International consensus definitions of clinical trial outcomes for kidney failure: 2020

Levin, Adeera; Agarwal, Rajiv; Herrington, William G.; Heerspink, Hiddo Lambers; Mann, Johannes F.E.; Shahinfar, Shahnaz; Tuttle, Katherine R.; Donner, Jo Ann; Jha, Vivekanand; Nangaku, Masaomi; Zeeuw, Dick de; Jardine, Meg; Mahaffey, Kenneth W.; Thompson, Aliza; Beaucage, Mary; Chong, Kate; Roberts, Glenda V.; Sunwold, Duane; Vorster, Hans; Warren, Madeleine; Damster, Sandrine; Malik, Charu; Perkovic, Vlado; Anand, Shuchi; Argent, Nicholas B.; Babak, E A; Banerjee, Debasish; Barratt, Jonathan; Bello, Aminu K.; Bernardo, Angelito; Blais, Jaime D.; Canovatchel, William; Caskey, Fergus; Coresh, Josef; Boer, Ian H. de; Eckardt, Kai Uwe; Evans, Rhys; Feldman, Harold I.; Fogo, Agnes B.; Guðmundsdóttir, Hrefna; Hamano, Takayuki; Harris, David C.H.; Hauske, Sibylle J.; Haynes, Richard; Herzog, Charles A.; Hiemstra, Thomas F.; Idorn, Thomas; Inker, Lesley A.; Ishida, Julie H.; Johnson, David W.; Jones-Burton, Charlotte; Joseph, Amer; Koïtka-Weber, Audrey; Kretzler, Matthias; Lawatscheck, Robert; Liew, Adrian; Moist, Louise; Naicker, Saraladevi; Nakashima, Ruka; Patel, Uptal D.; Pecoits‐Filho, Roberto; Rose, Jennifer B.; Rosenberg, Noah; Sinsakul, Marvin; Smoyer, William E.; Solá, Laura; Sood, Amy R.; Stengel, Bénédicte; Taal, Maarten W.; Tanaka, Mototsugu; Tonelli, Marcello; Tong, Allison; Toto, Robert; Trask, Michele; Ulasi, Ifeoma; Wanner, Christoph; Wheeler, David C.; Wolthers, Benjamin Ole; Wright, Harold M.; Yamada, Yoshihisa; Zakharova, Elena

doi:10.1016/j.kint.2020.07.013

Cited by 83 publications

(92 citation statements)

References 36 publications

(46 reference statements)

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“…Based on recent literature, an international consensus on definitions of endpoints for clinical trials of kidney failure has emerged, coming to the conclusion that the preferred threshold for kidney function loss is a sustained ≥40% decline in eGFR from baseline. 3 This threshold of kidney function loss is clinically meaningful, predictive of future need for kidney replacement therapy, and can be captured within the relatively brief timeframe of outcome trials.…”

Section: Discussionmentioning

confidence: 99%

“…Previous meta‐analyses of kidney outcomes from SGLT2 inhibitor trials have not, however, used uniform definitions of “significant kidney function decline”, which have differed between the trials 1 . The importance of using consistent definitions of eGFR decline has been emphasized by recent expert consensus statements, as thresholds for kidney function loss must be clinically relevant and also feasible over the 2–4 year time frame of clinical outcome trials 3,4 . Accordingly, our aim was to examine kidney composite outcome data from four SGLT2 inhibitor CVOTs using a uniform sustained ≥40% eGFR decline definition 3,4 …”

Section: Introductionmentioning

confidence: 99%

“… 3 , 4 Accordingly, our aim was to examine kidney composite outcome data from four SGLT2 inhibitor CVOTs using a uniform sustained ≥40% eGFR decline definition. 3 , 4 …”

Section: Introductionmentioning

confidence: 99%

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Kidney outcomes using a sustained ≥40% decline in eGFR: A meta‐analysis of SGLT2 inhibitor trials

Cherney

Dagogo‐Jack

McGuire

et al. 2021

Clinical Cardiology

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Background A recent meta‐analysis of sodium–glucose cotransporter 2 (SGLT2) inhibitor outcome trials reported that SGLT2 inhibitors were associated with reduction in the risk of adverse composite kidney outcomes, with moderate heterogeneity across the trials; however, the endpoints were defined differently across the trials. Hypothesis The apparent heterogeneity of the meta‐analysis of kidney composite outcomes of SGLT2 inhibitor trials will be substantially reduced by using a consistent assessment of sustained ≥40% decline in eGFR/chronic kidney dialysis/transplantation/renal death across trials. Methods We performed a meta‐analysis of kidney composite outcomes from the four SGLT2 cardiovascular outcome trial programs conducted in general type 2 diabetes mellitus populations, which included, as a surrogate of progression to kidney failure, a sustained ≥40% decline in eGFR along with kidney replacement therapy and kidney death. The trials assessed were VERTIS CV (NCT01986881), CANVAS Program (NCT01032629 and NCT01989754), DECLARE‐TIMI 58 (NCT01730534), and EMPA‐REG OUTCOME (NCT01131676). Results Data from the trials comprised 42 516 individual participants; overall, 998 composite kidney events occurred. SGLT2 inhibition was associated with a significant reduction in the kidney composite endpoint (HR 0.58 [95% CI 0.51–0.65]) and with a highly consistent effect across the trials (Q statistic p = .64; I2 = 0.0%). Conclusions Our meta‐analysis highlights the value of using similarly defined endpoints across trials and supports the finding of consistent protection against kidney disease progression with SGLT2 inhibitors as a class in patients with type 2 diabetes mellitus who either have established atherosclerotic cardiovascular disease or are at high cardiovascular risk with multiple cardiovascular risk factors.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Kidney outcomes using a sustained ≥40% decline in eGFR: A meta‐analysis of SGLT2 inhibitor trials

