Trace proteinuria is a high-risk marker for developing ESRD and for shortening the lifespan: Findings from an 18-year follow-up cohort with half a million Asian participants

Abstract

[[abstract]]Background: Trace proteinuria, obtained by urine dipstick, has not received its due attention in clinic visits. It was particularly overlooked in the younger people, even though it had three times more trace proteinuria than the elderly. This study aims to investigate its role in kidney diseases such as End Stage Renal Disease and its association with mortality outcomes and life-shortening effects in a large Asian cohort. Methods: A cohort of 646,987 adults, who have undergone health screening programs successively since 1994, were followed for a median of 18 years. Through encrypted identification numbers, 49,216 deaths and 4,101 ESRD cases were identified. Dipstick, in contrast to the old color-comparison method, is a semi-automated computer- assisted urinalysis system. Results reported as trace, 1+, 2+, and more. The association between proteinuria, ESRD, and mortality risks was evaluated using Cox proportional hazards models. Results: Trace proteinuria existed around 5% among healthy adults, contributed to nearly half of all CKD (9.5%), with younger adults (age <60 years) having a threefold higher prevalence than the elderly (age 60 years). Trace proteinuria significantly increased the risk of ESRD independent of eGFR, with up to 4-5 folds in normal eGFR subjects. The HR was 3.54, 95% CI: 2.67, 4.69 when eGFR 90 ; HR: 3.86, 95% CI: 3.08, 4.84 when eGFR 60-89; HR: 12.26, 95% CI: 9.24, 16.28 when eGFR 45-59; HR: 44.60, 95% CI: 31.39, 60.55 when eGFR 30-44 ml/min/1.73m^2) when compared with negative proteinuria. Participants with trace proteinuria also had a significantly higher risk of all-cause mortality (HR: 1.48, 95% CI: 1.42, 1.54), and associated with a reduction in life expectancy of up to 4-5 years. Dipstick tests demonstrated relatively high sensitivity (84%) and specificity (96%) in detecting microalbuminuria. Conclusions: Trace proteinuria, overlooked in the clinics, was associated with a 4-5 fold increase in developing ESRD later in life and a shortened lifespan of five years, with nearly 50% increase in all-cause mortality. Trace proteinuria can be screened easily in the clinic or among the public with a dipstick, an inexpensive test with instant results. More than 80% with microalbuminuria in an apparently healthy population could be identified