Home / Deep Research / Focal Segmental Glomerulosclerosis

Focal Segmental Glomerulosclerosis

1. Disease Information

2026-05-08
Falcon MONDO:0100313 Model: Edison Scientific Literature 34 citations

1. Disease Information

1.1 Definition and overview

1.2 Disease identifiers and ontology mapping

  • MONDO (available from retrieved evidence):
  • “Inherited focal segmental glomerulosclerosis” MONDO_0005363 (OpenTargets Search: Focal segmental glomerulosclerosis)
  • Example inherited subtype entities returned by Open Targets include “FSGS 1” MONDO_0011303 (OpenTargets Search: Focal segmental glomerulosclerosis)
  • Open Targets disease ID: FSGS is indexed as EFO_0004236 in Open Targets output (OpenTargets Search: Focal segmental glomerulosclerosis).

Gap note (knowledge-base readiness): ICD-10/ICD-11, MeSH, Orphanet, and OMIM cross-references were not present in the retrieved texts and therefore cannot be asserted here without additional ontology lookups.

1.3 Synonyms / alternative names

1.4 Source type of information

2. Etiology

2.1 Primary causes (etiologic categories)

Recent reviews explicitly recommend an etiology-based framework: - Primary FSGS: typically conceptualized as immune-mediated and/or driven by circulating permeability factors, presenting with abrupt nephrotic syndrome and diffuse foot process effacement (cos2023noveltreatmentparadigms pages 1-2, salfi2023currentunderstandingof pages 1-2). - Genetic FSGS: monogenic podocyte/GBM disorders with variable presentations; often steroid-resistant (cos2023noveltreatmentparadigms pages 1-2, salfi2023currentunderstandingof pages 4-5). - Secondary FSGS: maladaptive (e.g., hyperfiltration) or associated with drugs/infections; secondary forms may show glomerulomegaly in contexts such as obesity, reflux nephropathy, and low birth weight (cos2023noveltreatmentparadigms pages 1-2). - FSGS of undetermined cause (FSGS-UC): diagnosis when data are insufficient for classification; immunosuppression is discouraged in non-nephrotic presentations (mirioglu2024managementofadult pages 2-3).

The KDIGO-aligned classification and initial treatment branching are summarized visually in a figure from de Cos et al. (2023) (cos2023noveltreatmentparadigms media ecc573cd).

2.2 Risk factors

  • Demographic risk: higher incidence is reported in adult males and Black individuals in a 2023 immunology-focused review (salfi2023currentunderstandingof pages 1-2).
  • Progression risk factors (clinical): high-grade proteinuria, impaired kidney function, presence of FSGS lesions on biopsy, and interstitial fibrosis/tubular atrophy are associated with progression (mirioglu2024managementofadult pages 2-3).

2.3 Protective factors

  • No specific genetic or environmental protective factors were identified in the retrieved evidence.

2.4 Gene–environment interactions

  • The retrieved evidence strongly supports ancestry-linked genetic risk for APOL1 (see Genetics), but does not provide a mechanistically explicit gene–environment interaction model for FSGS beyond this population/ancestry association.

3. Phenotypes

3.1 Core clinical phenotypes and diagnostic features

Common phenotype cluster (nephrotic syndrome spectrum): - Proteinuria / nephrotic-range proteinuria and nephrotic syndrome are central clinical manifestations; primary FSGS often presents with abrupt marked proteinuria and overt nephrotic syndrome (cos2023noveltreatmentparadigms pages 1-2, salfi2023currentunderstandingof pages 1-2). - FSGS exhibits the lowest glucocorticoid response among idiopathic nephrotic syndrome forms; steroid resistance is commonly reported (salfi2023currentunderstandingof pages 1-2).

