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renal.lupus-nephritis.v1PRODUCTION
renal.lupus-nephritis.v1

Lupus Nephritis (ISN/RPS Classes I-VI)

nephrologychronicacuteadult
Hard-required inputs
0 / 10
Care setting:

Encounter flow

12/12 authored

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

Current phase

Frame

Detailed

Confirm SLE per EULAR/ACR 2019 + renal involvement; biopsy ISN/RPS class drives therapy (KDIGO 2024 GN; ISN/RPS 2003)

Inputs
3
Actions
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Advance rule
Set
Advance when

SLE confirmed + renal involvement documented (KDIGO 2024 GN)

Patient inputs (10)

Age informs induction agent selection (CY fertility risk in young women; voclosporin/belimumab approved adults) (KDIGO 2024 GN; EULAR/ACR 2019)

Pregnancy + LN special considerations — MMF/CY teratogenic; azathioprine + HCQ + steroids preferred (EULAR/ACR 2019)

eGFR + AKI vs CKD trajectory drives urgency + agent dosing (KDIGO 2024 GN)

BP target <130/80 (or <120/70 if high CV risk); ACEi/ARB renoprotection (KDIGO 2024 GN)

EULAR/ACR 2019 SLE criteria threshold — ANA ≥1:80 plus weighted features ≥10 (EULAR/ACR 2019)

Active sediment + proteinuria define renal involvement (KDIGO 2024 GN)

Proteinuria quantification drives class III/IV/V escalation; nephrotic-range >3500 mg/d (KDIGO 2024 GN)

Low C3/C4 marks active LN flare; tracks induction response (KDIGO 2024 GN; EULAR/ACR 2019)

Active disease marker; rises in LN flare; tracks induction response (EULAR/ACR 2019)

Diagnostic anchor for SLE per EULAR/ACR 2019 classification (EULAR/ACR 2019 PMID 31385462)

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Severity triggers (12)

12 need judgement
  • informationallife_threateningclass_4_diffuse_proliferative
    ISN/RPS Class IV — diffuse proliferative LN; ≥50% glomeruli involved (most severe class; aggressive induction mandatory) (ISN/RPS 2003; KDIGO 2024 GN)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationallife_threateningmixed_class_3_5_or_4_5
    Mixed proliferative + membranous lupus — Class III+V or IV+V; combines proliferative and nephrotic phenotypes (ISN/RPS 2003; KDIGO 2024 GN)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationallife_threateningtma_on_ln_overlap
    TMA-on-LN overlap — microangiopathic hemolytic anemia + thrombocytopenia + AKI on LN background (anti-phospholipid syndrome, atypical HUS, or LN-MAT); PLEX + immunosuppression escalation (EULAR/ACR 2019)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationallife_threateningpulmonary_renal_in_lupus
    Pulmonary-renal syndrome in LN — alveolar hemorrhage + AKI; route renal.rpgn.core.v1 for PLEX + ICU protocol (KDIGO 2024 GN; PEXIVAS 2020)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalsevereclass_3_focal_proliferative
    ISN/RPS Class III — focal proliferative LN; <50% glomeruli involved by endocapillary or extracapillary GN ± mesangial alterations (ISN/RPS 2003; KDIGO 2024 GN)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalsevereclass_5_membranous_lupus
    ISN/RPS Class V — pure membranous lupus; subepithelial immune deposits ± mesangial alterations; nephrotic presentation common (ISN/RPS 2003; KDIGO 2024 GN)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalsevereclass_6_advanced_sclerotic
    ISN/RPS Class VI — advanced sclerotic LN; ≥90% globally sclerotic glomeruli without residual activity (ISN/RPS 2003; KDIGO 2024 GN)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalseverenephrotic_range_proteinuria_ge_3500mg
    Nephrotic-range proteinuria ≥3.5 g/d in LN — guarded prognosis; CNI add-on (voclosporin AURORA-1) often indicated (KDIGO 2024 GN; Rovin Lancet 2021)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalsevererefractory_to_induction_2_or_more_agents
    Refractory LN — persistent disease despite ≥2 induction agents (MMF + CY tried OR MMF + voclosporin/belimumab tried); consider rituximab + repeat biopsy (KDIGO 2024 GN; EULAR/ACR 2019)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalseverepregnancy_with_ln
    Pregnancy in LN — MMF/CY teratogenic; switch to AZA + HCQ + low-dose steroid 3-6 months pre-conception; close maternal-fetal medicine + nephrology + rheumatology comanagement (EULAR/ACR 2019; KDIGO 2024 GN)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalmildisn_rps_class_1_minimal_mesangial
    ISN/RPS Class I — minimal mesangial lupus nephritis; mesangial immune deposits on IF without histologic abnormality on LM (ISN/RPS 2003; KDIGO 2024 GN)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalmildclass_2_mesangial_proliferative
    ISN/RPS Class II — mesangial proliferative LN; purely mesangial hypercellularity or expansion (ISN/RPS 2003; KDIGO 2024 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

