Summary

KDIGO 2021 updates the 2012 glomerulonephritis guideline, covering IgA nephropathy/vasculitis, membranous nephropathy, nephrotic syndrome in children, MCD and FSGS in adults, infection-related GN, MPGN/C3 glomerulopathy, ANCA vasculitis, lupus nephritis, and anti-GBM disease. New features include practice points (consensus guidance where evidence is insufficient), risk-stratified treatment for MN, expanded role of rituximab, and recognition that anti-PLA2R serology can diagnose MN without biopsy. Treatment paradigms shift toward minimizing glucocorticoid exposure and individualized risk-based immunosuppression.

Key Recommendations

Target SBP <120 mm Hg (standardized office measurement) in most adults with glomerular disease; use ACEi or ARB titrated to maximally tolerated dose as first-line for hypertension and/or proteinuria >0.5 g/d.
For IgAN with proteinuria >0.75–1 g/d despite ≥90 days of optimized supportive care, consider a 6-month course of glucocorticoids only after discussing toxicity, particularly avoiding if eGFR <30 ml/min/1.73 m².
For MN with at least one risk factor for progression, use rituximab, cyclophosphamide plus alternate-month glucocorticoids for 6 months, or CNI-based therapy for ≥6 months; anti-PLA2R-positive nephrotic patients can be diagnosed without biopsy.
Initial treatment of childhood nephrotic syndrome is prednisone 60 mg/m²/d (max 60 mg/d) for 4–6 weeks followed by alternate-day tapering, for a total of 8–12 weeks.
For frequently relapsing or steroid-dependent nephrotic syndrome in children, use glucocorticoid-sparing agents (cyclophosphamide, levamisole, MMF, rituximab, or CNI).
For steroid-resistant nephrotic syndrome in children and steroid-resistant primary FSGS in adults, use cyclosporine or tacrolimus for ≥6 months.
Treat adult MCD with high-dose oral glucocorticoids (1 mg/kg/d, max 80 mg) for up to 16 weeks; use cyclophosphamide, CNI, MMF, or rituximab for frequently relapsing/steroid-dependent disease.
For new-onset ANCA-associated vasculitis, induce with glucocorticoids plus either rituximab or cyclophosphamide; maintain remission with rituximab or azathioprine plus low-dose glucocorticoids for 18 months to 4 years.
Add plasma exchange in AAV with SCr >5.7 mg/dl (500 µmol/l), dialysis requirement, rapidly rising creatinine, diffuse alveolar hemorrhage with hypoxemia, or anti-GBM overlap.
All SLE/LN patients should receive hydroxychloroquine unless contraindicated; treat active Class III/IV LN with glucocorticoids plus low-dose IV cyclophosphamide (Euro-Lupus) or MPAA, followed by MPAA maintenance for ≥36 months total.
Treat anti-GBM disease without delay with cyclophosphamide (2–3 months) plus glucocorticoids (6 months) plus daily plasma exchange until antibodies undetectable; withhold immunosuppression if 100% crescents, dialysis-dependent, and no pulmonary hemorrhage.
Provide full anticoagulation for thromboembolism in nephrotic syndrome; consider prophylactic anticoagulation in MN when serum albumin <20–25 g/l (especially with additional risk factors), balancing against bleeding risk.

