Association Between Microscopic Hematuria and Proteinuria Remission in Adult Nephrotic Syndrome

Although the prognostic significance of hematuria has been established in various kidney diseases, few studies have investigated its role in nephrotic syndrome. This study aimed to characterize the prevalence and severity of microscopic hematuria at diagnosis and examine its association with proteinuria remission in adults with nephrotic syndrome.

Multicenter retrospective cohort study.

Adults diagnosed with nephrotic syndrome who underwent native kidney biopsy between January 2012 and June 2022 at 10 institutions in Japan, with histological diagnoses of minimal change disease, focal segmental glomerulosclerosis, or membranous nephropathy.

Microscopic hematuria, assessed by urine sediment examination at the time of kidney biopsy and defined as positive when ≥5 red blood cells per high-power field were observed.

Complete remission of proteinuria, defined as urine protein-creatinine ratio <0.3 g/g creatinine.

The association between microscopic hematuria at diagnosis and complete remission was evaluated using the log-rank test and multivariable Cox proportional hazards models.

A total of 430 patients were enrolled. Microscopic hematuria was observed in 44.0% of patients overall, with prevalence varying by histological type: 30.0% in minimal change disease, 53.6% in focal segmental glomerulosclerosis, and 57.7% in membranous nephropathy. The rate of complete remission was significantly lower in the positive hematuria group (P = 0.001, log-rank test). Multivariable Cox regression analysis demonstrated that microscopic hematuria was independently associated with a lower likelihood of achieving complete remission (hazard ratio, 0.68; 95% confidence interval, 0.52-0.90). Furthermore, this negative impact on remission was dose-dependent, increasing with the severity of hematuria. The robustness of these findings was confirmed through distinct sensitivity analyses.

Changes in hematuria over time and recurrence were not assessed.

In this cohort of adults with nephrotic syndrome, microscopic hematuria at diagnosis was independently associated with a lower rate of proteinuria remission.