Biopsy and pathology phenotypes: - Light microscopy: focal/segmental glomerular scarring is required for diagnosis (cos2023noveltreatmentparadigms pages 1-2, bensink2024kidneyfailureattributed pages 1-2). - Electron microscopy: foot process effacement (FPE) extent helps distinguish etiologies; one study summarized in a 2024 ERA working group review reported primary FSGS had FPE >80%, whereas genetic/maladaptive forms had no cases with FPE >50% (mirioglu2024managementofadult pages 2-3). - Immunofluorescence: may show non-specific IgM/C3 staining in sclerotic areas (mirioglu2024managementofadult pages 2-3).

3.2 Phenotype characteristics (onset, severity, progression)

  • Course is often chronic and progressive in non-remitting disease; in adult FSGS cohorts, “Over half of the patients with nephrotic-range proteinuria progress to ESKD” (mirioglu2024managementofadult pages 2-3).

3.3 Frequencies / statistics (recent)

3.4 Suggested HPO terms (non-exhaustive, evidence-aligned)

(These are ontology suggestions; exact IDs should be validated against HPO.) - Nephrotic syndrome (cos2023noveltreatmentparadigms pages 1-2) - Proteinuria / Nephrotic-range proteinuria (cos2023noveltreatmentparadigms pages 1-2) - Podocyte foot process effacement (cos2023noveltreatmentparadigms pages 1-2, mirioglu2024managementofadult pages 2-3) - Segmental glomerulosclerosis (cos2023noveltreatmentparadigms pages 1-2, bensink2024kidneyfailureattributed pages 1-2) - Glomerulomegaly (secondary forms) (cos2023noveltreatmentparadigms pages 1-2) - Steroid resistance (cos2023noveltreatmentparadigms pages 1-2, salfi2023currentunderstandingof pages 1-2) - Progression to end-stage kidney disease (ESKD) (mirioglu2024managementofadult pages 2-3)

3.5 Quality of life impact

  • Direct quality-of-life instrument results (e.g., SF-36, EQ-5D) were not present in retrieved evidence.

4. Genetic / Molecular Information

4.1 Causal genes and genetic architecture

Key genes highlighted (examples): - AR/early-onset genes: NPHS1, NPHS2, PLCE1, TTC21B (xie2024precisionmedicinefor pages 1-3). - Additional genes frequently observed in cohorts: WT1, NPHS1/NPHS2 (PodoNet); adult genetic FSGS includes COL4A3–5 (reported as most common single-gene pathogenic mutation) and INF2 (xie2024precisionmedicinefor pages 1-3). - The immunology-focused 2023 review enumerates important adult/familial genes including INF2, ACTN4, TRPC6, PAX2, and core nephrotic syndrome genes NPHS1/NPHS2/WT1 (salfi2023currentunderstandingof pages 4-5).

4.2 Population differences and APOL1

4.3 Open Targets disease–gene associations (translation-focused)

Open Targets returned high-confidence FSGS associations for multiple genes, including APOL1, TRPC6, INF2, ACTN4, NPHS1, NPHS2, PAX2, CD2AP, MYO1E, CRB2, ANLN, LMX1B, with supporting evidence rows including genetics and curated sources (OpenTargets Search: Focal segmental glomerulosclerosis).

4.4 Variant-level details

  • Specific pathogenic variant nomenclature and allele frequencies (gnomAD/ExAC) were not present in retrieved evidence and therefore are not asserted here.

4.5 Modifier genes, epigenetics, chromosomal abnormalities

  • Not available in the retrieved evidence.

5. Environmental Information

  • Secondary FSGS mechanisms include maladaptive states (e.g., obesity-related hyperfiltration) and secondary causes such as low birth weight and reflux nephropathy-associated glomerulomegaly (cos2023noveltreatmentparadigms pages 1-2).
  • Specific toxin/occupational risk factors and explicit infectious triggers were not detailed in the retrieved 2023–2024 evidence excerpts.

6. Mechanism / Pathophysiology

6.1 Causal chain (high-level)

A consistent mechanistic chain across reviews is: 1) Upstream trigger (immune/circulating factor, genetic defect, maladaptive hyperfiltration, etc.) → 2) Podocyte injury and foot process effacement → 3) Proteinuria → 4) Podocyte depletion and progressive scarring → 5) Declining GFR and potential progression to ESKD (salfi2023currentunderstandingof pages 1-2, cos2023noveltreatmentparadigms pages 1-2).

