Risk of end-stage renal disease in Japanese patients with chronic kidney disease increases proportionately to decline in estimated glomerular filtration rate.
Predominantly based on North American and European studies, 30% to 40% declines in estimated glomerular filtration rate (eGFR) over a few years are strongly associated with the risk of end-stage renal disease (ESRD) and have been proposed as surrogate endpoints of ESRD for clinical research. However, this association has not been systematically quantified in Asian populations. To do this we studied adult Japanese patients with baseline eGFR 10-59 ml/min/1.73m2. Changes in eGFR from baseline measured by centrally assessed serum creatinine were linked to subsequent ESRD in 2410 patients after one year and in 2079 patients after year 2. After year 1, 1.4% experienced a 53% decrease in eGFR (equivalent to doubling of serum creatinine), whereas 4.3% and 9.7% had eGFR decrease of 40% or 30% or more, respectively. The corresponding numbers after 2 years were 4.2%, 10.9%, and 19.3%, respectively. After year 1 baseline period, 498 patients developed ESRD over a median follow-up of 2.9 years (365 ESRD cases over a median follow-up of 2 years after year 2). In year 1, after accounting for potential confounders, a strong linear association was found between eGFR declines and subsequent ESRD, with adjusted hazard ratios of 20.7 (95% confidence interval 14.3-30.1) for a 53% decrease, 9.6 (7.4-12.5) for a 40% decrease, and 5.3 (4.1-6.9) for a 30% decrease compared to no change. Corresponding hazard ratios for year two analysis were 17.3 (11.8-25.3), 6.5 (4.7-9.1), and 3.1 (2.2-4.4), respectively. The associations were consistent across demographics and kidney diseases. Thus, 30% to 40% declines in eGFR are strongly associated with the risk of ESRD in Japanese patients with reduced eGFR, broadening global implications as a surrogate endpoint in clinical research.
Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA; Welch Center for Prevention, Epidemiology, and Clinical Research, Baltimore, Maryland, USA. Electronic address: kmatsus5@jhmi.edu.
Kunihiro
K
Matsushita
Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA; Welch Center for Prevention, Epidemiology, and Clinical Research, Baltimore, Maryland, USA.
Jingsha
J
Chen
Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA; Welch Center for Prevention, Epidemiology, and Clinical Research, Baltimore, Maryland, USA.
Yingying
Y
Sang
Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA; Welch Center for Prevention, Epidemiology, and Clinical Research, Baltimore, Maryland, USA.
Shoshana H
SH
Ballew
R&D Division, Kyowa Hakko Kirin Co., Ltd., Tokyo, Japan.
Ryutaro
R
Shimazaki
Division of Nephrology, Endocrinology and Metabolism, Tokai University School of Medicine, Isehara, Japan.
Masafumi
M
Fukagawa
Nakayamadera Imai Clinic, Takarazuka, Japan.
Enyu
E
Imai
Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA; Welch Center for Prevention, Epidemiology, and Clinical Research, Baltimore, Maryland, USA.
Josef
J
Coresh
Yaizu City Hospital, Yaizu, Japan.
Akira
A
Hishida
D000368:Aged; D015331:Cohort Studies; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D007564:Japan / Q000453:epidemiology; D007676:Kidney Failure, Chronic / Q000175:diagnosis / Q000453:epidemiology*; D008297:Male; D008875:Middle Aged
chronic kidney disease progression; end-stage renal disease; glomerular filtration rate; prospective study; surrogate endpoints