Lupus nephritis class-stratified induction + maintenance (KDIGO 2024 GN; EULAR/ACR 2019 SLE; ALMS Appel JASN 2009; BLISS-LN Furie NEJM 2020; AURORA-1 Rovin Lancet 2021)
axis: lupus_nephritis_induction_maintenancestep step_universal_hcq - Universal — Hydroxychloroquine (HCQ) for ALL LN patients (reduces flare + improves renal survival)
Selected step "Universal — Hydroxychloroquine (HCQ) for ALL LN patients (reduces flare + improves renal survival)" — All LN patients regardless of class (KDIGO 2024 GN; EULAR/ACR 2019)
  • hydroxychloroquine
    first line
    antimalarial_immunomodulator
    5 mg/kg/day PO (max 400 mg/day) • PO • daily
    triggers: lupus_nephritis_any_class
    KDIGO 2024 GN + EULAR/ACR 2019 — HCQ reduces flare + improves renal survival + lowers thrombosis + lipid benefit; annual ophthalmology screen for retinopathy after 5 years
    rxcui 5521

outpatient playbook — drug actions (8)

  1. 1. hydroxychloroquine
    5 mg/kg/day (max 400 mg/day) • PO • daily
    trigger: All LN lifelong
    KDIGO 2024 GN; EULAR/ACR 2019
  2. 2. MMF induction or maintenance
    Induction 2-3 g/d divided BID; maintenance 1-2 g/d • PO • BID
    trigger: Class III/IV/V
    ALMS Appel JASN 2009 PMID 19369404
  3. 3. belimumab IV/SC add-on
    10 mg/kg IV q4w (after loading) or 200 mg SC weekly • IV or SC • q4w IV or weekly SC
    trigger: Active LN on standard induction
    BLISS-LN Furie NEJM 2020 PMID 32937045; FDA 2020
  4. 4. voclosporin add-on
    23.7 mg PO BID with food • PO • BID
    trigger: Proteinuria persistent on MMF + steroid
    AURORA-1 Rovin Lancet 2021 PMID 33971155; FDA 2021
  5. 5. prednisone taper
    Per protocol — 0.5 mg/kg → wean to ≤5 mg/d • PO • daily
    trigger: Active taper or maintenance
    KDIGO 2024 GN
  6. 6. ACEi/ARB max-dose
    Lisinopril 10-40 mg PO daily • PO • daily
    trigger: Proteinuria or HTN
    KDIGO 2024 GN renoprotection
  7. 7. SGLT2i (empa/dapa) emerging adjunct
    10 mg PO daily • PO • daily
    trigger: Persistent proteinuria post-induction
    EMPA-KIDNEY (KDIGO 2024 CKD)
  8. 8. TMP-SMX prophylaxis
    160/800 PO M-W-F or 80/400 daily • PO • 3x/week or daily
    trigger: Active immunosuppression
    PJP prevention (KDIGO 2024 GN)

Auto-drafted A&P note

outpatient

Subjective

- Possible entry pathways: New proteinuria (UPCR >0.5 g/g) in SLE patient (KDIGO 2024 GN; EULAR/ACR 2019); Active urinary sediment (RBC casts, dysmorphic RBCs) in SLE (KDIGO 2024 GN); AKI with low C3/C4 + positive ANA/anti-dsDNA → class III/IV lupus nephritis suspected (KDIGO 2024 GN).

Objective

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

Assessment

**Lupus Nephritis (ISN/RPS Classes I-VI)** (renal.lupus-nephritis.v1).
Phenotype framing: LN Class I-VI / mixed Class III+V or IV+V / TMA-on-LN / drug-induced lupus / overlap with other GN (anti-GBM, ANCA) (KDIGO 2024 GN)
Scope: Confirm SLE per EULAR/ACR 2019 + renal involvement; biopsy ISN/RPS class drives therapy (KDIGO 2024 GN; ISN/RPS 2003)

No severity triggers fired against current inputs.