6.2 Immune involvement and circulating factors (primary FSGS)

  • The 2023 review states “a growing body of evidence emphasizes the pivotal role of the immune system” and notes that T cells, B cells, and complement have been implicated as crucial actors, with various molecules proposed as “circulating factors” contributing to disease and post-transplant recurrence (salfi2023currentunderstandingof pages 1-2).

6.3 Suggested ontology terms (for knowledge-base annotation)

Cell types (CL suggestions): - Podocyte (inferred central cell type) (cos2023noveltreatmentparadigms pages 1-2, salfi2023currentunderstandingof pages 1-2)

Biological process (GO suggestions): - Podocyte differentiation/maintenance; regulation of glomerular filtration; actin cytoskeleton organization; regulation of cell–substrate adhesion; inflammatory response; extracellular matrix organization; fibrotic process (mechanistic categories supported broadly by the reviews emphasizing podocyte injury and inflammation/fibrosis in FSGS) (salfi2023currentunderstandingof pages 1-2).

Anatomy (UBERON suggestions): - Kidney; glomerulus; renal corpuscle; podocyte; glomerular basement membrane (cos2023noveltreatmentparadigms pages 1-2, salfi2023currentunderstandingof pages 1-2).

7. Anatomical Structures Affected

8. Temporal Development

9. Inheritance and Population

9.1 Epidemiology (recent statistics)

9.2 Inheritance patterns

  • Autosomal recessive early-onset forms (NPHS1/NPHS2/PLCE1/TTC21B) and autosomal dominant later-onset forms (COL4A3–5, INF2) are emphasized in the 2024 precision-medicine review (xie2024precisionmedicinefor pages 1-3).

10. Diagnostics

10.1 Clinical testing and biopsy

10.2 Electron microscopy criterion supporting etiology

10.3 Genetic testing strategy

10.4 Differential diagnosis

11. Outcome / Prognosis

12. Treatment

A structured treatment summary (with MAXO and NCT mapping) is provided in the artifact table below.

