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]

Question 2 (10 marks)

Explain the role of complement measurement and streptococcal serology in confirming the diagnosis, and describe how your management and counselling would change if the C3 had not normalised by eight weeks. [1]

The complement profile is the single most important blood test in PSGN. A low C3 with a normal C4 at presentation, recovering to normal within six to eight weeks, is diagnostic of typical PSGN in the right clinical context. The low C3 reflects consumption downstream of the alternative-pathway C3 convertase, and the preserved C4 reflects relative sparing of the classical pathway, with the lectin pathway also contributing. I would measure both C3 and C4 at presentation, and crucially I would recheck the C3 at six to eight weeks to confirm recovery, because a C3 that stays low beyond eight weeks is no longer typical PSGN. [3]

Streptococcal serology confirms the preceding infection. The antistreptolysin O titre rises in around 80 percent of children after pharyngitis, and this boy's raised ASO titre supports a recent throat infection. However, the ASO is less reliable after skin disease, where the anti-DNase B antibody is the more sensitive test because it stays elevated for many months. A single raised titre confirms past exposure, and a rising titre between acute and convalescent samples is more specific. Throat and skin swabs may be negative by the time PSGN presents, so a negative culture does not exclude the diagnosis. [1]

If his C3 had not normalised by eight weeks, I would change the working diagnosis. Persistent hypocomplementaemia after eight weeks is not a slow recovery; it raises C3 glomerulopathy, membranoproliferative glomerulonephritis, or lupus nephritis. C3 glomerulopathy can follow an apparent streptococcal illness and behaves as a chronic complement-mediated disease rather than a self-limiting one, and lupus nephritis lowers both C3 and C4, so I would also check the C4 and an autoimmune screen. I would refer him urgently to a paediatric nephrologist and arrange a renal biopsy to confirm the diagnosis histologically, because these conditions have fundamentally different management that may include immunosuppression. [1]

My counselling would shift accordingly. For a typical case I would reassure the family that over 95 percent of children recover completely, that the C3 will normalise within eight weeks, and that he needs follow-up of blood pressure and urinalysis. For the atypical persistent case I would explain that the diagnosis is now uncertain, that biopsy is needed, and that the disease is likely to require long-term nephrology care, while continuing the supportive measures of blood-pressure control and monitoring of renal function in the interim. I would weigh his follow-up toward the risk factors for chronicity, namely heavier proteinuria, persistent hypertension, persistent low C3, and a higher presenting creatinine. [1]