Plan

Regimen axis: **Lupus nephritis class-stratified induction + maintenance (KDIGO 2024 GN; EULAR/ACR 2019 SLE; ALMS Appel JASN 2009; BLISS-LN Furie NEJM 2020; AURORA-1 Rovin Lancet 2021)** — step "Universal — Hydroxychloroquine (HCQ) for ALL LN patients (reduces flare + improves renal survival)".
1. hydroxychloroquine 5 mg/kg/day PO (max 400 mg/day) PO daily (antimalarial_immunomodulator, first line) — KDIGO 2024 GN + EULAR/ACR 2019 — HCQ reduces flare + improves renal survival + lowers thrombosis + lipid benefit; annual ophthalmology screen for retinopathy after 5 years

Setting playbook (outpatient) — Primary management setting — biopsy follow-up, induction → maintenance → long-term remission; q3-6 month renal + rheumatology visits; CV-risk + bone + fertility (KDIGO 2024 GN; EULAR/ACR 2019)
2. hydroxychloroquine 5 mg/kg/day (max 400 mg/day) PO daily — All LN lifelong (KDIGO 2024 GN; EULAR/ACR 2019)
3. MMF induction or maintenance Induction 2-3 g/d divided BID; maintenance 1-2 g/d PO BID — Class III/IV/V (ALMS Appel JASN 2009 PMID 19369404)
4. belimumab IV/SC add-on 10 mg/kg IV q4w (after loading) or 200 mg SC weekly IV or SC q4w IV or weekly SC — Active LN on standard induction (BLISS-LN Furie NEJM 2020 PMID 32937045; FDA 2020)
5. voclosporin add-on 23.7 mg PO BID with food PO BID — Proteinuria persistent on MMF + steroid (AURORA-1 Rovin Lancet 2021 PMID 33971155; FDA 2021)
6. prednisone taper Per protocol — 0.5 mg/kg → wean to ≤5 mg/d PO daily — Active taper or maintenance (KDIGO 2024 GN)
7. ACEi/ARB max-dose Lisinopril 10-40 mg PO daily PO daily — Proteinuria or HTN (KDIGO 2024 GN renoprotection)
8. SGLT2i (empa/dapa) emerging adjunct 10 mg PO daily PO daily — Persistent proteinuria post-induction (EMPA-KIDNEY (KDIGO 2024 CKD))
9. TMP-SMX prophylaxis 160/800 PO M-W-F or 80/400 daily PO 3x/week or daily — Active immunosuppression (PJP prevention (KDIGO 2024 GN))

Non-pharmacologic actions:
- Annual vaccination per ACIP 2026 — flu, COVID, PCV20, HBV; AVOID live vaccines on immunosuppression (KDIGO 2024 GN)
- Sun protection counselling (EULAR/ACR 2019)
- Smoking cessation (EULAR/ACR 2019)
- CV-risk modification — statin per ACC/AHA Lipid 2026 (KDIGO 2024 GN)
- Bone health Ca + vit D + bisphosphonate per FRAX (KDIGO 2024 GN)
- Contraception + pre-conception planning (switch MMF → AZA 3-6 months pre-conception) (EULAR/ACR 2019)
- Cervical/skin cancer surveillance (long-term immunosuppression; KDIGO 2024 GN)
- Patient action card — flare red-flags reinforced (KDIGO 2024 GN)

AVOID / contraindication checks:
- Hcq annual ophthalmology screen after 5 years (EULAR/ACR 2019)
- Cy fertility counseling mesna uroprotect (KDIGO 2024 GN; ACR ANCA 2021)
- Mmf teratogenic pregnancy prevention rems (KDIGO 2024 GN)
- Voclosporin bp monitoring interactions (AURORA 1 Rovin Lancet 2021)
- Belimumab vaccinate prior no live vaccines (BLISS LN Furie NEJM 2020)
- Steroid pjp prophylaxis and bone health (KDIGO 2024 GN)
- Tmp smx prophylaxis during induction (KDIGO 2024 GN)
- Hbv reactivation screen pre immunosuppression (KDIGO 2024 GN)
- Strongyloides screen pre steroid (KDIGO 2024 GN)

Monitoring

Regimen monitoring:
- UPCR + UACR q1-3 months on induction (KDIGO 2024 GN)
- eGFR + Cr q1-3 months (KDIGO 2024 GN)
- Complement (C3/C4) q1-3 months — tracks induction response (EULAR/ACR 2019)
- Anti-dsDNA q3 months — flare surveillance (EULAR/ACR 2019)
- CBC q1-2 weeks during CY induction (KDIGO 2024 GN)
- BP at each visit, target <130/80 (KDIGO 2024 GN)
- BMP for hyperkalemia on ACEi/ARB; CK if myopathy concerns (KDIGO 2024 GN)
- Voclosporin BP + eGFR monitoring (AURORA-1)
- HCQ ophthalmology screen baseline + annual after 5 years (EULAR/ACR 2019)
- DEXA at 6-12 months on steroid (KDIGO 2024 GN)
- Annual cancer screen on long-term immunosuppression (KDIGO 2024 GN)

