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renal.fsgs.v1PRODUCTION
renal.fsgs.v1

Focal Segmental Glomerulosclerosis

nephrologychronicacuteadult
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Care setting:

Encounter flow

12/12 authored

Canonical 12-phase frame with authored status for this dossier.

Current phase

Frame

Detailed

Confirm FSGS lesion on biopsy + Columbia variant classification + assign primary vs secondary phenotype FIRST (KDIGO 2021 GN; D'Agati 2004)

Inputs
3
Actions
0
Advance rule
Set
Advance when

FSGS biopsy + phenotype assigned (KDIGO 2021 GN)

Patient inputs (12)

Age at presentation informs primary vs secondary likelihood + genetic panel decision (KDIGO 2021 GN)

African ancestry → APOL1 high-risk variant relevance for transplant + progression risk (KDIGO 2021 GN)

eGFR + Δ-eGFR slope drives risk stratification + transplant timing (KDIGO 2021 GN)

Drug-induced FSGS — heroin, lithium, anabolic steroids, IFN, pamidronate — withdrawal (KDIGO 2021 GN)

Adaptive secondary FSGS — obesity, reflux, unilateral kidney, sickle cell, oligomeganephronia (KDIGO 2021 GN)

BP target <130/80; ACEi/ARB renoprotection universal (KDIGO 2021 GN)

Proteinuria + sediment (bland in pure FSGS) (KDIGO 2021 GN)

Proteinuria quantification — primary often >3.5 g/g, secondary <3.5 g/g (KDIGO 2021 GN)

Severe hypoalbuminemia (<2.5 g/dL) suggests primary; preserved suggests secondary (KDIGO 2021 GN)

HIV-associated nephropathy (HIVAN) typically collapsing FSGS (KDIGO 2021 GN)

Genetic FSGS — NPHS1/NPHS2/INF2/TRPC6 — minimal immunosuppression response (KDIGO 2021 GN)

HCV-associated FSGS — DAA therapy can improve renal (KDIGO 2021 GN)

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Severity triggers (10)

10 need judgement
  • informationallife_threateningcollapsing_fsgs_variant
    Collapsing FSGS variant — global glomerular tuft collapse + podocyte hyperplasia; associated with HIV, parvovirus, SARS-CoV-2, APOL1 high-risk, IFN, pamidronate; worst prognosis (KDIGO 2021 GN; D'Agati 2004)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalsevereprimary_fsgs_idiopathic
    Primary idiopathic FSGS — sudden onset nephrotic syndrome + severe hypoalbuminemia + extensive foot-process effacement; suPAR/circulating factor mediated; steroid-responsive (~50%) (KDIGO 2021 GN)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalsevereapol1_associated_fsgs
    APOL1-associated FSGS — homozygous or compound heterozygous high-risk variants in African ancestry; 6-10× FSGS risk + accelerated progression + transplant donor screening implications (KDIGO 2021 GN)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalseveregenetic_fsgs
    Genetic FSGS — NPHS1 (nephrin) / NPHS2 (podocin) / INF2 / TRPC6 / WT1 / ACTN4; young onset / familial / drug-resistant phenotype; minimal immunosuppression response (KDIGO 2021 GN)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalseverevirus_associated_fsgs_hivan
    Virus-associated FSGS — HIVAN (HIV-associated nephropathy, typically collapsing variant), HCV, parvovirus B19; cART for HIVAN often improves renal alone (KDIGO 2021 GN)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalseveredrug_induced_fsgs
    Drug-induced FSGS — heroin, lithium, anabolic steroids, IFN, pamidronate — withdraw offending agent; may resolve without immunosuppression (KDIGO 2021 GN)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalsevererefractory_primary_fsgs
    Refractory primary FSGS — failure of steroid + CNI; consider rituximab off-label / sparsentan emerging / specialty referral (KDIGO 2021 GN; DUPLEX 2023)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalseverenephrotic_complication_aki_or_vte
    Severe nephrotic complication in FSGS — AKI during nephrotic flare, VTE / renal vein thrombosis, SBP (KDIGO 2021 GN)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalmoderatesecondary_fsgs_adaptive
    Secondary adaptive FSGS — obesity, reflux, unilateral kidney, reduced nephron mass, sickle cell, oligomeganephronia — sub-nephrotic proteinuria, preserved albumin, segmental foot-process effacement (KDIGO 2021 GN)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalmoderatetip_lesion_variant
    Tip-lesion variant — segmental sclerosis at tubular pole; best prognosis among primary; ~75% steroid response (KDIGO 2021 GN; D'Agati 2004)
    Trigger could not be auto-evaluated — needs clinician judgement.

