Makindo Medical Notes

Related Subjects: |Metabolic acidosis |Lactic acidosis |Acute Kidney Injury (AKI) / Acute Renal Failure |Renal/Kidney Physiology |Chronic Kidney Disease (CKD) |Anaemia in Chronic Kidney Disease |Analgesic Nephropathy |Medullary Sponge kidney |IgA Nephropathy (Berger's disease) |HIV associated nephropathy (HIVAN) |Balkan endemic nephropathy (BEN) |Autosomal Dominant Polycystic kidney disease

Lupus nephritis (LN) is one of the most serious complications of systemic lupus erythematosus (SLE). It occurs in 30–70% of patients and is a major determinant of prognosis. Regular urine testing and BP monitoring are essential for early detection of treatable disease.

About

• Seen in 30–70% of those with SLE, especially in younger women and Afro-Caribbean patients.
• Strongly influences morbidity, mortality, and progression to chronic kidney disease (CKD).
• Immune-mediated inflammation of the glomeruli due to immune complex deposition (dsDNA + complement).

Presentation 🩺

• Microscopic or macroscopic haematuria.
• Proteinuria (may progress to nephrotic syndrome with oedema, ascites, hyperlipidaemia).
• Rising serum creatinine, reduced GFR.
• Hypertension (common, may be severe).
• Renal artery or vein thrombosis (esp. in antiphospholipid antibody-positive patients).
• Can be asymptomatic – detected on screening urinalysis.

Aetiology & Pathophysiology 🧬

• Immune complex deposition: dsDNA-anti-dsDNA immune complexes deposit in glomeruli → activate complement → inflammation & damage.
• Complement dysregulation: Low C3/C4 and low C1q during active nephritis.
• Genetic susceptibility: HLA-DR2, DR3, and polymorphisms in complement pathway genes.
• Environmental triggers: Infections, UV exposure, and smoking can precipitate flares.

ISN/RPS Classification of Lupus Nephritis (2003, updated 2018) 📊

• Class I: Minimal mesangial LN (immune deposits, normal light microscopy).
• Class II: Mesangial proliferative LN (mesangial hypercellularity & matrix expansion).
• Class III: Focal LN (<50% glomeruli; segmental or global proliferative lesions).
• Class IV: Diffuse LN (>50% glomeruli; segmental/global proliferative). Most severe form.
• Class V: Membranous LN (subepithelial deposits; nephrotic syndrome).
• Class VI: Advanced sclerosing LN (≥90% glomeruli sclerosed → ESRD).

Signs of Histological Activity 🔬

• Endocapillary hypercellularity with leukocyte infiltration.
• Karyorrhexis (nuclear fragmentation).
• Cellular or fibrocellular crescents.
• Subendothelial deposits on EM (“wire-loop” lesions).
• Intraluminal immune aggregates.
• Fibrinoid necrosis, GBM rupture.

Investigations 🔎

• Serology: ANA positive; anti-dsDNA correlates with activity; anti-Ro/La may co-exist.
• Complement: C3, C4, C1q often low in active nephritis.
• CRP: Typically normal even in flares (contrast with infection, where CRP rises).
• Urine: Proteinuria (dipstick/24h), haematuria, cellular casts.
• Bloods: U&E, eGFR, FBC (for cytopenias), lipids.
• Imaging: Renal ultrasound to rule out obstruction.
• Definitive: Renal biopsy — required for classification & guiding therapy.

Management 💊

• Class I/II: Usually conservative ± hydroxychloroquine. BP & urine monitoring.
• Class III/IV (proliferative):
  • Induction: High-dose glucocorticoids + mycophenolate mofetil (MMF) or IV cyclophosphamide.
  • Maintenance: MMF or azathioprine + low-dose steroids.
• Class V: If nephrotic-range proteinuria → MMF or cyclophosphamide ± steroids.
• Class VI: Supportive care (ACE inhibitors/ARBs for proteinuria, BP control, dialysis or transplant for ESRD).
• Biologics: Rituximab or belimumab in refractory disease.
• General measures: Hydroxychloroquine for all unless contraindicated; BP control (ACEi/ARB); avoid nephrotoxins (NSAIDs); vaccinations; sun protection.

Clinical Pearls ✨

• 🧪 dsDNA rises + complement falls = active flare.
• ⚡ CRP normal in active LN but rises with infection → helps distinguish flare vs sepsis.
• 👩‍⚕️ Always screen for antiphospholipid antibodies in SLE with renal disease (risk of thrombosis).
• ❤️ ACE inhibitors/ARBs are renoprotective in proteinuria (↓ intraglomerular pressure).
• 🧬 Monitoring: BP, urinalysis, U&E, dsDNA, complements every 1–3 months in active disease.