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. 2024 Jan 1;19(1):56-66.
doi: 10.2215/CJN.0000000000000309. Epub 2023 Sep 21.

The Significance of Hematuria in Podocytopathies

Dorota Marchel  1 , Howard Trachtman  1 , Maria Larkina  2 , Margaret Helmuth  2 , Jennifer Y Lai Yee  1 , Damian Fermin  2 , Andrew S Bomback  3 , Pietro A Canetta  3 , Debbie S Gipson  1 , Amy K Mottl  4 , Rulan S Parekh  5 , Manish K Saha  4 , Matthew G Sampson  6   7   8   9 , Richard A Lafayette  10 , Laura H Mariani  2 ; Nephrotic Syndrome Study Network (NEPTUNE) and Cure Glomerulonephropathy (CureGN)
Collaborators, Affiliations

The Significance of Hematuria in Podocytopathies

Dorota Marchel et al. Clin J Am Soc Nephrol. .

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 m 2 ) 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.

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Conflict of interest statement

A.S. Bomback reports consultancy for Amgen, Apellis, Catalyst, Genentech, Kezar, Novartis, Q32, Silence Therapeutics, and Visterra and honoraria from Alexion, ANI, Aurinia, Calliditas, GlaxoSmithKline, Principio, Travere, and UpToDate. P.A. Canetta reports consultancy for Chinook, Novartis, Otsuka, and Travere and research funding from Calliditas, Novartis, and Travere. D. Fermin reports employment with University of Michigan and ownership interest in 10X Genomics, AstraZeneca, Moderna, and Thermo-Fisher Scientific. D.S. Gipson reports employment with NIH/NIDDK/KUH; consultancy between AstraZeneca, Boehringer-Ingelheim, Genentech (no individual consultancy agreements), Goldfinch Bio, Roche, University of Michigan, and Vertex; research funding to University of Michigan from Boehringer-Ingelheim, Genentech/Roche, Goldfinch Bio, Novartis, Reata, and Travere; role on advisory boards/steering committees for AstraZeneca, Goldfinch Bio, Roche/Genentech, and Vertex; member of the Kidney Health Initiative focal segmental glomerulosclerosis and Pediatric IgA Nephropathy projects; Editorial Board member of JASN; collaboration with NephCure Kidney International in efforts to promote pediatric participation in clinical trials for glomerular diseases (PIONEER); and other interests or relationships with Nephrotic Syndrome Patient-Reported Outcome Consortium (public-private partnership, with Goldfinch Bio, GSK, NephCure Kidney International, and Pfizer) and as the Co-chair for National Kidney Foundation Improving Vaccinations in Kidney Disease Workshop. M. Helmuth reports employment with Arbor Research Collaborative for Health, Red Viking, and the University of Michigan. R.A. Lafayette reports consultancy for Alexion, Inc., Aurinia, Calliditas, Inc., Chemocentryx, Chinook, Inc., Novartis, Omeros, Inc., Otsuka, Inc., Travere, Inc., Vera, Inc., and Visterra, Inc. and research funding from Apellis, Calliditas, Inc., Chemocentryx, Chinook, Inc., NIH, Omeros, Inc., Otsuka, Inc., Pfizer, Roche, Travere, Inc., and Vera, Inc. M. Larkina and J.Y. Lai Yee report employment with University of Michigan. D. Marchel reports employment with Centers for Medicare & Medicaid Services. L.H. Mariani reports employment with University of Michigan; consultancy for Calliditas Therapeutics Advisory Board, Chinook Therapeutics Advisory Board, Reata Pharmaceuticals CKD Advisory Committee, and Travere Therapeutics Advisory Board; research funding from Boehringer-Ingelheim and Travere Therapeutics; honoraria from Calliditas Therapeutics Advisory Board, Chinook Therapeutics Advisory Board, Reata Pharmaceuticals CKD Advisory Committee, and Travere Therapeutics Advisory Board; and advisory or leadership roles for Calliditas Therapeutics, Chinook Therapeutics, Reata Pharmaceuticals, and Travere Therapeutics. A.K. Mottl reports consultancy for Bayer, Chinook, and ProKidney; research funding from Alexion, Bayer, Calliditas, Duke Clinical Research Institute, Pfizer, and University of Pennsylvania; honoraria from UpToDate; and advisory or leadership roles for Bayer and Chinook. R.S. Parekh reports consultancy for Vertx as part of the clinical trial support; ownership interest in Coramed-stock, SpineFx, and Synaptive-stock; research funding from the Canadian Institute of Health Research (CIHR), NIH, and Ontario Ministry; patents or royalties from IZI and SpineFx; serving as an Associate Editor of CJASN, a Board Member of Bishop Strachan School, a Board Member of Conference of Independent Schools of Ontario, a Board Member of Baycrest Academy, and a Board Member of Baycrest Hospital; and an advisory or leadership role for ISN Council. R.S. Parekh’s spouse reports patents or royalties from Coramed and serves as an officer of Coramed and SpineFx. M.K. Saha reports consultancy for Calliditas; ownership interest in AMZN, CMG, Novavax, and NVDA; and honoraria from Calliditas, Chemocentryx, Elseiver, and Travere Therapeutics. M.G. Sampson reports an advisory or leadership role for Natera. H. Trachtman reports consultancy for Maze Therapeutics Inc; employment with RenalStrategies LLC and University of Michigan; consultancy for Aclipse, Akebia, Alexion (inactive), Angion, Astellas (inactive), Boehringer-Ingelheim, Bristol Meyers Squibb (inactive), Chemocentryx (DMSB), Complexa (inactive), Goldfinch Bio, Kaneka (inactive), Natera (RenaSight), Otsuka (DSMB Chair for Pediatric Trials), PhaseV, Travere Therapeutics, and Walden; ownership interest in Aclipse and PhaseV; research funding for support for trial design from Goldfinch, Travere Therapeutics, and Walden; honoraria for attendance at glomerular disease panels organized by Astellas and Reata; patents or royalties for design of the EPPIK trial conducted by Travere Therapeutics, planned submission; advisory or leadership roles for Chair of DSMB Otsuka trials of tolvaptan in children, DSMB for ANCA vasculitis for Chemocentryx (completed), DSMB bumetanide-seizure trial (completed), DSMB RIVUR Trial (completed), MEDCAC committee member, Steering Committee for Abatacept Trial for BMS (completed), Steering Committee for DUPRO (DUPLEX and PROTECT trials) for Travere Therapeutics, Steering Committee for Goldfinch Bio (Steering Committee), and Kidney Health Initiative Board of Directors; role on Editorial Boards for Kidney360, Glomerular Disease, and Pediatric Nephrology; and serves as a partner with NephCure Kidney International in efforts to promote pediatric participation in clinical trials for glomerular diseases (PIONEER).

Figures

None
Graphical abstract
Figure 1
Figure 1
Prevalence of hematuria at the first study visit in various subgroups, including by sex, age, level of proteinuria, and study cohort. CureGN, Cure Glomerulonephropathy; MCD, minimal change disease; MN, membranous nephropathy; NEPTUNE, Nephrotic Syndrome Study Network; UPCR, urine protein-to-creatinine ratio.
Figure 2
Figure 2
Survival estimates for outcomes. Unadjusted Kaplan–Meier curve survival estimate for (A) composite outcome (40% decline in eGFR to a value <60 ml/min per 1.73 m2 or kidney failure) and (B) complete remission in participants with UPCR >1.0 at study enrollment by presence of hematuria.
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