lupus erythematosus:almost 10-20 % of ptns with lupus
nephritishave MN, called class V lupus nephritis. Some ptns with membranous
lupuspresent only with renal disease with no Sms or serologicevidence of lupus, despite they may arise several mo after appearance
with NS. Lupus should be expected in any 👉 young womanwith idiopathicMN. Moreover, there’re some histologiccriteriaon IF(IgG2, IgG3, IgA, IgM, & C1q stain) & EM (subendothelial + subepithelial deposits + tubuloreticular structures in glomerular
endothelialcells) denoting underlying lupus.PLA2R AB
are 👉 typically negative
in class Vlupus
However, ptns with PLA2R-related primary MN may also have +ve ANAif they also have non-renal SLE. Additional features, e.g., +ve PLA2R, lack of C1q st., predominant IgG4, absolute subepithelial dense
absent tubular BM staining will help DD primary MN from class Vlupus
 Drugs: Exposure to medications treating rheumatoid arthritishas been involved in developing MN, including NSAIDs, penicillamine, parenteral
gold salts, alemtuzumab, mercurial
salt, elemental mercury & possibly anti-TNFagents (etanercept, infliximab). 3 criteria in favor of accusing NSAID👉:
1)Noother evidentcause for MN
of proteinuria after NSAID cessation
Many of the ptns who developed MN had been ttt
with diclofenac, but probably any NSAID can be involved, including COX2inhibitors. Incidence of MN may reach 7 % in penicillamine & 1-3 % in parenteral gold(risk of oral gold is lower). Tiopronin is likepenicillamine,used for cystine stones (incidence is
High-dose captopril, with free thiol group, has also been implicated.
alleles DRB1*0301 (DR3) & DQA1*0501 > susceptible to develop MN, as well as drug-induced lupus, after gold salts. These alleleshave also been identified as risk allelesfor primary MNin Caucasians.
Proteinuria may develop within 1st6-12 mo of therapy but can occur as late as 3-4 y. Drug withdrawal
> resolution of proteinuria, but with penicillamine & gold,proteinuria may persistently rise for 1st1-12 mo (2 mo) after holding therapy. Mean time to
resolution of proteinuria is 9-12 months. Gold& NSAIDscan also lead to minimal
change disease, whilst
penicillamine can > immune complex crescentic GN. Anti-TNF> new onset lupus nephritis& pauci-immune necrotizing & crescenticGN.
Hepatitis B virus:MN of HBV primarily seen in children in endemiczones, many cases are asymptomaticwithout active hepatitis. Liver transaminases usually normalor only slightly raised, & serology is +ve
for HBs Ag, anti-core AB, & e Ag. It seems that the eAg & anti-e AB are
mainly deposited in the glomeruli.
HBV + lupus > only form of MNthat may be associated with hypocomplementemia. Spontaneous
resolutionof proteinuria is commonly seen in childrenbut NOT in adults, who may exhibit progressive illness.
Hepatitis C virus:MN is uncommonly observed with
chronic HCV hepatitis.
Syphilis: eithercongenital or secondaryhave been correlated with MN. Treponema Ags have been recognized in glomeruli by IF, results from glomerular depositswith anti-Treponema pallidum AB. Moreover, ttt of syphilis can resolve
the glomerular lesions.
 Malignancy: about👉 5-20
% of adult MN ptns, especially > 65 ys, have been reported to show underlying
mostly solid tumours (e.g., carcinoma prostate, lung, breast, bladder, or GIT), less commonly hematologic malignancy, e.g., CLL. Risk of malignancy with MN may be from 2-12
times higherthan general population. The postulated
mechanism:deposited tumour Ags upon glomeruli > AB
deposition & complement activation, > epithelial & GBM injury, & proteinuria. On contrary for these reports, other cases may
show coincident disease, rather than direct relation, as:
with tumours is common in males > 50ys, same cohort tends to have MN.
of NS with removalof tumour does not mean a therapeutic effect, as a high rateof spontaneous remissioncan be seen MN.
Primary vs secondaryMN: Several histological criteriaby IM & EM have been recognised that may help DD between primary& secondary types of MN:
structuresin the glomerular
endothelialcells (caused by interferon a) is robust indicator for lupus MN seen
prior to the typical systemic& serologic criteria of SLE.
depositson EM are typically subepithelial & intramem-branous. Mesangial depositsare not common. Secondary
are often mesangialand/or subendothelial deposits, suggesting circulating immune cx.
3)Tubular BMstaining for IgG on IM is rare in primary MN but is common in secondaryMN e.g., SLE. Some ptns develop anti-tubularBM AB with tubulointerstitial nephritis.
subepithelial immune depositsin primary MN predominantly
stain +ve for IgG & C3 by IF. Presence of IgA, M, & C1q (= "full
house" pattern) suggest > secondary aetiology e.g.,
class Vlupus nephritis.
5)IgG deposits in primary MN are mainly IgG4, other isotypeshv bn observed in some causes of secondary MN, e.g., lupus-associated MN, IgG1 & 3may predominate; by contrast, predominant IgG1&2
has been observed in putative malignancy-with MN.
6)Ag phospholipaseA2 receptor (PLA2R) or thrombospondin