mg/day plus 8 mg/day) was associated with a 24.4% (SEM 7.7%) decrease from baseline in mean UPCR (change in UPCR vs placebo 0.74; 95% CI 0.59-0.94; p=0.0066). At 9 months, mean UPCR had decreased by 27.3% in 48 patients who received 16 mg/day (0.71; 0.53-0.94; p=0.0092) and 21.5% in the 51 patients who received 8 mg/day (0.76; 0.58-1.01; p=0.0290); 50 patients who received placebo had an increase in mean UPCR of 2.7%. The effect was sustained throughout followup. Incidence of adverse events was similar in all groups (43 [88%] of 49 in the TRF-budesonide 16 mg/day group, 48 [94%] of 51 in the TRF-budesonide 8 mg/day, and 42 [84%] of 50 controls). Two of 13 serious adverse events were possibly associated with TRF-budesonide-deep vein thrombosis (16 mg/day) and unexplained deterioration in renal function in follow-up (patients were tapered from 16 mg/day to 8 mg/day over 2 weeks and follow-up was assessed 4 weeks later).

    Interpretation: TRF-budesonide 16 mg/day, added to optimised RAS blockade, reduced proteinuria in patients with IgA nephropathy. This effect is indicative of a reduced risk of future progression to end-stage renal disease. TRF-budesonide could become the first specific treatment for IgA nephropathy targeting intestinal mucosal immunity upstream of disease manifestation.

  • 22.
    Fellström, Bengt
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Njurmedicin.
    Holdaas, Hallvard
    Jardine, Alan
    Functional Cardiopulmonary Exercise Testing in Potential Renal Transplant Recipients2014Inngår i: Journal of the American Society of Nephrology, ISSN 1046-6673, E-ISSN 1533-3450, Vol. 25, nr 1, s. 8-9Artikkel i tidsskrift (Annet vitenskapelig)
  • 23.
    Fellström, Bengt
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Njurmedicin.
    Holmdahl, J.
    Univ Gothenburg, Sahlgrenska Acad, Dept Nephrol, Gothenburg, Sweden.
    Sundvall, N.
    Sunderby Hosp, Unit Nephrol, Lulea, Sweden.
    Cockburn, E.
    Astellas Pharma, Kastrup, Denmark.
    Kilany, S.
    Astellas Pharma, Kastrup, Denmark.
    Wennberg, L.
    Karolinska Univ Hosp, Div Transplantat Surg, Huddinge, Sweden;Karolinska Univ Hosp, CLINTEC, Huddinge, Sweden;Karolinska Inst, Stockholm, Sweden.
    Adherence of Renal Transplant Recipients to Once-daily, Prolonged-Release and Twice-daily, Immediate-release Tacrolimus-based Regimens in a Real-life Setting in Sweden2018Inngår i: Transplantation Proceedings, ISSN 0041-1345, E-ISSN 1873-2623, Vol. 50, nr 10, s. 3275-3282Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background. In this study we investigated medication adherence of kidney transplant patients (KTPs) to an immediate-release tacrolimus (IR-T) regimen and, after conversion, to a prolonged-release tacrolimus (PR-T) regimen in routine clinical practice. Methods. This was a non-interventional, observational, multicenter Swedish study. We included adult KTPs with stable graft function, remaining on IR-T or converting from IR-T to PR-T. Data were collected at baseline, and months 3, 6, and 12 post-baseline. The primary endpoint was adherence using the Basel Assessment of Adherence to Immunosuppressive Medication Scale (BAASIS). Secondary assessments included tacrolimus dose and trough levels, clinical laboratory parameters (eg, estimated glomerular filtration rate), and adverse drug reactions (ADRs). Results. Overall, data from 233 KTPs were analyzed (PR-T, n = 175; IR-T, n = 58). Mean change in PR-T dose from baseline (4.8 mg/d) to month 12 was -0.2 mg/d, and for IR-T (4.2 mg/d) was-0.4 mg/d; tacrolimus trough levels remained similar. Overall adherence was similar between baseline and month 12 in both groups (PR-T: 54.4% vs 57.0%, respectively; IR-T: 65.5% vs 69.4%); timing adherence followed a similar pattern. The probability of taking adherence improved between baseline and month 12 (odds ratio, 1.97; P =.0092) in the PR-T group only. Mean BAASIS visual analog scale score at baseline was 94.3 11.1% (PR-T) and 95.3 7.6% (IR-T), and >95% at subsequent visits. Laboratory parameters remained stable. Eight (4.6%) patients receiving PR-T (none receiving IR-T) had ADRs considered probably/possibly treatment-related. Conclusion. Disparity existed between high, patient-perceived and low, actual adherence. Overall adherence to the immunosuppressive regimen (measured by BAASIS) did not improve significantly over 12 months in stable KTPs converting to PR-T or remaining on IR-T; renal function remained stable.

