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renal.membranous-nephropathy.v1PRODUCTION
renal.membranous-nephropathy.v1

Membranous Nephropathy

nephrologychronicacuteadult
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12/12 authored

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

Current phase

Frame

Detailed

Confirm MN by biopsy (subepithelial deposits + GBM thickening) and primary vs secondary phenotype assignment via PLA2R/THSD7A/NELL1 + viral + lupus + drug + malignancy workup (KDIGO 2021 GN)

Inputs
4
Actions
0
Advance rule
Set
Advance when

MN biopsy + phenotype assigned (KDIGO 2021 GN)

Patient inputs (13)

Older age (>65) raises malignancy-associated MN suspicion; NELL1+ more common (KDIGO 2021 GN)

eGFR + Δ-eGFR slope drives KDIGO 2021 GN risk tier (KDIGO 2021 GN)

Drug-induced MN — NSAID, captopril, gold, anti-TNF, penicillamine — withdrawal (KDIGO 2021 GN)

Malignancy-associated MN — solid tumors 5-10% adults (lung, GI, prostate, breast); age-appropriate cancer screen mandatory (KDIGO 2021 GN)

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

Proteinuria + bland sediment expected in pure MN; active sediment → reconsider lupus class V (KDIGO 2021 GN)

Proteinuria quantification drives risk tier — <4 / 4-8 / >8 g/d cutoffs (KDIGO 2021 GN)

Severe hypoalbuminemia <2.5 g/dL drives VTE anticoag decision (MN highest VTE risk) (KDIGO 2021 GN; Lin)

Anti-PLA2R antibody — ~70% of primary MN; titer correlates with activity + treatment response (Beck NEJM 2009)

HBV-associated MN — treat with entecavir/tenofovir; antiviral often improves MN (KDIGO 2021 GN)

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

ANA / anti-dsDNA / complement — exclude lupus class V membranous (route renal.lupus-nephritis.v1) (KDIGO 2021 GN)

Pregnancy-associated MN special considerations — CY/MMF teratogenic; rituximab risk-benefit case-by-case (KDIGO 2021 GN)

* = hard-required. Engine cannot meaningfully run until these are filled.

Severity triggers (9)

9 need judgement
  • informationallife_threateningthromboembolic_complication_highest_risk
    MN has highest VTE/RVT/PE risk of any nephrotic cause — albumin <2.5 g/dL → anticoag prophylaxis (warfarin INR 2-3 or DOAC); PE with hemodynamic compromise → ICU + thrombolysis (KDIGO 2021 GN; Lin nephrotic anticoag)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalsevereprimary_idiopathic_pla2r_positive
    Primary idiopathic PLA2R-positive MN — ~70% of primary; antibody titer correlates with activity; PLA2R IHC on biopsy is highly specific (Beck NEJM 2009)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalsevereprimary_thsd7a_positive
    Primary THSD7A-positive MN — ~3% of primary; higher malignancy association in some series — age-appropriate cancer screen mandatory (KDIGO 2021 GN)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalsevereprimary_nell1_positive_malignancy_associated
    Primary NELL1-positive MN — ~5%; older patients; malignancy-associated in many series; intensified cancer screen (KDIGO 2021 GN)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalseveresecondary_lupus_class_v
    Secondary lupus class V membranous — full-house IF (IgG/IgM/IgA/C3/C1q); positive ANA + anti-dsDNA + low complement; route renal.lupus-nephritis.v1 (KDIGO 2021 GN)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalseveresecondary_hbv_hcv_associated
    Secondary HBV- or HCV-associated MN — treat underlying virus first (entecavir/tenofovir for HBV; DAA for HCV); antiviral often improves MN without immunosuppression (KDIGO 2021 GN)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalseveresecondary_malignancy_associated
    Secondary malignancy-associated MN — solid tumors 5-10% (lung, colon, breast, prostate, gastric); age-appropriate cancer screen + treat tumor (KDIGO 2021 GN)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalseverepregnancy_associated_mn
    Pregnancy-associated MN — CY/MMF teratogenic; rituximab risk-benefit case-by-case; close maternal-fetal medicine + nephrology comanagement (KDIGO 2021 GN)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalmoderatesecondary_drug_induced
    Secondary drug-induced MN — NSAID, captopril, gold, anti-TNF, penicillamine, lithium, mercury; withdrawal often resolves without immunosuppression (KDIGO 2021 GN)
    Trigger could not be auto-evaluated — needs clinician judgement.

Workflow calculators

Run this disease's risk and dosing calculators inline.

