Primary Membranous Nephropathy

Abstract

Membranous nephropathy (MN) is a unique glomerular lesion that is the most common cause of idiopathic nephrotic syndrome in nondiabetic white adults. About 80% of cases are renal limited (primary MN, PMN) and 20% are associated with other systemic diseases or exposures (secondary MN). This review focuses only on PMN. Most cases of PMN have circulating IgG4 autoantibody to the podocyte membrane antigen PLA2R (70%), biopsy evidence PLA2R staining indicating recent immunologic disease activity despite negative serum antibody levels (15%), or serum anti-THSD7A (3%-5%). The remaining 10% without demonstrable anti-PLA2R/THSd7A antibody or antigen likely have PMN probably secondary to a different, still unidentified, anti-podocyte antibody. Considerable clinical and experimental data now suggests these antibodies are pathogenic. Clinically, 80% of patients with PMN present with nephrotic syndrome and 20% with non-nephrotic proteinuria. Untreated, about one third undergo spontaneous remission, especially those with absent or low anti-PLA2R levels, one-third progress to ESRD over 10 years, and the remainder develop nonprogressive CKD. Proteinuria can persist for months after circulating anti-PLA2R/THSD7A antibody is no longer detectable (immunologic remission). All patients with PMN should be treated with supportive care from the time of diagnosis to minimize protein excretion. Patients with elevated anti-PLA2R/THSD7A levels and proteinuria >3.5 g/d at diagnosis, and those who fail to reduce proteinuria to <3.5 g after 6 months of supportive care or have complications of nephrotic syndrome, should be considered for immunosuppressive therapy. Accepted regimens include steroids/cyclophosphamide, calcineurin inhibitors, and B cell depletion. With proper management, only 10% or less will develop ESRD over the subsequent 10 years.

Histological grading in primary membranous nephropathy is essential for clinical management and predicts outcome of patients

“…Clinical parameters, such as age, male sex, hypertension and degree of proteinuria and histological findings, including obsolescent glomeruli, presence of focal sclerosis and vascular hyalinosis, severity of tubular atrophy and interstitial fibrosis, correlated with severity of renal function impairment at the time of renal biopsy. These findings are in agreement with previous results, which showed that clinical parameters with predictive significance were age, male sex, hypertension and renal insufficiency …”

“…Primary membranous nephropathy (PMN) remains the most common cause of nephrotic syndrome in white adults, representing 20–30% of cases in 50–60‐year‐old patients, rising to 40% in ages greater than 60 years …”

“…Decisions concerning immunosuppressive Introduction Primary membranous nephropathy (PMN) remains the most common cause of nephrotic syndrome in white adults, representing 20-30% of cases in 50-60-year-old patients, rising to 40% in ages greater than 60 years. [1][2][3] Diagnosis of MN is based on optical microscopy and immunohistochemistry and/or immunofluoresence findings, showing thickening of glomerular basement membrane with or without spikes and granular deposition of immunoglobulin (Ig)G and C3 along the glomerular capillary walls. Electron microscopy demonstrates the subepithelial deposits and helps in disease classification.…”

Membranous Nephropathy: Approaches to Treatment

“…5) [72] and has been the subject of recent reviews [73,74]. Increasing or persistently elevated anti-PLA 2 R levels suggest that development of spontaneous remission is unlikely and support early initiation of immunosuppressive treatment.…”

Remission of Membranous Nephropathy after Treatment of Localised Prostate Cancer

“…A second IgG4 antibody specific for THSD7A, another podocyte membrane antigen, has been identified in 2–5% patients. There is a higher frequency of associated malignancies and a female predominance with anti-THSD7A [4]. Our patient was negative for both anti-PLA2R and anti-THSD7A antibodies.…”