The deleterious effect of proteinuria in residual kidney function in hemodialysis patients

Residual kidney function (RKF) is a major prognostic determinant in hemodialysis (HD), strongly influencing morbidity, mortality and quality of life. Although proteinuria is a well-established marker of chronic kidney disease progression, its prognostic relevance at the initiation of HD remains uncertain. This study aimed to assess the association between baseline proteinuria and RKF decline during the first year of HD.

We performed a prospective study of incident online hemodiafiltration (online-HDF) patients with preserved RKF, defined as kidney urea clearance (KrU) ≥2.5 mL/min and urine output >500 mL/day. The primary endpoint was RKF loss at 1 year, defined as KrU <2.5 mL/min. Secondary endpoints included changes in creatinine clearance (KrCr), glomerular filtration rate and 24-h urine volume. Proteinuria was quantified using both 24-h urinary protein excretion and the urine protein-to-creatinine ratio.

Ninety-seven patients were included; 74.2% were male, with a mean age of 64.3 ± 15 years. Among the 35 patients who reached the primary outcome, 62.9% had nephrotic-range proteinuria, compared with 25.5% with proteinuria <3.5 g/24 h (P = .02). Of those whose urine output fell below 500 mL/day at 1 year, 73% had baseline proteinuria ≥3.5 g/24 h. The most frequent underlying nephropathies among patients with RKF loss were diabetic kidney disease (43%), vascular disease (17%) and glomerulonephritis (17%). Patients with proteinuria ≥3.5 g/24 h reached RKF loss significantly earlier (log-rank = 5.25; P = .02). Nephrotic-range proteinuria was associated with a higher risk of RKF decline (hazard ratio 2.04; 95% confidence interval 1.03-4.02; P = .04), a finding that remained consistent across adjusted models. β2-microglobulin levels were also significantly higher in this group.

Nephrotic-range proteinuria at online-HDF initiation is an independent predictor of accelerated RKF loss, including progression to anuria. Its association with elevated β2-microglobulin supports its value as a prognostic marker. Early identification of high-proteinuria patients may enable personalized strategies to preserve RKF and improve outcomes.