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rheum.lupus-nephritis.core.v1PRODUCTION
rheum.lupus-nephritis.core.v1

Lupus nephritis

rheumatologyacutechronicadultpregnancy
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12/12 authored

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

Current phase

Frame

Detailed

SLE patient with renal involvement — organ-specific (renal-domain) flare engine. New-onset SLE without renal signs routes to rheum.sle.core.v1; non-renal flare to rheum.sle-flare.core.v1; pauci-immune GN to rheum.mpa.core.v1

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renal-domain LN scope confirmed

Patient inputs (13)

HCQ adherence, prior MMF/CYC/CNI/belimumab exposure informs induction choice + refractory pathway (KDIGO 2024)

MMF/CYC CONTRAINDICATED in pregnancy → AZA/tacrolimus; LN flare vs preeclampsia distinction (KDIGO 2024; EULAR)

Differentiates LN from primary GN / new-onset SLE; biopsy-proven prior LN informs relapse vs de novo class (KDIGO 2024)

Rising Cr / falling eGFR defines renal flare severity + drug dosing; rapidly rising = RPGN red flag (KDIGO 2024)

UPCR ≥0.5 g/g triggers biopsy + induction decision; >3 g/g nephrotic-range (KDIGO 2024)

Dysmorphic RBC / RBC casts / WBC = active sediment = proliferative LN signal (KDIGO 2024; ACR)

Low/falling C3/C4 supports active immune-complex LN but does NOT replace biopsy for therapy (EULAR/ERA-EDTA)

Rising titer correlates with renal flare; serology guides suspicion not class (EULAR/ERA-EDTA)

Hypoalbuminemia defines nephrotic syndrome (membranous class V) — thrombosis risk + anticoagulation decision (KDIGO 2024)

Concurrent hematologic flare; TMA screen (schistocytes/platelets); ISD myelotoxicity baseline (KDIGO 2024)

Severe HTN accelerates renal injury; BP/proteinuria target central to all classes (KDIGO 2024)

ISN/RPS 2018 class (I–VI) + activity/chronicity indices is THE therapy pivot — biopsy not serology decides (KDIGO 2024)

APS-nephropathy / TMA differential; nephrotic membranous + APS → anticoagulation; pregnancy risk (KDIGO 2024; ACR)

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

Severity triggers (6)

6 need judgement
  • informationallife_threateningrapidly_progressive_gn_aki
    Rapidly rising creatinine + active sediment ± crescents on biopsy (RPGN/AKI in LN)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationallife_threateningnephrotic_with_thrombosis_membranous_aps
    Nephrotic-range proteinuria + thrombosis (pure membranous class V + APS)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationallife_threateningconcurrent_severe_extrarenal_flare
    Concurrent NPSLE / diffuse alveolar hemorrhage / severe cytopenias with active LN
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalseverepregnancy_active_ln_vs_preeclampsia
    Pregnancy with active LN — distinguish renal flare from preeclampsia
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalsevererefractory_proliferative_class_iv
    Class IV proliferative LN not responding to adequate induction (no partial response by 3–6 mo / no complete by 12 mo)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalsevereinfection_mimicking_renal_flare
    Fever + renal signs + elevated CRP / positive cultures in immunosuppressed LN patient
    Trigger could not be auto-evaluated — needs clinician judgement.

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RISK_STRATIFICATIONoptionalDrives severity classification
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Recommended regimen

