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renal.membranous-nephropathy.v1

Membranous Nephropathy

nephrologychronicacuteadultoutpatientinpatient
Start encounter →Print handoutPRODUCTION

Promoted to INTEGRATED 2026-05-22 (shard-4 build campaign): added registry-resolving workups (le_edema, hematuria); every evidence.pmid re-sourced and live-verified via PubMed; every regimen RxCUI reverse-looked-up live at RxNav. Membranous nephropathy: anti-PLA2R-driven risk stratification (KDIGO 2021), supportive RAAS + VTE prophylaxis (highest nephrotic VTE/RVT risk), immunosuppression for moderate/high risk — rituximab (MENTOR/GEMRITUX), cyclophosphamide-steroid Ponticelli, or tacrolimus-rituximab (STARMEN). PMID anchors (live-verified PubMed 2026-05-22): 34556256 KDIGO 2021 Glomerular Diseases, 31269364 MENTOR, 27352623 GEMRITUX, 33166580 STARMEN, 19571279 anti-PLA2R (Beck). Prior corrected to 34556256; other fabricated PMIDs removed. RxCUI corrections (reverse-verified at RxNav): tacrolimus 42316, entecavir 306266, tenofovir disoproxil fumarate 322248 (prior 10318/358263/643826 were wrong-drug or invalid). Sibling routing: renal.minimal-change.v1, renal.fsgs.v1, neph.ckd.core.v1.

Entry points (5)

  • symptom
    Gradual onset nephrotic syndrome — edema + heavy proteinuria + hypoalbuminemia (KDIGO 2021 GN)
    gradual_nephrotic_syndrome
  • lab_abnormality
    Adult-onset nephrotic-range proteinuria UPCR >3.5 g/g (KDIGO 2021 GN)
    adult_nephrotic_proteinuria
  • lab_abnormality
    Positive serum PLA2R antibody — primary MN biomarker (Beck NEJM 2009)
    pla2r_antibody_positive
  • imaging
    Renal biopsy with subepithelial immune deposits + GBM thickening + spike formation (KDIGO 2021 GN)
    biopsy_membranous_subepithelial_deposits
  • problem_list
    Membranous nephropathy on problem list (continuation visit)
    membranous_nephropathy_known

Required inputs (13)

  • agerequired
    demographic • used at CONTEXT
    Older age (>65) raises malignancy-associated MN suspicion; NELL1+ more common (KDIGO 2021 GN)
  • pregnancy_status
    demographic • used at CONTEXT
    Pregnancy-associated MN special considerations — CY/MMF teratogenic; rituximab risk-benefit case-by-case (KDIGO 2021 GN)
  • creatininerequired
    lab • used at CONTEXT
    eGFR + Δ-eGFR slope drives KDIGO 2021 GN risk tier (KDIGO 2021 GN)
  • urinalysisrequired
    lab • used at INITIAL_WORKUP
    Proteinuria + bland sediment expected in pure MN; active sediment → reconsider lupus class V (KDIGO 2021 GN)
  • upcrrequired
    lab • used at INITIAL_WORKUP
    Proteinuria quantification drives risk tier — <4 / 4-8 / >8 g/d cutoffs (KDIGO 2021 GN)
  • serum_albuminrequired
    lab • used at INITIAL_WORKUP
    Severe hypoalbuminemia <2.5 g/dL drives VTE anticoag decision (MN highest VTE risk) (KDIGO 2021 GN; Lin)
  • pla2r_antibodyrequired
    lab • used at INITIAL_WORKUP
    Anti-PLA2R antibody — ~70% of primary MN; titer correlates with activity + treatment response (Beck NEJM 2009)
  • hbv_serologyrequired
    lab • used at INITIAL_WORKUP
    HBV-associated MN — treat with entecavir/tenofovir; antiviral often improves MN (KDIGO 2021 GN)
  • hcv_serologyrequired
    lab • used at INITIAL_WORKUP
    HCV-associated MN — DAA therapy can improve (KDIGO 2021 GN)
  • anarequired
    lab • used at INITIAL_WORKUP
    ANA / anti-dsDNA / complement — exclude lupus class V membranous (route renal.lupus-nephritis.v1) (KDIGO 2021 GN)
  • drug_exposure_nsaid_captopril_goldrequired
    history • used at CONTEXT
    Drug-induced MN — NSAID, captopril, gold, anti-TNF, penicillamine — withdrawal (KDIGO 2021 GN)
  • malignancy_screen_symptomsrequired
    history • used at CONTEXT
    Malignancy-associated MN — solid tumors 5-10% adults (lung, GI, prostate, breast); age-appropriate cancer screen mandatory (KDIGO 2021 GN)
  • sbprequired
    vital • used at CONTEXT
    BP target <130/80; ACEi/ARB renoprotective (KDIGO 2021 GN)

