Estimated GFR Decline as a Surrogate End Point for Kidney Failure: A Post Hoc Analysis From the Reduction of End Points in Non–Insulin-Dependent Diabetes With the Angiotensin II Antagonist Losartan (RENAAL) Study and Irbesartan Diabetic Nephropathy Trial (IDNT)

Heerspink, Hiddo J L; Weldegiorgis, Misghina; Inker, Lesley A.; Gansevoort, Ron T.; Parving, Hans Henrik; Dwyer, Jamie P.; Mondal, Hasi; Coresh, Josef; Greene, Tom; Levey, Andrew S.; Zeeuw, Dick de

doi:10.1053/j.ajkd.2013.09.016

Cited by 61 publications

(37 citation statements)

References 14 publications

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“…This rate of decline may be a predictive factor [8] and has also been used as a criterion for evaluating the efficacy of renoprotective agents. In addition to increases in the serum creatinine level of 1.5- and 2-fold, a 40% or 30% decline in the estimated glomerular filtration rate (eGFR) from baseline have recently been proposed as new surrogate endpoints [9–11]. …”

Section: Introductionmentioning

confidence: 99%

Longitudinal Study of the Decline in Renal Function in Healthy Subjects

et al. 2015

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BackgroundChronic kidney disease is an important concern in preventive medicine, but the rate of decline in renal function in healthy population is not well defined. The purpose of this study was to determine reference values for the estimated glomerular filtration rate (eGFR) and rate of decline of eGFR in healthy subjects and to evaluate factors associated with this decline using a large cohort in Japan.MethodsRetrospective cross-sectional and longitudinal studies were performed with healthy subjects aged ≥18 years old who received a medical checkup. Reference values for eGFR were obtained using a nonparametric method and those for decline of eGFR were calculated by mixed model analysis. Relationships of eGFR decline rate with baseline variables were examined using a linear least-squares method.ResultsIn the cross-sectional study, reference values for eGFR were obtained by gender and age in 72,521 healthy subjects. The mean (±SD) eGFR was 83.7±14.7ml/min/1.73m2. In the longitudinal study, reference values for eGFR decline rate were obtained by gender, age, and renal stage in 45,586 healthy subjects. In the same renal stage, there was little difference in the rate of decline regardless of age. The decline in eGFR depended on the renal stage and was strongly related to baseline eGFR, with a faster decline with a higher baseline eGFR and a slower decline with a lower baseline eGFR. The mean (±SD) eGFR decline rate was ‒1.07±0.42ml/min/1.73m2/year (‒1.29±0.41%/year) in subjects with a mean eGFR of 81.5±11.6ml/min/1.73m2.ConclusionsThe present study clarified for the first time the reference values for the rate of eGFR decline stratified by gender, age, and renal stage in healthy subjects. The rate of eGFR decline depended mainly on baseline eGFR, but not on age, with a slower decline with a lower baseline eGFR.

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Section: Introductionmentioning

confidence: 99%

Longitudinal Study of the Decline in Renal Function in Healthy Subjects

et al. 2015

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“…Attenuation of the hazard ratio of the treatment effect for lesser eGFR declines compared to the hazard ratio for the clinical endpoint can outweigh the benefit of an increased number of endpoint events. 11,22 Third, since the number and type of trials in CKD are limited, particularly with respect to length of follow-up and number of ESRD events reached, simulation studies are necessary to assess a wide range of potential scenarios to evaluate the utility, robustness and power of lesser eGFR declines. 23 In particular, simulation studies can address the impact of short-term (acute) effects on kidney function in the same or opposite direction from the long term (chronic) effect of a treatment, such as lower blood pressure or renin-angiotensin system inhibition.…”

Section: Discussionmentioning

confidence: 99%

“…6 Other studies focused on mortality and cardiovascular disease since these outcomes occur more commonly than ESRD and showed a strong relationship with various definitions for CKD progression. 7-11 A systematic evaluation across studies using a uniform analytic approach is needed to provide a more rigorous basis for determining the prognosis associated with specific declines in eGFR. Clinical trials with doubling of serum creatinine or ESRD as an end-point typically have follow-up of approximately 5 years.…”

Section: Introductionmentioning

confidence: 99%

Decline in Estimated Glomerular Filtration Rate and Subsequent Risk of End-Stage Renal Disease and Mortality

