{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T16:07:30Z","timestamp":1787069250519,"version":"build-2736575974"},"reference-count":18,"publisher":"Oxford University Press (OUP)","license":[{"start":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T00:00:00Z","timestamp":1786924800000},"content-version":"am","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>In both clinical research and study design, the definition of outcomes for chronic kidney disease (CKD) is changing. New molecules available for testing in humans, and the fact that kidney diseases are best treated earlier in their course, make the duration of studies requiring \u2018hard endpoints\u2019 longer than is feasible for registration purposes and funding agencies. Improved mathematical modelling and statistical analyses, and the availability of electronic medical records and registries have also impacted nephrology clinical research. Thus, estimated glomerular filtration rate (eGFR) slopes have been promoted as surrogate endpoints for kidney failure, competing-risk methods have exposed the limitations of standard survival analysis in high-mortality CKD and dialysis populations, and pragmatic, registry-based trials enroll patients who resemble those seen in daily practice.<\/jats:p>\n                  <jats:p>This review suggests that eGFR slopes, time to kidney failure, and competing-risk factors must be considered in their totality, so that CKD and cardiovascular evidence can be understood in clinical practice by patients and clinicians. We propose that eGFR slopes may provide a clinically intuitive summary of \u2018kidney time\u2019, showing how, under appropriate conditions, chronic slope differences may be translated into approximate \u2018years of dialysis delayed\u2019 at the population level. We frame competing risks as a clinical, not only statistical, issue, and we examine how pragmatic CKD trials can integrate slope-based endpoints and competing-risk analyses into their design and reporting.<\/jats:p>\n                  <jats:p>To advance the nephrology research, we must embrace these changes in study design and methodology to ensure that clinicians and patients understand them, and thus are more prepared to implement trial results.<\/jats:p>","DOI":"10.1093\/ndt\/gfag176","type":"journal-article","created":{"date-parts":[[2026,8,16]],"date-time":"2026-08-16T11:26:27Z","timestamp":1786879587000},"source":"Crossref","is-referenced-by-count":0,"title":["Reframing kidney outcomes in CKD trials: eGFR slopes, competing risks, and pragmatic trial design"],"prefix":"10.1093","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6616-1996","authenticated-orcid":false,"given":"Carmine","family":"Zoccali","sequence":"first","affiliation":[{"name":"Institute of Molecular Biology and Genetics (BIOGEM) , Ariano Irpino ,","place":["Italy"]},{"name":"Renal Research Institute , NY ,","place":["USA"]},{"name":"Associazione Ipertensione Nefrologia Trapianto Renale (IPNET) , Reggio Calabria ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adeera","family":"Levin","sequence":"additional","affiliation":[{"name":"University of British Columbia Division of Nephrology, Department of Medicine, , Vancouver, British Columbia ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,8,17]]},"reference":[{"key":"2026081810415780400_bib1","doi-asserted-by":"publisher","first-page":"1867","DOI":"10.1038\/s41591-023-02418-0","article-title":"A meta-analysis of GFR slope as a surrogate endpoint for kidney failure","volume":"29","author":"Inker","year":"2023","journal-title":"Nat Med"},{"key":"2026081810415780400_bib2","doi-asserted-by":"crossref","first-page":"183","DOI":"10.2215\/CJN.0000000000000050","article-title":"Evaluation of variation in the performance of GFR slope as a surrogate end point for kidney failure in clinical trials that differ by severity of CKD","volume":"18","author":"Collier","year":"2023","journal-title":"Clin J Am Soc Nephrol"},{"key":"2026081810415780400_bib3","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1016\/j.kint.2025.10.004","article-title":"From progression to remission: a new paradigm for success in chronic kidney disease","volume":"109","author":"Tangri","year":"2026","journal-title":"Kidney Int"},{"key":"2026081810415780400_bib4","doi-asserted-by":"publisher","first-page":"2670","DOI":"10.1093\/ndt\/gft355","article-title":"When do we need competing risks methods for survival analysis in nephrology?","volume":"28","author":"Noordzij","year":"2013","journal-title":"Nephrol Dial Transplant"},{"key":"2026081810415780400_bib5","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1093\/eurheartj\/ehr352","article-title":"The win ratio: a new approach to the analysis of composite endpoints in clinical trials based on clinical priorities","volume":"33","author":"Pocock","year":"2012","journal-title":"Eur