Table (click to expand)
Therapy/Approach MAXO term suggestion Indication/Patient subgroup Key evidence and quantitative outcomes Key trial IDs (NCT) Source (author year) URL Evidence type
Supportive care: RAAS blockade, blood-pressure control, salt restriction MAXO: angiotensin receptor antagonist treatment; angiotensin-converting enzyme inhibitor treatment; blood pressure control; dietary sodium restriction All FSGS categories as baseline care; especially supportive strategy for secondary and genetic FSGS KDIGO-aligned supportive care includes RAAS blockade, BP control, and salt restriction; de Cos notes these as core background therapy for FSGS. Figure-based treatment algorithm shows RAAS blockade first, with etiology-specific escalation. No quantitative effect size for FSGS-specific remission provided in the gathered excerpt (cos2023noveltreatmentparadigms pages 1-2, cos2023noveltreatmentparadigms media ecc573cd) — de Cos 2023 https://doi.org/10.1016/j.ekir.2022.10.004 Review/guideline summary
SGLT2 inhibitors as adjunct supportive therapy MAXO: sodium-glucose cotransporter 2 inhibitor treatment Proteinuric FSGS as adjunct supportive care; not established as disease-specific immunologic therapy Discussed as supportive option in FSGS; de Cos reports dapagliflozin showed non-significant benefit in the FSGS substudy. Endothelin-review notes concomitant SGLT2i may help optimize ERA safety, but no definitive FSGS-specific efficacy estimate is given in the extracted text (cos2023noveltreatmentparadigms pages 1-2, ma2025theroleof pages 8-9) NCT02585804 (dapagliflozin trial listed in ClinicalTrials.gov search) (OpenTargets Search: Focal segmental glomerulosclerosis) de Cos 2023; ClinicalTrials.gov search https://doi.org/10.1016/j.ekir.2022.10.004 Review; trial registry
High-dose glucocorticoids MAXO: corticosteroid treatment Presumed primary FSGS with nephrotic syndrome; first-line for immune-mediated/primary disease KDIGO-referenced first-line therapy for primary FSGS. Mirioglu reports FSGS remission in 47–66% with 25–36% relapse and steroid resistance in 40–60%; Salfi reports steroid resistance across studies in 26–80%. Not recommended for non-nephrotic FSGS-UC/secondary forms (mirioglu2024managementofadult pages 2-3, salfi2023currentunderstandingof pages 1-2) — Mirioglu 2024; Salfi 2023 https://doi.org/10.1093/ndt/gfae025; https://doi.org/10.3389/fimmu.2023.1247606 Review/guideline update
Calcineurin inhibitors (cyclosporine, tacrolimus) MAXO: calcineurin inhibitor treatment Steroid-resistant primary FSGS; steroid-intolerant patients; generally not for clear genetic/secondary disease unless another indication Salfi states evidence most strongly supports CNIs for steroid-resistant primary FSGS for at least 6 months. de Cos lists CNIs as KDIGO-recommended for steroid-resistant or steroid-intolerant primary disease. No pooled remission percentage for CNIs alone was extracted from the gathered text (salfi2023currentunderstandingof pages 1-2, cos2023noveltreatmentparadigms pages 1-2) — Salfi 2023; de Cos 2023 https://doi.org/10.3389/fimmu.2023.1247606; https://doi.org/10.1016/j.ekir.2022.10.004 Review/guideline summary
Sparsentan vs irbesartan (pooled RCT evidence) MAXO: endothelin receptor antagonist treatment; angiotensin II receptor antagonist treatment Proteinuric FSGS, including primary FSGS populations enrolled in DUET/DUPLEX Meta-analysis of randomized trials: greater UP/C reduction with sparsentan (ratio of percentage reduction 0.66, 95% CI 0.58–0.74, P<0.001); complete remission RR 2.57 (95% CI 1.73–3.81); partial remission RR 1.63 (95% CI 1.40–1.91); no significant eGFR difference (MD 1.98 mL/min/1.73 m2, 95% CI -1.05 to 5.01); hypotension increased (RR 2.02, 95% CI 1.30–3.16) (elnaga2024safetyandefficacy pages 1-2) NCT01613118; NCT03493685 (OpenTargets Search: Focal segmental glomerulosclerosis) Elnaga 2024 https://doi.org/10.1186/s12882-024-03713-9 Meta-analysis
