Direct, progressive association of cardiovascular risk factors with incident proteinuria: Results from the Korea Medical Insurance Corporation (KMIC) study

Background: Proteinuria is a major risk factor for the progression of kidney disease and the development of cardiovascular disease. Little is known, however, about risk factors for incident proteinuria. Methods: We conducted a 10-year prospective cohort study of 104 523 Korean men and 52 854 women, aged 35 to 59 years, who attended Korea Medical Insurance Corporation health examinations and who did not have proteinuria at baseline. Incident proteinuria was assessed at biennial examinations during the next 10 years. We performed Cox proportional hazards analyses. Results: During 10 years of follow-up, proteinuria developed in 3951 men (3.8%) and 1527 women (2.9%). The adjusted relative risk (RR) of proteinuria associated with diabetes was 3.27 (95% confidence interval [CI], 2.98-3.58) in men and 2.60 (95% CI, 1.98-3.43) in women; with body mass index (calculated as weight in kilograms divided by the square of height in meters), it was 1.43 (95% CI, 1.35-1.50) in men and 1.45 (95% CI, 1.35-1.55) in women per 5-U increment. Compared with subjects with serum cholesterol levels of less than 200 mg/dL (<5.18 mmol/L), the adjusted RRs associated with serum cholesterol levels of 200 to 239 mg/dL (5.18-6.19 mmol/L) and 240 mg/dL or more (≥6.22 mmol/L) were 1.13 (95% CI, 1.05-1.21) and 1.40 (95% CI, 1.27-1.54), respectively, in men and 1.14 (95% CI, 1.01-1.28) and 1.22 (95% CI, 1.00-1.37), respectively, in women. Persons with stages 1 and 2 hypertension had a greater adjusted RR of incident proteinuria compared with those with normal blood pressure (1.62 [95% CI, 1.47-1.79] and 2.06 [95% CI, 1.81-2.34], respectively, in men and 1.37 [95% CI, 1.14-1.65] and 2.10 [95% CI, 1.59-2.76], respectively, in women). Conclusions: Fasting glucose and cholesterol levels, body mass index, and blood pressure were direct and independent predictors of incident proteinuria in Korean adults. These associations were present even at low levels of exposure, emphasizing the importance of early detection and management of these modifiable risk factors.