  • 24.
    Ferraz, Natalia
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Nanoteknologi och funktionella material.
    Carlsson, Daniel O.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Nanoteknologi och funktionella material.
    Hong, Jaan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Larsson, Rolf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Fellström, Bengt
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Njurmedicin.
    Nyholm, Leif
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Oorganisk kemi.
    Strømme, Maria
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Nanoteknologi och funktionella material.
    Mihranyan, Albert
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Nanoteknologi och funktionella material.
    Haemocompatibility and ion exchange capability of nanocellulose polypyrrole membranes intended for blood purification2012Inngår i: Journal of the Royal Society Interface, ISSN 1742-5689, E-ISSN 1742-5662, Vol. 9, nr 73, s. 1943-1955Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Composites of nanocellulose and the conductive polymer polypyrrole (PPy) are presented as candidates for a new generation of haemodialysis membranes. The composites may combine active ion exchange with passive ultrafiltration, and the large surface area (about 80 m2 g−1) could potentially provide compact dialysers. Herein, the haemocompatibility of the novel membranes and the feasibility of effectively removing small uraemic toxins by potential-controlled ion exchange were studied. The thrombogenic properties of the composites were improved by applying a stable heparin coating. In terms of platelet adhesion and thrombin generation, the composites were comparable with haemocompatible polymer polysulphone, and regarding complement activation, the composites were more biocompatible than commercially available membranes. It was possible to extract phosphate and oxalate ions from solutions with physiological pH and the same tonicity as that of the blood. The exchange capacity of the materials was found to be 600 ± 26 and 706 ± 31 μmol g−1 in a 0.1 M solution (pH 7.4) and in an isotonic solution of phosphate, respectively. The corresponding values with oxalate were 523 ± 5 in a 0.1 M solution (pH 7.4) and 610 ± 1 μmol g−1 in an isotonic solution. The heparinized PPy–cellulose composite is consequently a promising haemodialysis material, with respect to both potential-controlled extraction of small uraemic toxins and haemocompatibility.

  • 25.
    Furuland, Hans
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Njurmedicin.
    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 CKD2018Inngår i: Nephrology, Dialysis and Transplantation, ISSN 0931-0509, E-ISSN 1460-2385, Vol. 33, nr Supplement: 1, s. 157-157Artikkel i tidsskrift (Annet vitenskapelig)
  • 26.
    Furuland, Hans
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Njurmedicin.
    McEwan, Phil
    Evans, Marc
    Linde, Cecilia
    Ayoubkhani, Daniel
    Bakhai, Ameet
    Palaka, Eirini
    Bennett, Hayley
    Qin, Lei
    Serum potassium as a predictor of adverse clinical outcomes in patients with chronic kidney disease: new risk equations using the UK clinical practice research datalink2018Inngår i: BMC Nephrology, ISSN 1471-2369, E-ISSN 1471-2369, Vol. 19, artikkel-id 211Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: To address a current paucity of European data, this study developed equations to predict risks of mortality, major adverse cardiac events (MACE) and renin angiotensin-aldosterone system inhibitor (RAASi) discontinuation using time-varying serum potassium and other covariates, in a UK cohort of chronic kidney disease (CKD) patients.

    Methods: This was a retrospective observational study of adult CKD patients listed on the Clinical Practice Research Datalink, with a first record of CKD (stage 3a-5, pre-dialysis) between 2006 and 2015. Patients with heart failure at index were excluded. Risk equations developed using Poisson Generalized Estimating Equations were utilised to estimate adjusted incident rate ratios (IRRs) between serum potassium and adverse outcomes, and identify other predictive clinical factors.

    Results: Among 191,964 eligible CKD patients, 86,691 (45.16%), 30,629 (15.96%) and 9440 (4.92%) experienced at least one hyperkalaemia episode, when defined using serum potassium concentrations 5.0-< 55 mmol/L, 55-< 6.0 mmol/L and >= 6.0 mmol/L, respectively. Relative to the reference category (4.5 to < 5.0 mmol/L), adjusted IRRs for mortality and MACE exhibited U-shaped associations with serum potassium, with age being the most important predictor of both outcomes (P < 0.0001). A J-shaped association between serum potassium and RAASi discontinuation was observed; estimated glomerular filtration rate was most predictive of RAASi discontinuation (P < 0.0001).

    Conclusions: Hyperkalaemia was associated with increased mortality and RAASi discontinuation risk These risk equations represent a valuable tool to predict clinical outcomes among CKD patients; and identify those likely to benefit from strategies that treat hyperkalaemia, prevent RAASi discontinuation, and effectively manage serum potassium levels.