Setting (outpatient) monitoring:
- UPCR + eGFR + complement + anti-dsDNA q1-3 months (KDIGO 2024 GN; EULAR/ACR 2019)
- CBC + BMP + LFTs per agent schedule (KDIGO 2024 GN)
- BP at each visit (KDIGO 2024 GN)
- Voclosporin BP + eGFR + drug interactions (AURORA-1)
- Annual eye exam after 5 years HCQ (EULAR/ACR 2019)
- DEXA q1-2 years on steroid (KDIGO 2024 GN)

Follow-up plan: Maintenance immunosuppression 3-5 years; CV-risk modification (statin, BP, glycemic); contraception/fertility planning; vaccination per ACIP 2026 (avoid live vaccines on immunosuppression); pregnancy planning post-remission (KDIGO 2024 GN; EULAR/ACR 2019)
- Close-out criterion: Long-term plan documented (KDIGO 2024 GN)

Monitoring phase: UPCR + eGFR + complement + anti-dsDNA q1-3 months during induction; CBC for CY/MMF toxicity; infection surveillance; flare detection (KDIGO 2024 GN; EULAR/ACR 2019)

Disposition

Current setting: outpatient — Primary management setting — biopsy follow-up, induction → maintenance → long-term remission; q3-6 month renal + rheumatology visits; CV-risk + bone + fertility (KDIGO 2024 GN; EULAR/ACR 2019)

Disposition criteria:
- Continue outpatient q1-3 months if stable (KDIGO 2024 GN)
- Admit for biopsy or induction protocol if newly diagnosed Class III/IV/V (KDIGO 2024 GN)
- Transition to transplant clinic if approaching ESRD (KDIGO 2024 CKD)

Escalation triggers (move to higher acuity):
- Rising UPCR or falling eGFR on induction → re-biopsy + escalate (belimumab / voclosporin / switch CY↔MMF) (KDIGO 2024 GN)
- Active sediment + rising anti-dsDNA + falling complement → flare → admit if AKI (EULAR/ACR 2019)
- New fever / leukopenia / hypoxia → ED with immunosuppressed alert (KDIGO 2024 GN)
- New chest pain / hemoptysis / pulmonary-renal → ED + ICU triage (KDIGO 2024 GN)
- CKD progression toward ESRD → transplant evaluation (KDIGO 2024 CKD)

Earlier-Return Triggers

Return-precaution thresholds (watch for):
- [LIFE_THREATENING] ISN/RPS Class IV — diffuse proliferative LN; ≥50% glomeruli involved (most severe class; aggressive induction mandatory) (ISN/RPS 2003; KDIGO 2024 GN)
- [LIFE_THREATENING] Mixed proliferative + membranous lupus — Class III+V or IV+V; combines proliferative and nephrotic phenotypes (ISN/RPS 2003; KDIGO 2024 GN)
- [LIFE_THREATENING] TMA-on-LN overlap — microangiopathic hemolytic anemia + thrombocytopenia + AKI on LN background (anti-phospholipid syndrome, atypical HUS, or LN-MAT); PLEX + immunosuppression escalation (EULAR/ACR 2019)

Citations

- KDIGO 2021 Glomerular Diseases guideline (lupus nephritis chapter; KDIGO 2024 GN update pending) + EULAR/ACR 2019 SLE classification criteria + ALMS Appel JASN 2009 (MMF vs CY induction) + BLISS-LN Furie NEJM 2020 (belimumab adjunct) + AURORA-1 Rovin Lancet 2021 (voclosporin adjunct) + Euro-Lupus low-dose IV CY regimen [PMID:34556256](https://pubmed.ncbi.nlm.nih.gov/34556256/)
- Cited evidence (PMID 31385462) [PMID:31385462](https://pubmed.ncbi.nlm.nih.gov/31385462/)
- Cited evidence (PMID 32937045) [PMID:32937045](https://pubmed.ncbi.nlm.nih.gov/32937045/)
- Cited evidence (PMID 33971155) [PMID:33971155](https://pubmed.ncbi.nlm.nih.gov/33971155/)
- Cited evidence (PMID 19369404) [PMID:19369404](https://pubmed.ncbi.nlm.nih.gov/19369404/)

Last reconciled with current guidelines: 2026-05-22.
References
  • KDIGO 2021 Glomerular Diseases guideline (lupus nephritis chapter; KDIGO 2024 GN update pending) + EULAR/ACR 2019 SLE classification criteria + ALMS Appel JASN 2009 (MMF vs CY induction) + BLISS-LN Furie NEJM 2020 (belimumab adjunct) + AURORA-1 Rovin Lancet 2021 (voclosporin adjunct) + Euro-Lupus low-dose IV CY regimen — PMID:34556256
  • Cited evidence (PMID 31385462) — PMID:31385462
  • Cited evidence (PMID 32937045) — PMID:32937045
  • Cited evidence (PMID 33971155) — PMID:33971155
  • Cited evidence (PMID 19369404) — PMID:19369404