RISK_STRATIFICATIONrequiredDrives severity classification
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Recommended regimen

Membranous nephropathy risk-stratified ladder — low/moderate conservative 6 mo → high-risk rituximab (MENTOR) / Ponticelli CY-steroid / CNI → secondary cause-directed → universal anticoag + statin + vaccinations (KDIGO 2021 GN; MENTOR Fervenza NEJM 2019; Beck PLA2R NEJM 2009)
axis: membranous_risk_stratified_ladderstep step_1_low_risk_conservative - Step 1 — Low-risk conservative (eGFR>60 + UPCR<4 + albumin>3 + stable)
Selected step "Step 1 — Low-risk conservative (eGFR>60 + UPCR<4 + albumin>3 + stable)" — Low-risk MN by KDIGO 2021 GN criteria (KDIGO 2021 GN)
  • lisinopril
    first line
    acei
    10 mg PO daily, titrate to max tolerated (typically 40 mg) • PO • daily
    triggers: low_risk_mn
    KDIGO 2021 GN — RAS blockade max-dose foundational; ~30% spontaneous remission at 12-18 months
    rxcui 29046
  • losartan
    first line
    arb
    50-100 mg PO daily • PO • daily
    triggers: acei_intolerant
    KDIGO 2021 GN — ARB alternative
    rxcui 52175

outpatient playbook — drug actions (8)

  1. 1. ACEi/ARB max-dose (universal)
    Lisinopril 10-40 or losartan 50-100 • PO • daily
    trigger: All MN
    KDIGO 2021 GN universal
  2. 2. warfarin prophylaxis if alb<2.5
    INR-titrated 2-3 • PO • daily
    trigger: Severe hypoalbuminemia
    Lin nephrotic anticoag
  3. 3. rituximab (high-risk MENTOR)
    1000 mg IV × 2 (d0, d14) or 375 mg/m² weekly × 4 • IV • q14d × 2 or weekly × 4
    trigger: High-risk MN — preferred over cyclosporine
    MENTOR Fervenza NEJM 2019
  4. 4. Ponticelli alternating-month CY+steroid
    mPSL 1 g IV × 3 then prednisone 0.5 mg/kg/d × 27 d (odd mo) / CY 2 mg/kg/d × 30 d (even mo) • IV+PO • alternating 6 mo
    trigger: Non-PLA2R or rapidly progressive high-risk
    Ponticelli alternating-month protocol
  5. 5. cyclosporine or tacrolimus (third option)
    Trough-titrated • PO • BID
    trigger: Rituximab/Ponticelli unavailable or contraindicated
    KDIGO 2021 GN
  6. 6. entecavir or tenofovir if HBV
    0.5 mg or 300 mg PO daily • PO • daily
    trigger: HBV-associated MN
    KDIGO 2021 GN
  7. 7. atorvastatin
    20-40 mg PO daily • PO • daily
    trigger: Severe nephrotic dyslipidemia
    ACC/AHA Lipid 2026
  8. 8. TMP-SMX prophylaxis on immunosuppression
    160/800 PO M-W-F or 80/400 daily • PO • 3x/wk or daily
    trigger: On rituximab or Ponticelli
    PJP prevention (KDIGO 2021 GN)

Auto-drafted A&P note

outpatient

Subjective

- Possible entry pathways: Gradual onset nephrotic syndrome — edema + heavy proteinuria + hypoalbuminemia (KDIGO 2021 GN); Adult-onset nephrotic-range proteinuria UPCR >3.5 g/g (KDIGO 2021 GN); Positive serum PLA2R antibody — primary MN biomarker (Beck NEJM 2009).

Objective

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

Assessment

**Membranous Nephropathy** (renal.membranous-nephropathy.v1).
Phenotype framing: Primary PLA2R+ / THSD7A+ / NELL1+ / lupus class V / HBV / HCV / malignancy / drug / pregnancy / other (KDIGO 2021 GN)
Scope: Confirm MN by biopsy (subepithelial deposits + GBM thickening) and primary vs secondary phenotype assignment via PLA2R/THSD7A/NELL1 + viral + lupus + drug + malignancy workup (KDIGO 2021 GN)

No severity triggers fired against current inputs.