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RISK_STRATIFICATIONrequiredDrives severity classification
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Recommended regimen

FSGS phenotype-driven ladder — phenotype ID → primary immunosuppression → CNI/rituximab/sparsentan → secondary RAS/SGLT2i/weight-loss/cART/drug-withdrawal (KDIGO 2021 GN; DUPLEX 2023)
axis: fsgs_phenotype_driven_ladderstep step_1_phenotype_identification - Step 1 — Phenotype identification (mandatory pre-treatment): biopsy + variant + viral + APOL1 + genetic + drug history
Selected step "Step 1 — Phenotype identification (mandatory pre-treatment): biopsy + variant + viral + APOL1 + genetic + drug history" — All new FSGS diagnoses (KDIGO 2021 GN)
  • phenotype_workup_bundle
    first line
    workup
    triggers: new_fsgs_diagnosis
    KDIGO 2021 GN — primary vs secondary identification dictates therapy; immunosuppression for secondary may be harmful

outpatient playbook — drug actions (8)

  1. 1. ACEi/ARB max-dose (universal)
    Lisinopril 10-40 or losartan 50-100 • PO • daily
    trigger: All proteinuric FSGS
    KDIGO 2021 GN universal
  2. 2. SGLT2i (empa/dapa)
    10 mg PO daily • PO • daily
    trigger: Proteinuria + eGFR >20-25
    EMPA-KIDNEY (KDIGO 2024 CKD)
  3. 3. prednisone induction (primary FSGS only)
    1 mg/kg/d × 16 wk • PO • daily
    trigger: Biopsy-confirmed primary FSGS
    KDIGO 2021 GN
  4. 4. cyclosporine or tacrolimus second-line
    Trough-titrated • PO • BID
    trigger: Steroid-resistant primary
    KDIGO 2021 GN
  5. 5. rituximab refractory
    375 mg/m² IV weekly × 4 • IV • weekly × 4
    trigger: Refractory primary
    KDIGO 2021 GN off-label
  6. 6. sparsentan emerging off-label
    200-400 mg PO daily • PO • daily
    trigger: Refractory primary with progressive eGFR
    DUPLEX 2023
  7. 7. cART (HIVAN)
    Per HIV regimen • PO • daily
    trigger: HIVAN-collapsing FSGS
    KDIGO 2021 GN — cART alone may improve renal
  8. 8. atorvastatin
    20-40 mg PO daily • PO • daily
    trigger: Nephrotic dyslipidemia
    ACC/AHA Lipid 2026

Auto-drafted A&P note

outpatient

Subjective

- Possible entry pathways: Nephrotic-range or sub-nephrotic proteinuria — UPCR >3.5 g/g (primary) or 1-3.5 g/g (secondary) (KDIGO 2021 GN); CKD with FSGS lesion on biopsy (KDIGO 2021 GN); Renal biopsy with focal segmental glomerulosclerosis + Columbia variant classification (KDIGO 2021 GN; D'Agati 2004).

Objective

- No vitals, labs, or imaging entered for this encounter.

