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J Am Soc Nephrol. 2019 Sep;30(9):1746-1755. doi: 10.1681/ASN.2019010008. Epub 2019 Jul 10.

Evaluating Glomerular Filtration Rate Slope as a Surrogate End Point for ESKD in Clinical Trials: An Individual Participant Meta-Analysis of Observational Data.

Author information

1
Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
2
Departments of Medicine and.
3
Population Health Sciences, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin.
4
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
5
Geisinger Health System and Department of Epidemiology and Health Services Research, Geisinger Health System, Kidney Health Research Institute, Danville, Pennsylvania.
6
Division of Nephrology, Tufts Medical Center, Boston, Massachusetts.
7
General Practice & Primary Health Care, University of Auckland, Auckland, New Zealand.
8
Division of Nephrology, Department of Medicine, University of Tennessee Health Science Center, Memphis, Tennessee.
9
Nephrology Section, Memphis Veterans Affairs Medical Center, Memphis, Tennessee.
10
Nephrology Division, Kaiser Permanente, Hawaii Region, Moanalua Medical Center, Honolulu, Hawaii.
11
British Columbia Provincial Renal Agency and University of British Columbia, Vancouver, British Columbia, Canada.
12
Department of Medicine and Institute of Health Policy, Management and Evaluation, Sunnybrook Hospital, University of Toronto, Toronto, Ontario, Canada.
13
Departments of Clinical Pharmacy and Pharmacology and.
14
Department of Quantitative Health Sciences and.
15
Center for Populations Health Research, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio.
16
Medical Division, Maccabi Healthcare Services, and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
17
Department of Nephrology, Radboud University Medical Center, Radboud Institute of Health Sciences, Nijmegen, The Netherlands.
18
The George Institute for Global Health, University of Oxford, Oxford, United Kingdom; and.
19
The George Institute for Global Health, University of New South Wales, Sydney, New South Wales, Australia.
20
Nephrology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
21
Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland; ckdpc@jhmi.edu.

Abstract

BACKGROUND:

Decline in eGFR is a biologically plausible surrogate end point for the progression of CKD in clinical trials. However, it must first be tested to ensure strong associations with clinical outcomes in diverse populations, including patients with higher eGFR.

METHODS:

To investigate the association between 1-, 2-, and 3-year changes in eGFR (slope) with clinical outcomes over the long term, we conducted a random effects meta-analysis of 3,758,551 participants with baseline eGFR≥60 ml/min per 1.73 m2 and 122,664 participants with eGFR<60 ml/min per 1.73 m2 from 14 cohorts followed for an average of 4.2 years.

RESULTS:

Slower eGFR decline by 0.75 ml/min per 1.73 m2 per year over 2 years was associated with lower risk of ESKD in participants with baseline eGFR≥60 ml/min per 1.73 m2 (adjusted hazard ratio, 0.70; 95% CI, 0.68 to 0.72) and eGFR<60 ml/min per 1.73 m2 (0.71; 95% CI, 0.68 to 0.74). The relationship was stronger with 3-year slope. For a rapidly progressing population with predicted 5-year risk of ESKD of 8.3%, an intervention that reduced eGFR decline by 0.75 ml/min per 1.73 m2 per year over 2 years would reduce the ESKD risk by 1.6%. For a hypothetical low-risk population with a predicted 5-year ESKD risk of 0.58%, the same intervention would reduce the risk by only 0.13%.

CONCLUSIONS:

Slower decline in eGFR was associated with lower risk of subsequent ESKD, even in participants with eGFR≥60 ml/min per 1.73 m2, but those with the highest risk would be expected to benefit the most.

KEYWORDS:

chronic kidney disease; end-stage renal disease; glomerular filtration rate; progression of chronic renal failure

PMID:
31292199
PMCID:
PMC6727262
[Available on 2020-09-01]
DOI:
10.1681/ASN.2019010008

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