Thresholds & Doses

Target SBP <120 mm Hg in adults (standardized office BP); pediatric target 24-h MAP ≤50th percentile for age/sex/height.
Dietary sodium restriction <2.0 g/d (<90 mmol/d).
Proteinuria treatment target generally <1 g/d (disease-specific); pediatric goal PCR <200 mg/g (<20 mg/mmol).
IgAN: glucocorticoid trial reserved for proteinuria >0.75–1 g/d after ≥90 days optimized supportive care; avoid if eGFR <30 ml/min/1.73 m² or BMI >30.
MN risk stratification: low risk = normal eGFR + proteinuria <3.5 g/d + albumin >30 g/l; high risk = eGFR <60 or proteinuria >8 g/d; PLA2R Ab >50 RU/ml adds risk.
MN cyclophosphamide regimen: 2.5 mg/kg/d cyclical alternating months × 6, or 1.5 mg/kg/d continuous × 6 months; cumulative dose cap ~25–36 g (10 g if fertility preservation).
MN rituximab: 1 g IV × 2 doses 2 weeks apart, or 375 mg/m² weekly × 4.
Pediatric NS initial prednisone: 60 mg/m²/d or 2 mg/kg/d (max 60 mg/d) × 4–6 weeks, then 40 mg/m² (max 50 mg) alternate days × 4–6 weeks.
Sick-day dosing for FRNS/SDNS: prednisone 0.5 mg/kg/d during URI for 5–7 days.
Adult MCD initial prednisone: 1 mg/kg/d (max 80 mg) or 2 mg/kg every other day (max 120 mg), max duration 16 weeks; taper over ≥24 weeks after remission.
Primary FSGS: prednisone 1 mg/kg/d (max 80 mg) or 2 mg/kg alternate-day (max 120 mg), continued ≥4 weeks until remission or max 16 weeks; total ≥6 months.
FSGS CNI dosing: cyclosporine 3–5 mg/kg/d (target trough 100–175 ng/ml); tacrolimus 0.05–0.1 mg/kg/d (target trough 5–10 ng/ml); ≥12 months if responsive.
AAV induction cyclophosphamide: oral 2 mg/kg/d × 3–6 months, or IV 15 mg/kg at weeks 0,2,4 then every 3 weeks (Euro-Lupus alternative: 500 mg IV every 2 weeks × 6); reduce dose by 25% age >60, 50% age >70, and for GFR <30 ml/min/1.73 m².
AAV rituximab induction: 375 mg/m²/week × 4 weeks.
AAV plasma exchange triggers: SCr >5.7 mg/dl (500 µmol/l), dialysis-requiring, rapidly rising SCr, alveolar hemorrhage with hypoxemia.
AAV maintenance rituximab (MAINRITSAN): 500 mg at months 6, 12, 18 after induction; azathioprine 1.5–2 mg/kg/d for 18 months–4 years.
LN Euro-Lupus cyclophosphamide: 500 mg IV every 2 weeks × 6 doses (3 months).
LN MMF induction: 2–3 g/d; maintenance 1.5–2 g/d; total immunosuppression ≥36 months.
Voclosporin for LN requires baseline eGFR ≥45 ml/min/1.73 m².
Anti-GBM cyclophosphamide: oral 2–3 mg/kg/d (reduce to 2 mg/kg if age >55) × 3 months; prednisone 1 mg/kg/d tapered to 20 mg/d by 6 weeks, total 6 months.
Anti-GBM plasma exchange: 40–50 ml/kg ideal body weight daily against 5% albumin until antibodies undetectable (~14 days).
HBV-associated GN treatment threshold: HBV DNA >2000 IU/ml indicates antiviral therapy with nucleos(t)ide analogues.
Cyclophosphamide lifetime cumulative dose limits: <10 g if fertility preservation, <36 g to limit malignancy risk.
Anticoagulation prophylaxis consideration in nephrotic syndrome: serum albumin <20–25 g/l (BCG) or <20 g/l (BCP/immunoassay), especially with proteinuria >10 g/d, BMI >35, or other risk factors.

Citations

Chapter 1 (General principles) — supportive care including BP target, RAS blockade, edema/lipid/anticoagulation management
Chapter 2, Recommendations 2.3.1.1–2.3.2 — IgAN supportive care, RAS blockade, glucocorticoid trial in high-risk disease
Chapter 3, Recommendation 3.3.1 and Figures 30–31 — risk-based treatment of MN with rituximab, cyclophosphamide, or CNI
Chapter 4, Recommendations 4.3.1.1, 4.3.2.1–4.3.2.2, 4.4.1 — pediatric nephrotic syndrome glucocorticoid regimens and second-line agents
Chapter 5, Recommendation 5.3.1 and Practice Points — adult MCD initial therapy and FR/SD management
Chapter 6, Recommendations 6.2.2.1 and 6.3.1.1 and Figures 54–55 — primary FSGS glucocorticoids and CNI for steroid-resistant disease
Chapter 9, Recommendations 9.3.1.1 and 9.3.2.1 and Figures 76–84 — AAV induction and maintenance therapy
Chapter 10, Recommendations 10.2.1.1, 10.2.3.1.1, 10.2.3.2.1 and Figures 87–95 — lupus nephritis hydroxychloroquine, Class III/IV induction with cyclophosphamide or MPAA, MPAA maintenance
Chapter 11, Recommendation 11.2.1 and Figures 98–99 — anti-GBM cyclophosphamide, glucocorticoids, and plasma exchange protocol