Nephritic Syndrome and Rapidly Progressive GN — Advanced

Post-infectious GN commonly follows an infection (classically streptococcal pharyngitis or skin infection) with a latency of 1–3 weeks in adults and presents with nephritic features (haematuria, RBC casts, oedema, hypertension). Complement profile typically shows low C3 with normal or near-normal C4 because the alternative complement pathway is activated. IgA nephropathy classically presents with synpharyngitic haematuria (concurrent with infection) and usually normal complement levels. ANCA-associated GN is pauci-immune and typically has normal complement levels. Anti-GBM disease shows rapidly progressive GN often with pulmonary haemorrhage and IF demonstrates linear IgG; complement is usually not characteristically low. Class V lupus nephritis (membranous) would more commonly have nephrotic-range proteinuria and both C3 and C4 are often low in active lupus.

In a patient with life‑threatening pulmonary haemorrhage and rapidly progressive renal failure where anti‑GBM disease or small‑vessel vasculitis is strongly suspected, immediate treatment should not be delayed for confirmatory tests. High‑dose intravenous steroids and urgent plasma exchange are indicated when anti‑GBM disease is suspected, particularly with alveolar haemorrhage, because plasma exchange removes pathogenic antibodies. Concurrent immunosuppression (cyclophosphamide or rituximab according to the clinical scenario) is usually given. Waiting for tests risks deterioration. Antibiotics are not indicated unless there is clear infection. Monotherapy with cyclophosphamide without steroids/plasma exchange is inadequate for life‑threatening pulmonary haemorrhage.

Linear, smooth, diffuse IgG staining along the glomerular basement membrane on immunofluorescence is the hallmark of anti‑GBM disease (Goodpasture’s). Post‑infectious GN and immune complex diseases (e.g. IgA nephropathy) show granular 'lumpy-bumpy' immune complex deposition. C3 glomerulopathy is characterised by dominant C3 staining (often without strong IgG), reflecting alternative pathway activation. ANCA‑associated GN is typically pauci‑immune with little or no immune complex deposition on IF.

Randomised evidence (e.g. trials synthesised in guideline updates) has not supported routine use of plasma exchange for all patients with severe ANCA‑associated renal disease to prevent end‑stage kidney disease. Current practice is to reserve PLEX for patients with life‑threatening pulmonary haemorrhage and consider it selectively in very severe renal failure (though routine use is not recommended). PLEX is not indicated because of infection alone, is not considered harmful in general when used appropriately, and should not replace induction immunosuppression; rather it may be used in addition to immunosuppressive therapy in selected cases.

Class IV (diffuse proliferative) lupus nephritis is characterised by diffuse endocapillary proliferation affecting >50% of glomeruli and prominent subendothelial immune complex deposition, often visualised as 'wire-loop' lesions on light microscopy and granular immune complexes on immunofluorescence. Subepithelial humps are more typical of post‑infectious GN. Mesangial‑only deposits typify class II. Paucity of immune complexes suggests pauci‑immune (ANCA) disease, not lupus. Thickened GBMs with capillary wall granular deposits alone are more typical of membranous (class V) lupus nephritis.

When hyperkalaemia is associated with ECG changes (peaked T waves, widening QRS), the immediate priority is to stabilise the cardiac membrane with intravenous calcium (calcium gluconate or chloride). This does not lower serum potassium but reduces the risk of malignant arrhythmia while potassium‑lowering measures are instituted (insulin/dextrose, nebulised salbutamol, bicarbonate if acidotic) and preparations are made for definitive therapy such as diuretics or dialysis. Nebulised salbutamol or insulin/dextrose are temporising measures to shift potassium intracellularly but are not the immediate membrane stabiliser. Oral resins act slowly and are not suitable for immediate stabilisation. Dialysis may be required urgently but one should stabilise the patient first and institute measures to lower potassium while arranging dialysis.

In infection‑associated (eg. infective endocarditis) immune-complex GN, the primary intervention is eradication of the underlying infection with appropriate intravenous antibiotics ± surgical source control. Immunosuppression (steroids, cyclophosphamide) is generally contraindicated while infection is active because it may worsen infection. Plasmapheresis is not routinely used for infective endocarditis–related GN and carries risk. ACE inhibitors may be used cautiously for blood pressure/proteinuria control but do not replace treating the infection and should not preclude aggressive infection management. Therefore, treat the infection first and reassess renal disease once infection is controlled.

Cellular crescents represent an acute, potentially reversible stage of crescent formation. When crescents are predominantly cellular and chronic changes (interstitial fibrosis, tubular atrophy) are minimal, there is a higher likelihood of renal recovery with timely and appropriate aggressive immunosuppressive therapy. Fibrous crescents and extensive chronic tubulo‑interstitial damage predict poor recovery. Cellular crescents do not mandate withholding immunosuppression; rather they often indicate a window for effective treatment. Statements that minimize the importance of chronicity or assert immediate dialysis based solely on low crescent fraction are incorrect.

For ANCA‑associated vasculitis, maintenance therapy is usually required after induction to reduce relapse risk. Rituximab given at fixed intervals (eg. 6‑monthly) has been shown to be effective for maintenance and is commonly used, especially in patients with PR3‑ANCA or those at higher risk of relapse. Long‑term cyclophosphamide is avoided because of cumulative toxicity. No maintenance is inappropriate due to relapse risk. Lifelong high‑dose steroids is not a recommended strategy owing to adverse effects. Short mycophenolate alone is not optimal maintenance for higher‑risk PR3‑ANCA patients.

Absolute (urgent) indications for dialysis include refractory fluid overload (pulmonary oedema) despite maximal medical therapy, life‑threatening hyperkalaemia unresponsive to medical measures, severe metabolic acidosis, and overt uraemic complications (pericarditis, encephalopathy). Refractory pulmonary oedema causing hypoxia despite diuretics is thus a clear indication for urgent dialysis. Elevated creatinine alone without symptoms or uncontrolled metabolic disturbances does not mandate immediate dialysis. Proteinuria and anaemia without other complications are not urgent dialysis indications.