Sparsentan DUET phase 2 + open-label extension MAXO: proteinuria-reducing therapy; endothelin receptor antagonist treatment; angiotensin II receptor antagonist treatment FSGS with UP/C ≥1.0 g/g and eGFR >30 mL/min/1.73 m2; long-term treatment follow-up DUET/OLE analysis: 108 patients received sparsentan; median follow-up 47.0 months; 46/108 (43%) achieved at least one complete remission (UP/C ≤0.3 g/g), and 61% of complete remissions occurred within 12 months. OLE report: 52.8% achieved FSGS partial remission within 9 months; remission associated with slower eGFR decline vs nonresponders (overall slope -2.70 vs -6.56 mL/min/1.73 m2/year, P=0.03; first 2 years -1.69 vs -6.46, P=0.03). Common TEAEs included headache, peripheral edema, URI, hyperkalemia, hypotension; no heart failure events or deaths reported (trachtman2023implicationsofcomplete pages 1-2, campbell2024sparsentanforfocal pages 1-2) NCT01613118 (OpenTargets Search: Focal segmental glomerulosclerosis) Trachtman 2023; Campbell 2024 https://doi.org/10.1016/j.ekir.2023.07.022; https://doi.org/10.1016/j.xkme.2024.100833 Phase 2 RCT extension / open-label follow-up
Sparsentan DUPLEX phase 3 MAXO: endothelin receptor antagonist treatment; angiotensin II receptor antagonist treatment Primary FSGS / proteinuric FSGS enrolled in pivotal phase 3 study Extracted review summary reports DUPLEX randomized sparsentan 800 mg vs irbesartan 300 mg over 108 weeks in 371 participants; partial remission endpoint favored sparsentan (UPCR ≤1.5 g/g and >40% reduction; p=0.0094). Review/meta-analysis materials note strong antiproteinuric effect; detailed AE frequencies not fully extracted from the gathered snippet (rakotoarison2024endothelininhibitorsin pages 8-9, ma2025theroleof pages 8-9) NCT03493685 (OpenTargets Search: Focal segmental glomerulosclerosis) Rakotoarison 2024; Ma 2025 review of trial https://doi.org/10.3390/jcm13206056; https://doi.org/10.1080/0886022x.2025.2465810 Phase 3 RCT summary / review
Immunosuppression avoidance in non-primary disease MAXO: avoidance of immunosuppressive therapy; supportive care FSGS of undetermined cause without nephrotic syndrome, and many genetic/secondary forms ERA Immunonephrology review emphasizes unmet need to identify who should receive immunosuppression vs supportive care; immunosuppression is generally reserved for presumed primary FSGS, and patients with FSGS-UC without nephrotic syndrome should not receive immunosuppression (mirioglu2024managementofadult pages 2-3) — Mirioglu 2024 https://doi.org/10.1093/ndt/gfae025 Review/guideline update
Genetic testing / precision medicine MAXO: genetic testing; precision medicine approach Suspected monogenic FSGS, steroid-resistant disease, unclear etiology, biopsy-contraindicated/high-risk settings de Cos and Mirioglu recommend integrating genetic testing into diagnosis/classification; genetic testing is especially recommended when steroid resistance suggests a genetic form. Precision-medicine review highlights clinical significance of next-generation sequencing and biomarker-guided stratification to avoid unnecessary immunosuppression, but no diagnostic yield percentage was present in extracted snippets (mirioglu2024managementofadult pages 2-3, salfi2023currentunderstandingof pages 1-2, cos2023noveltreatmentparadigms pages 1-2) — Mirioglu 2024; Salfi 2023; de Cos 2023 https://doi.org/10.1093/ndt/gfae025; https://doi.org/10.3389/fimmu.2023.1247606; https://doi.org/10.1016/j.ekir.2022.10.004 Review / precision-medicine framework
Rituximab / other targeted or adjunct therapies under study MAXO: anti-CD20 monoclonal antibody treatment; B-cell depletion therapy Selected relapsing/refractory podocytopathies; role in primary FSGS remains less established than in MCD Mirioglu notes rituximab is highlighted particularly for MCD and discusses ongoing trials in podocytopathies; clinical trial registry search identified FSGS-focused rituximab and abatacept studies, but gathered evidence did not provide robust 2023–2024 quantitative efficacy estimates for routine FSGS use (mirioglu2024managementofadult pages 2-3, OpenTargets Search: Focal segmental glomerulosclerosis) NCT00550342; NCT01573533; NCT00981838; NCT04369183; NCT02592798 (OpenTargets Search: Focal segmental glomerulosclerosis) Mirioglu 2024; ClinicalTrials.gov search https://doi.org/10.1093/ndt/gfae025 Review; trial registry
Real-world implementation / care burden in kidney failure attributed to FSGS MAXO: kidney replacement therapy; kidney transplantation; hemodialysis Advanced FSGS progressing to kidney failure USRDS cohort: 72.1% initiated in-center hemodialysis; 7.3% had an initial transplant; transplant rates were 15% at 1 year and 34% at 5 years; about one-third died during follow-up. These data reflect real-world downstream management burden rather than disease-modifying therapy efficacy (bensink2024kidneyfailureattributed pages 1-2) — Bensink 2024 https://doi.org/10.1016/j.xkme.2023.100760 Registry/observational

