Lupus Nephritis Management (ACR 2024)

Algorithm Steps

1. ▶

   Start

   SLE Patient - Kidney Evaluation

   Patient with SLE requiring renal screening or known LN

   1. ●

      Action

      Screening for Lupus Nephritis

      Strong recommendation

      • Screen q6-12 months if no known kidney disease
      • Screen at extrarenal flares
      • Urine protein/creatinine ratio (UPCR)
      • Urinalysis with microscopy
      • Serum creatinine and eGFR
      1. ◆

         Decision

         Proteinuria >0.5 g/g or Impaired eGFR?

         Unexplained by other causes

         1. ●

            Action

            Kidney Biopsy

            Conditional recommendation

            • Biopsy if UPCR >0.5 g/g and/or unexplained impaired eGFR
            • Classify per ISN/RPS 2003 (or 2018 revision)
            • Assess activity index and chronicity index
            • Identify concurrent pathology (TMA, APS nephropathy)
            1. ◆

               Decision

               LN Class?

               Based on kidney biopsy findings

               • Class I/II: Minimal/mesangial - mild disease
               • Class III: Focal proliferative (<50% glomeruli)
               • Class IV: Diffuse proliferative (≥50% glomeruli)
               • Class V: Membranous (can be pure or combined)
               • Class VI: Sclerotic (>90% sclerosis) - limited treatment options
               1. ●

                  Action

                  Class I/II LN

                  Minimal/mesangial disease

                  • Usually no immunosuppression needed for LN itself
                  • Treat extrarenal SLE as indicated
                  • HCQ continuation mandatory
                  • ACEi/ARB if proteinuria or hypertension
                  • Monitor for progression
                  1. ✓

                     Outcome

                     LN Controlled

                     Complete response, stable renal function, maintenance therapy

               2. ●

                  Action

                  Class III/IV LN (Proliferative)

                  Triple immunosuppressive therapy

                  • Glucocorticoid + TWO additional IS agents (Conditional):
                  • Option 1: MMF + Belimumab
                  • Option 2: MMF + Calcineurin inhibitor (voclosporin or tacrolimus)
                  • Option 3: Cyclophosphamide-based (Euro-Lupus or NIH regimen)
                  • HCQ continuation mandatory
                  1. ●

                     Action

                     Glucocorticoid Protocol

                     Lower-dose regimen (Conditional)

                     • IV pulse methylprednisolone 250-1000mg x1-3 days
                     • Then oral prednisone 0.5 mg/kg/day (MAX 40 mg/day)
                     • TAPER to ≤5 mg/day by 6 months
                     • Goal: lowest effective dose or discontinuation
                     • Add IS early to enable GC reduction
                     1. ⚠

                        Warning

                        ⚠️ Voclosporin Considerations

                        FDA-approved for LN

                        • 23.7 mg BID (fixed dose, not weight-based)
                        • Avoid if eGFR <45 mL/min/1.73m²
                        • Monitor for nephrotoxicity
                        • Drug interactions: avoid strong CYP3A4 inhibitors
                        • Hypertension management
                        1. ◆

                           Decision

                           Response Assessment

                           Monitor proteinuria, creatinine, urinalysis

                           • Complete response: UPCR <0.5 g/g + stable eGFR
                           • Partial response: ≥50% reduction in proteinuria
                           • If not in complete response: check q3 months (Strong)
                           • If sustained complete response: check q3-6 months
                           1. ●

                              Action

                              Maintenance Therapy

                              3-5 years for complete responders

                              • Continue MMF (or azathioprine if MMF intolerant)
                              • Continue HCQ (lifelong in SLE)
                              • May continue belimumab or voclosporin if used in induction
                              • Minimize/discontinue glucocorticoids
                              • Regular monitoring for flares and drug toxicity
                           2. ●

                              Action

                              Refractory LN

                              Failure to respond or relapse

                              • Consider repeat biopsy to assess activity vs chronicity
                              • Switch induction regimen (e.g., CYC to MMF or vice versa)
                              • Add rituximab (off-label but evidence-supported)
                              • Intensify CNI if not used
                              • Clinical trial or transplant evaluation if ESRD
                              1. ⚠

                                 Warning

                                 Nephrology Co-Management

                                 Refractory disease, declining eGFR, ESRD planning

               3. ●

                  Action

                  Pure Class V LN (Membranous)

                  If proteinuria >1 g/g

                  • Glucocorticoid + MMF + Calcineurin inhibitor (Conditional)
                  • Voclosporin preferred CNI (FDA approved)
                  • Alternative: MMF alone or with rituximab
                  • HCQ continuation mandatory
                  • ACEi/ARB for proteinuria reduction
         2. ●

            Action

            Supportive Measures

            For all LN patients

            • ACEi or ARB for proteinuria/hypertension
            • BP target <130/80 mmHg
            • Lipid management (statins if indicated)
            • Vitamin D supplementation
            • Infection prophylaxis during intense IS
            • Bone protection if prolonged GC use