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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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
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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