Table: This table summarizes current FSGS treatment approaches, emphasizing 2023-2024 evidence, patient subgroups, quantitative outcomes, and implementation details. It is useful for mapping supportive care, immunosuppression, sparsentan trial data, and precision-medicine strategies to a knowledge base.

12.1 Sparsentan (dual endothelin–angiotensin receptor antagonist)

  • Efficacy (2024 meta-analysis): sparsentan improved proteinuria compared with irbesartan (ratio of percentage reduction 0.66, 95% CI 0.58–0.74) and increased complete and partial remission probabilities (CR RR 2.57; PR RR 1.63). Kidney function effects were not significantly different in pooled eGFR change (MD 1.98 mL/min/1.73m², P=0.20), and hypotension was more frequent (RR 2.02) (elnaga2024safetyandefficacy pages 1-2).
  • Long-term extension (DUET OLE): partial remission achieved by 52.8% within 9 months, with slower eGFR decline in responders (overall slope −2.70 vs −6.56 mL/min/1.73m²/year; P=0.03) and no heart failure events or deaths reported (campbell2024sparsentanforfocal pages 1-2).

12.2 Immunosuppression and supportive care selection

12.3 Real-world implementation downstream

13. Prevention

  • Primary prevention strategies are not well-defined for primary FSGS; secondary prevention focuses on early detection of proteinuria and implementation of renoprotective strategies (RAAS blockade, BP control). Specific guideline-grade prevention programs were not present in retrieved evidence.

14. Other Species / Natural Disease

  • Not available in the retrieved evidence.

15. Model Organisms

  • Specific model-organism details were not extracted from the 2023–2024 evidence presented here.

Key Epidemiology & Prognosis Snapshot (2023–2024)

The following table consolidates identifiers and key statistics (registry + recent reviews).

Table (click to expand)
Category Data Source (first author year) PMID URL Evidence type
Identifiers/Synonyms FSGS = focal segmental glomerulosclerosis; described as a histologic pattern of glomerular injury / podocytopathy, not a single disease entity; classified into primary, genetic, secondary, and FSGS of undetermined cause (cos2023noveltreatmentparadigms pages 1-2, mirioglu2024managementofadult pages 2-3) de Cos 2023; Mirioglu 2024 https://doi.org/10.1016/j.ekir.2022.10.004; https://doi.org/10.1093/ndt/gfae025 Review
Identifiers/Synonyms Histologic lesion defined by segmental sclerosis in some glomeruli with variable podocyte foot-process effacement on EM; primary FSGS often presents with abrupt nephrotic syndrome (cos2023noveltreatmentparadigms pages 1-2) de Cos 2023 https://doi.org/10.1016/j.ekir.2022.10.004 Review
Epidemiology FSGS accounts for about 20% of nephrotic syndrome in children and 40% in adults; annual incidence estimated 0.2–2.5 per 100,000 (salfi2023currentunderstandingof pages 1-2) Salfi 2023 https://doi.org/10.3389/fimmu.2023.1247606 Review
Epidemiology In the USRDS 2008–2018 cohort, mean annual prevalence of FSGS-attributed kidney failure was 87.6 per 1,000,000 US persons and incidence was 7.5 per 1,000,000; prevalence rose from 76.5/million (2008) to 96.0/million (2018) (bensink2024kidneyfailureattributed pages 1-2, bensink2024kidneyfailureattributed pages 2-3) Bensink 2024 https://doi.org/10.1016/j.xkme.2023.100760 Registry/retrospective cohort
Epidemiology Historical U.S. incidence of FSGS (all disease, 2004–2013) reported as about 3.2 per 100,000 person-years, a 41% increase vs 1994–2003 (bensink2024kidneyfailureattributed pages 1-2) Bensink 2024 https://doi.org/10.1016/j.xkme.2023.100760 Registry/retrospective cohort
Progression/Prognosis “Over half of the patients with nephrotic-range proteinuria progress to ESKD” (mirioglu2024managementofadult pages 2-3) Mirioglu 2024 https://doi.org/10.1093/ndt/gfae025 Review
Progression/Prognosis FSGS remission rates: 47–66% remit; among those, 25–36% relapse; steroid resistance encountered in 40–60% of patients (mirioglu2024managementofadult pages 2-3) Mirioglu 2024 https://doi.org/10.1093/ndt/gfae025 Review
Progression/Prognosis Across studies, steroid resistance reported in 26–80% of patients; adults respond less favorably than children, and <50% of initially steroid-sensitive patients maintain stable remission (salfi2023currentunderstandingof pages 1-2) Salfi 2023 https://doi.org/10.3389/fimmu.2023.1247606 Review
Progression/Prognosis In USRDS, 7-year kidney survival for FSGS was 69% (vs 88% membranous nephropathy; 82% IgA nephropathy); >50% progress to kidney failure within 5–10 years (bensink2024kidneyfailureattributed pages 2-3) Bensink 2024 https://doi.org/10.1016/j.xkme.2023.100760 Registry/retrospective cohort
Transplant recurrence Small series: anti-nephrin antibodies identified in 11/14 (79%) patients with recurrence of primary FSGS after kidney transplantation (mirioglu2024managementofadult pages 2-3) Mirioglu 2024 https://doi.org/10.1093/ndt/gfae025 Review
Demographics Incidence/prevalence are higher in male adults and Black individuals (salfi2023currentunderstandingof pages 1-2) Salfi 2023 https://doi.org/10.3389/fimmu.2023.1247606 Review
Demographics USRDS prevalence lower in children <18 y: 31.4/million vs adults ≥18 y: 104.9/million; higher in males 108.0/million vs females 67.9/million (bensink2024kidneyfailureattributed pages 2-3) Bensink 2024 https://doi.org/10.1016/j.xkme.2023.100760 Registry/retrospective cohort
Demographics Highest prevalence of FSGS-attributed kidney failure in Native Hawaiian/Pacific Islander: 262.9/million and Black/African American: 256.3/million groups (bensink2024kidneyfailureattributed pages 2-3) Bensink 2024 https://doi.org/10.1016/j.xkme.2023.100760 Registry/retrospective cohort

