Rationale and design of the Renal Lifecycle trial assessing the effect of dapagliflozin on cardiorenal outcomes in severe chronic kidney disease

Bakker WM, Heerspink HJ, Berger SP, Wanner C, Badve SV, Arnott C, Abrahams AC, Van Den Born JC, Van Faassen TC, Gaillard CA, Gelens MA, Górris JL, Hemmelder MH, Jakulj L, Van Kruijsdijk RC, Kuypers DR, Van Der Meer P, Van Der Net JB, Nijmeijer HH, Vervloet MG, De Vries AP, Walsh M, Wang AY, Gansevoort RT, Adema AY, Alphen AM, Bax WA, Bayrak J, Boom H, Boonstra AH, Brinkman N, De Maar E, De Waal Y, Eshuis M, Hermans M, Hesselink DA, Hoogeveen EK, Huitema J, Jansen WM, Jonker JT, Keet SW, Konings S, Later A, Leurs P, Logtenberg S, Luik P, Ocak G, Ozyilmaz A, Rood J, Schouten M, Siddiqi-Nadery L, Siegert C, Slebe J, Stifft F, Van Bemmel T, Van Breda GF, Van Der Heijden J, Van Der Leeuw J, Van Eck Van Der Sluijs A, Van Etten R, Van Mil D, Waanders F, Wiegersma JS, Banas B, Budde K, Busch M, Girndt M, Guthoff M, Herzog AL, Hohenstein B, Schiffer M, Schlieper G, Schömig M, Schröppel B, Seeger W, Stegbauer J, Strutz F, Wanner C, Weinmann-Menke J, Zeier M, Holt J, Jesudason S, Keung K, Krishnasamy R, Kulkarni H, Makris A, Masterson R, Mather A, Palamuthusingam D, Pedagogos E, Smyth B, Srivastava V, Talaulikar G, Wong G, Wong M, Wyburn K, Dejagere T, Francois K, Lemahieu W, Mahieu E, Meeus G, Alamo BS, Blanco M, Buades J, Conde ML, Cruzado JM, Garcia N, Goiciechea M, Gonzales F, Porras AB, MacIa M, Marques M, Monzó JJ, Munar MA, Ortiz A, Saborido MI, Salgueira M, Soler MJ, Sancho A, Liu YL, Teo BW, Sreekanth K, Lee WZ (2025)

Publication Type: Journal article

Publication year: 2025

Journal

Book Volume: 40

Pages Range: 1746-1755

Journal Issue: 9

DOI: 10.1093/ndt/gfaf046

Abstract

Background Several clinical trials have shown beneficial effects of sodium-glucose co-transporter 2 (SGLT2) inhibitors on kidney disease progression and cardiovascular morbidity and mortality in patients with chronic kidney disease (CKD) with and without type 2 diabetes mellitus. However, some subgroups of patients with CKD have been excluded from participation in these trials, such as patients with severely impaired kidney function, patients on dialysis and kidney transplant recipients. Methods The Renal Lifecycle trial (NCT05374291) is a pragmatic, international, multicentre, investigator-initiated, randomized, placebo-controlled clinical trial planned to enrol ≈1500 patients with an estimated glomerular filtration rate (eGFR) ≤25 ml/min/1.73 m², on haemodialysis or peritoneal dialysis or after a kidney transplant and an eGFR ≤45 ml/min/1.73 m², who will be randomized 1:1 to receive either dapagliflozin 10 mg once daily or matching placebo. Results The primary endpoint is a composite of heart failure hospitalization, all-cause mortality or, for those not on dialysis, kidney failure (start of dialysis >1 month, receiving a kidney transplant or death due to kidney failure). The trial is event driven, indicating that it will end after 468 first primary endpoint events have occurred, with a power of 80% and an α of 0.05 to detect a 25% relative risk reduction assuming an annual 12.5% incidence of the primary outcome. The secondary endpoints include a separate analysis of the incidence of each component of the primary endpoint in the overall trial population as well as the incidence of the combined primary endpoint in each of the three subgroups of patients. Other (exploratory) endpoints are efficacy, safety, tolerability, health-related quality of life and cognition. Conclusion The Renal Lifecycle trial aims to investigate the effects of the SGLT2 inhibitor dapagliflozin compared with placebo on the incidence of kidney failure, heart failure, mortality and safety in three subgroups of patients with advanced CKD.

