In United States, lupus Nephritis is managed by nephrologists. Lupus nephritis is glomerular injury caused by systemic lupus erythematosus, affecting roughly 40-60% of adults and 60-80% of children with SLE within 5 years of diagnosis. Immune complexes containing anti-double-stranded DNA antibody and nuclear antigens deposit in the glomerulus, triggering complement activation, mesangial proliferation, and capillary wall injury.
Lupus nephritis (ICD-10: M32.14, N08) is glomerular injury secondary to systemic lupus erythematosus, caused by deposition of circulating immune complexes containing anti-nuclear and anti-DNA antibodies in the kidney. The disease is histologically heterogeneous and is classified by the 2018 revised International Society of Nephrology/Renal Pathology Society (ISN/RPS) system into six classes: class I (minimal mesangial), class II (mesangial proliferative), class III (focal, less than 50% of glomeruli involved), class IV (diffuse, 50% or more of glomeruli involved, the most severe proliferative form), class V (membranous), and class VI (advanced sclerosing, more than 90% globally sclerosed). Classes III and IV are subclassified as active (A), chronic (C), or both, and class V may coexist with III or IV. Immunofluorescence typically shows a 'full-house' pattern (IgG, IgA, IgM, C3, and C1q) — a feature highly suggestive of lupus when present.
The key symptoms of Lupus Nephritis are: Foamy urine and ankle swelling reflecting proteinuria above 0.5-3.5 g/day, the most common presenting feature., Cola-coloured or visibly bloody urine during severe class III or IV flares, with dysmorphic red blood cells and red cell casts on microscopy., Bilateral lower extremity oedema, periorbital swelling, and weight gain from nephrotic syndrome in class V or mixed disease., New or worsening hypertension, often resistant to single-agent therapy, in 30-50% of patients at presentation., Fatigue, malaise, and reduced exercise tolerance from anemia of chronic disease, uremia, or active lupus., Malar (butterfly) rash, photosensitive cutaneous lupus, oral ulcers, alopecia, and arthralgia signalling concurrent systemic lupus activity., Pleuritic chest pain and serositis with pleural or pericardial effusions during severe SLE flares..
Diagnosis begins with routine SLE surveillance — urinalysis, urine protein-to-creatinine ratio, blood pressure, serum creatinine, complement (C3 and C4), and anti-dsDNA at every clinic visit. Suspected lupus nephritis is defined by KDIGO 2024 and ACR criteria as proteinuria above 0.5 g/day (or urine protein-to-creatinine ratio above 500 mg/g) and/or active urinary sediment (red cells, red cell casts) in a patient meeting SLE classification criteria. A kidney biopsy is recommended in nearly all patients with proteinuria above 0.5 g/day to confirm the diagnosis, define the ISN/RPS class, score activity and chronicity, and exclude alternative or coexisting disease (lupus podocytopathy, APOL1 nephropathy, thrombotic microangiopathy). Light microscopy assesses glomerular and tubulointerstitial changes; immunofluorescence usually shows the characteristic full-house pattern (IgG, IgA, IgM, C3, C1q); electron microscopy localises deposits (mesangial, subendothelial, subepithelial). Class III, IV, V, and mixed lesions carry distinct treatment implications. Adjunctive investigations include antiphospholipid antibody screen (anticardiolipin, anti-beta-2-glycoprotein-I, lupus anticoagulant), thrombotic microangiopathy markers (haptoglobin, LDH, blood film), and viral hepatitis screen before immunosuppression. The activity and chronicity indices (NIH or modified) guide intensity of induction therapy.
Prognosis has improved substantially over the past 50 years. Five-year renal survival is now above 90% and 10-year survival 80-85% with modern induction-maintenance regimens. Complete renal response (proteinuria under 0.5 g/day, normal creatinine) at 6-12 months is the strongest predictor of long-term outcome — patients in complete response have under 5% risk of ESKD at 10 years, versus 30-40% in patients with no response. Class IV disease, mixed class IV/V, high chronicity index, hypertension, Black ancestry, and male sex predict worse outcomes. Cardiovascular disease, infection, and ESKD account for most premature deaths. Pregnancy outcomes are good when nephritis has been quiescent for at least 6 months pre-conception. Approximately 10-30% of patients still progress to ESKD within 10-15 years, but kidney transplantation offers excellent results with under 10% recurrence and 5-year graft survival above 80%.
Lupus nephritis is managed jointly by nephrology and rheumatology. Early specialist referral allows timely biopsy, ISN/RPS classification, and induction therapy — delays beyond 3 months from proteinuria onset are associated with worse renal survival. Refractory or rapidly progressive disease, pregnancy, and end-stage kidney disease should be managed at tertiary centres.
Find specialists →Proteinuria begins to fall within 4-8 weeks of starting induction therapy. Complete renal response (proteinuria under 0.5 g/g and normal creatinine) is achieved by 6-12 months in 25-45% with mycophenolate plus glucocorticoids and 40-50% when belimumab or voclosporin is added. Maintenance therapy continues for at least 3-5 years; relapses occur in 20-40% over 5 years and are managed with reinduction.
Aerobic exercise at moderate intensity (150 minutes per week) reduces fatigue and improves cardiovascular outcomes in SLE. Add two resistance sessions to offset steroid-induced muscle loss and osteoporosis. Avoid extreme exertion during active flares. Patients with eGFR under 30 mL/min/1.73 m2 should adjust intensity and discuss exercise plans with their renal team.
Choose a nephrologist with a percutaneous biopsy programme and a rheumatologist experienced in SLE classification and biologic therapy. For pregnant or pregnancy-planning patients, identify a high-risk obstetric unit experienced in lupus nephritis. Ask whether the centre uses lower-dose glucocorticoid protocols and has access to belimumab and voclosporin.
Medically reviewed by AIHealz Medical Editorial Board · May 13, 2026
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