Lupus nephritis — ISN/RPS class-driven (biopsy not serology decides; 2024 KDIGO LN)
axis: lupus_nephritis_isn_rps_class_drivenstep 1 - Biopsy-driven class triage + universal background (ALL classes)
Selected step "Biopsy-driven class triage + universal background (ALL classes)" — Any biopsy-proven LN (class I–VI) — background applies before/with class-specific therapy
  • hydroxychloroquine
    first line
    antimalarial
    ≤5 mg/kg actual weight (typically 200–400 mg/d) • PO • daily
    triggers: any_lupus_nephritis_universal
    2024 KDIGO — HCQ for ALL LN unless contraindicated; renal response + flare + survival benefit; retina screen baseline + annual after 5 y
    rxcui 5521
  • lisinopril
    first line
    ACE_inhibitor
    Titrate to max tolerated for BP <130/80 + proteinuria reduction • PO • daily
    triggers: proteinuria_present, not_pregnant
    2024 KDIGO — RAAS blockade for all proteinuric LN; antiproteinuric + renoprotective; HOLD/avoid in pregnancy (fetotoxic) — substitute labetalol/nifedipine
    rxcui 29046
  • losartan
    contraindication substitute
    ARB
    Titrate to BP/proteinuria target • PO • daily
    triggers: ace_inhibitor_intolerant_cough, not_pregnant
    ARB alternative when ACEi-intolerant; same pregnancy contraindication
    rxcui 52175
  • inactivated vaccination pre-immunosuppression
    add on
    preventive_immunization
    Pneumococcal, influenza, COVID, recombinant zoster, HBV per status • IM/SC • per schedule before ISD
    triggers: planned_immunosuppression
    KDIGO/EULAR — vaccinate before immunosuppression; LIVE vaccines contraindicated once immunosuppressed

outpatient playbook — drug actions (4)

  1. 1. HCQ verify / restart
    ≤5 mg/kg actual weight • PO • daily
    trigger: Any LN
    Universal background — renal + survival benefit (KDIGO 2024)
  2. 2. RAAS blockade
    ACEi/ARB titrated to BP <130/80 + proteinuria reduction • PO • daily
    trigger: Proteinuria, not pregnant
    Antiproteinuric + renoprotective (KDIGO 2024)
  3. 3. reduced-dose GC + MMF (after biopsy)
    Prednisone 0.5–0.6 mg/kg taper + MMF 2–3 g/d • PO • daily / BID
    trigger: Biopsy-proven proliferative III/IV
    Class-driven induction, steroid-minimisation (KDIGO 2024)
  4. 4. triple-therapy add-on
    Belimumab 200 mg SC weekly OR voclosporin 23.7 mg PO BID • SC/PO • weekly / BID
    trigger: Better renal response sought
    BLISS-LN / AURORA (KDIGO 2024)

Auto-drafted A&P note

outpatient

Subjective

- Possible entry pathways: New proteinuria — UPCR ≥0.5 g/g in known/suspected SLE; Active urinary sediment — dysmorphic RBC / RBC casts; Rising creatinine / falling eGFR in SLE patient.

Objective

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

Assessment

**Lupus nephritis** (rheum.lupus-nephritis.core.v1).
Phenotype framing: Class I/II minimal/mesangial; class III/IV (±V) proliferative; pure class V membranous; class VI sclerotic. Distinguish from infection mimicking flare, drug toxicity (CNI/NSAID), TMA / APS-nephropathy, pauci-immune ANCA GN, hypertensive nephrosclerosis, preeclampsia in pregnancy
Scope: SLE patient with renal involvement — organ-specific (renal-domain) flare engine. New-onset SLE without renal signs routes to rheum.sle.core.v1; non-renal flare to rheum.sle-flare.core.v1; pauci-immune GN to rheum.mpa.core.v1

No severity triggers fired against current inputs.

Plan

Regimen axis: **Lupus nephritis — ISN/RPS class-driven (biopsy not serology decides; 2024 KDIGO LN)** — step "Biopsy-driven class triage + universal background (ALL classes)".
1. hydroxychloroquine ≤5 mg/kg actual weight (typically 200–400 mg/d) PO daily (antimalarial, first line) — 2024 KDIGO — HCQ for ALL LN unless contraindicated; renal response + flare + survival benefit; retina screen baseline + annual after 5 y
2. lisinopril Titrate to max tolerated for BP <130/80 + proteinuria reduction PO daily (ACE_inhibitor, first line) — 2024 KDIGO — RAAS blockade for all proteinuric LN; antiproteinuric + renoprotective; HOLD/avoid in pregnancy (fetotoxic) — substitute labetalol/nifedipine
3. losartan Titrate to BP/proteinuria target PO daily (ARB, contraindication substitute) — ARB alternative when ACEi-intolerant; same pregnancy contraindication
4. inactivated vaccination pre-immunosuppression Pneumococcal, influenza, COVID, recombinant zoster, HBV per status IM/SC per schedule before ISD (preventive_immunization, add on) — KDIGO/EULAR — vaccinate before immunosuppression; LIVE vaccines contraindicated once immunosuppressed

