Red Flags
- Rapidly progressive glomerulonephritis (creatinine doubling within 3 months, dysmorphic haematuria, red cell casts) — emergency nephrology; same-day biopsy and immunosuppression[1]
- Pulmonary-renal syndrome (haemoptysis with AKI) — anti-GBM, ANCA vasculitis; emergency immunosuppression and plasma exchange[1]
- Nephrotic syndrome with thromboembolism (PE, DVT, renal vein thrombosis) — anticoagulate and treat underlying disease; consider prophylactic anticoagulation if albumin <25 g/L on no anticoagulant[1]
- Severe hypertension with target organ damage in glomerular disease — admit; IV antihypertensive; treat underlying disease[1]
First-line treatment
Interventions
- Foundation supportive therapy[1]All glomerular disease — sodium restriction, RAS blockade titrated to maximum tolerated, blood-pressure target <120/80 (standardised office), statin per cardiovascular risk, treat oedema with loop diuretic, vaccinate before immunosuppression, manage VTE risk
First-line drug therapy
| Drug | Class | Adult | Paediatric | Notes |
|---|---|---|---|---|
| Prednisolone (induction)[1] | Systemic corticosteroid | Minimal change: 1 mg/kg/day (max 80 mg) PO × 4–8 weeks then taper. Lupus nephritis class III/IV: methylprednisolone IV pulse 250–500 mg × 3 days then prednisolone 0.5–1 mg/kg/day (max 60 mg) tapering rapidly | MCD: 60 mg/m²/day (max 60 mg) × 4–6 weeks then alternate-day taper | Ulcer prophylaxis, calcium/vitamin D, glucose monitoring, infection prophylaxis (PJP) per regimen |
| Mycophenolate mofetil[1] | Inosine monophosphate dehydrogenase inhibitor | Lupus nephritis induction 2–3 g/day PO in divided doses × 6 months; maintenance 1–2 g/day | 600 mg/m² BD (max 2 g/day) | First-line induction and maintenance for lupus nephritis class III/IV; teratogenic — strict contraception and switch ≥6 weeks before pregnancy |
| Cyclophosphamide[1] | Alkylating agent | Euro-Lupus 500 mg IV every 2 weeks × 6 doses for lupus nephritis. ANCA vasculitis: 15 mg/kg IV every 2 weeks × 3 then every 3 weeks (max 1.2 g/dose, age- and renal-adjusted) | Per local paediatric nephrology protocol | Counsel about gonadal toxicity and bladder cancer; mesna with high-dose IV; lifetime cumulative dose monitoring; PJP prophylaxis |
| Rituximab[1] | Anti-CD20 monoclonal antibody | Membranous nephropathy: 1 g IV × 2 doses 2 weeks apart, repeat at 6 months by anti-PLA2R titre. ANCA vasculitis: 375 mg/m² IV weekly × 4 induction; 1 g IV every 6 months maintenance | — | First-line for high-risk membranous nephropathy and ANCA vasculitis; screen and prophylax HBV; live-vaccine hold |
| Tacrolimus or ciclosporin[1] | Calcineurin inhibitor | Tacrolimus 0.05–0.1 mg/kg/day PO BD aiming trough 4–8 ng/mL; ciclosporin 3–5 mg/kg/day | Per paediatric nephrology | Steroid-resistant FSGS, frequently relapsing minimal change, refractory membranous nephropathy; nephrotoxicity, hypertension, glucose intolerance, hirsutism (ciclosporin) or alopecia (tacrolimus) |
| Belimumab or voclosporin (lupus nephritis adjunct)[1] | Anti-BAFF monoclonal antibody / calcineurin inhibitor | Belimumab 10 mg/kg IV at 0, 2, 4 weeks then monthly; voclosporin 23.7 mg PO BD | — | Add-on to MMF + steroid for lupus nephritis class III/IV/V to deepen response; contraindicated eGFR <45 (voclosporin) |
| Sparsentan[1] | Dual endothelin and angiotensin receptor antagonist | 200 mg PO daily, increase to 400 mg if BP and electrolytes tolerate | — | IgA nephropathy with persistent proteinuria despite RAS inhibitor; replaces ACEi/ARB (do not combine); monitor LFTs |
| Targeted-release budesonide (Nefecon)[1] | Locally-acting glucocorticoid | 16 mg PO once daily × 9 months | — | IgA nephropathy with persistent proteinuria UPCR ≥0.5 g/g despite optimised supportive care; reduces systemic steroid exposure |
Prednisolone (induction)[1]
