Nephrotic Syndrome Viva

Long Case Viva Defence

The patient

"Mrs Examiner, this is Mr James Wright, a 56-year-old engineer who presents to the renal outpatient clinic with three months of progressive anasarca and a new diagnosis of primary membranous nephropathy with nephrotic syndrome. His PCR is 680 mg/mmol, albumin 18 g/L, creatinine 95, anti-PLA2R strongly positive, and biopsy confirms stage II membranous nephropathy. He has past hepatitis B infection with anti-HBc positivity but is HBsAg negative. His main problems are: one, primary membranous nephropathy requiring cause-specific immunosuppression; two, hypoalbuminaemia at a threshold mandating anticoagulation; three, hypertension and hyperlipidaemia; four, hepatitis B reactivation risk with rituximab; and five, the need for ongoing surveillance for progression to CKD and for occult malignancy at his age." ^[1]

Problem list

1. Primary membranous nephropathy (anti-PLA2R positive, stage II on biopsy) with nephrotic syndrome
2. Hypoalbuminaemia at 18 g/L — thrombotic risk threshold met
3. Hypertension 148/92 and hyperlipidaemia
4. Past hepatitis B infection (anti-HBc positive) — reactivation risk with planned rituximab
5. Need for occult malignancy surveillance at age 56 ^[1]

Integrated management plan

"My plan addresses each problem. First, I confirm the diagnosis — the strongly positive anti-PLA2R and the biopsy are diagnostic of primary membranous nephropathy. I exclude secondary causes with ANA, complement, free light chains, viral serology — all normal here. I would still do an age-appropriate malignancy screen — chest X-ray, colorectal screening, prostate assessment — because solid tumour membranous is PLA2R-negative but paraneoplastic processes can rarely coexist, and I would re-screen at intervals." ^[1]

"Second, anti-proteinuric therapy for every patient — an ACE inhibitor at maximum tolerated dose. I would start ramipril 5 mg and titrate to 10 mg, accepting up to a 30 per cent creatinine rise, monitoring potassium, and not combining with an ARB. I would add an SGLT2 inhibitor for additional proteinuria reduction per KDIGO 2024. Blood pressure target less than 130/80, individualised." ^[1]

"Third, cause-specific immunosuppression. He meets the criteria — persistent nephrotic-range proteinuria and hypoalbuminaemia with a high anti-PLA2R titre and normal GFR. Per the MENTOR trial, my preferred first-line agent is rituximab 1 gram intravenously on day 1 and day 15, with a repeat course at 6 months if the titre remains high. MENTOR showed rituximab was non-inferior to cyclosporine at 6 months and superior at 24 months. Critically, before rituximab, I address his hepatitis B — anti-HBc positivity means past infection, and rituximab can reactivate hepatitis B with fulminant hepatitis. I would start prophylactic entecavir or tenofovir before rituximab and continue for at least 12 months, monitoring HBV DNA." ^[1]

"Fourth, complication prevention. His albumin is 18 — well below the 25 to 30 g/L threshold for prophylactic anticoagulation in membranous nephropathy, the highest-risk substrate. I would start a DOAC or warfarin for the duration of the nephrotic state. I would give pneumococcal and influenza vaccination now, avoid live vaccines during rituximab-induced B-cell depletion, and start atorvastatin for his hyperlipidaemia. For his oedema, salt restriction and frusemide 80 mg daily, adding a thiazide if resistant, aiming for 0.5 to 1 kg weight loss per day and avoiding over-diuresis." ^[1]

"Fifth, follow-up. I would monitor PCR, albumin, creatinine, and anti-PLA2R titre monthly. The anti-PLA2R titre fall precedes and predicts clinical remission — a falling titre confirms response. I would re-image for renal vein thrombosis if he develops any acute flank pain, haematuria, or sudden GFR fall, because renal vein thrombosis is commonest in membranous nephropathy." ^[1]