The Significance of Hematuria in Podocytopathies

Abstract

Background Hematuria is frequently present in podocytopathies, but its significance and prognostic value is not well described in these proteinuric kidney diseases. This study describes the prevalence and association between hematuria and kidney-related outcomes in these disorders. Methods Hematuria was assessed at the initial urinalysis in participants with the following podocytopathies—membranous nephropathy, minimal change disease, and FSGS—in the Nephrotic Syndrome Study Network and Cure Glomerulonephropathy cohorts with >24 months of follow-up. Multivariable Cox proportional hazards models were fit for time to composite outcome (kidney failure or 40% decline in eGFR and eGFR <60 ml/min per 1.73 m2) and proteinuria remission (urine protein-to-creatinine ratio [UPCR] <0.3 mg/mg). Results Among the 1516 adults and children in the study, 528 participants (35%) had FSGS, 499 (33%) had minimal change disease, and 489 (32%) had membranous nephropathy. Median (interquartile range) time from biopsy until the initial study urinalysis was 260 (49–750) days, and 498 participants (33%) were positive for hematuria. Participants with hematuria compared with those without were older (37 [16–55] versus 33 [12–55] years), more likely to have an underlying diagnosis of membranous nephropathy (44% versus 27%), had shorter time since biopsy (139 [27–477] versus 325 [89–878] days), and had higher UPCR (3.8 [1.4–8.0] versus 0.9 [0.1–3.1] g/g). After adjusting for diagnosis, age, sex, UPCR, eGFR, time since biopsy, and study cohort, hematuria was associated with a higher risk of reaching the composite outcome (hazard ratio, 1.31; 95% confidence interval, 1.04 to 1.65; P value, 0.02) and lower rate of reaching proteinuria remission (hazard ratio, 0.80; 95% confidence interval, 0.65 to 0.98; P value, 0.03). Conclusions Hematuria is prevalent among participants with the three podocytopathies and is significantly and independently associated with worse kidney-related outcomes, including both progressive loss of kidney function and remission of proteinuria.