Therapies for Membranous Nephropathy: A Tale From the Old and New Millennia

Abstract

Primary Membranous Nephropathy (PMN) is the most frequent cause of nephrotic syndrome in adults. If untreated, PMN can lead to end-stage renal disease; moreover, affected patients are at increased risk of complications typical of nephrotic syndrome such as fluid overload, deep vein thrombosis and infection. The association of PMN with HLA-DQA1 and the identification in around 70% of cases of circulating autoantibodies, mainly directed towards the phospholipase A2 receptor, supports the autoimmune nature of the disease. In patients not achieving spontaneous remission or in the ones with deteriorating kidney function and severe nephrotic syndrome, immunosuppression is required to increase the chances of achieving remission. The aim of this review is to discuss the evidence base for the different immunosuppressive regimens used for PMN in studies published so far; the manuscript also includes a section where the authors propose, based upon current evidence, their recommendations regarding immunosuppression in the disease, while highlighting the still significant knowledge gaps and uncertainties.

The Role of Rituximab in Primary Focal Segmental Glomerular Sclerosis of the Adult

“…30,31 This finding may also lead to speculations as to whether RTX dose may affect response, as already questioned in other glomerulonephritides. 25,32 In our study, where heterogeneous RTX dosing regimens were used, no clear dose-response association emerged, although in the context of an underpowered analysis.…”

“…Response to treatment was evaluated at 3, 6, and 12 months after RTX and during the subsequent follow-up. Response was subclassified as complete response and partial response (PR), in keeping with the standard definitions used in nephrotic syndrome studies ( Supplementary Methods ) 25 ; moreover, the tapering of other immunosuppressive drugs was a criterion required to classify the patient as responder. Lack of response was classified as no response (NR) ( Supplementary Methods ).…”

Salvianolic acid B attenuates membranous nephropathy by activating renal autophagy via microRNA-145-5p/phosphatidylinositol 3-kinase/AKT pathway

“…MN is a primary glomerular disease accompanied by immune-mediated inflammation [ 26 ]. Thus, proinflammatory mediators and macrophage infiltration in the kidney were examined.…”

An Alternative Therapy for Membranous Glomerulonephritis: A Case Report

“…In the last 10 years a lot of research has taken place the fi rst of them following the experimental model of Heymann Nephritis described in 1959 by a Pediatrician and his team in Cleveland [5]. Since then sevaral studies have been carried one to try to defi ne the podocyte antigen in humans with the identifi cation of PLA 2 [6] being the Target Podocyte Antigen, THSD7A [4] which is a glomerular transmembrane glycoprotein, fi nally in cases of GMN (-) both to PLA 2 R and THSD7A it have been isolated two proteins Exostosin 1 and 2 that accumulated in the subepithelial deposits [5] about 40% of the patients will undergo an spontaneous remission and another 30% a poor o no response to immuno-suppressive therapy and will progress to End Stage Kidney Disease (ESKD) and will require Renal Function Replacement Therapy (RFRT) [7].…”

“…Inmuno fl orescence reveled a deposition with a granular pattern of light epimembranous positive graded 2 for IgG, Kappa and Lambda, scarce C3c while the rest of inmune reactants were negative, a diagnosis of Idiophatic Membranous Glomerunonephritis was established asociated to mild interstitial fi brosis and tubular atrophy (15%). Therapies of Membranous Nephropathy have change with the time [7]. With all the above fi ndings I started on 01/19/17 Micophenolic acid 500 mg tid and due to the presence of fi brosis and atrophy I placed on an anti-infl ammatory protocol that I reported been usefull in a previous article [8] and started on pioglitazone 45 mg 1qd, febuxostat 80 mg 1 qd, Vit D 4000 U/day, Atorvastatin 20 mg 1 qd pentoxifi line 400 mg 1 qd.…”