Relationship between predicted creatinine clearance and proteinuria and the risk of developing ESRD in Okinawa, Japan

Background: Chronic kidney disease and a low creatinine clearance (CrCl) are relatively common, particularly in the aged population. However, the renal outcome of a low CrCl is not known. Methods: Participants in a 1993 mass screening conducted by the Okinawa General Health Maintenance Association in Okinawa, Japan, were investigated. A total of 95,255 subjects (40,157 men, 55,098 women) older than 20 years for whom serum creatinine (SCr) data were available were studied. CrCl was calculated as a surrogate marker of glomerular filtration rate by using the Cockcroft-Gault method. All dialysis patients who were treated in Okinawa were independently registered in the Okinawa Dialysis Study registry. Participants in the 1993 screening who later entered a dialysis program were identified by using the 2 computer registries. The cumulative incidence of end-stage renal disease (ESRD) was calculated according to baseline CrCl level in quartiles. The significance of CrCl for the risk for developing ESRD was evaluated by means of Cox analysis after adjusting for age, sex, blood pressure, and proteinuria. Results: CrCl values were distributed into quartiles: CrCl I, less than 50.2 mL/min (<0.84 mL/s; n = 23,076); CrCl II, 50.2 to 63.9 mL/min (0.84 to 1.07 mL/s; n = 23,039); CrCl III, 64.0 to 79.3 mL/min (1.07 to 1.32 mL/s; n = 23,147); and CrCl IV, 79.4 mL/min or greater (>= 1.32 mL/s; n = 23,036). One hundred eighty-one subjects with data for SCr level were identified in the dialysis registry. Seven-year cumulative incidences of ESRD per 1,000 subjects were 86.8 in CrCl I, 13.6 in CrCl II, 8.3 in CrCl III, and 7.9 in CrCl IV in patients who had proteinuria, whereas they were 1.2, 0.7, 0.04, and 0.13 in those who did not have proteinuria, respectively. As CrCl category decreased, the adjusted hazard ratio for the risk of developing ESRD was 4.353 (95% confidence interval, 3.412 to 5.553; P < 0.0001). Conclusion: The prevalence of a low CrCl (CrCl 1, <50.2 mL/min [<0.84 mL/s]) was relatively high in the elderly population. Subjects with a low CrCl who had proteinuria were at high risk of developing ESRD. However, the cumulative incidence of ESRD was not as high in patients with a low CrCl not associated with proteinuria. Screening by means of dipstick for proteinuria is useful, particularly among the elderly, to identify subjects in a high-risk population.