  • 27.
    Groopman, Emily E.
    et al.
    Hammer Hlth Sci, Dept Med, New York, NY USA.
    Marasa, Maddalena
    Hammer Hlth Sci, Dept Med, New York, NY USA.
    Cameron-Christie, Sophia
    AstraZeneca Ctr Genom Res Precis Med & Genom, Innovat Med & Early Dev IMED Biotech Uni, Cambridge, England.
    Petrovski, Slavé
    AstraZeneca Ctr Genom Res Precis Med & Genom, Innovat Med & Early Dev IMED Biotech Uni, Cambridge, England.
    Aggarwal, Vimla S.
    Hammer Hlth Sci, Div Nephrol, Dept Pathol, New York, NY USA.
    Milo-Rasouly, Hila
    Hammer Hlth Sci, Dept Med, New York, NY USA.
    Li, Yifu
    Hammer Hlth Sci, Dept Med, New York, NY USA.
    Zhang, Junying
    Hammer Hlth Sci, Dept Med, New York, NY USA.
    Nestor, Jordan
    Hammer Hlth Sci, Dept Med, New York, NY USA.
    Krithivasan, Priya
    Hammer Hlth Sci, Dept Med, New York, NY USA.
    Lam, Wan Yee
    Hammer Hlth Sci, Dept Med, New York, NY USA.
    Mitrotti, Adele
    Hammer Hlth Sci, Dept Med, New York, NY USA.
    Piva, Stacy
    Hammer Hlth Sci, Dept Med, New York, NY USA.
    Kil, Byum H.
    Hammer Hlth Sci, Dept Med, New York, NY USA.
    Chatterjee, Debanjana
    Hammer Hlth Sci, Dept Med, New York, NY USA.
    Reingold, Rachel
    Hammer Hlth Sci, Dept Med, New York, NY USA.
    Bradbury, Drew
    Hammer Hlth Sci, Dept Med, New York, NY USA.
    DiVecchia, Michael
    Hammer Hlth Sci, Dept Med, New York, NY USA.
    Snyder, Holly
    Hammer Hlth Sci, Dept Med, New York, NY USA.
    Mu, Xueru
    Hammer Hlth Sci, Dept Med, New York, NY USA.
    Mehl, Karla
    Hammer Hlth Sci, Dept Med, New York, NY USA.
    Balderes, Olivia
    Hammer Hlth Sci, Dept Med, New York, NY USA.
    Fasel, David A.
    Hammer Hlth Sci, Dept Biomed Informat, New York, NY USA.
    Weng, Chunhua
    Hammer Hlth Sci, Dept Biomed Informat, New York, NY USA.
    Radhakrishnan, Jai
    Hammer Hlth Sci, Dept Med, New York, NY USA.
    Canetta, Pietro
    Hammer Hlth Sci, Dept Med, New York, NY USA.
    Appel, Gerald B.
    Hammer Hlth Sci, Dept Med, New York, NY USA.
    Bomback, Andrew S.
    Hammer Hlth Sci, Dept Med, New York, NY USA.
    Ahn, Wooin
    Hammer Hlth Sci, Dept Med, New York, NY USA.
    Uy, Natalie S.
    Hammer Hlth Sci, Dept Pediat, New York, NY USA.
    Alam, Shumyle
    Hammer Hlth Sci, Dept Urol, New York, NY USA.
    Cohen, David J.
    Hammer Hlth Sci, Dept Med, New York, NY USA.
    Crew, Russell J.
    Hammer Hlth Sci, Dept Med, New York, NY USA.
    Dube, Geoffrey K.
    Hammer Hlth Sci, Dept Med, New York, NY USA.
    Rao, Maya K.
    Hammer Hlth Sci, Dept Med, New York, NY USA.
    Kamalakaran, Sitharthan
    Hammer Hlth Sci, Inst Genom Med, New York, NY USA.
    Copeland, Brett
    Hammer Hlth Sci, Inst Genom Med, New York, NY USA.
    Ren, Zhong
    Hammer Hlth Sci, Inst Genom Med, New York, NY USA.
    Bridgers, Joshua
    Hammer Hlth Sci, Inst Genom Med, New York, NY USA.
    Malone, Colin D.
    Hammer Hlth Sci, Inst Genom Med, New York, NY USA.
    Mebane, Caroline M.
    Hammer Hlth Sci, Inst Genom Med, New York, NY USA.
    Dagaonkar, Neha
    Hammer Hlth Sci, Inst Genom Med, New York, NY USA.
    Fellström, Bengt C.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Njurmedicin.
    Haefliger, Carolina
    AstraZeneca Ctr Genom Res Precis Med & Genom, Innovat Med & Early Dev IMED Biotech Uni, Cambridge, England.
    Mohan, Sumit
    Hammer Hlth Sci, Dept Med, New York, NY USA;Columbia Univ, Dept Epidemiol, Mailman Sch Publ Hlth, New York, NY USA.
    Sanna-Cherchi, Simone
    Hammer Hlth Sci, Dept Med, New York, NY USA.
    Kiryluk, Krzysztof
    Hammer Hlth Sci, Dept Med, New York, NY USA.
    Fleckner, Jan
    AstraZeneca Ctr Genom Res Precis Med & Genom, Innovat Med & Early Dev IMED Biotech Uni, Cambridge, England.
    March, Ruth
    AstraZeneca Ctr Genom Res Precis Med & Genom, Innovat Med & Early Dev IMED Biotech Uni, Cambridge, England.
    Platt, Adam
    AstraZeneca Ctr Genom Res Precis Med & Genom, Innovat Med & Early Dev IMED Biotech Uni, Cambridge, England.
    Goldstein, David B.
    Hammer Hlth Sci, Inst Genom Med, New York, NY USA;Hammer Hlth Sci, Dept Genet & Dev, New York, NY USA.
    Gharavi, Ali G.
    Hammer Hlth Sci, Dept Med, New York, NY USA;Hammer Hlth Sci, Inst Genom Med, New York, NY USA.
    Diagnostic Utility of Exome Sequencing for Kidney Disease2019Inngår i: New England Journal of Medicine, ISSN 0028-4793, E-ISSN 1533-4406, Vol. 380, nr 2, s. 142-151Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND Exome sequencing is emerging as a first-line diagnostic method in some clinical disciplines, but its usefulness has yet to be examined for most constitutional disorders in adults, including chronic kidney disease, which affects more than 1 in 10 persons globally.