Setting playbook (outpatient) — Detect renal flare early, expedite biopsy, start class-driven induction with steroid-minimisation, exclude infection / drug mimic, nephrology + rheumatology co-management
5. HCQ verify / restart ≤5 mg/kg actual weight PO daily — Any LN (Universal background — renal + survival benefit (KDIGO 2024))
6. RAAS blockade ACEi/ARB titrated to BP <130/80 + proteinuria reduction PO daily — Proteinuria, not pregnant (Antiproteinuric + renoprotective (KDIGO 2024))
7. reduced-dose GC + MMF (after biopsy) Prednisone 0.5–0.6 mg/kg taper + MMF 2–3 g/d PO daily / BID — Biopsy-proven proliferative III/IV (Class-driven induction, steroid-minimisation (KDIGO 2024))
8. triple-therapy add-on Belimumab 200 mg SC weekly OR voclosporin 23.7 mg PO BID SC/PO weekly / BID — Better renal response sought (BLISS-LN / AURORA (KDIGO 2024))

Non-pharmacologic actions:
- Expedite percutaneous renal biopsy for ISN/RPS class + indices (KDIGO 2024)
- Sun protection + vaccination before immunosuppression (EULAR 2023)
- Bone protection (calcium, vitamin D, DEXA, bisphosphonate per cumulative steroid) (ACR)
- Cardiovascular risk modification (BP, lipids, ASCVD) (KDIGO 2024)
- Dietary sodium restriction for proteinuria/BP (KDIGO 2024)

AVOID / contraindication checks:
- MMF and CYC contraindicated in pregnancy switch to AZA or tacrolimus (KDIGO 2024; EULAR 2023)
- Live vaccines contraindicated on immunosuppression vaccinate before ISD (KDIGO 2024)
- CYC gonadotoxicity fertility counsel and MESNA uroprotection (Houssiau Euro Lupus 2002; ACR)
- Therapy is biopsy class driven not serology driven (KDIGO 2024; EULAR/ERA EDTA)
- HCQ retinal screen baseline and annual after 5y (AAO 2024; EULAR 2023)
- ACEi ARB contraindicated in pregnancy substitute labetalol or nifedipine (KDIGO 2024)
- Voclosporin block with strong CYP3A inhibitors monitor eGFR and BP (AURORA Rovin 2021)
- Rituximab obinutuzumab HBV screen pre dose (KDIGO 2024)
- Azathioprine TPMG TPMT test pre prescription (EULAR 2023)
- PJP prophylaxis on prednisone 20mg 4 weeks or CYC (EULAR 2023)

Monitoring

Regimen monitoring:
- UPCR creatinine eGFR q2 weeks during induction then q1-3 months (KDIGO 2024)
- anti-dsDNA C3 C4 q1-3 months (EULAR/ERA-EDTA 2024)
- BP and proteinuria to target <130/80 and UPCR <0.5-0.7 (KDIGO 2024)
- CNI trough voclosporin tacrolimus and eGFR surveillance (AURORA Rovin 2021)
- CBC LFT for MMF AZA CYC myelotoxicity (EULAR 2023)
- CYC cytopenia nadir at 7-14 days (Houssiau Euro-Lupus 2002)
- infection surveillance CMV HSV PCR if immunosuppressed (EULAR 2023)
- pregnancy renal and fetal surveillance distinguish flare vs preeclampsia (KDIGO 2024)
- complete renal response by 12 months partial by 3-6 months (KDIGO 2024)
- HCQ retina baseline then annual after 5 years (AAO 2024; EULAR 2023)

