Kodgo classification of glomerular diseases
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KDIGO 2021 classification glomerular diseases nephrology
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KDIGO 2021 glomerular diseases FSGS classification podocytopathy categories chapters
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I now have comprehensive information to write a complete answer. Here is the full KDIGO classification of glomerular diseases:
KDIGO Classification of Glomerular Diseases
"KDIGO" stands for Kidney Disease: Improving Global Outcomes. The landmark classification and management framework is the KDIGO 2021 Clinical Practice Guideline for the Management of Glomerular Diseases (published in Kidney International, October 2021, Vol. 100, S1-S276), which updated the original 2012 guideline. It is the most extensive KDIGO guideline to date. The KDIGO 2021 GD Guideline is being continuously updated on a chapter-by-chapter basis, with the IgAN/IgAV chapter already updated in 2025.
Overarching Classification: Primary vs. Secondary
The foundational framework divides glomerular diseases into two broad categories:
| Category | Definition | Examples |
|---|---|---|
| Primary (Renal-Limited) | Glomerular disease confined to the kidney with no systemic cause | IgA nephropathy, MCD, FSGS, MN |
| Secondary (Systemic) | Kidney involvement is part of a systemic disorder | Lupus nephritis, ANCA vasculitis, Diabetic nephropathy |
Note: This separation is acknowledged as imperfect - some diseases (IgAN, ANCA GN, anti-GBM GN, MN) can occur as either primary or secondary forms (Brenner and Rector's The Kidney, 2-Volume Set, p. 1334).
The 11 Chapters of KDIGO 2021 (Disease-Based Classification)
The guideline is organized into 11 chapters, 10 of which cover specific glomerular diseases:
Chapter 1 - General Principles
Common management principles applicable to all glomerular diseases: blood pressure control, proteinuria reduction (RAS blockade), immunosuppression principles, and supportive care.
Chapter 2 - IgA Nephropathy (IgAN) / IgA Vasculitis (IgAV)
- IgAN: Primary glomerular disease with mesangial IgA deposits; most common primary GN worldwide
- IgAV (formerly Henoch-Schonlein purpura): Systemic IgA vasculitis with renal involvement
- Risk stratification uses the Oxford MEST-C Score (Mesangial hypercellularity, Endocapillary hypercellularity, Segmental sclerosis, Tubular atrophy/interstitial fibrosis, Crescents)
- Updated independently in the KDIGO 2025 IgAN/IgAV Guideline
Chapter 3 - Membranous Nephropathy (MN)
- Primary MN: Autoimmune; anti-PLA2R antibodies (~70%), anti-THSD7A antibodies (~5-10%)
- Secondary MN: Due to lupus, malignancy, infections, drugs
- Anti-PLA2R antibody testing allows non-invasive diagnosis of primary MN
- Treatment decisions guided by antibody titer monitoring
Chapter 4 - Nephrotic Syndrome in Children
- Encompasses steroid-sensitive nephrotic syndrome (SSNS) and steroid-resistant nephrotic syndrome (SRNS)
- Management recommendations from the International Pediatric Nephrology Association (IPNA) are incorporated
- Most children have MCD as the underlying pathology
Chapter 5 - Minimal Change Disease (MCD) in Adults
- A podocytopathy - injury at the level of the podocyte foot processes
- No identifiable underlying cause in most cases
- Pathogenesis: T-cell dysregulation driving podocytopathy (B-cell involvement also implicated)
- Rare causes: Hodgkin's lymphoma, lithium, NSAIDs
- First-line: high-dose glucocorticoids (no more than 16 weeks)
Chapter 6 - Focal Segmental Glomerulosclerosis (FSGS) in Adults
This chapter introduced the most significant new classification of the 2021 guidelines. The old binary (idiopathic vs. secondary) was replaced with a 5-category classification:
| FSGS Category | Key Features | Treatment |
|---|---|---|
| Primary FSGS | Caused by circulating podocyte-toxic factor; full-blown nephrotic syndrome, sudden onset, diffuse foot process effacement | Immunosuppression (glucocorticoids, CNI) |
| Secondary FSGS | Due to known cause: obesity, reflux nephropathy, sickle cell, reduced nephron mass | Treat underlying cause; supportive care only |
| Genetic FSGS | Monogenic podocyte mutations (NPHS1, NPHS2, WT1, ACTN4, TRPC6, etc.) | No immunosuppression; genetic counseling |
| FSGS of Undetermined Cause (FSGS-UC) | FSGS on biopsy but no identifiable cause AND does not fit primary FSGS criteria | Watchful waiting; repeat biopsy if features change |
| Virus-associated / Drug-induced FSGS | HIV, parvovirus B19; heroin, bisphosphonates, interferon | Treat underlying cause |
Key point: The term "idiopathic FSGS" is eliminated. "Primary FSGS" now specifically refers to the presumed podocyte-toxic factor-mediated entity. FSGS-UC is a new, important holding category.