    METHODS We conducted exome sequencing and diagnostic analysis in two cohorts totaling 3315 patients with chronic kidney disease. We assessed the diagnostic yield and, among the patients for whom detailed clinical data were available, the clinical implications of diagnostic and other medically relevant findings.

    RESULTS In all, 3037 patients (91.6%) were over 21 years of age, and 1179 (35.6%) were of self-identified non-European ancestry. We detected diagnostic variants in 307 of the 3315 patients (9.3%), encompassing 66 different monogenic disorders. Of the disorders detected, 39 (59%) were found in only a single patient. Diagnostic variants were detected across all clinically defined categories, including congenital or cystic renal disease (127 of 531 patients [23.9%]) and nephropathy of unknown origin (48 of 281 patients [17.1%]). Of the 2187 patients assessed, 34 (1.6%) had genetic findings for medically actionable disorders that, although unrelated to their nephropathy, would also lead to subspecialty referral and inform renal management.

    CONCLUSIONS Exome sequencing in a combined cohort of more than 3000 patients with chronic kidney disease yielded a genetic diagnosis in just under 10% of cases.

  • 28. Haynes, Richard
    et al.
    Lewis, David
    Emberson, Jonathan
    Reith, Christina
    Agodoa, Lawrence
    Cass, Alan
    Craig, Jonathan C.
    de Zeeuw, Dick
    Feldt-Rasmussen, Bo
    Fellström, Bengt
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Njurmedicin.
    Levin, Adeera
    Wheeler, David C.
    Walker, Rob
    Herrington, William G.
    Baigent, Colin
    Landray, Martin J.
    Effects of Lowering LDL Cholesterol on Progression of Kidney Disease2014Inngår i: Journal of the American Society of Nephrology, ISSN 1046-6673, E-ISSN 1533-3450, Vol. 25, nr 8, s. 1825-1833Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Lowering LDL cholesterol reduces the risk of developing atherosclerotic events in CKD, but the effects of such treatment on progression of kidney disease remain uncertain. Here, 6245 participants with CKD (not on dialysis) were randomly assigned to simvastatin (20 mg) plus ezetimibe (10 mg) daily or matching placebo. The main prespecified renal outcome was ESRD (defined as the initiation of maintenance dialysis or kidney transplantation). During 4.8 years of follow-up, allocation to simvastatin plus ezetimibe resulted in an average LDL cholesterol difference (SEM) of 0.96 (0.02) mmol/L compared with placebo. There was a nonsignificant 3% reduction in the incidence of ESRD (1057 [33.9%] cases with simvastatin plus ezetimibe versus 1084 [34.6%] cases with placebo; rate ratio, 0.97; 95% confidence interval [95% CI], 0.89 to 1.05; P=0.41). Similarly, allocation to simvastatin plus ezetimibe had no significant effect on the prespecified tertiary outcomes of ESRD or death (1477 [47.4%] events with treatment versus 1513 [48.3%] events with placebo; rate ratio, 0.97; 95% CI, 0.90 to 1.04; P=0.34) or ESRD or doubling of baseline creatinine (1189 [38.2%] events with treatment versus 1257 [40.2%] events with placebo; rate ratio, 0.93; 95% CI, 0.86 to 1.01; P=0.09). Exploratory analyses also showed no significant effect on the rate of change in eGFR. Lowering LDL cholesterol by 1 mmol/L did not slow kidney disease progression within 5 years in a wide range of patients with CKD.