Heart J"},{"key":"2026081810415780400_bib6","doi-asserted-by":"publisher","first-page":"1546","DOI":"10.1161\/CIRCULATIONAHA.123.067786","article-title":"Win ratio: a seductive but potentially misleading method for evaluating evidence from clinical trials","volume":"149","author":"Butler","year":"2024","journal-title":"Circulation"},{"key":"2026081810415780400_bib7","doi-asserted-by":"crossref","first-page":"720","DOI":"10.1016\/j.jacbts.2023.05.004","article-title":"Fallacies of using the win ratio in cardiovascular trials: challenges and solutions","volume":"8","author":"Ajufo","year":"2023","journal-title":"JACC Basic Transl Sci"},{"key":"2026081810415780400_bib8","doi-asserted-by":"crossref","first-page":"684","DOI":"10.1016\/j.kint.2023.10.016","article-title":"Executive summary of the KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease: known knowns and known unknowns","volume":"105","author":"Levin","year":"2024","journal-title":"Kidney Int"},{"key":"2026081810415780400_bib9","doi-asserted-by":"crossref","first-page":"1436","DOI":"10.1056\/NEJMoa2024816","article-title":"Dapagliflozin in patients with chronic kidney disease","volume":"383","author":"Heerspink","year":"2020","journal-title":"N Engl J Med"},{"key":"2026081810415780400_bib10","doi-asserted-by":"crossref","first-page":"2295","DOI":"10.1056\/NEJMoa1811744","article-title":"Canagliflozin and renal outcomes in type 2 diabetes and nephropathy","volume":"380","author":"Perkovic","year":"2019","journal-title":"N Engl J Med"},{"key":"2026081810415780400_bib11","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1056\/NEJMoa2204233","article-title":"Empagliflozin in patients with chronic kidney disease","volume":"388","author":"Herrington","year":"2023","journal-title":"N Engl J Med"},{"key":"2026081810415780400_bib12","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/S0140-6736(18)32590-X","article-title":"SGLT2 inhibitors for primary and secondary prevention of cardiovascular and renal outcomes in type 2 diabetes: a systematic review and meta-analysis of cardiovascular outcome trials","volume":"393","author":"Zelniker","year":"2019","journal-title":"Lancet"},{"key":"2026081810415780400_bib13","doi-asserted-by":"crossref","first-page":"2219","DOI":"10.1056\/NEJMoa2025845","article-title":"Effect of finerenone on chronic kidney disease outcomes in type 2 diabetes","volume":"383","author":"Bakris","year":"2020","journal-title":"N Engl J Med"},{"key":"2026081810415780400_bib14","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1038\/nrneph.2015.4","article-title":"Nephrology in the developing world. Chronic kidney disease in disadvantaged populations. Nature reviews","volume":"11","author":"Garcia-Garcia","year":"2015","journal-title":"Nat Rev Nephrol"},{"key":"2026081810415780400_bib15","doi-asserted-by":"crossref","first-page":"1223","DOI":"10.1136\/bmj.a2390","article-title":"Improving the reporting of pragmatic trials: an extension of the CONSORT statement","volume":"337","author":"Zwarenstein","year":"2008","journal-title":"BMJ"},{"key":"2026081810415780400_bib16","doi-asserted-by":"crossref","first-page":"2096","DOI":"10.1016\/S0140-6736(10)61271-8","article-title":"Glomerular filtration rate, proteinuria, and the incidence and consequences of acute kidney injury: a cohort study","volume":"376","author":"James","year":"2010","journal-title":"Lancet"},{"key":"2026081810415780400_bib17","doi-asserted-by":"crossref","first-page":"2948","DOI":"10.1681\/ASN.2015111264","article-title":"Pragmatic clinical trials in CKD: opportunities and challenges","volume":"27","author":"de\u00a0Boer","year":"2016","journal-title":"J Am Soc Nephrol"},{"key":"2026081810415780400_bib18","doi-asserted-by":"crossref","first-page":"1579","DOI":"10.1056\/NEJMp1310102","article-title":"The randomized registry trial\u2014the next disruptive technology in clinical research?","volume":"369","author":"Lauer","year":"2013","journal-title":"N Engl J Med"}],"container-title":["Nephrology Dialysis Transplantation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/ndt\/advance-article-pdf\/doi\/10.1093\/ndt\/gfag176\/70665261\/gfag176.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ndt\/advance-article-pdf\/doi\/10.1093\/ndt\/gfag176\/70665261\/gfag176.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T15:20:02Z","timestamp":1787066402000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ndt\/advance-article\/doi\/10.1093\/ndt\/gfag176\/8762564"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,17]]},"references-count":18,"URL":"https:\/\/doi.org\/10.1093\/ndt\/gfag176","relation":{},"ISSN":["0931-0509","1460-2385"],"issn-type":[{"value":"0931-0509","type":"print"},{"value":"1460-2385","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,17]]},"article-number":"gfag176"}}