GFR Decline and Subsequent Risk of Established Kidney Outcomes: A Meta-analysis of 37 Randomized Controlled Trials

Heerspink, Hiddo J L; Tighiouart, Hocine; Sang, Yingying; Ballew, Shoshana H.; Mondal, Hasi; Matsushita, Kunihiro; Coresh, Josef; Levey, Andrew S.; Inker, Lesley A.

doi:10.1053/j.ajkd.2014.08.018

Cited by 112 publications

(61 citation statements)

References 16 publications

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“…37 However, in a recent meta-analysis of 37 trials among persons with kidney disease of varying etiologies, rapid decline was strongly associated with higher risk for ESRD. 24 Taken together, our findings suggest that the clinical significance of rapid kidney function decline may vary based on whether or not the eGFR change is observed in the setting of active, aggressive BP lowering. Given the results of the SPRINT trial, many patients may find their anti-hypertensive treatment intensified in the near future.…”

Section: Discussionmentioning

confidence: 61%

“…This definition is recommended as a valid surrogate outcome for kidney disease trials, and it is a strong predictor of adverse cardiovascular events, death and ESRD. 22-24 In sensitivity analyses, we defined rapid decline as ≥40%, as this outcome has been shown to have even stronger associations with ESRD, 22, 23 and we also examined rates of incident CKD during the entire study period, defined as eGFR <60 ml/min/1.73m 2 plus a decline ≥30% among persons with eGFR >60 at baseline, consistent with SPRINT. 15 …”

Section: Methodsmentioning

confidence: 99%

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Effect of Intensive Versus Usual Blood Pressure Control on Kidney Function Among Individuals With Prior Lacunar Stroke

et al. 2016

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Background The effect of intensive blood pressure (BP) lowering on kidney function among persons with established cerebrovascular disease and preserved estimated glomerular filtration rate (eGFR) is not established. Methods and Results Among 2610 participants randomized to lower SBP target (<130 mmHg) vs. higher (130-149 mmHg) with repeated measures of serum creatinine, we evaluated differences by study arm in annualized eGFR decline and rapid decline (eGFR decline >30%) using linear mixed models and logistic regression, respectively. We assessed associations of both treatment and kidney function decline with stroke, major vascular events (MVE) and the composite stroke, death, MVE or myocardial infarction, using multivariable Cox regression, separately and jointly including test for interaction. Analyses were conducted by treatment arm. Mean age was 63±11; 949 (36%) were diabetic, mean eGFR was 80±19 ml/min/1.73m2. At 9 months, achieved SBP was 137±15 in higher vs. 127±14 mmHg in lower BP group, and differences were maintained throughout follow-up (mean 3.2 years). Compared with higher, lower BP target had -0.50 (95% CI - 0.79 to -0.21) ml/min/1.73m2/year faster eGFR decline. Differences were most pronounced during the first year (-2.1 ml/min/1.73m2 (95% CI -0.97 to -3.2)), whereas rates of eGFR decline did not differ after year 1 (-0.095, -0.47 to 0.23). A total of 313 (24%) persons in the lower BP group had rapid kidney function decline, compared with 247 (19%) in higher (OR 1.4 (95% CI 1.1 to 1.6)). Differences in rapid decline by treatment arm were apparent in the first year (OR 1.4, 1.1-1.8), but were not significant after year 1 (OR 1.0, 0.73-1.4). Rapid decline was associated with higher risk for stroke, MVE and composite after full adjustment among persons randomized to the higher BP target (Stroke HR 1.93 (1.15 to 3.21), but not the lower BP arm, stroke HR 0.93 (0.50 to 1.75) (all p interaction <0.06). Conclusions In persons with prior lacunar stroke and relatively preserved kidney function, intensive BP lowering was associated with greater likelihood of rapid kidney function decline. Differences were primarily observed during the first year of anti-hypertensive treatment. Rapid kidney function decline was not associated with increased risk for clinical events among those undergoing intensive BP lowering. Clinical Trial Registration Information ClinicalTrials.gov. Identifier: NCT00059306.