  • 29. Herrington, William
    et al.
    Emberson, Jonathan
    Mihaylova, Borislava
    Blackwell, Lisa
    Reith, Christina
    Solbu, Marit
    Mark, Patrick
    Fellström, Bengt
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Njurmedicin.
    Jardine, Alan
    Wanner, Christoph
    Holdaas, Hallvard
    Fulcher, Jordan
    Haynes, Richard
    Landray, Martin
    Keech, Anthony
    Simes, John
    Collins, Rory
    Baigent, Colin
    Impact of renal function on the effects of LDL cholesterol lowering with statin-based regimens: a meta-analysis of individual participant data from 28 randomised trials2016Inngår i: The Lancet Diabetes and Endocrinology, ISSN 2213-8587, E-ISSN 2213-8595, Vol. 4, nr 10, s. 829-839, artikkel-id S2213-8587(16)30156-5Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: Statin therapy is effective for the prevention of coronary heart disease and stroke in patients with mild-to-moderate chronic kidney disease, but its effects in individuals with more advanced disease, particularly those undergoing dialysis, are uncertain.

    METHODS: We did a meta-analysis of individual participant data from 28 trials (n=183 419), examining effects of statin-based therapy on major vascular events (major coronary event [non-fatal myocardial infarction or coronary death], stroke, or coronary revascularisation) and cause-specific mortality. Participants were subdivided into categories of estimated glomerular filtration rate (eGFR) at baseline. Treatment effects were estimated with rate ratio (RR) per mmol/L reduction in LDL cholesterol.

    FINDINGS: Overall, statin-based therapy reduced the risk of a first major vascular event by 21% (RR 0·79, 95% CI 0·77-0·81; p<0·0001) per mmol/L reduction in LDL cholesterol. Smaller relative effects on major vascular events were observed as eGFR declined (p=0·008 for trend; RR 0·78, 99% CI 0·75-0·82 for eGFR ≥60 mL/min per 1·73 m(2); 0·76, 0·70-0·81 for eGFR 45 to <60 mL/min per 1·73 m(2); 0·85, 0·75-0·96 for eGFR 30 to <45 mL/min per 1·73 m(2); 0·85, 0·71-1·02 for eGFR <30 mL/min per 1·73 m(2) and not on dialysis; and 0·94, 0·79-1·11 for patients on dialysis). Analogous trends by baseline renal function were seen for major coronary events (p=0·01 for trend) and vascular mortality (p=0·03 for trend), but there was no significant trend for coronary revascularisation (p=0·90). Reducing LDL cholesterol with statin-based therapy had no effect on non-vascular mortality, irrespective of eGFR.

    INTERPRETATION: Even after allowing for the smaller reductions in LDL cholesterol achieved by patients with more advanced chronic kidney disease, and for differences in outcome definitions between dialysis trials, the relative reductions in major vascular events observed with statin-based treatment became smaller as eGFR declined, with little evidence of benefit in patients on dialysis. In patients with chronic kidney disease, statin-based regimens should be chosen to maximise the absolute reduction in LDL cholesterol to achieve the largest treatment benefits.

    FUNDING: UK Medical Research Council, British Heart Foundation, Cancer Research UK, European Community Biomed Programme, Australian National Health and Medical Research Council, Australian National Heart Foundation.

  • 30. Herrington, William
    et al.
    Emberson, Jonathan
    Staplin, Natalie
    Blackwell, Lisa
    Fellström, Bengt
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Njurmedicin.
    Walker, Robert
    Levin, Adeera
    Hooi, Lai Seong
    Massy, Ziad A
    Tesar, Vladimir
    Reith, Christina
    Haynes, Richard
    Baigent, Colin
    Landray, Martin J
    The effect of lowering LDL cholesterol on vascular access patency: post hoc analysis of the Study of Heart and Renal Protection2014Inngår i: Clinical journal of the American Society of Nephrology : CJASN, ISSN 1555-905X, Vol. 9, nr 5, s. 914-919Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND AND OBJECTIVES:

    Reducing LDL cholesterol (LDL-C) with statin-based therapy reduces the risk of major atherosclerotic events among patients with CKD, including dialysis patients, but the effect of lowering LDL-C on vascular access patency is unclear.

    DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS:

    The Study of Heart and Renal Protection (SHARP) randomized patients with CKD to 20 mg simvastatin plus 10 mg ezetimibe daily versus matching placebo. This study aimed to explore the effects of treatment on vascular access occlusive events, defined as any access revision procedure, access thrombosis, removal of an old dialysis access, or formation of new permanent dialysis access.