Authors with CRIS profile

Involved external institutions

University Medical Center Groningen (UMCG) / Universitair Medisch Centrum Groningen Netherlands (NL) Northwest Clinics / Noordwest Ziekenhuisgroep Netherlands (NL) Onze Lieve Vrouwe Gasthuis Netherlands (NL) Universitätsklinikum Düsseldorf Germany (DE) Nierenzentrum Wiesbaden Germany (DE) Julius-Maximilians-Universität Würzburg Germany (DE) Universitätsmedizin der Johannes Gutenberg-Universität Mainz Germany (DE) Ruprecht-Karls-Universität Heidelberg Germany (DE) Wollongong Hospital Australia (AU) Royal Adelaide Hospital Australia (AU) Prince of Wales Hospital (POWH) Australia (AU) Sunshine Coast University Hospital Australia (AU) East Metropolitan Health Service (EMHS) Australia (AU) Liverpool Hospital Australia (AU) Royal Melbourne Hospital (RMH) Australia (AU) Royal North Shore Hospital (RNSH) Australia (AU) Universitätsklinikum Würzburg Germany (DE) University of New South Wales (UNSW) Australia (AU) University Medical Centre Utrecht (UMC Utrecht) Netherlands (NL) Maastricht University Netherlands (NL) Hospital Clínico Universitario de Valencia Spain (ES) Nephrologisches Zentrum Villingen-Schwenningen Germany (DE) Universitätsklinikum Ulm Germany (DE) Hospital Universitario Ramón y Cajal Spain (ES) Coruña University Hospital / Complexo Hospitalario Universitario A Coruña (CHUAC) Spain (ES) Hospital Universitari Són Llàtzer Spain (ES) Bellvitge University Hospital / Hospital Universitari de Bellvitge Spain (ES) Clínica Universidad de Navarra Spain (ES) Hospital General Universitario Gregorio Marañón Spain (ES) Complejo Hospitalario Torrecárdenas Spain (ES) Hospital del Mar Spain (ES) Hospital Universitario Puerta de Hierro - Majadahonda Spain (ES) Hospital Clínic de Barcelona Spain (ES) Hospital Universitari Son Espases / Hospital Universitario Son Espases Spain (ES) Fundación Jiménez Díaz Spain (ES) Hospital Universitari Germans Trias i Pujol Spain (ES) Hospitales Universitarios Virgen Macarena y Virgen del Rocío Spain (ES) Vall d'Hebron University Hospital / Hospital Universitari Vall d'Hebron Spain (ES) Hospital Universitario Dr. Peset Aleixandre Spain (ES) National University of Singapore (NUS) Singapore (SG) National University of Defense Technology China (CN) Hospital Universitario Nuestra Señora de Candelaria (HUNSC) Spain (ES) Charité - Universitätsmedizin Berlin Germany (DE) Universitätsklinikum Jena Germany (DE) Universitätsklinikum Halle (Saale) Germany (DE) Universitätsklinikum Tübingen Germany (DE) Sengkang General Hospital (SKH) / Hospital Besar Sengkang / 盛港综合医院 Singapore (SG) Royal Brisbane and Women's Hospital Australia (AU) St George's Hospital United Kingdom (GB) Townsville University Hospital Australia (AU) Canberra Health Services Australia (AU) Westmead Hospital Australia (AU) Concord Repatriation General Hospital Australia (AU) Royal Prince Alfred Hospital Australia (AU) Jessa Ziekenhuis Belgium (BE) Universitair Ziekenhuis Brussel Belgium (BE) az groeninge Belgium (BE) Amsterdam University Medical Centers (Amsterdam UMC) / Amsterdam Universitair Medische Centra Netherlands (NL) Radboud University Nijmegen Medical Centre / Radboudumc of voluit Radboud Universitair Medisch Centrum (UMC) Netherlands (NL) University Hospital Leuven (UZ) / Universitaire ziekenhuizen Leuven Belgium (BE) Albert Schweitzer Ziekenhuis Netherlands (NL) Leiden University Medical Center Netherlands (NL) McMaster University Canada (CA) Singapore General Hospital Singapore (SG) Medisch Centrum Leeuwarden Netherlands (NL) Maasstad Ziekenhuis Netherlands (NL) Reinier de Graaf Hospital Netherlands (NL) Flevoziekenhuis Netherlands (NL) Medisch Spectrum Twente (MST) Netherlands (NL) Ziekenhuis Bernhoven Netherlands (NL) VieCuri Medisch Centrum / VieCuri Medical Center Netherlands (NL) Erasmus University Medical Center (MC) Netherlands (NL) Jeroen Bosch Hospital Netherlands (NL) Laurentius Ziekenhuis Netherlands (NL) Martini Ziekenhuis Netherlands (NL) Alrijne Ziekenhuis Netherlands (NL) Maxima Medisch Centrum MMC Veldhoven Netherlands (NL) Catharina Hospital / Catharina Ziekenhuis Netherlands (NL) St Jansdal Hospital Netherlands (NL) Admiraal De Ruyter Ziekenhuis Netherlands (NL) Diakonessenhuis Utrecht Netherlands (NL) Meander Medisch Centrum Netherlands (NL) Antonius Ziekenhuis Sneek Netherlands (NL) Dialyse Centrum Groningen Netherlands (NL) Diapriva Dialysezentrum Amsterdam Netherlands (NL) Tergooi MC Netherlands (NL) Elyse Klinieken voor Nierzorg Netherlands (NL) Zuyderland Medical Center Netherlands (NL) Gelre ziekenhuizen Apeldoorn Netherlands (NL) Spaarne Gasthuis Germany (DE) Franciscus Gasthuis & Vlietland Netherlands (NL) Deventer Ziekenhuis Netherlands (NL) Amphia Ziekenhuis Netherlands (NL) Ommelander Ziekenhuis Groningen Netherlands (NL) Universitätsklinikum Regensburg Germany (DE) Bravis Hospital Netherlands (NL)

How to cite

APA:

Bakker, W.M., Heerspink, H.J., Berger, S.P., Wanner, C., Badve, S.V., Arnott, C.,... Lee, W.Z. (2025). Rationale and design of the Renal Lifecycle trial assessing the effect of dapagliflozin on cardiorenal outcomes in severe chronic kidney disease. Nephrology Dialysis Transplantation, 40(9), 1746-1755. https://doi.org/10.1093/ndt/gfaf046

MLA:

Bakker, Wisanne M., et al. "Rationale and design of the Renal Lifecycle trial assessing the effect of dapagliflozin on cardiorenal outcomes in severe chronic kidney disease." Nephrology Dialysis Transplantation 40.9 (2025): 1746-1755.

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