Plan

Regimen axis: **Membranous nephropathy risk-stratified ladder — low/moderate conservative 6 mo → high-risk rituximab (MENTOR) / Ponticelli CY-steroid / CNI → secondary cause-directed → universal anticoag + statin + vaccinations (KDIGO 2021 GN; MENTOR Fervenza NEJM 2019; Beck PLA2R NEJM 2009)** — step "Step 1 — Low-risk conservative (eGFR>60 + UPCR<4 + albumin>3 + stable)".
1. lisinopril 10 mg PO daily, titrate to max tolerated (typically 40 mg) PO daily (acei, first line) — KDIGO 2021 GN — RAS blockade max-dose foundational; ~30% spontaneous remission at 12-18 months
2. losartan 50-100 mg PO daily PO daily (arb, first line) — KDIGO 2021 GN — ARB alternative

Setting playbook (outpatient) — Primary management setting — risk stratification, conservative trial (6 mo low/mod), high-risk immunosuppression rituximab/Ponticelli/CNI, PLA2R titer monitoring, transplant prep (KDIGO 2021 GN; MENTOR 2019)
3. ACEi/ARB max-dose (universal) Lisinopril 10-40 or losartan 50-100 PO daily — All MN (KDIGO 2021 GN universal)
4. warfarin prophylaxis if alb<2.5 INR-titrated 2-3 PO daily — Severe hypoalbuminemia (Lin nephrotic anticoag)
5. rituximab (high-risk MENTOR) 1000 mg IV × 2 (d0, d14) or 375 mg/m² weekly × 4 IV q14d × 2 or weekly × 4 — High-risk MN — preferred over cyclosporine (MENTOR Fervenza NEJM 2019)
6. Ponticelli alternating-month CY+steroid mPSL 1 g IV × 3 then prednisone 0.5 mg/kg/d × 27 d (odd mo) / CY 2 mg/kg/d × 30 d (even mo) IV+PO alternating 6 mo — Non-PLA2R or rapidly progressive high-risk (Ponticelli alternating-month protocol)
7. cyclosporine or tacrolimus (third option) Trough-titrated PO BID — Rituximab/Ponticelli unavailable or contraindicated (KDIGO 2021 GN)
8. entecavir or tenofovir if HBV 0.5 mg or 300 mg PO daily PO daily — HBV-associated MN (KDIGO 2021 GN)
9. atorvastatin 20-40 mg PO daily PO daily — Severe nephrotic dyslipidemia (ACC/AHA Lipid 2026)
10. TMP-SMX prophylaxis on immunosuppression 160/800 PO M-W-F or 80/400 daily PO 3x/wk or daily — On rituximab or Ponticelli (PJP prevention (KDIGO 2021 GN))

Non-pharmacologic actions:
- Annual vaccination per ACIP 2026 — flu, COVID, PCV20, HBV; AVOID live on immunosuppression (KDIGO 2021 GN)
- Pre-immunosuppression PCV20 + HBV + flu (KDIGO 2021 GN)
- Contraception + pre-conception planning on CY (KDIGO 2021 GN)
- Bone health Ca + vit D + bisphosphonate per FRAX on Ponticelli (KDIGO 2021 GN)
- CV-risk modification — statin per ACC/AHA Lipid 2026 (KDIGO 2021 GN)
- Cancer surveillance — age-appropriate; intensified if NELL1+ (KDIGO 2021 GN)
- Compression stockings if reduced mobility (VTE prevention) (KDIGO 2021 GN)
- Patient action card — VTE / nephrotic-flare red-flags reinforced (KDIGO 2021 GN)

AVOID / contraindication checks:
- Rituximab hbv screen vaccinate pre no live vaccines (MENTOR)
- Cy fertility counseling bladder toxicity mesna (Ponticelli)
- Steroid pjp prophylaxis bone health glucose monitoring (KDIGO 2021 GN)
- Cni bp egfr magnesium interactions (KDIGO 2021 GN)
- Warfarin inr monitoring bleeding risk (Lin nephrotic anticoag)
- Tmp smx prophylaxis during induction (KDIGO 2021 GN)
- Hbv reactivation screen pre rituximab or cy (KDIGO 2021 GN)
- Vaccinate pre immunosuppression no live during (KDIGO 2021 GN)

Monitoring

Regimen monitoring:
- UPCR + PLA2R antibody titer + serum albumin + eGFR q3 months (KDIGO 2021 GN; Beck 2009)
- BP at each visit, target <130/80 (KDIGO 2021 GN)
- CBC + LFTs q1w during CY induction; q1-3 months on rituximab (KDIGO 2021 GN)
- CNI trough monitoring per agent (KDIGO 2021 GN)
- INR q1w on warfarin (Lin nephrotic anticoag)
- HBV viral load on entecavir/tenofovir (KDIGO 2021 GN)
- Glucose + bone health on Ponticelli steroid pulses (KDIGO 2021 GN)

