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Phys Topicsrenal

Phys · renal

Glomerulonephritis (Nephritic Spectrum)

Also known as glomerulonephritis · GN · nephritic syndrome · rapidly progressive glomerulonephritis · RPGN · crescentic glomerulonephritis · IgA nephropathy · Berger disease · post-streptococcal glomerulonephritis · PSGN · lupus nephritis · ANCA-associated vasculitis · AAV · anti-GBM disease · Goodpasture syndrome · pauci-immune glomerulonephritis · granulomatosis with polyangiitis · GPA · microscopic polyangiitis · MPA · C3 glomerulopathy

Consultant-physician-depth guide to glomerulonephritis — nephritic syndrome, RPGN classification (anti-GBM, immune complex, pauci-immune/ANCA), IgA nephropathy (Oxford MEST-C), post-streptococcal GN, lupus nephritis (ISN/RPS), pulmonary-renal syndromes, complement interpretation, biopsy immunofluorescence, and evidence-based immunosuppression. Structured for FRACP DWE and DCE preparation.

high13 referencesUpdated 11 July 202621 min readVerification in progress

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Red flags

  • Rapidly progressive GN (creatinine rising over days to weeks with active sediment) — a renal emergency requiring biopsy within 24 to 48 hours
  • Pulmonary haemorrhage with AKI (pulmonary-renal syndrome) — anti-GBM or ANCA vasculitis; needs plasma exchange and immunosuppression immediately
  • Macroscopic haematuria with AKI in a patient with active infection — crescentic IgA nephropathy flare can be rapidly destructive
  • Nephrotic-range proteinuria with hypoalbuminaemia and oedema from advanced glomerular disease — high VTE risk, needs anticoagulation assessment
  • Double-positive ANCA and anti-GBM antibodies — behaves as anti-GBM disease and requires plasma exchange regardless of ANCA status
  • Lupus nephritis class IV with rapidly rising creatinine — needs urgent biopsy and induction within days to prevent irreversible scarring
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FRACP DWEFRACP DCEMRCP Part 1MRCP Part 2MRCP PACESABIM Internal Medicine

Red flags

  • Rapidly progressive GN (creatinine rising over days to weeks with active sediment) — a renal emergency requiring biopsy within 24 to 48 hours
  • Pulmonary haemorrhage with AKI (pulmonary-renal syndrome) — anti-GBM or ANCA vasculitis; needs plasma exchange and immunosuppression immediately
  • Macroscopic haematuria with AKI in a patient with active infection — crescentic IgA nephropathy flare can be rapidly destructive
  • Nephrotic-range proteinuria with hypoalbuminaemia and oedema from advanced glomerular disease — high VTE risk, needs anticoagulation assessment
  • Double-positive ANCA and anti-GBM antibodies — behaves as anti-GBM disease and requires plasma exchange regardless of ANCA status
  • Lupus nephritis class IV with rapidly rising creatinine — needs urgent biopsy and induction within days to prevent irreversible scarring

Glomerulonephritis (Nephritic Spectrum)

The answer first

Glomerulonephritis is immune-mediated inflammation of the glomerulus that presents across a clinical spectrum from asymptomatic microscopic haematuria to rapidly progressive glomerulonephritis (RPGN) causing acute kidney injury over days to weeks. The nephritic syndrome is the constellation of haematuria (dysmorphic red cells and red cell casts), proteinuria (usually sub-nephrotic), hypertension, oedema, and a rise in creatinine. The nephrotic syndrome sits at the other end of the same spectrum — heavy proteinuria above 3.5 g/day, hypoalbuminaemia, and oedema [1].

