Post-infectious glomerulonephritis: SAQ

This boy has typical post-streptococcal glomerulonephritis. The combination of smoky brown urine, periorbital and ankle oedema, and hypertension two weeks after an untreated sore throat, with dysmorphic red cells and red cell casts, a low C3 with a normal C4, and a raised antistreptolysin O titre, is diagnostic. The latency of two weeks after pharyngitis, the low C3 with preserved C4, and the raised ASO titre together distinguish PSGN from IgA nephropathy and from the other hypocomplementaemic glomerulonephritides. ^[1]

Question 1 (10 marks)

Outline the pathophysiology of this condition and explain the acute management of this child, including fluid and blood-pressure control and streptococcal eradication. ^[2]

The pathophysiology is an immune-complex glomerulonephritis in which nephritogenic streptococcal antigens lodge in the glomerulus and activate complement in situ. The nephritis-associated plasmin receptor, a glyceraldehyde-3-phosphate dehydrogenase on the streptococcal surface, binds mesangium and podocytes and activates plasmin, which drives alternative-pathway complement activation and C3-dominant injury. Streptococcal pyrogenic exotoxin B colocalises with the deposits. Because the alternative and lectin pathways are engaged while the classical pathway is relatively spared, the C3 falls while the C4 stays normal, which is the serological fingerprint of PSGN. The inflamed capillary wall leaks red cells and protein and retains salt and water, producing the haematuria, oedema, hypertension, and acute kidney injury. ^[3]

The acute management is supportive, because typical PSGN resolves spontaneously and no immunosuppression changes its course. I would first attend to the airway, breathing, and circulation, and assess for the complications of hypertensive encephalopathy and pulmonary oedema, neither of which is present here but which I would actively exclude. His blood pressure of 128 over 84 is above the 95th centile for age, so I would treat the hypertension with a calcium channel blocker such as amlodipine, starting at 0.1 mg per kg once daily and titrating to a maximum of 10 mg per day. ^[2]

Fluid and salt balance is the cornerstone. Because he is overloaded rather than dehydrated, I would restrict fluids to insensible losses plus urine output and give a no-added-salt diet, monitoring his daily weight. His oedema and his volume-dependent hypertension would respond to a loop diuretic, and I would give oral frusemide at 1 to 2 mg per kg per dose. I would monitor renal function and electrolytes for acute kidney injury and hyperkalaemia, and treat these expectantly, reserving dialysis for refractory hyperkalaemia, severe metabolic acidosis, or pulmonary oedema unresponsive to diuretics. ^[2]

Streptococcal eradication clears the nephritogenic strain, prevents spread to contacts, and removes ongoing antigen, although it does not change the established glomerulonephritis. I would give phenoxymethylpenicillin (penicillin V) orally for 10 days, at 500 mg twice daily because he is over 20 kg, or a single intramuscular dose of benzathine penicillin if adherence were uncertain. If he were penicillin-allergic I would use a macrolide. I would not give corticosteroids, because typical PSGN is self-limiting and immunosuppression exposes a resolving disease to harm. ^[1]