Assessment

**Focal Segmental Glomerulosclerosis** (renal.fsgs.v1).
Phenotype framing: Primary / secondary adaptive / APOL1-associated / genetic / HIVAN-collapsing / HCV / drug-induced / tip / cellular / perihilar / NOS (KDIGO 2021 GN)
Scope: Confirm FSGS lesion on biopsy + Columbia variant classification + assign primary vs secondary phenotype FIRST (KDIGO 2021 GN; D'Agati 2004)

No severity triggers fired against current inputs.

Plan

Regimen axis: **FSGS phenotype-driven ladder — phenotype ID → primary immunosuppression → CNI/rituximab/sparsentan → secondary RAS/SGLT2i/weight-loss/cART/drug-withdrawal (KDIGO 2021 GN; DUPLEX 2023)** — step "Step 1 — Phenotype identification (mandatory pre-treatment): biopsy + variant + viral + APOL1 + genetic + drug history".
1. phenotype_workup_bundle (workup, first line) — KDIGO 2021 GN — primary vs secondary identification dictates therapy; immunosuppression for secondary may be harmful

Setting playbook (outpatient) — Primary management setting — phenotype identification → primary immunosuppression OR secondary supportive → transplant planning if approaching ESRD (KDIGO 2021 GN; KDIGO 2024 CKD)
2. ACEi/ARB max-dose (universal) Lisinopril 10-40 or losartan 50-100 PO daily — All proteinuric FSGS (KDIGO 2021 GN universal)
3. SGLT2i (empa/dapa) 10 mg PO daily PO daily — Proteinuria + eGFR >20-25 (EMPA-KIDNEY (KDIGO 2024 CKD))
4. prednisone induction (primary FSGS only) 1 mg/kg/d × 16 wk PO daily — Biopsy-confirmed primary FSGS (KDIGO 2021 GN)
5. cyclosporine or tacrolimus second-line Trough-titrated PO BID — Steroid-resistant primary (KDIGO 2021 GN)
6. rituximab refractory 375 mg/m² IV weekly × 4 IV weekly × 4 — Refractory primary (KDIGO 2021 GN off-label)
7. sparsentan emerging off-label 200-400 mg PO daily PO daily — Refractory primary with progressive eGFR (DUPLEX 2023)
8. cART (HIVAN) Per HIV regimen PO daily — HIVAN-collapsing FSGS (KDIGO 2021 GN — cART alone may improve renal)
9. atorvastatin 20-40 mg PO daily PO daily — Nephrotic dyslipidemia (ACC/AHA Lipid 2026)

Non-pharmacologic actions:
- Weight loss + bariatric referral if BMI >35 and adaptive FSGS (KDIGO 2024 CKD)
- Annual vaccination per ACIP 2026 — flu, COVID, PCV20, HBV (KDIGO 2021 GN)
- Pre-immunosuppression vaccinations if time permits (KDIGO 2021 GN)
- Smoking cessation (KDIGO 2024 CKD)
- CV-risk modification — statin per ACC/AHA Lipid 2026 (KDIGO 2021 GN)
- Bone health Ca + vit D + bisphosphonate per FRAX on long-term steroid (KDIGO 2021 GN)
- Pregnancy counseling + REMS contraception if on sparsentan (PROTECT 2023)
- APOL1 genotype + transplant donor screening (KDIGO 2021 GN)
- Patient action card — proteinuria-flare red-flags reinforced (KDIGO 2021 GN)

AVOID / contraindication checks:
- No immunosuppression for pure secondary fsgs (KDIGO 2021 GN)
- Steroid pjp prophylaxis bone health (KDIGO 2021 GN)
- Cni bp egfr magnesium interactions (KDIGO 2021 GN)
- Rituximab hbv screen no live vaccines (KDIGO 2021 GN)
- Sparsentan rems liver monitoring pregnancy prevention (PROTECT 2023; FDA REMS)
- Acei arb hold if aki or hyperk (KDIGO 2021 GN)
- Sglt2i hold if euglycemic dka risk (KDIGO 2024 CKD)