The single most important clinical task is to recognise RPGN as a renal emergency. A patient with a rapidly rising creatinine and an active urinary sediment has crescentic glomerulonephritis until proven otherwise. Irreversible glomerular destruction occurs over days to weeks. The mandate is: [1]

  1. Send the urgent serological panel immediately — ANA, anti-dsDNA, ANCA (MPO and PR3), anti-GBM antibody, C3 and C4, serum IgA, hepatitis B and C, HIV, and ASO/anti-DNase B if post-infectious is suspected.
  2. Biopsy within 24 to 48 hours — light microscopy, immunofluorescence, and electron microscopy.
  3. Start immunosuppression as soon as the diagnosis is secured — high-dose corticosteroids plus cyclophosphamide or rituximab, with plasma exchange for anti-GBM disease and selected cases of severe ANCA vasculitis.
  4. Treat pulmonary-renal syndromes as the highest priority — pulmonary haemorrhage from anti-GBM or ANCA vasculitis is immediately life-threatening. [1]

DWE high-yield: The complement profile is the single most discriminating serological test. Low C3 with normal C4 suggests alternative pathway activation (post-infectious GN, C3 glomerulopathy). Low C3 and low C4 suggests classical pathway activation (lupus, endocarditis, cryoglobulinaemia). Normal complement is found in IgA nephropathy, ANCA-associated vasculitis, and anti-GBM disease — do not be reassured by a normal complement. [1]


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References13ShowHide
  1. [1]Kidney Disease: Improving Global Outcomes (KDIGO) Glomerular Diseases Work Group KDIGO 2021 Clinical Practice Guideline for the Management of Glomerular Diseases Kidney Int, 2021.PMID 34556256
  2. [2]Jayne DR, Gaskin G, Rasmussen N, et al. Randomized trial of plasma exchange or high-dosage methylprednisolone as adjunctive therapy for severe renal vasculitis J Am Soc Nephrol, 2007.PMID 17582159
  3. [3]Walsh M, Merkel PA, Peh CA, et al. Plasma Exchange and Glucocorticoids in Severe ANCA-Associated Vasculitis N Engl J Med, 2020.PMID 32053298
  4. [4]Stone JH, Merkel PA, Spiera R, et al. Rituximab versus cyclophosphamide for ANCA-associated vasculitis N Engl J Med, 2010.PMID 20647199
  5. [5]Jones RB, Tervaert JW, Hauser T, et al. Rituximab versus cyclophosphamide in ANCA-associated renal vasculitis N Engl J Med, 2010.PMID 20647198
  6. [6]Roberts IS, Cook HT, Troyanov S, et al. The Oxford classification of IgA nephropathy: pathology definitions, correlations, and reproducibility Kidney Int, 2009.PMID 19571790
  7. [7]Lv J, Zhang H, Wong MG, et al. Effect of Oral Methylprednisolone on Clinical Outcomes in Patients With IgA Nephropathy: The TESTING Randomized Clinical Trial JAMA, 2017.PMID 28763548
  8. [8]Lv J, Wong MG, Hladunewich MA, et al. Effect of Oral Methylprednisolone on Decline in Kidney Function or Kidney Failure in Patients With IgA Nephropathy: The TESTING Randomized Clinical Trial JAMA, 2022.PMID 35579642
  9. [9]Rauen T, Eitner F, Fitzner C, et al. Intensive Supportive Care plus Immunosuppression in IgA Nephropathy N Engl J Med, 2015.PMID 26630142
  10. [10]Houssiau FA, Vasconcelos C, D'Cruz D, et al. The 10-year follow-up data of the Euro-Lupus Nephritis Trial comparing low-dose and high-dose intravenous cyclophosphamide Ann Rheum Dis, 2010.PMID 19155235
  11. [11]Appel GB, Contreras G, Dooley MA, et al. Mycophenolate mofetil versus cyclophosphamide for induction treatment of lupus nephritis J Am Soc Nephrol, 2009.PMID 19369404
  12. [12]Rovin BH, Furie R, Latinis K, et al. Efficacy and safety of rituximab in patients with active proliferative lupus nephritis: the Lupus Nephritis Assessment with Rituximab study Arthritis Rheum, 2012.PMID 22231479
  13. [13]Rovin BH, Jayne DRW, Sanders JF, et al. Kidney Disease: Improving Global Outcomes (KDIGO) responds to the retraction of the ADVOCATE trial of avacopan for the treatment of ANCA-associated vasculitis Kidney Int, 2026.PMID 42710838

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