Table: This table summarizes how recent 2023-2024 sources define and classify FSGS and compiles key epidemiology, prognosis, recurrence, and demographic statistics directly from the available evidence snippets.

Visual Evidence: Classification and Treatment Algorithm

A KDIGO-aligned classification and management flow is available as a figure from de Cos et al. 2023 (cos2023noveltreatmentparadigms media ecc573cd).

Direct abstract-supported statements (quotes)

The following direct statements come from abstracts of retrieved peer-reviewed papers: - “The pathogenetic mechanisms underlying the onset and the post-transplant recurrence of primary focal segmental glomerulosclerosis (FSGS) are complex and remain yet to be fully elucidated. However, a growing body of evidence emphasizes the pivotal role of the immune system…” (Frontiers in Immunology, 2023-09) (salfi2023currentunderstandingof pages 1-2). - “Kidney biopsy remains central to diagnosis…” in the ERA Immunonephrology Working Group update on podocytopathies (Nephrology Dialysis Transplantation, 2024-02) (mirioglu2024managementofadult pages 2-3). - In the sparsentan meta-analysis abstract: “Sparsentan was superior to irbesartan in improving urine protein to creatinine ratio…” and hypotension was higher (BMC Nephrology, 2024-09) (elnaga2024safetyandefficacy pages 1-2).

Limitations / Evidence Gaps for Knowledge Base Completion

  • ICD-10/ICD-11, MeSH, OMIM, and Orphanet identifiers were not available in retrieved texts; additional ontology lookups are needed.
  • Variant-level details (HGVS nomenclature, allele frequency in gnomAD), epigenetic mechanisms, and quality-of-life instrument results were not present in the retrieved evidence.
  • Environmental/toxin and infectious triggers for secondary FSGS were only partially represented in retrieved excerpts.

References

  1. (cos2023noveltreatmentparadigms pages 1-2): Marina de Cos, Kristin Meliambro, and Kirk N. Campbell. Novel treatment paradigms: focal segmental glomerulosclerosis. Kidney International Reports, 8:30-35, Jan 2023. URL: https://doi.org/10.1016/j.ekir.2022.10.004, doi:10.1016/j.ekir.2022.10.004. This article has 41 citations and is from a peer-reviewed journal.

