Lower levels of proteinuria are associated with elevated mortality in incident dialysis patients

Abstract

Introduction Proteinuria is a potent predictor of adverse events in general, although a few large studies have reported a J-shaped association between proteinuria and mortality in individuals with glomerular filtration rate <30 ml/min/1.73m2. However, this association has not been specifically evaluated among incident dialysis patients. Methods Among 1,380 Japanese patients who initiated dialysis, we quantified the association of pre-dialysis dipstick proteinuria (negative/trace, 1+, 2+, and ≥3+) with mortality using Cox models adjusting for potential confounders, such as age, gender, clinical history of hypertension, diabetes, and cardiovascular disease. Results Mean age of study participants was 67.4 (SD 13.0) years, and 67.6% were men. The most common dipstick proteinuria category was ≥3+ (55.4%), followed by 2+ (31.2%), 1+ (9.9%), and negative or trace (3.5%). Patients with lower proteinuria level were older than those with higher proteinuria. Lower proteinuria was significantly associated with a higher risk of all-cause mortality, even after accounting for potential confounders (p for trend <0.001). In those with negative/trace dipstick proteinuria compared to those with dipstick proteinuria ≥3+, the adjusted hazard ratio was 2.60 [95% CI: 1.62–4.17] in the fully adjusted model. Similar findings were observed when analyses were restricted to patients older than 70 years, and when cardiovascular mortality and non-cardiovascular mortality were analyzed separately. Conclusions In incident dialysis patients, pre-dialysis proteinuria was inversely associated with mortality risk. Although future studies are needed to identify mechanisms, our findings suggest the need to carefully interpret proteinuria in patients with incident dialysis.