Coresh

Turin

Matsushita

et al. 2014

JAMA

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821

768

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Importance The established chronic kidney disease (CKD) progression endpoint, end-stage renal disease (ESRD) or doubling of serum creatinine (corresponding to a change in estimated glomerular filtration rate (eGFR) of −57% or greater) is a late event, limiting feasibility of nephrology clinical trials. Objective To characterize the association of decline in eGFR with subsequent progression to ESRD, with implications for using lesser declines in eGFR as potential alternative endpoints for CKD progression. Since most people with CKD die before reaching ESRD, we also investigated mortality risk. Data Sources Individual meta-analysis of up to 1.7 million participants with 12,344 ESRD events and 223,944 deaths from 35 cohorts. Study Selection Cohorts in the CKD Prognosis Consortium with a repeated measure of serum creatinine over 1-3 years and outcome data. Data Extraction and Synthesis Transfer of individual participant data or standardized analysis of outputs for random effects meta-analysis took place between July 2012 and September 2013 with baseline eGFRs during 1975-2012. Main Outcomes and Measures ESRD (initiation of dialysis or transplantation) or all-cause mortality risk related to percent change in eGFR over 2 years adjusted for potential confounders and first eGFR. Results The adjusted hazard ratios (HR) of ESRD and mortality were exponentially higher with larger eGFR decline. Among participants with baseline eGFR <60 ml/min/1.73m2, the adjusted HRs for ESRD were 32.1 (95% CI 22.3-46.3) and 5.4 (4.5-6.4) for −57% and −30% eGFR changes, respectively. However, changes of −30% or greater were much more common than changes of −57% (6.9% (6.4-7.4%) vs. 0.79% (0.52-1.06%) in the whole consortium). This association was strong and consistent across length of baseline (1 or 3 years), baseline eGFR, age, diabetes status, or albuminuria. Average adjusted 10-year risk of ESRD for eGFR changes of −57%, −40%, −30% and 0% were 99% (95-100%), 83% (71-93%), 64% (52-77%), vs. 18% (15-22%) respectively at baseline eGFR of 35 ml/min/1.73m2. Corresponding mortality risks were 77% (71-82%), 60% (56-63%), 50% (47-52%), vs. 32% (31-33%), showing a similar but weaker pattern. Conclusions and Relevance Declines in eGFR smaller than doubling of serum creatinine occur more commonly and are strongly and consistently associated with the risk of ESRD and mortality, supporting consideration of lesser declines in eGFR, such as 30% reduction over 2 years, as an alternative endpoint for CKD progression.

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“…With regard to the change in eGFR, studies have consistently demonstrated that one-year change in eGFR is strongly related to the risks of ESRD, 56 cardiovascular disease, 78 and mortality 57–10 among NDD-CKD patients. Recently, not only declining eGFR but also increasing eGFR has been shown to be independently associated with higher mortality.…”

Section: Discussionmentioning

confidence: 99%

“…Several studies have demonstrated strong associations between change in estimated glomerular filtration rate (eGFR) over one year and risk of ESRD, 56 cardiovascular disease, 78 and mortality 57–10 among NDD-CKD patients. However, these studies have focused primarily on patients with relatively preserved kidney function, and only a few studies have examined the association between increasing eGFR trajectory and risk of adverse outcomes.…”

Section: Introductionmentioning

confidence: 99%

Association of Slopes of Estimated Glomerular Filtration Rate With Post–End-Stage Renal Disease Mortality in Patients With Advanced Chronic Kidney Disease Transitioning to Dialysis

Sumida

Molnár

Potukuchi

et al. 2016

Mayo Clinic Proceedings

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Objective To investigate the association of estimated glomerular filtration rate (eGFR) slopes prior to dialysis initiation with cause-specific mortality following dialysis initiation. Patients and Methods In this retrospective cohort study of 18,874 United States veterans who had transitioned to dialysis from October 1, 2007, through September 30, 2011, we examined the association of pre-end-stage renal disease (ESRD) eGFR slopes with all-cause, cardiovascular, and infection-related mortality during the post-ESRD period over a median follow-up of 2.0 years (interquartile range; 1.1–3.2 years). Associations were examined using Cox models with adjustment for potential confounders. Results Prior to transitioning to dialysis, 4,485 (23.8%), 5,633 (29.8%), and 7,942 (42.1%) patients experienced fast, moderate, and slow eGFR decline, respectively, and 814 (4.3%) had increasing eGFR (defined as eGFR slopes of <−10, −10 to <−5, −5 to <0, and ≥0 mL/min/1.73 m2/year). During the study period, a total of 9,744 all-cause, 2,702 cardiovascular, and 604 infection-related deaths were observed. Compared with patients with slow eGFR decline, those with moderate and fast eGFR decline had a higher risk of all-cause (adjusted hazard ratio [HR]: 1.06; 95% confidence interval [CI] 1.00–1.11 and HR: 1.11; 95%CI 1.04–1.18, respectively) and cardiovascular mortality (HR: 1.11; 95%CI 1.01–1.23 and HR: 1.13; 95%CI 1.00–1.27, respectively). In contrast, increasing eGFR was only associated with higher infection-related mortality (HR: 1.49; 95%CI 1.03–2.17). Conclusion Rapid eGFR decline is associated with higher all-cause and cardiovascular mortality, and increasing eGFR is associated with higher infection-related mortality among incident dialysis patients.

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Estimated GFR Decline as a Surrogate End Point for Kidney Failure: A Post Hoc Analysis From the Reduction of End Points in Non–Insulin-Dependent Diabetes With the Angiotensin II Antagonist Losartan (RENAAL) Study and Irbesartan Diabetic Nephropathy Trial (IDNT)

Cited by 61 publications

References 14 publications

Longitudinal Study of the Decline in Renal Function in Healthy Subjects

Longitudinal Study of the Decline in Renal Function in Healthy Subjects

Decline in Estimated Glomerular Filtration Rate and Subsequent Risk of End-Stage Renal Disease and Mortality

Association of Slopes of Estimated Glomerular Filtration Rate With Post–End-Stage Renal Disease Mortality in Patients With Advanced Chronic Kidney Disease Transitioning to Dialysis

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