Chapter 7 - Infection-Related Glomerulonephritis (GN)
| Type | Causative Agent | Pattern |
|---|---|---|
| Post-streptococcal GN | Group A Streptococcus | Diffuse proliferative GN |
| Bacterial | Staph-associated, endocarditis, shunt nephritis | MPGN or diffuse proliferative |
| Viral | HIV-associated nephropathy (HIVAN), HBV, HCV | FSGS (collapsing), MPGN |
| Parasitic | Malaria, schistosomiasis | MPGN |
- HIV-associated GN prognosis depends on viral replication, antiviral response, APOL1 risk alleles, coinfection
Chapter 8 - Immunoglobulin- and Complement-Mediated Glomerular Diseases with an MPGN Pattern
This chapter replaced the old standalone MPGN chapter with a mechanistic, immunofluorescence-based classification:
| Category | IF Pattern | Mechanism |
|---|---|---|
| Immune Complex-Mediated MPGN | IgG + complement (C3) deposits | Immune complex deposition (SLE, HCV, cryoglobulinemia, IgAN) |
| Complement-Mediated MPGN / C3 Glomerulopathy | Predominant C3 staining, minimal Ig | Dysregulation of alternative complement pathway |
| - C3 Glomerulonephritis (C3GN) | C3 dominant | Fluid-phase complement dysregulation |
| - Dense Deposit Disease (DDD) | C3 dominant, osmiophilic deposits | C3 nephritic factor, Factor H mutations |
| Monoclonal Ig-Mediated MPGN | Monoclonal Ig deposits | Paraprotein-related (MGRS) |
This framework represents a major paradigm shift from morphologic to mechanistic classification.
Chapter 9 - ANCA-Associated Vasculitis (AAV)
| Disease | ANCA Target | LM Pattern |
|---|---|---|
| Granulomatosis with Polyangiitis (GPA) | PR3-ANCA (~75%) | Pauci-immune crescentic GN |
| Microscopic Polyangiitis (MPA) | MPO-ANCA (~75%) | Pauci-immune crescentic GN |
| Eosinophilic GPA (EGPA) | MPO-ANCA (~50%) | Pauci-immune crescentic GN |
- PR3-ANCA, lung involvement, or upper airway involvement = higher relapse risk
- Treatment: rituximab vs. cyclophosphamide for remission induction (compared and contrasted in the 2021 update)
Chapter 10 - Lupus Nephritis (LN)
Uses the ISN/RPS classification (being reassessed as it doesn't consider tubulointerstitial injury or podocytopathies):
| Class | Description |
|---|---|
| Class I | Minimal mesangial LN |
| Class II | Mesangial proliferative LN |
| Class III | Focal LN (<50% of glomeruli) |
| Class IV | Diffuse LN (>50% of glomeruli) |
| Class V | Membranous LN |
| Class VI | Advanced sclerotic LN (>90% sclerosis) |
- Classes III/IV (with or without membranous component) - treat with glucocorticoids + low-dose IV cyclophosphamide OR mycophenolate mofetil (MMF) (1B recommendation)
- Antimalarials recommended for ALL patients with LN
- Proteinuria at 1 year is the best predictor of long-term renal outcome
Chapter 11 - Anti-GBM Antibody GN (Goodpasture Disease)
- Antibodies against the NC1 domain of the alpha-3 chain of type IV collagen
- Rapidly progressive crescentic GN
- With pulmonary hemorrhage = Goodpasture syndrome
- Crescents with fibrinoid necrosis in adjacent segments (distinguishes from other crescentic GN)
- Treatment: plasmapheresis + immunosuppression (urgent)
Summary: Glomerular Diseases by Mechanism (KDIGO Conceptual Framework)
| Mechanism | Diseases |
|---|---|
| Podocytopathy | MCD, primary FSGS, genetic FSGS |
| Immune Complex-Mediated | IgAN, post-infectious GN, lupus nephritis (III/IV/V), MN |
| Autoantibody-Mediated | Anti-GBM disease, primary MN (anti-PLA2R), MCD/FSGS |
| Complement-Mediated | C3GN, DDD (complement pathway dysregulation) |
| Pauci-Immune (ANCA) | GPA, MPA, EGPA |
| Infection-Associated | HIVAN, HBV/HCV-related, post-streptococcal |
| Paraprotein-Related | Monoclonal Ig-mediated MPGN, AL amyloid |
Diseases Excluded from KDIGO 2021 (but Clinically Important)
The following were not addressed due to rarity or lack of controlled trial data:
- Fibrillary GN (DNAJB9 autoantibody-associated)
- Immunotactoid GN (evaluate for monoclonal gammopathy)
- IgM nephropathy
- AL/AA amyloidosis and immunoglobulin deposition diseases
- Alport syndrome
- Thrombotic microangiopathies (TMA)
Key references:
- The KDIGO 2021 GD Guideline Executive Summary (Rovin BH et al. Kidney Int. 2021;100:753-779, PMID 34556300)
- Brenner and Rector's The Kidney, 2-Volume Set, p. 1334 (primary vs. secondary framework)
- KDIGO 2025 IgAN/IgAV Guideline (most recent chapter update)
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