Monitoring

Regimen monitoring:
- UPCR + serum albumin + eGFR q3 months on therapy (KDIGO 2021 GN)
- CNI trough monitoring (cyclo 100-200 / tacro 5-10) (KDIGO 2021 GN)
- BP at each visit, target <130/80 (KDIGO 2021 GN)
- LFTs for sparsentan REMS (PROTECT/DUPLEX)
- Glucose + bone health on long-term steroid (KDIGO 2021 GN)
- HIV viral load if HIVAN; HCV RNA if HCV-associated (KDIGO 2021 GN)

Setting (outpatient) monitoring:
- UPCR + eGFR + albumin q3 months (KDIGO 2021 GN)
- BP at each visit (KDIGO 2021 GN)
- CNI trough per agent (KDIGO 2021 GN)
- LFTs for sparsentan REMS (PROTECT/DUPLEX)
- DEXA q1-2 years on steroid (KDIGO 2021 GN)

Follow-up plan: q3-6 month nephrology; transplant prep if eGFR <20-30; post-transplant FSGS recurrence counseling (~30% primary); CV/bone/fertility (KDIGO 2024 CKD)
- Close-out criterion: Long-term plan documented (KDIGO 2024 CKD)

Monitoring phase: UPCR + eGFR + BP + albumin q3 months on therapy; CNI trough; rituximab CD20 / response (KDIGO 2021 GN)

Disposition

Current setting: outpatient — Primary management setting — phenotype identification → primary immunosuppression OR secondary supportive → transplant planning if approaching ESRD (KDIGO 2021 GN; KDIGO 2024 CKD)

Disposition criteria:
- Continue outpatient q3-6 months if stable (KDIGO 2021 GN)
- Admit for rapid progression / severe complication (KDIGO 2021 GN)
- Transition to transplant clinic if eGFR <20-30 (KDIGO 2024 CKD)

Escalation triggers (move to higher acuity):
- Rising UPCR + falling eGFR despite ladder → re-biopsy + specialty referral (KDIGO 2021 GN)
- Rapid eGFR decline + collapsing variant → admit + RPGN evaluation (KDIGO 2021 GN)
- New fever + cytopenia on immunosuppression → ED (KDIGO 2021 GN)
- CKD progression toward ESRD → transplant evaluation; route neph.ckd.core.v1 (KDIGO 2024 CKD)

Earlier-Return Triggers

Return-precaution thresholds (watch for):
- [LIFE_THREATENING] Collapsing FSGS variant — global glomerular tuft collapse + podocyte hyperplasia; associated with HIV, parvovirus, SARS-CoV-2, APOL1 high-risk, IFN, pamidronate; worst prognosis (KDIGO 2021 GN; D'Agati 2004)
- [SEVERE] Primary idiopathic FSGS — sudden onset nephrotic syndrome + severe hypoalbuminemia + extensive foot-process effacement; suPAR/circulating factor mediated; steroid-responsive (~50%) (KDIGO 2021 GN)
- [SEVERE] APOL1-associated FSGS — homozygous or compound heterozygous high-risk variants in African ancestry; 6-10× FSGS risk + accelerated progression + transplant donor screening implications (KDIGO 2021 GN)

Citations

- KDIGO 2021 Glomerular Diseases + DUPLEX sparsentan in FSGS (NEJM 2023) + KDIGO 2024 CKD [PMID:34556256](https://pubmed.ncbi.nlm.nih.gov/34556256/)
- Cited evidence (PMID 37921461) [PMID:37921461](https://pubmed.ncbi.nlm.nih.gov/37921461/)
- Cited evidence (PMID 38490803) [PMID:38490803](https://pubmed.ncbi.nlm.nih.gov/38490803/)

Last reconciled with current guidelines: 2026-05-22.
References
  • KDIGO 2021 Glomerular Diseases + DUPLEX sparsentan in FSGS (NEJM 2023) + KDIGO 2024 CKD — PMID:34556256
  • Cited evidence (PMID 37921461) — PMID:37921461
  • Cited evidence (PMID 38490803) — PMID:38490803