# Membranous Nephropathy > Membranous nephropathy for NEET-SS Nephrology: anti-PLA2R antibody, Ponticelli and rituximab, risk stratification, secondary causes and thrombosis notes. - Canonical URL: https://prepelephant.com/topics/neet-ss/nephrology/membranous-nephropathy-dm - Exam / course: NEET-SS · Subject: Nephrology - Publisher: PrepElephant (https://prepelephant.com) — Prepared and reviewed by the PrepElephant Academic Review Team - First published: 2026-10-02 - Last updated: 2026-10-02 - How to cite: "Membranous Nephropathy", PrepElephant, https://prepelephant.com/topics/neet-ss/nephrology/membranous-nephropathy-dm ## Direct answer Antibodies against the M-type phospholipase A2 receptor on podocytes drive roughly 70 to 80 per cent of primary membranous nephropathy, making this the first glomerular disease with a commercially readable circulating marker that tracks activity, guides immunosuppression and warns of relapse. The kidney biopsy shows subepithelial immune deposits with spike-and-dome basement membrane reaction on electron microscopy and granular IgG — predominantly IgG4 — along the capillary loops, with complement characteristically normal. Management opens with six months of optimised supportive care, because spontaneous remission claims about a third of patients, and only persistent high-risk disease — proteinuria above 8 grams per day with falling function or a high antibody titre — moves to rituximab or a Ponticelli steroid-cyclophosphamide course. ## What you must remember - **Anti-PLA2R:** positive in 70–80 per cent of primary disease; titres parallel activity, precede clinical relapse and should be undetectable in remission; THSD7A accounts for a small residue. - **Rule of thirds:** a third spontaneous remission, a third persistent proteinuria, a third progressive disease — the justification for watchful waiting. - **Secondary causes:** hepatitis B (a leading driver in endemic regions including India), lupus class V, solid malignancy in the over-sixties, and drugs such as NSAIDs and penicillamine — treat the cause before the kidney. - **Risk categories:** low risk — proteinuria under 4 g/day with normal function; high risk — over 8 g/day persisting beyond six months, declining eGFR, or a high anti-PLA2R titre. - **Ponticelli regimen:** alternating cycles of steroids and cyclophosphamide over six months — the classic cyclical protocol rituximab now rivals. - **Rituximab:** first-line for moderate-to-high risk primary disease in current practice, with remission building over months. - **Complement quirk:** C3 and C4 stay normal in primary membranous — a low C3 with this biopsy appearance points to lupus. - **Thrombosis:** renal vein thrombosis risk climbs steeply when serum albumin falls below 25 g/L; anticoagulation is individualised, balancing bleeding risk. ## Six months of watchful waiting, then a decision A 54-year-old man presents with ankle oedema and a month of frothy urine: proteinuria 6.5 g/day, albumin 24 g/L, creatinine 0.9 mg/dL, complement normal, hepatitis B surface antigen negative, anti-PLA2R titre strongly positive. The opening prescription is not chemotherapy — it is an ACE inhibitor or ARB at tolerated maximum, blood pressure to below 130/80, a moderate protein restriction, lipid management and vaccination review, because a third of such patients remit on their own and cyclophosphamide carries bladder and marrow costs he may never need to pay. Month three: proteinuria 7 g. Month six: 9.2 g with albumin now 19 g/L and creatinine drifting to 1.15 mg/dL — he has declared himself high risk, and waiting longer now costs nephrons. Rituximab is chosen over Ponticelli for its fertility-sparing and malignancy-sparing profile; the anti-PLA2R titre, checked at three and six months, should fall first, with proteinuria following over the next two quarters. Had he returned instead with flank pain and a swollen left leg at month four, the calculus changes: a renal vein thrombosis on CT would trigger formal anticoagulation, since albumin below 25 g/L marks the threshold where the thrombotic risk begins to outrank the bleeding risk in most scoring approaches. ## Where the examiner hunts Three traps recur. First, the hepatitis B stem: membranous nephropathy with a positive surface antigen in a young Indian adult is treated with a nucleos(t)ide analogue first, because blanket immunosuppression can precipitate fulminant hepatitis reactivation — a sequence every viva examiner enjoys probing. Second, the age rule: membranous in a patient over sixty mandates malignancy screening — colonoscopy, chest imaging, and in men prostate assessment — because the kidney may be the paraneoplastic herald. Third, the antibody-clinical mismatch: a high anti-PLA2R titre with a falling creatinine clearance means active disease despite stable proteinuria, and the exam expects you to say the titre, not the urine dipstick, is the earlier warning. A fourth, quieter point: spontaneous remission can arrive as late as fourteen to eighteen months, so patience in genuinely low-risk disease is a mark of judgement, not negligence. ## Frequently asked questions ### Which antibody defines primary membranous nephropathy? Anti-PLA2R, positive in about 70–80 per cent; its titre tracks disease activity and foreshadows relapse. ### When is immunosuppression indicated? Persisting proteinuria above 8 g/day, declining renal function, or a high anti-PLA2R titre after a period of supportive care; low-risk disease is managed expectantly. ### What is the Ponticelli regimen? Six months of alternating corticosteroid and cyclophosphamide cycles — the historical standard that rituximab now challenges. ### Why screen every older patient with new membranous disease? Solid-organ malignancy is a recognised cause, and the kidney lesion may precede the cancer diagnosis by months. ### At what albumin does renal vein thrombosis risk justify anticoagulation? Commonly below 25 g/L, individualised for bleeding risk — the nephrotic state is profoundly prothrombotic. ### What does the electron microscope show? Continuous subepithelial deposits with spike-and-dome basement membrane reaction — the architectural signature of the disease.