. 2025 Feb 10;7(4):100975.

doi: 10.1016/j.xkme.2025.100975. eCollection 2025 Apr.

Clinical Decision-Making About Immunosuppressive Treatment in Focal Segmental Glomerulosclerosis

Brooke Blazius¹, Jonathan P Troost¹, Jeffrey B Kopp², Rulan S Parekh^{3

4

5}, Brenda Gillespie⁶, Isabelle Ayoub⁷, Mahmoud Kallash⁸, Rasheed Gbadegesin⁹, Pietro A Canetta¹⁰, Tarak Srivastava¹¹, Tracy E Hunley¹², Katherine E Twombley¹³, Yonatan A Peleg¹⁴, Larry A Greenbaum¹⁵, Aftab S Chishti¹⁶, Carla M Nester¹⁷, Amy K Mottl¹⁸, Susan L Hogan¹⁸, Virginie Royal¹⁹, Vivette D D'Agati²⁰, Kimberly J Reidy²¹, Krzysztof Mucha^{22

23}, Julia Steinke²⁴, Simone Sanna-Cherchi¹⁰, David T Selewski¹³, Dhruti P Chen¹⁸, C John Sperati²⁵, Ronald J Falk¹⁸, Howard Trachtman¹, Jason M Kidd²⁶; Cure GlomeruloNephropathy (CureGN) Study Consortium

Affiliations

¹ Division of Nephrology, Department of Pediatrics, University of Michigan, Ann Arbor, MI.
² Kidney Disease Section, Kidney Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD.
³ Division of Pediatric Nephrology, Hospital for Sick Children, Toronto, ON, Canada.
⁴ Child Health Evaluative Sciences, Research Institute, Hospital for Sick Children, Toronto, ON, Canada.
⁵ Department of Medicine, Division of Nephrology, University Health Network, Toronto, ON, Canada.
⁶ Department of Biostatistics, School of Public Health, University of Michigan, Ann Arbor, MI.
⁷ Department of Medicine, Division of Nephrology, The Ohio State University Wexner Medical Center, Columbus, OH.
⁸ Division of Pediatric Nephrology, Nationwide Children's Hospital, Columbus, OH.
⁹ Department of Pediatric Nephrology, Duke Children's Hospital and Health Center, Durham, NC.
¹⁰ Division of Nephrology, Department of Medicine, Columbia University College of Physicians and Surgeons, New York, NY.
¹¹ Children's Mercy Hospital and University of Missouri-Kansas City School of Medicine, Kansas City, MO.
¹² Division of Pediatric Nephrology, Vanderbilt University Medical Center, Nashville, TN.
¹³ Department of Pediatric Nephrology, Medical University of South Carolina, Charleston, SC.
¹⁴ Division of Nephrology and Hypertension, Northwestern University Feinberg School of Medicine, Chicago, IL.
¹⁵ Division of Pediatric Nephrology, Emory University and Children's Healthcare of Atlanta, Atlanta, GA.
¹⁶ Division of Nephrology, Hypertension and Renal Transplantation, University of Kentucky, Lexington, Kentucky.
¹⁷ Division of Pediatric Nephrology, Dialysis and Transplantation, Stead Family Department of Pediatrics, University of Iowa, Iowa City, Iowa.
¹⁸ Division of Nephrology and Hypertension, Kidney Center, Department of Medicine, University of North Carolina, Chapel Hill, NC.
¹⁹ Division of Pathology, Hôpital Maisonneuve-Rosemont, Université de Montréal, Montréal, QC, Canada.
²⁰ Department of Pathology, Columbia University Medical Center, New York, NY.
²¹ Department of Pediatric Nephrology, Children's Hospital at Montefiore, Albert Einstein College of Medicine, Bronx, NY.
²² Department of Immunology, Transplantology and Internal Diseases, Medical University of Warsaw, Warsaw, Poland.
²³ Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Warsaw, Poland.
²⁴ Texas Children's Hospital, Pediatric Kidney Transplant Division of Pediatric Nephrology, Houston, TX.
²⁵ Division of Nephrology, Johns Hopkins University School of Medicine, Baltimore, MD.
²⁶ Division of Nephrology, Virginia Commonwealth University, Richmond, Virginia.

PMID: 40212319
PMCID: PMC11982957
DOI: 10.1016/j.xkme.2025.100975

Clinical Decision-Making About Immunosuppressive Treatment in Focal Segmental Glomerulosclerosis

Brooke Blazius et al. Kidney Med. 2025.

. 2025 Feb 10;7(4):100975.

doi: 10.1016/j.xkme.2025.100975. eCollection 2025 Apr.

