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The relationships between proteinuria, serum creatinine, glomerular filtration rate and cardiovascular disease mortality in the Japanese general population
Fujiko Irie1, M.D., Ph.D.
Hiroyasu Iso2, M.D., Ph.D., MPH
1Department of Health and Social Services, Ibaraki Prefectural Government
2Department of Social and Environmental Medicine, Osaka University, Graduate School of Medicine

Proteinuria, high serum creatinine and reduced glomerular filtration rate (GFR) have been associated with increased cardiovascular disease (CVD) and all cause mortalitys. However, the combined effect of proteinuria with serum creatinine and GFR on CVD or all-cause mortality has not been well investigated.

We conducted a 10-year prospective cohort study of 30,764 men and 60,668 women aged 40-79 years who participated in annual health checkups in 1993. The Cox proportional hazards model was used to estimate the relative risk (RR) after adjusting for age, smoking, and other cardiovascular risk factors.

The multivariable RR (95% confidence interval (CI)) of CVD death for positive vs negative proteinuria was 1.38(1.05-1.79) among men and 2.15(1.64- 2.81) among women. The respective RR for the highest vs lowest creatinine groups (≥1.3 vs ≤0.8 mg/dl for men and ≥1.1 vs ≤0.6 mg/dl for women) was 1.56(1.19-2.04) among men and 2.15(1.58-2.93) among women. The respective RR for GFR<60 vs ≥100ml/min/1.73m2 was 1.65(1.25-2.18) among men and 1.81(1.39-2.36) among women. For individuals with proteinuria combined with hypercreatininemia or reduced GFR, the risk of CVD death was two-fold higher in men and 4-6-fold higher in women compared to those without proteinuria and with normal creatinine level or GFR. Similar associations were observed for stroke, coronary heart disease, and all-cause mortality.

Proteinuria, and hypercreatininemia or reduced GFR and their combinations were significant predictors of CVD and all-cause mortality. (Kidney Int 2006; 69, 1264-1271)

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