Systemic corticosteroid
- Adult
- Minimal change: 1 mg/kg/day (max 80 mg) PO × 4–8 weeks then taper. Lupus nephritis class III/IV: methylprednisolone IV pulse 250–500 mg × 3 days then prednisolone 0.5–1 mg/kg/day (max 60 mg) tapering rapidly
- Paediatric
- MCD: 60 mg/m²/day (max 60 mg) × 4–6 weeks then alternate-day taper
Ulcer prophylaxis, calcium/vitamin D, glucose monitoring, infection prophylaxis (PJP) per regimen
Mycophenolate mofetil[1]
Inosine monophosphate dehydrogenase inhibitor
- Adult
- Lupus nephritis induction 2–3 g/day PO in divided doses × 6 months; maintenance 1–2 g/day
- Paediatric
- 600 mg/m² BD (max 2 g/day)
First-line induction and maintenance for lupus nephritis class III/IV; teratogenic — strict contraception and switch ≥6 weeks before pregnancy
Cyclophosphamide[1]
Alkylating agent
- Adult
- Euro-Lupus 500 mg IV every 2 weeks × 6 doses for lupus nephritis. ANCA vasculitis: 15 mg/kg IV every 2 weeks × 3 then every 3 weeks (max 1.2 g/dose, age- and renal-adjusted)
- Paediatric
- Per local paediatric nephrology protocol
Counsel about gonadal toxicity and bladder cancer; mesna with high-dose IV; lifetime cumulative dose monitoring; PJP prophylaxis
Rituximab[1]
Anti-CD20 monoclonal antibody
- Adult
- Membranous nephropathy: 1 g IV × 2 doses 2 weeks apart, repeat at 6 months by anti-PLA2R titre. ANCA vasculitis: 375 mg/m² IV weekly × 4 induction; 1 g IV every 6 months maintenance
- Paediatric
- —
First-line for high-risk membranous nephropathy and ANCA vasculitis; screen and prophylax HBV; live-vaccine hold
Tacrolimus or ciclosporin[1]
Calcineurin inhibitor
- Adult
- Tacrolimus 0.05–0.1 mg/kg/day PO BD aiming trough 4–8 ng/mL; ciclosporin 3–5 mg/kg/day
- Paediatric
- Per paediatric nephrology
Steroid-resistant FSGS, frequently relapsing minimal change, refractory membranous nephropathy; nephrotoxicity, hypertension, glucose intolerance, hirsutism (ciclosporin) or alopecia (tacrolimus)
Belimumab or voclosporin (lupus nephritis adjunct)[1]
Anti-BAFF monoclonal antibody / calcineurin inhibitor
- Adult
- Belimumab 10 mg/kg IV at 0, 2, 4 weeks then monthly; voclosporin 23.7 mg PO BD
- Paediatric
- —
Add-on to MMF + steroid for lupus nephritis class III/IV/V to deepen response; contraindicated eGFR <45 (voclosporin)
Sparsentan[1]
Dual endothelin and angiotensin receptor antagonist
- Adult
- 200 mg PO daily, increase to 400 mg if BP and electrolytes tolerate
- Paediatric
- —
IgA nephropathy with persistent proteinuria despite RAS inhibitor; replaces ACEi/ARB (do not combine); monitor LFTs
Targeted-release budesonide (Nefecon)[1]
Locally-acting glucocorticoid
- Adult
- 16 mg PO once daily × 9 months
- Paediatric
- —
IgA nephropathy with persistent proteinuria UPCR ≥0.5 g/g despite optimised supportive care; reduces systemic steroid exposure
Safety-net
- On immunosuppression: any new fever, productive cough, herpes zoster rash, oral thrush, or unexplained fatigue — same-day medical review (opportunistic infection)[1]
- Take rituximab and other infusion-based therapy on schedule — gaps allow B-cell return and disease relapse[1]
- Pregnancy — many disease-modifying drugs are teratogenic (mycophenolate, cyclophosphamide, sparsentan); plan ≥3–6 months ahead with your nephrologist[1]
Referral criteria
- Any newly suspected glomerular disease (proteinuria UACR ≥30 mg/mmol with or without haematuria, AKI, or hypertension)Nephrology[1]
- Rapidly progressive glomerulonephritis or pulmonary-renal syndromeNephrology and HDU[1]
- Nephrotic syndrome (UPCR ≥3.0 g/g, albumin <30 g/L, oedema)Nephrology[1]
- Refractory or relapsed disease on first-line immunosuppressionTertiary glomerular disease centre[1]
Clinical summary
Diagnosis and immunosuppressive management of primary and secondary glomerular diseases (IgA nephropathy, FSGS, MN, MCD, lupus nephritis, ANCA vasculitis).