Cherney

Dagogo‐Jack

McGuire

et al. 2021

Clinical Cardiology

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“…CKD described in the eligible studies must have been identified by a physician and the diagnosis must have been made based on the criteria from the Improving Global Outcomes (KDIGO) Consensus Conference which defines CKD as kidney damage (albumin-to-creatinine ratio > 30 mg/g in two of three spot urine specimens) or glomerular filtration rate (GFR) < 60 mL/min/1.73m 2 for 3 months or more, irrespective of the cause [ 19 – 21 ]. Silent myocardial ischemia (SMI) must have been diagnosed by a physician and diagnosed in patients who display no symptoms during an exercise or pharmaceutical stress test but who exhibit transient ST-segment changes, perfusion defects, or reversible regional wall motion abnormalities [ 22 ], or patients who display no symptoms and a myocardial ischemia is later diagnosed based on myocardial imaging evidence or pathological findings on autopsy [ 23 , 24 ].…”

Section: -Methodsmentioning

confidence: 99%

Prevalence of unrecognized or “silent” myocardial ischemia in chronic kidney disease patients: Protocol for a systematic review and meta-analysis

et al. 2021

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Introduction Chronic kidney disease (CKD) patients are at an extremely high risk of silent myocardial ischemia (SMI). However, there is a dearth of evidence on the worldwide prevalence of this very lethal and yet unrecognizable complication of CKD. The proposed systematic review and meta-analysis aims to estimate the global prevalence of SMI among CKD patients. Methods and analyses This protocol was conceived according to the preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) statement. The systematic review will involve all observational studies and clinical trials published until April 30, 2021, and reporting on the prevalence of SMI in CKD patients. Electronic sources including MEDLINE, Embase, Web of Science, and Cochrane database of systematic reviews will be perused for potentially eligible studies, restricted to only studies published in English or French. Two investigators will independently select studies and use a pre-pilot tested form to extract data. Further, they will independently perform a qualitative assessment of the risk of bias and overall quality of the selected studies, followed by a quantitative assessment using funnel plots and Egger’s tests. The heterogeneity between studies will be assessed with the Cochrane’s Q statistic, and the I2 statistic will measure the percentage of variation across studies that is due to their heterogeneity rather than chance; the I2 will decide if a meta-analysis can be conducted. In case it cannot be conducted, a descriptive analysis will be performed. Otherwise, study-specific estimates will be pooled using either a fixed-effects or a random-effects model, depending on the value of the I2 statistic. Subgroup and random effects meta-regression analyses will further investigate the potential sources of heterogeneity. Finally, sensitivity analyses will be performed to measure the impact of low-quality studies on the results of the meta-analysis, and power calculations will determine the probability that we will detect a true effect if it does exist. PROSPERO registration number CRD42020211929 Strengths and limitations of this study The intended systematic review and meta-analysis will fill the knowledge gap on the global prevalence of silent myocardial ischemia (SMI) in CKD patients. The eligible studies will be identified through a methodic literature search followed by a rigorous screening process; we will then use robust meta-analysis tools to pool the data and provide reliable estimates of the global prevalence of SMI in CKD patients. Two major limitations could be: the predominance of clinical trials that might limit the generalizability of the findings, given that some informative patients might have been sidelined by the strict inclusion criteria of these studies; the high probability of type 1 error originating from the important number of subgroup and sensitivity analyses.

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“…The consensus definition has recently been published with subsequent audit of its use planned. 3 Future goals of ISN-ACT Maximum benefit of any intervention requires it to be generalizable, which requires testing in diverse populations around the world. Few trials are undertaken in low-and middle-income countries, despite this being where most of the world's population lives.…”

Section: International Consensus Definitions Of Clinical Trial Outcomes For Kidney Failurementioning

confidence: 99%

The International Society of Nephrology Advancing Clinical Trials (ISN-ACT) Network: current activities and future goals

Evans

Smyth

Levin

et al. 2021

Kidney International

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International consensus definitions of clinical trial outcomes for kidney failure: 2020

Cited by 83 publications

References 36 publications

Kidney outcomes using a sustained ≥40% decline in eGFR: A meta‐analysis of SGLT2 inhibitor trials

Kidney outcomes using a sustained ≥40% decline in eGFR: A meta‐analysis of SGLT2 inhibitor trials

Prevalence of unrecognized or “silent” myocardial ischemia in chronic kidney disease patients: Protocol for a systematic review and meta-analysis

The International Society of Nephrology Advancing Clinical Trials (ISN-ACT) Network: current activities and future goals

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