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

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/1.73m(2). 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.