12-phase flow (12)

  1. 1FRAME
    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: upcr, serum_albumin, creatinine, pla2r_antibody
    advance: MN biopsy + phenotype assigned (KDIGO 2021 GN)
  2. 2ENTRY
    Gradual nephrotic syndrome / adult-onset proteinuria / PLA2R+ / biopsy-confirmed MN (KDIGO 2021 GN)
    inputs: upcr, serum_albumin
    advance: Presentation phenotype identified (KDIGO 2021 GN)
  3. 3CONTEXT
    Capture age (malignancy screen if >65), pregnancy, drug exposure (NSAID/captopril/gold/anti-TNF/penicillamine), malignancy screen symptoms, BP (KDIGO 2021 GN)
    inputs: age, drug_exposure_nsaid_captopril_gold, malignancy_screen_symptoms, sbp
    advance: Context captured (KDIGO 2021 GN)
  4. 4RED_FLAGS
    Severe hypoalbuminemia + VTE (MN has highest VTE risk of any nephrotic cause); pulmonary embolism; renal vein thrombosis; rapid eGFR decline; spontaneous bacterial peritonitis (KDIGO 2021 GN)
    advance: No emergent phenotype OR routed appropriately (KDIGO 2021 GN)
  5. 5INITIAL_WORKUP
    UA + UPCR + albumin + lipids + BMP + anti-PLA2R + HBV/HCV/HIV + ANA + complement (lupus exclusion) + age-appropriate cancer screen (CT chest/abd/pelvis if NELL1+ or >65) (KDIGO 2021 GN)
    inputs: urinalysis, upcr, serum_albumin, creatinine, pla2r_antibody, hbv_serology, hcv_serology, ana
    actions: panel.renal, panel.cbc, panel.lft, panel.lipid
    advance: Initial labs complete + secondary causes screened (KDIGO 2021 GN)
  6. 6BRANCHING_WORKUP
    Renal biopsy with IF + EM + PLA2R IHC stain on tissue (more sensitive than serum); THSD7A / NELL1 IHC if PLA2R negative (KDIGO 2021 GN; Beck 2009)
    advance: Biopsy + IHC + antibody panel documented (KDIGO 2021 GN)
  7. 7DIFFERENTIAL
    Primary PLA2R+ / THSD7A+ / NELL1+ / lupus class V / HBV / HCV / malignancy / drug / pregnancy / other (KDIGO 2021 GN)
    advance: Differential resolved (KDIGO 2021 GN)
  8. 8RISK_STRATIFICATION
    KDIGO 2021 GN risk tier composite — low (eGFR>60 + UPCR<4 + albumin>3 + stable) / moderate (UPCR 4-8) / high (UPCR>8 or eGFR decline) / very-high (life-threatening complications) (KDIGO 2021 GN)
    inputs: creatinine, upcr, serum_albumin
    actions: calc.ckd_epi_2021
    advance: Risk tier set + treatment plan determined (KDIGO 2021 GN)
  9. 9TREATMENT
    Step 1 — low-risk conservative (RAS + salt + observe 6 mo); Step 2 — moderate-risk conservative + close obs + anticoag if alb<2.5; Step 3 — high-risk immunosuppression: rituximab (MENTOR Fervenza 2019) OR Ponticelli CY+steroid OR CNI; Step 4 — secondary cause treatment (lupus→renal.lupus-nephritis.v1; HBV→entecavir; HCV→DAA; malignancy→treat tumor; drug→withdraw); Step 5 — universal anticoag prophylaxis if alb<2.5 + statin + vaccinations (KDIGO 2021 GN)
    inputs: upcr, serum_albumin, creatinine
    advance: Treatment tier executed (KDIGO 2021 GN)
  10. 10DISPOSITION
    Outpatient primary; admit for severe nephrotic / VTE / PE / RVT / Ponticelli protocol initiation / rapid eGFR decline (KDIGO 2021 GN)
    advance: Disposition set (KDIGO 2021 GN)
  11. 11MONITORING
    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)
    inputs: creatinine, upcr, serum_albumin, pla2r_antibody
    actions: panel.renal
    advance: Monitoring schedule documented (KDIGO 2021 GN)
  12. 12FOLLOWUP
    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)
    advance: Long-term plan documented (KDIGO 2024 CKD)