    RESULTS:

    Among 2353 SHARP participants who had functioning vascular access at randomization, allocation to simvastatin plus ezetimibe resulted in a 13% proportional reduction in vascular access occlusive events (355 [29.7%] for simvastatin/ezetimibe versus 388 [33.5%] for placebo; risk ratio [RR], 0.87; 95% confidence interval [95% CI], 0.75 to 1.00; P=0.05). There was no evidence that the effects of treatment differed for any of the separate components of this outcome. To test the hypothesis raised by SHARP, comparable analyses were performed using the AURORA (A Study to Evaluate the Use of Rosuvastatin in Subjects on Regular Hemodialysis: An Assessment of Survival and Cardiovascular Events) trial cohort. AURORA did not provide independent confirmation (vascular access occlusive events: 352 [28.9%] for rosuvastatin versus 337 [27.6%] for placebo; RR, 1.06, 95% CI, 0.91 to 1.23; P=0.44). After combining the two trials, the overall effect of reducing LDL-C with a statin-based regimen on vascular access occlusive events was not statistically significant (707 [29.3%] with any LDL-C-lowering therapy versus 725 [30.5%] with placebo; RR, 0.95, 95% CI, 0.85 to 1.05; P=0.29).

    CONCLUSIONS:

    Exploratory analyses from SHARP suggest that lowering LDL-C with statin-based therapy may improve vascular access patency, but there was no evidence of benefit in AURORA. Taken together, the available evidence suggests that any benefits of lowering LDL-C on vascular access patency are likely to be modest.

  • 31. Holme, Ingar
    et al.
    Fellström, Bengt C.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Njurmedicin.
    Jardine, Alan G.
    Hartmann, Anders
    Holdaas, Hallvard
    Model Comparisons of Competing Risk and Recurrent Events for Graft Failure in Renal Transplant Recipients2013Inngår i: American Society of Nephrology. Clinical Journal, ISSN 1555-9041, E-ISSN 1555-905X, Vol. 8, nr 2, s. 241-247Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background and objectives Risk factor analysis of long-term graft survival in kidney transplant recipients is usually based on Cox regression models of time to first occurrence of doubling of serum creatinine or graft loss (DSCGL). However, death is a competing cause of failure, and censoring patients who die could bias estimates. We therefore compared estimates of time to first event versus estimates that included death as a competing risk and recurrent events. Design, setting, participants, & measurements A Cox regression analysis of 1997-2002 data from the Assessment of Lescol in Renal Transplant (ALERT) trial population identified an eight-factor risk model, by analyzing time to first occurrence of DSCGL. The same factors were re-analyzed, allowing for death as competing. The probability of survival free of DSCGL was estimated; and two recurrent models (marginal and conditional) were used for time to events. Results Creatinine, systolic BP, and HLA-DR mismatches lost 33%-46% of their strength of association with DSCGL when death was included as a competing risk. Small changes were observed if recurrent events were analyzed in the marginal model. Conclusion The relationship between serum creatinine and DSCGL was attenuated when death was considered as a competing risk; inclusion of recurrent events had little effect. These findings have important implications for analysis and trial design in populations at high mortality risk.

  • 32.
    Jensen, Gert
    et al.
    Univ Gothenburg, Sahlgrenska Acad, Inst Med, Dept Mol & Clin Med Nephrol, S-41345 Gothenburg, Sweden.
    Göransson, Lasse G.
    Stavanger Univ Hosp, Dept Internal Med, Stavanger, Norway.
    Femström, Anders
    Linkoping Univ, Dept Nephrol, Linkoping, Sweden;Linkoping Univ, Dept Med & Hlth Sci, Linkoping, Sweden.
    Furuland, Hans
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Njurmedicin.
    Christensen, Jeppe H.
    Aalborg Univ Hosp, Dept Nephrol, Aalborg, Denmark.
    Treatment of iron deficiency in patients with chronic kidney disease: A prospective observational study of iron isomaltoside (NIMO Scandinavia)2019Inngår i: Clinical Nephrology, ISSN 0301-0430, Vol. 91, nr 4, s. 246-253Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Aims: Iron deficiency is common in patients with chronic kidney disease (CKD). Appropriate iron substitution is critical and intravenous iron is an established therapy for these patients. The objective of this study was to assess treatment routine, effectiveness, and safety of iron isomaltoside (Monofer (R), Pharmacosmos A/S, Holbaek, Denmark) in CKD patients in clinical practice.

    Materials and methods: This was a prospective observational study conducted in predialysis CKD patients treated with iron isomaltoside according to the product label and to routine clinical care.