Setting (outpatient) monitoring:
- UPCR + PLA2R titer + albumin + eGFR q3 months (KDIGO 2021 GN)
- BP at each visit (KDIGO 2021 GN)
- INR q1-2 weeks on warfarin (Lin nephrotic anticoag)
- CD20 + IgG levels on rituximab maintenance (KDIGO 2021 GN)
- HBV viral load on antiviral (KDIGO 2021 GN)
- DEXA q1-2 years on Ponticelli steroid (KDIGO 2021 GN)

Follow-up plan: q3-6 month nephrology; post-transplant MN recurrence ~10%; CV/bone/fertility; PLA2R antibody monitoring for relapse prediction; transplant evaluation if approaching ESRD (KDIGO 2024 CKD)
- Close-out criterion: Long-term plan documented (KDIGO 2024 CKD)

Monitoring phase: UPCR + PLA2R antibody titer + serum albumin + eGFR q3 months on therapy; immunological remission (titer becoming negative) precedes clinical remission by 6-12 mo (KDIGO 2021 GN)

Disposition

Current setting: outpatient — Primary management setting — risk stratification, conservative trial (6 mo low/mod), high-risk immunosuppression rituximab/Ponticelli/CNI, PLA2R titer monitoring, transplant prep (KDIGO 2021 GN; MENTOR 2019)

Disposition criteria:
- Continue outpatient q3-6 months if stable (KDIGO 2021 GN)
- Admit for severe nephrotic / VTE / Ponticelli initiation if monitoring difficult (KDIGO 2021 GN)
- Transition to transplant clinic if approaching ESRD (KDIGO 2024 CKD)

Escalation triggers (move to higher acuity):
- VTE/PE/RVT confirmed → ED + therapeutic anticoag + admit if PE (KDIGO 2021 GN)
- Rising PLA2R titer despite therapy → treatment failure → switch class (RTX↔CY) (Beck 2009)
- Rapid eGFR decline → ED + repeat biopsy consideration (KDIGO 2021 GN)
- Active sediment + new low complement + positive ANA → reroute to renal.lupus-nephritis.v1 (KDIGO 2021 GN)
- CKD progression toward ESRD → transplant evaluation (KDIGO 2024 CKD)

Earlier-Return Triggers

Return-precaution thresholds (watch for):
- [LIFE_THREATENING] MN has highest VTE/RVT/PE risk of any nephrotic cause — albumin <2.5 g/dL → anticoag prophylaxis (warfarin INR 2-3 or DOAC); PE with hemodynamic compromise → ICU + thrombolysis (KDIGO 2021 GN; Lin nephrotic anticoag)
- [SEVERE] Primary idiopathic PLA2R-positive MN — ~70% of primary; antibody titer correlates with activity; PLA2R IHC on biopsy is highly specific (Beck NEJM 2009)
- [SEVERE] Primary THSD7A-positive MN — ~3% of primary; higher malignancy association in some series — age-appropriate cancer screen mandatory (KDIGO 2021 GN)

Citations

- KDIGO 2021 Glomerular Diseases + MENTOR rituximab (NEJM 2019) + GEMRITUX (JASN 2017) + STARMEN (Kidney Int 2021) + anti-PLA2R antibody (Beck NEJM 2009) [PMID:34556256](https://pubmed.ncbi.nlm.nih.gov/34556256/)
- Cited evidence (PMID 31269364) [PMID:31269364](https://pubmed.ncbi.nlm.nih.gov/31269364/)
- Cited evidence (PMID 27352623) [PMID:27352623](https://pubmed.ncbi.nlm.nih.gov/27352623/)
- Cited evidence (PMID 33166580) [PMID:33166580](https://pubmed.ncbi.nlm.nih.gov/33166580/)
- Cited evidence (PMID 19571279) [PMID:19571279](https://pubmed.ncbi.nlm.nih.gov/19571279/)

Last reconciled with current guidelines: 2026-05-22.
References
  • KDIGO 2021 Glomerular Diseases + MENTOR rituximab (NEJM 2019) + GEMRITUX (JASN 2017) + STARMEN (Kidney Int 2021) + anti-PLA2R antibody (Beck NEJM 2009) — PMID:34556256
  • Cited evidence (PMID 31269364) — PMID:31269364
  • Cited evidence (PMID 27352623) — PMID:27352623
  • Cited evidence (PMID 33166580) — PMID:33166580
  • Cited evidence (PMID 19571279) — PMID:19571279