Setting (outpatient) monitoring:
- UPCR, creatinine, eGFR q2-4 weeks during titration (KDIGO 2024)
- C3/C4, anti-dsDNA q1-3 months (EULAR/ERA-EDTA 2024)
- CNI trough + eGFR if voclosporin/tacrolimus (AURORA Rovin 2021)
- HCQ retina baseline + annual after 5 years (AAO 2024)

Follow-up plan: Prolonged maintenance ≥3 yr (MMF/AZA + low-dose GC + HCQ); treat-to-target proteinuria <0.5–0.7 g/g; CV + infection risk modification; vaccinations; ESKD/transplant planning + post-transplant LN recurrence surveillance; pregnancy planning when stable ≥6 mo on compatible drugs
- Close-out criterion: long-term maintenance + ESKD/pregnancy plan documented

Monitoring phase: UPCR + creatinine + eGFR (q2 wk during induction, then q1–3 mo), anti-dsDNA / C3-C4 q1–3 mo, BP + proteinuria target, CNI trough levels (voclosporin/tacrolimus), CBC/LFT for ISD myelotoxicity, CYC nadir at 7–14 d, infection surveillance, HCQ retina screen, pregnancy renal + fetal surveillance

Disposition

Current setting: outpatient — Detect renal flare early, expedite biopsy, start class-driven induction with steroid-minimisation, exclude infection / drug mimic, nephrology + rheumatology co-management

Disposition criteria:
- Continue outpatient co-management unless RPGN, nephrotic+thrombosis, severe HTN, or severe extrarenal flare (KDIGO 2024)

Escalation triggers (move to higher acuity):
- Rapidly rising creatinine / RPGN then ED + urgent inpatient biopsy + pulse MP (KDIGO 2024)
- Nephrotic + thrombosis (membranous + APS) then admit + anticoagulate (KDIGO 2024)
- Severe uncontrolled HTN then admit (KDIGO 2024)
- Concurrent NPSLE / alveolar hemorrhage / severe cytopenias then ED + ICU (EULAR 2023)
- Pregnancy with active LN then MFM co-management urgently (KDIGO 2024)

Earlier-Return Triggers

Return-precaution thresholds (watch for):
- [LIFE_THREATENING] Rapidly rising creatinine + active sediment ± crescents on biopsy (RPGN/AKI in LN)
- [LIFE_THREATENING] Nephrotic-range proteinuria + thrombosis (pure membranous class V + APS)
- [LIFE_THREATENING] Concurrent NPSLE / diffuse alveolar hemorrhage / severe cytopenias with active LN

Citations

- 2024 KDIGO Lupus Nephritis Guideline + 2023/2024 EULAR/ERA-EDTA LN recommendations + ACR; AURORA voclosporin; BLISS-LN belimumab; Euro-Lupus [PMID:38182286](https://pubmed.ncbi.nlm.nih.gov/38182286/)
- Cited evidence (PMID 37827694) [PMID:37827694](https://pubmed.ncbi.nlm.nih.gov/37827694/)
- Cited evidence (PMID 32220834) [PMID:32220834](https://pubmed.ncbi.nlm.nih.gov/32220834/)
- Cited evidence (PMID 33971155) [PMID:33971155](https://pubmed.ncbi.nlm.nih.gov/33971155/)
- Cited evidence (PMID 37466424) [PMID:37466424](https://pubmed.ncbi.nlm.nih.gov/37466424/)

Last reconciled with current guidelines: 2026-05-22.
References
  • 2024 KDIGO Lupus Nephritis Guideline + 2023/2024 EULAR/ERA-EDTA LN recommendations + ACR; AURORA voclosporin; BLISS-LN belimumab; Euro-Lupus — PMID:38182286
  • Cited evidence (PMID 37827694) — PMID:37827694
  • Cited evidence (PMID 32220834) — PMID:32220834
  • Cited evidence (PMID 33971155) — PMID:33971155
  • Cited evidence (PMID 37466424) — PMID:37466424