  2. (salfi2023currentunderstandingof pages 1-2): Giuseppe Salfi, Federica Casiraghi, and Giuseppe Remuzzi. Current understanding of the molecular mechanisms of circulating permeability factor in focal segmental glomerulosclerosis. Frontiers in Immunology, Sep 2023. URL: https://doi.org/10.3389/fimmu.2023.1247606, doi:10.3389/fimmu.2023.1247606. This article has 45 citations and is from a peer-reviewed journal.

  3. (mirioglu2024managementofadult pages 2-3): Safak Mirioglu, Lisa Daniel-Fischer, Ilay Berke, Syed Hasan Ahmad, Ingeborg M Bajema, Annette Bruchfeld, Gema M Fernandez-Juarez, Jürgen Floege, Eleni Frangou, Dimitrios Goumenos, Megan Griffith, Sarah M Moran, Cees van Kooten, Stefanie Steiger, Kate I Stevens, Kultigin Turkmen, Lisa C Willcocks, and Andreas Kronbichler. Management of adult patients with podocytopathies: an update from the era immunonephrology working group. Nephrology Dialysis Transplantation, 39:569-580, Feb 2024. URL: https://doi.org/10.1093/ndt/gfae025, doi:10.1093/ndt/gfae025. This article has 33 citations and is from a domain leading peer-reviewed journal.

  4. (OpenTargets Search: Focal segmental glomerulosclerosis): Open Targets Query (Focal segmental glomerulosclerosis, 19 results). Buniello, A. et al. (2025). Open Targets Platform: facilitating therapeutic hypotheses building in drug discovery. Nucleic Acids Research.

  5. (bensink2024kidneyfailureattributed pages 1-2): Mark E. Bensink, Deborah Goldschmidt, Zheng-Yi Zhou, Kaijun Wang, Richard Lieblich, and C. Martin Bunke. Kidney failure attributed to focal segmental glomerulosclerosis: a usrds retrospective cohort study of epidemiology, treatment modalities, and economic burden. Kidney Medicine, 6:100760, Feb 2024. URL: https://doi.org/10.1016/j.xkme.2023.100760, doi:10.1016/j.xkme.2023.100760. This article has 11 citations.

  6. (elnaga2024safetyandefficacy pages 1-2): Ahmed A. Abo Elnaga, Mohamed A. Alsaied, Abdelrahman M. Elettreby, Alaa Ramadan, Mohamed Abouzid, Raghda Shetta, and Yazan A. Al-Ajlouni. Safety and efficacy of sparsentan versus irbesartan in focal segmental glomerulosclerosis and iga nephropathy: a systematic review and meta-analysis of randomized controlled trials. BMC Nephrology, Sep 2024. URL: https://doi.org/10.1186/s12882-024-03713-9, doi:10.1186/s12882-024-03713-9. This article has 4 citations and is from a peer-reviewed journal.

  7. (salfi2023currentunderstandingof pages 4-5): Giuseppe Salfi, Federica Casiraghi, and Giuseppe Remuzzi. Current understanding of the molecular mechanisms of circulating permeability factor in focal segmental glomerulosclerosis. Frontiers in Immunology, Sep 2023. URL: https://doi.org/10.3389/fimmu.2023.1247606, doi:10.3389/fimmu.2023.1247606. This article has 45 citations and is from a peer-reviewed journal.

  8. (cos2023noveltreatmentparadigms media ecc573cd): Marina de Cos, Kristin Meliambro, and Kirk N. Campbell. Novel treatment paradigms: focal segmental glomerulosclerosis. Kidney International Reports, 8:30-35, Jan 2023. URL: https://doi.org/10.1016/j.ekir.2022.10.004, doi:10.1016/j.ekir.2022.10.004. This article has 41 citations and is from a peer-reviewed journal.

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