The Significance of Hematuria in Podocytopathies

Dorota Marchel; Howard Trachtman; Maria Larkina; Margaret Helmuth; Jennifer Y Lai Yee; Damian Fermin; Andrew S Bomback; Pietro A Canetta; Debbie S Gipson; Amy K Mottl; Rulan S Parekh; Manish K Saha; Matthew G Sampson; Richard A Lafayette; Laura H Mariani; Nephrotic Syndrome Study Network (NEPTUNE); Cure Glomerulonephropathy (CureGN)

doi:10.2215/CJN.0000000000000309

The Significance of Hematuria in Podocytopathies

Clin J Am Soc Nephrol. 2023 Sep 21;19(1):56-66. doi: 10.2215/CJN.0000000000000309. Online ahead of print.

Authors

Dorota Marchel¹, Howard Trachtman¹, Maria Larkina², Margaret Helmuth², Jennifer Y Lai Yee², Damian Fermin², Andrew S Bomback³, Pietro A Canetta³, Debbie S Gipson¹, Amy K Mottl⁴, Rulan S Parekh⁵, Manish K Saha⁴, Matthew G Sampson^{6

7

8

9}, Richard A Lafayette¹⁰, Laura H Mariani²; Nephrotic Syndrome Study Network (NEPTUNE); Cure Glomerulonephropathy (CureGN)

Affiliations

¹ Department of Pediatrics, Division of Nephrology, University of Michigan, Ann Arbor, MI, 48104, USA.
² Department of Internal Medicine, Division of Nephrology, University of Michigan, Ann Arbor, MI, 48104, USA.
³ Division of Nephrology, Columbia University Irving Medical Center, New York, NY, 10032, USA.
⁴ Department of Medicine, Division of Nephrology and Hypertension, University of North Carolina, Chapel Hill, NC, 27516, USA.
⁵ Department of Medicine and Pediatrics, Women's College Hospital, Hospital for Sick Children and University of Toronto, Toronto, Ontario, M5S 1B2, Canada.
⁶ Division of Pediatric Nephrology, Boston Children's Hospital, Boston, MA, 2115, USA.
⁷ Harvard Medical School, Boston, MA, 2115, USA.
⁸ Kidney Disease Initiative and Medical Population Genetics Groups, Broad Institute, Cambridge, MA, 2142, USA.
⁹ Division of Kidney Medicine, Brigham and Women's Hospital, Boston, MA, 2115, USA.
¹⁰ Division of Nephrology, Stanford University Medical Center, Stanford, CA, 94305, USA.

PMID: 37733352
PMCID: PMC10843204 (available on 2025-01-01)
DOI: 10.2215/CJN.0000000000000309

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 focal segmental glomerulosclerosis, in the Nephrotic Syndrome Study Network (NEPTUNE) and Cure Glomerulonephropathy (CureGN) cohorts with >24 months of follow-up. Multivariable Cox proportional hazards models were fit for time to composite outcome (end-stage kidney disease or 40% decline in estimated glomerular filtration rate (eGFR) and eGFR <60 ml/min/1.73 m2) and proteinuria remission (UPCR <0.3 mg/mg).

Results: Among the 1,516 adults and children in the study, 528 (35%) participants had focal segmental glomerulosclerosis, 499 (33%) had minimal change disease, and 489 (32%) had membranous nephropathy. Median (IQR) time from biopsy until the initial study urinalysis was 260 days (49, 750), and 498 (33%) participants were positive for hematuria. Participants with hematuria compared to those without, were older (37 [16, 55] vs 33 years [12, 55]), more likely to have an underlying diagnosis of membranous nephropathy (44% vs 27%), had shorter time since biopsy (139 [27, 477] vs 325 [89, 878] days) and higher UPCR (3.8 [1.4, 8.0] vs 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 riskof reaching the composite outcome (HR 1.31 [1.04, 1.65], p-value 0.02) and lower rate of reaching proteinuria remission (HR 0.80 [0.65-0.98], 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 remission of proteinuria.

Abstract

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