Lupus Nephritis
Summary
Lupus Nephritis (LN) is one of the most serious manifestations of Systemic Lupus Erythematosus (SLE), affecting 40-60% of patients. It involves immune complex deposition in the glomeruli. Without treatment, it progresses to End Stage Renal Disease (ESRD). Prognosis relies heavily on renal biopsy classification (I-VI). [1,2]
Clinical Pearls
The "Active" Sediment: In LN, the urine tells the story. "Active Sediment" means Red Cell Casts, dysmorphic red cells, and protein. This implies active glomerular inflammation (Proliferative disease - Class III/IV) requiring aggressive immunosuppression. Bland urine suggests damage is done (Class VI) or purely membranous (Class V).
Hydroxychloroquine: This drug is "Life Insurance" for Lupus patients. It reduces flares, reduces renal damage, and reduces cardiovascular risk. Every patient with SLE should be on it unless contraindicated.
Biopsy is Mandatory: You cannot treat LN blindly. You must know the Class. Treating Class II with Cyclophosphamide is malpractice (overkill). Treating Class IV with just steroids is malpractice (undertreatment).
Demographics
- SLE Prevalence: 1 in 1000. Female:Male 9:1.
- Renal Involvement: More common and more severe in Non-Caucasian populations (African, Asian, Hispanic ancestry).
- Mortality: Patients with LN have significantly higher mortality than SLE patients without renal involvement.
Mechanism
- Autoantibodies: Anti-dsDNA binds to nucleosomes.
- Immune Complexes: These deposit in the kidney.
- Location Matters:
- Mesangial: (Class I/II) - Mild.
- Sub-endothelial: (Class III/IV) - Exposed to blood, recruits massive inflammation -> Proliferative (Aggressive).
- Sub-epithelial: (Class V) - Under podocytes, less inflammation but causes leak -> Membranous (Nephrotic).
| Class | Name | Features | Treatment |
|---|---|---|---|
| I | Minimal Mesangial | Normal light microscopy. | None (for kidney) |
| II | Mesangial Proliferative | Mesangial hypercellularity. Microhaematuria. | Low level |
| III | Focal | less than 50% glomeruli affected. Subendothelial deposits. | Aggressive |
| IV | Diffuse | >50% glomeruli affected. "Wire loop" lesions. Worst prognosis. | Aggressive |
| V | Membranous | Subepithelial spikes. Nephrotic syndrome. | ACEi + MMF |
| VI | Sclerotic | >90% scarred. ESRD. | Dialysis/Transplant |
Symptoms
Investigations
Serology
- ANA: Positive (>95%).
- Anti-dsDNA: High titres correlate with Renal Flares.
- Complements (C3/C4): Low during active nephritis (consumed by immune complexes).
Renal Biopsy
- Gold Standard.
- Indicates: Activity (reversible inflammation) vs Chronicity (irreversible scarring).
Management Algorithm (Class III/IV - Proliferative)
ACTIVE PROLIFERATIVE LN (III/IV)
↓
INDUCTION THERAPY (3-6 Months)
"Hit hard to save nephrons"
High Dose Steroids (IV Methylpred pulses)
+
┌───────────┴───────────┐
MMF (Mycophenolate) CYCLOPHOSPHAMIDE
(Preferred usually) (Euro-Lupus regimen)
(Save fertility) (Severe/Life threatening)
↓
RESPONSE ASSESSMENT
(Proteinuria < 0.5g, Stable Creatinine)
↓
MAINTENANCE THERAPY
- Low dose Prednisolone (less than 7.5mg)
- MMF or Azathioprine
- Continues for > 3-5 years
1. Adjunctive Therapy
- Hydroxychloroquine: For all.
- ACE Inhibitor/ARB: For all (antiproteinuric/BP control).
- Statins/Bone Protection.
2. New Biologicals
- Belimumab: Anti-BAFF. Approved for LN.
- Voclosporin: Calcineurin inhibitor. Added to MMF+Steroids for faster response.
3. Pregnancy
- Cyclophosphamide/MMF/Methotrexate: Teratogenic.
- Must switch to Azathioprine or Tacrolimus if planning pregnancy.
- High risk of pre-eclampsia and flare.
- ESRD: requiring dialysis/transplant.
- Infection: Due to heavy immunosuppression (leading cause of death).
- CVD: Accelerated atherosclerosis.
- Thrombosis: Especially if Nephrotic (losing Antithrombin III) or Anti-Phospholipid Syndrome.
- 10-year renal survival is now >80% (used to be less than 20% before cyclophosphamide).
- Relapses are common (30-40%).
Key Guidelines
| Guideline | Organisation | Key Recommendations |
|---|---|---|
| Lupus Nephritis | EULAR / ERA (2019) | MMF or Low-dose Cyclophosphamide (Euro-Lupus) are equivalent 1st line induction. |
| KDIGO | Glomerulonephrits | Target proteinuria less than 0.5-0.7g by 12 months. |
Landmark Evidence
1. ALMS Trial
- MMF vs Cyclophosphamide. Showed MMF was non-inferior for induction and superior for maintenance (fewer failures than Azathioprine). MMF is now standard of care (especially for fertility preservation).
2. Euro-Lupus Trial
- Low dose IV Cyclophosphamide (500mg x 6) is as effective as the old toxic NIH High Dose regimen, with far fewer infections.
What is Lupus Nephritis?
Lupus is a condition where your immune system attacks your own body. "Nephritis" means it is attacking the filters in your kidneys.
Is it serious?
Yes. If the inflammation isn't stopped, the kidneys scar up and stop working. You could end up needing dialysis. However, with strong treatment, most people recover well.
How do we treat it?
We use strong drugs to "switch off" the immune attack (Chemotherapy-style drugs or immunosuppressants) combined with steroids. You will likely need to be on some medication for several years to stop it reacting.
Primary Sources
- Fanouriakis A, et al. 2019 update of the EULAR recommendations for the management of systemic lupus erythematosus. Ann Rheum Dis. 2019.
- Appel GB, et al. Mycophenolate mofetil versus cyclophosphamide for induction treatment of lupus nephritis (ALMS). J Am Soc Nephrol. 2009.
Common Exam Questions
- Diagnosis: "Marker of activity?"
- Answer: High anti-dsDNA and Low C3/C4.
- Histology: "Wire loop lesion?"
- Answer: Class IV (Diffuse Proliferative).
- Pharmacology: "S/E of Cyclophosphamide?"
- Answer: Haemorrhagic Cystitis, Infertility, Bone Marrow Suppression.
- Pharmacology: "S/E of Hydroxychloroquine?"
- Answer: Retinal toxicity (Bull's eye maculopathy) - needs eye checks.
Viva Points
- RBC Casts: Explain pathophysiology. RBCs leak through damaged glomerulus, get stuck in Tam-Horsfall protein in the tubules, form a cylindrical "cast", then get flushed out. Signifies Glomerulonephritis.
- Full House: Immunofluorescence finding on biopsy. Positive for IgG, IgM, IgA, C3, C1q. Pathognomonic for Lupus.
Medical Disclaimer: MedVellum content is for educational purposes and clinical reference. Clinical decisions should account for individual patient circumstances. Always consult appropriate specialists.