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

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.

BibTeX: Download