Authors

Affiliations

¹ Division of Nephrology, Department of Pediatrics, University of Michigan, Ann Arbor, MI.
² Kidney Disease Section, Kidney Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD.
³ Division of Pediatric Nephrology, Hospital for Sick Children, Toronto, ON, Canada.
⁴ Child Health Evaluative Sciences, Research Institute, Hospital for Sick Children, Toronto, ON, Canada.
⁵ Department of Medicine, Division of Nephrology, University Health Network, Toronto, ON, Canada.
⁶ Department of Biostatistics, School of Public Health, University of Michigan, Ann Arbor, MI.
⁷ Department of Medicine, Division of Nephrology, The Ohio State University Wexner Medical Center, Columbus, OH.
⁸ Division of Pediatric Nephrology, Nationwide Children's Hospital, Columbus, OH.
⁹ Department of Pediatric Nephrology, Duke Children's Hospital and Health Center, Durham, NC.
¹⁰ Division of Nephrology, Department of Medicine, Columbia University College of Physicians and Surgeons, New York, NY.
¹¹ Children's Mercy Hospital and University of Missouri-Kansas City School of Medicine, Kansas City, MO.
¹² Division of Pediatric Nephrology, Vanderbilt University Medical Center, Nashville, TN.
¹³ Department of Pediatric Nephrology, Medical University of South Carolina, Charleston, SC.
¹⁴ Division of Nephrology and Hypertension, Northwestern University Feinberg School of Medicine, Chicago, IL.
¹⁵ Division of Pediatric Nephrology, Emory University and Children's Healthcare of Atlanta, Atlanta, GA.
¹⁶ Division of Nephrology, Hypertension and Renal Transplantation, University of Kentucky, Lexington, Kentucky.
¹⁷ Division of Pediatric Nephrology, Dialysis and Transplantation, Stead Family Department of Pediatrics, University of Iowa, Iowa City, Iowa.
¹⁸ Division of Nephrology and Hypertension, Kidney Center, Department of Medicine, University of North Carolina, Chapel Hill, NC.
¹⁹ Division of Pathology, Hôpital Maisonneuve-Rosemont, Université de Montréal, Montréal, QC, Canada.
²⁰ Department of Pathology, Columbia University Medical Center, New York, NY.
²¹ Department of Pediatric Nephrology, Children's Hospital at Montefiore, Albert Einstein College of Medicine, Bronx, NY.
²² Department of Immunology, Transplantology and Internal Diseases, Medical University of Warsaw, Warsaw, Poland.
²³ Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Warsaw, Poland.
²⁴ Texas Children's Hospital, Pediatric Kidney Transplant Division of Pediatric Nephrology, Houston, TX.
²⁵ Division of Nephrology, Johns Hopkins University School of Medicine, Baltimore, MD.
²⁶ Division of Nephrology, Virginia Commonwealth University, Richmond, Virginia.

PMID: 40212319
PMCID: PMC11982957
DOI: 10.1016/j.xkme.2025.100975

Abstract

Rationale & objective: Focal segmental glomerulosclerosis (FSGS) is a heterogeneous disorder with a high risk of progression to kidney failure. There are no approved therapies for FSGS, and futility of treatment is poorly defined. The Cure Glomerulonephropathy (CureGN) study offers the opportunity to describe the characteristics of participants who started immunosuppressive therapy (IST), never received IST, or in whom this treatment was discontinued.

Study design: An observational cohort.

Settings & participants: Participants enrolled in CureGN with FSGS and surveyed nephrologists.

Interventions: The clinical and laboratory data from participants with FSGS who were enrolled in the CureGN observational cohort were reviewed to define features associated with withholding initial IST or terminating ongoing IST. Nephrologists were surveyed about what factors would influence their decision to prescribe or withdraw IST in patients with FSGS.

Outcomes: (1) Identify factors associated with IST initiation and discontinuation in individuals with FSGS; and (2) Identify clinical and laboratory features nephrologists consider when they recommend against the use of IST at diagnosis (initiation of care) and during the course of disease.

Results: Based on quantitative findings from the CureGN cohort and survey responses from practicing nephrologists, a low estimated glomerular filtration rate at presentation, significant glomerulosclerosis, and interstitial fibrosis and tubular atrophy on kidney biopsy make initiation of IST less likely.

Limitations: Heterogeneous nature of the cohort and an inability to divide the patients into KDIGO subgroups of FSGS. Rationale for decision to stop or defer treatment was not available. More surveys were completed by pediatric providers, and the majority were completed by academic practitioners.

Conclusions: The factors that impact decisions about IST initiation and discontinuation were consistent among pediatric and internal medicine nephrologists, namely advanced scarring and lower estimated glomerular filtration rate. We suggest that this information should be incorporated into patient management guidelines and clinical trial design.

Keywords: Focal segmental glomerulosclerosis (FSGS); chronic kidney disease (CKD); glomerular disease; immunosuppressive treatment; nephrotic syndrome; proteinuria.

Plain language summary

Patients with focal segmental glomerulosclerosis (FSGS) are at high risk for progression to kidney failure and there are no approved therapies. This study from the CureGN consortium described clinical situations in which immunosuppressive therapy (IST) was started, not started, or discontinued in participants with FSGS. Furthermore, we surveyed nephrologists to better understand factors that influence the management of patients with FSGS. Participants in the CureGN cohort with a lower estimated glomerular filtration rate and advanced scarring on kidney biopsy were less likely to be started on IST and have this treatment discontinued, which was similar to what surveyed providers did in practice. Understanding the characteristics of these patients may help further develop management guidelines and assist in clinical trial design.

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Figures

**Figure 1**
Flow diagram of included patients.

**Figure 2**
Modified Delphi process outlining methods for FSGS IST futility characteristics. FSGS, focal segmental glomerulosclerosis; IST, immunosuppressive therapy.

**Figure 3**
Individual patient characteristics that influence physician decision not to start immunosuppressive therapy in a patient newly diagnosed with FSGS. FSGS, focal segmental glomerulosclerosis.

**Figure 4**
Individual patient characteristics that influence decisions by providers to stop immunosuppressive therapy in a patient previously diagnosed with FSGS who has received immunosuppressive therapy. FSGS, focal segmental glomerulosclerosis.

See this image and copyright information in PMC

References

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Clinical Decision-Making About Immunosuppressive Treatment in Focal Segmental Glomerulosclerosis

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Clinical Decision-Making About Immunosuppressive Treatment in Focal Segmental Glomerulosclerosis

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