Lupus Nephritis

Systemic lupus erythematosus (SLE) is an autoimmune disease where the immune system attacks the body's own tissues. The kidneys are involved in about 40% of UK SLE patients — this is lupus nephritis (LN).

It's caused by immune complexes (antibody + antigen) depositing in the kidney filters (glomeruli), triggering inflammation.

More Common In

• Women (9:1)
• Aged 15–45
• Black African, Caribbean, South Asian and Hispanic populations
• People with positive anti-double-stranded DNA antibodies

WITHOUT treatment, severe lupus nephritis leads to kidney failure within 5 years. WITH treatment, most patients now maintain kidney function for decades.

SYMPTOMS (often silent):

• Frothy urine (proteinuria)
• Ankle/leg swelling
• High blood pressure
• Fatigue, weight loss
• Blood in urine (visible or microscopic)
• Flares of joint pain, rash, hair loss, mouth ulcers

Investigations

• Urine ACR + microscopy (red cells, casts)
• Creatinine, eGFR
• Anti-dsDNA antibodies, complement (C3, C4) — low complement = active disease
• Antiphospholipid antibodies
• Lupus anticoagulant

KIDNEY BIOPSY — essential for diagnosis and class:

• Class I: minimal mesangial — observe
• Class II: mesangial proliferative — usually mild
• Class III: focal proliferative (< 50% glomeruli) — needs treatment
• Class IV: diffuse proliferative (≥ 50%) — MOST SEVERE; needs intensive treatment
• Class V: membranous — nephrotic syndrome; treatment depends on severity
• Class VI: advanced sclerosis — irreversible damage

Induction = getting active inflammation under control (typically 3–6 months).

FOR CLASS III/IV/MIXED ± V:

First-line Options

1. MYCOPHENOLATE MOFETIL (MMF) 2–3 g/day + IV methylprednisolone 500 mg ×3 + oral prednisolone tapering from 0.5 mg/kg ± VOCLOSPORIN (NICE TA850, 2022) — added to MMF, faster remission ± BELIMUMAB (NICE TA917) — added to MMF or cyclophosphamide

2. LOW-DOSE IV CYCLOPHOSPHAMIDE (Euro-Lupus regime: 500 mg ×6 fortnightly) + steroids — preferred for severe disease, non-Caucasian patients, or fertility preservation needed (with GnRH agonist)

1. RITUXIMAB — for refractory or relapsing disease, B-cell driven

FOR PURE CLASS V (membranous):

• MMF + low-dose steroids OR
• Calcineurin inhibitor (tacrolimus, ciclosporin) ± MMF

Supportive For All

• Hydroxychloroquine 200–400 mg daily (LIFELONG)
• ACE inhibitor or ARB to maximum tolerated dose
• Statin
• Vitamin D + calcium
• BP target < 130/80
• Bone protection (bisphosphonate if long steroids)
• Pneumocystis prophylaxis (co-trimoxazole) during heavy immunosuppression

MAINTENANCE (3–5 YEARS minimum):

• MMF 1–2 g/day OR azathioprine 1.5–2 mg/kg/day
• Low-dose prednisolone < 7.5 mg/day (aim to stop within 1–2 years)
• Continue hydroxychloroquine
• Continue ACE/ARB
• Consider continuing voclosporin or belimumab

Monitoring

• Monthly bloods during induction (FBC, U&E, LFT, urine ACR, dsDNA, complement)
• 3-monthly when stable
• 6-monthly after 2 years of stable remission

Relapse Signs

• Rising urine ACR
• Falling complement (C3, C4)
• Rising dsDNA
• Active urinary sediment (red cells, casts)
• Rising creatinine
• New extra-renal lupus symptoms

Pregnancy

• Wait 6 months of stable remission
• Stop MMF (teratogenic) — switch to azathioprine 3 months before conception
• Continue hydroxychloroquine and low-dose aspirin
• Joint renal–obstetric clinic care
• Higher risk of pre-eclampsia, prematurity — manageable with monitoring

Daily Life

• Sun protection (UV triggers flares) — SPF 50 daily, hats
• Vitamin D supplementation (most lupus patients are deficient)
• Stop smoking — worsens lupus
• Annual flu, COVID, 5-yearly pneumococcal vaccines
• Avoid live vaccines on immunosuppression
• Mental health support — depression rates are higher in lupus

Outcomes

• 5-year kidney survival: 85–95% (vs 50% in 1970s)
• 10-year kidney survival: 70–80%
• Transplantation outcomes are excellent — lupus rarely recurs in graft