Abstract

IntroductionProteinuria 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.MethodsAmong 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.ResultsMean 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.ConclusionsIn 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.

Highlights

  • Proteinuria is a potent predictor of adverse events in general, a few large studies have reported a J-shaped association between proteinuria and mortality in individuals with glomerular filtration rate

  • Pre-dialysis proteinuria was inversely associated with mortality risk

  • Increased levels of proteinuria are a potent predictor of several adverse health outcomes such as mortality, cardiovascular disease, and end-stage renal disease [1,2,3,4]

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Summary

Methods

Among 1,380 Japanese patients who initiated dialysis, we quantified the association of predialysis 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. We used data from the Aichi Cohort Study of Prognosis in Patients Newly Initiated into Dialysis (AICOPP), including 1,520 incident dialysis patients. Details of AICOPP were described previously [10]. This cohort recruited patients who initiated dialysis between October 2011 and September 2013 at 17 facilities in Aichi, Japan. We screened patients aged at least 20 years and enrolled who were discharged alive from hospitalization for dialysis initiation. Of 1,520 patients in AICOPP, we excluded 24 patients with missing values of proteinuria and 116 patients with missing values of covariates of interest, leaving a final study sample of 1,380 patients (S1 Fig)

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