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Section: Discussionmentioning

confidence: 61%

Section: Methodsmentioning

confidence: 99%

Effect of Intensive Versus Usual Blood Pressure Control on Kidney Function Among Individuals With Prior Lacunar Stroke

et al. 2016

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“…The ≥ 30% decline in eGFR, used as an index of kidney function decline in SPS3 and in participants without CKD at baseline in SPRINT, has been validated as a predictor of adverse cardiovascular events, death and ESRD based on meta-analyses of data from observational studies and randomized controlled trials of CKD progression 6–9 . An individual meta-analysis of data from nearly 1.7 milion persons with CKD in 35 cohorts within the CKD Prognosis Consortium demonstrated a strong relationship between decline in eGFR over 2 years of follow-up and ESRD or all-cause mortality 6 .…”

mentioning

confidence: 99%

“…A 30% decline in eGFR was associated with a 5-fold increased risk of ESRD and a 2-fold increased risk of death. Further, an analysis of clinical trials that tested various interventions, including intensive vs. usual BP control, renin-angiotensin system (RAS) blockade vs. control, RAS blockade vs calcium channel blocker, low-protein vs usual-protein diet, and immunosuppressive vs other therapy in patients with CKD showed that a 30% decline in eGFR over a 1–3 year period was strongly and consistently (across different causes of CKD and different interventions to slow its progression) associated with ESRD 7–9 . These analyses, undertaken in conjunction with a workshop, “GFR Declines as an Endpoint for Clinical Trials in CKD”, sponsored by the National Kidney Foundation and the US Food and Drug Administration, resulted in the recommendation that an eGFR decline of 30% (with stronger evidence for a 40% decline) could be a useful surrogate endpoint for progression to ESRD in future clinical trials of CKD 7 .…”

mentioning

confidence: 99%

SPS3 Evidence Supports Intensive Blood Pressure Control

Oparil

2016

Circulation

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“…Therefore, there has been growing interest in using lower levels of eGFR decline as surrogate endpoints. A number of studies have evaluated eGFR declines of 30 and 40 % as alternative surrogate endpoints [6, 54–56]. In December 2012, the National Kidney Foundation (NKF) and the FDA cosponsored a workshop to evaluate these lower thresholds as potential surrogate endpoints [53].…”

Section: Chronic Kidney Diseasementioning

confidence: 99%

Biomarkers and surrogate endpoints in kidney disease

Hartung

2015

Pediatr Nephrol

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Kidney disease and its related comorbidities impose a large public health burden. Despite this, the number of clinical trials in nephrology lags behind many other fields. An important factor contributing to the relatively slow pace of nephrology trials is that existing clinical endpoints have significant limitations. “Hard” endpoints for chronic kidney disease, such as progression to end-stage renal disease, may not be reached for decades. Traditional biomarkers, such as serum creatinine in acute kidney injury, may lack sensitivity and predictive value. Finding new biomarkers to serve as surrogate endpoints is therefore an important priority in kidney disease research and may help to accelerate nephrology clinical trials. In this paper, I first review key concepts related to the selection of clinical trial endpoints and discuss statistical and regulatory considerations related to the evaluation of biomarkers as surrogate endpoints. This is followed by a discussion of the challenges and opportunities in developing novel biomarkers and surrogate endpoints in three major areas of nephrology research: acute kidney injury, chronic kidney disease, and autosomal dominant polycystic kidney disease.

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GFR Decline and Subsequent Risk of Established Kidney Outcomes: A Meta-analysis of 37 Randomized Controlled Trials

Cited by 112 publications

References 16 publications

Effect of Intensive Versus Usual Blood Pressure Control on Kidney Function Among Individuals With Prior Lacunar Stroke

Effect of Intensive Versus Usual Blood Pressure Control on Kidney Function Among Individuals With Prior Lacunar Stroke

SPS3 Evidence Supports Intensive Blood Pressure Control

Biomarkers and surrogate endpoints in kidney disease

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