    Results: The study included 108 patients with predialysis CKD: 22 were in stage 2 - 3, 41 in stage 4, and 45 in stage 5. The mean (standard deviation) age was 67 (15) years, and 55% of patients were male. The majority of patients (65%) received one iron isomaltoside treatment In patients with a baseline Hb < 10 g/dL, the mean dose of iron isomaltoside in the study was lower than the estimated total iron requirement (567 mg versus 921 mg). A treatment response of Hb >= 1 g/dL was achieved in 16/28 (57%) of patients, and the mean post-treatment Hb level was 10.5 g/dL. The probability of retreatment did not correlate with dose, but no dose administered was > 1,000 mg. There were no serious adverse drug reactions. One nonserious adverse drug reaction - injection site discoloration - was reported, and the patient had an uneventful recovery.

    Conclusion: Iron isomaltoside shows a good effectiveness and safety profile in predialysis CKD patients. However, some patients did not receive adequate iron doses to allow for optimal correction of their iron deficiency anemia.

  • 33.
    Källström, Miikka
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Soveri, Inga
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Njurmedicin.
    Oldgren, Jonas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR). Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi.
    Laukkanen, Jari
    Faculty of Sport and Health Sciences and Central Finland Health Care District, Department of Internal Medicine, University of Jyväskylä, Jyväskylä, Finland; Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland.
    Ichiki, Tomoko
    Cardiovascular Medicine, Mayo Clinic and Cardiology, International University of Health and Welfare, Rochester, Minnesota; Cardiology, International University of Health and Welfare, Narita, Japan.
    Tei, Chuwa
    Waon Therapy Research Institute, Tokyo, Japan.
    Timmerman, Mark
    Department of Family Medicine, River Valley Clinic, Spring Green, Wisconsin.
    Berglund, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR). Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Hägglund, Hans
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Hematologi.
    Effects of sauna bath on heart failure: A systematic review and meta-analysis2018Inngår i: Clinical Cardiology, ISSN 0160-9289, E-ISSN 1932-8737, Vol. 41, nr 11, s. 1491-1501Artikkel, forskningsoversikt (Fagfellevurdert)
    Abstract [en]

    BACKGROUND:

    Sauna bath has potential as a lifestyle treatment modality for heart failure (HF). It is important to analyze the current evidence to help suggest paths of future study and potential for clinical application.

    HYPOTHESIS:

    Sauna bath has a positive effect on HF patients.

    METHODS:

    PubMed, Cochrane Library, and CINAHL databases were searched to identify randomized and nonrandomized controlled studies to compare effects of sauna bath with no sauna bath. Studies were searched for both infrared sauna bath and Finnish sauna bath. The strength of evidence was rated using a modified GRADE approach. Out of 1444 studies, nine met the inclusion criteria and were included in this review. Seven of these nine studies were included in the meta-analysis. Only studies with infrared sauna bath met the inclusion criteria.

    RESULTS:

    In the meta-analysis, exposure to an infrared sauna bath in 60°C for 15 minutes, followed by a 30-minute rest in warm environment, five times a week for 2 to 4 weeks, was associated with a significant reduction in B-type natriuretic peptide, cardiothoracic ratio, and an improvement in left-ventricular ejection fraction. There was no significant effect on left-ventricular end-diastolic diameter, left atrial diameter, systolic blood pressure, or diastolic blood pressure. The strength of evidence varied from moderate to insufficient.

    CONCLUSION:

    Infrared sauna bath was associated with short-term improvement in cardiac function. More evidence is needed about long-term effects of sauna bath and the effects of a Finnish sauna on cardiovascular health among patients with HF or other cardiovascular diseases.

  • 34.
    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 universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Njurmedicin.
    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 CKD2018Inngår i: Nephrology, Dialysis and Transplantation, ISSN 0931-0509, E-ISSN 1460-2385, Vol. 33, nr Supplement: 1, s. 145-145Artikkel i tidsskrift (Annet vitenskapelig)
  • 35.
    Linde, Cecilia
    et al.
    Karolinska Univ Hosp, Heart & Vasc Theme, Stockholm, Sweden; Karolinska Inst, Stockholm, Sweden.
    Qin, Lei
    AstraZeneca, Global Hlth Econ, Gaithersburg, MD USA.
    Bakhai, Ameet
    Royal Free Hosp, Dept Cardiol, London, England.
    Furuland, Hans
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Njurmedicin.
    Evans, Marc
    Llandough Hosp, Diabet Resource Ctr, Cardiff, S Glam, Wales.
    Ayoubkhani, Daniel
    Hlth Econ & Outcomes Res Ltd, Rhymney House,Unit A Copse Walk, Cardiff, S Glam, Wales.
    Palaka, Eirini
    AstraZeneca, Global Hlth Econ, Cambridge, England.
    Bennett, Hayley
    Hlth Econ & Outcomes Res Ltd, Rhymney House,Unit A Copse Walk, Cardiff, S Glam, Wales.
    McEwan, Phil
    Hlth Econ & Outcomes Res Ltd, Rhymney House,Unit A Copse Walk, Cardiff, S Glam, Wales; Swansea Univ, Sch Human & Hlth Sci, Swansea, W Glam, Wales.
    Serum potassium and clinical outcomes in heart failure patients: results of risk calculations in 21 334 patients in the UK2019Inngår i: ESC Heart Failure, E-ISSN 2055-5822, Vol. 6, nr 2, s. 280-290Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Aims: At present, the clinical burden of hypokalaemia and hyperkalaemia among European heart failure patients, and relationships between serum potassium and adverse clinical outcomes in this population, is not well characterized. The aim of this study was to investigate associations between mortality, major adverse cardiac events, and renin–angiotensin–aldosterone system inhibitor (RAASi) discontinuation across serum potassium levels, in a UK cohort of incident heart failure patients.

