Risk of end-stage renal disease in Japanese patients with chronic kidney disease increases proportionately to decline in estimated glomerular filtration rate

Abstract

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/1.73m. 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.

Guidelines for clinical evaluation of chronic kidney disease

“…On the other hand, the candidate cutoff level was 30% in the study by Coresh et al, 30% in that by Chang et al, and 30 or 40% in the CKD-JAC study [8,18,20]. In our studies, it was 30% or 40% in the analysis of the data of health examinations conducted in Okinawa, Japan, and 40% in the analysis of the ORIENT study.…”

“…On the other hand, in a CKD Japan Cohort (Chronic Kidney Disease Japan Cohort, CKD-JAC) study, the relationship between patient distribution and risk of ESRD based on percentage changes in eGFR over 1-2 years indicated 30 or 40% to be the surrogate endpoints [18]. In this study, the differences in patient background by age, gender, and the causes of CKD were evaluated, and the same correlation between percentage changes in eGFR and risk of ESRD was seen for each factor [20]. In this study, to investigate subjects different from these studies, the data of health examinations conducted in Okinawa, Japan, were analyzed.…”

“…The baseline period of 1 year cannot be said to be appropriate for observing renal protective effects and the onset of side effects [10]. The candidate baseline period was 2 years in the studies by Coresh et al, Chang et al, and in the CKD-JAC study [8,18,20]. In our studies, it was 2 or 3 years in the analysis of the data of OGHMA, and 2 years in the analysis conducted in the ORIENT study.…”

“…To date, epidemiological cohort studies on CKD patients in Japan have reported the correlation between percentage changes in eGFR and risk of ESRD [18,20]. According to the study on CKD patients by Chang et al, decrease in percentage changes in eGFR of more than 30% over 2 years correlated with ESRD strongly [18].…”

“…Details of the results of that cohort study were reported in a peer-reviewed journal, Kidney International (November 2016 issue). This section provides a key summary of that article [20]. The CKD-JAC was conducted to investigate risk factors for CKD progression in Japan, and its design and data gathering method have been presented in other papers [21,22].…”