    Methods and results: This was a retrospective observational cohort study of newly diagnosed heart failure patients listed in the Clinical Practice Research Datalink, with a first record of heart failure (index date) between 2006 and 2015. Hypokalaemia and hyperkalaemia episodes were defined as the number of serum potassium measurements exceeding each threshold (<3.5, ≥5.0, ≥5.5, and ≥6.0 mmol/L), without such a measurement in the preceding 7 days. Risk equations developed using Poisson generalized estimating equations were utilized to estimate adjusted incident rate ratios (IRRs) relating serum potassium and clinical outcomes (death, major adverse cardiac event, and RAASi discontinuation). Among 21,334 eligible heart failure patients, 1969 (9.2%), 7648 (35.9%), 2725 (12.8%), and 763 (3.6%) experienced episodes of serum potassium <3.5, ≥5.0, ≥5.5, and ≥6.0 mmol/L, respectively. The adjusted IRRs for mortality exhibited a U‐shaped association pattern with serum potassium. Relative to the reference category (4.5 to <5.0 mmol/L), adjusted IRRs for mortality were estimated as 1.98 (95% confidence interval: 1.69–2.33), 1.23 (1.12–1.36), 1.35 (1.14–1.60), and 3.02 (2.28–4.02), for patients with serum potassium <3.5, ≥5.0 to <5.5, ≥5.5 to <6.0, and ≥6.0 mmol/L, respectively. The adjusted IRRs for major adverse cardiac events demonstrated a non‐statistically significant relationship with serum potassium. Discontinuation of RAASi therapy exhibited a J‐shaped trend in association with serum potassium. Compared with the reference category (4.5 to <5.0 mmol/L), adjusted IRRs were estimated as 1.07 (0.89–1.28) in patients with serum potassium <3.5 mmol/L, increasing to 1.32 (1.14–1.53) and 2.19 (1.63–2.95) among those with serum potassium ≥5.5 to <6.0 and ≥6.0 mmol/L, respectively.

    Conclusions: In UK patients with new onset heart failure, both hypokalaemia and hyperkalaemia were associated with increased mortality risk, and hyperkalaemia was associated with increased likelihood of RAASi discontinuation. Our results demonstrate the potential importance of serum potassium monitoring for heart failure outcomes and management.

  • 36. 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 universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Njurmedicin.
    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 Protection2018Inngår i: Nephrology, Dialysis and Transplantation, ISSN 0931-0509, E-ISSN 1460-2385, Vol. 33, nr 2, s. 257-264Artikkel i tidsskrift (Fagfellevurdert)
    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.

  • 37. McQuarrie, EP
    et al.
    Fellström, Bengt
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Njurmedicin.
    Holdaas, H
    Jardine, AG
    Cardiovascular disease in renal transplant recipients2010Inngår i: Journal of Renal Care, ISSN 1755-6678, E-ISSN 1755-6686, Vol. 36, nr Suppl 1, s. 136-145Artikkel, forskningsoversikt (Fagfellevurdert)
    Abstract [en]

    Renal transplant recipients have a markedly increased risk of premature cardiovascular disease (CVD) compared with the general population, although considerably lower than that of patients receiving maintenance haemodialysis. CVD in transplant recipients is poorly characterised and differs from the nonrenal population, with a much higher proportion of fatal to nonfatal cardiac events. In addition to traditional ischaemic heart disease risk factors such as age, gender, diabetes and smoking, there are additional factors to consider in this population such as the importance of hypertension, left ventricular hypertrophy and uraemic cardiomyopathy. There are factors specific to transplantation such immunosuppressive therapies and graft dysfunction which contribute to this altered risk profile. However, understanding and treatment is limited by the absence of large randomised intervention trials addressing risk factor modification, with the exception of the ALERT study. The approach to managing these patients should begin early and be multifactorial in nature.

  • 38. Mjoen, Geir