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Systemic lupus erythematosus is associated with renal involvement in almost 50–80% of cases. Although proliferative lupus nephritis is the most common form, isolated membranous lupus nephritis (MLN or class V lupus nephritis) accounts for 11–20% of cases while mixed proliferative and MLN (Class III + V/IV + V) can be seen in another 21–30%. MLN can present as either sub-nephrotic or nephrotic proteinuria with or without microscopic hematuria or renal dysfunction. These patients are at high risk of cardiovascular and cerebrovascular complications due to thrombotic tendency, dyslipidemia and hypertension. Uniform evidence regarding prognostic factors, outcome and therapy of MLN are still elusive. Systematic analysis of several studies have shown that sustained nephrotic proteinuria, failure to achieve complete remission and associated proliferative lesions denotes poor prognosis. In general, the long term renal survival rate is 50–90%, while end stage renal disease occurs in 12–22% cases. Transformation to proliferative nephritis is also well known, thus a close follow up is warranted in all pure MLN cases. Those with persistent nephrotic proteinuria, renal dysfunction and mixed histology should be treated aggressively with immunosuppressive agent while less severe cases can be managed with adjunctive therapies.

Studies of paediatric patients with membranous lupus nephritis (MLN) have yielded variable results, mostly due to the inclusion of mixed, i.e. proliferative nephritis. The aim of this study was to describe clinical and laboratory findings at the diagnosis of paediatric non-proliferative MLN, report the outcome and identify predictors of remission.A single-center cohort study of consecutive children diagnosed with non-proliferative MLN was performed. Clinical and laboratory measures and treatment regimens were obtained in prospective standardized assessments. Renal outcome was measured by renal parameters and steroid requirement. Predictors for remission and time to remission were determined.A total of 30 children were identified with a median follow-up time 4.1 years. Of 21 patients followed for more than 2 years, 19 (90 %) achieved clinical remission, and 16 (76 %) achieved a state of maintained clinical remission on low-dose prednisone. Three patients developed proliferative nephritis on subsequent renal biopsy. Lower albumin at the time of biopsy was correlated with a lower rate of remission and longer time to remission.Among our paediatric patient cohort the outcome of non-proliferative MLN in systemic lupus erythematosus was good. The majority of patients did not require aggressive immunosuppressive treatment to reach a stable disease state on low-dose steroid treatment.

The aim of this study was to determine the distribution of the FcgammaRlla and FcgammaRIIIa polymorphisms and their association with clinical manifestations in Korean lupus patients. Three hundred SLE (systemic lupus erythematosus) patients (48 male, 252 female) meeting 1982 ACR criteria and 197 Korean disease-free controls were enrolled. Genotyping for FcgammaRlla 131 R/H and FcgammaRIIIa 176 F/V was performed by PCR of genomic DNA using allele-specific primers and the FcgammaRIIIa genotype was confirmed by direct sequencing of PCR product in some cases. There was significant skewing in the distribution of the three FcgammaRIIa genotypes between the SLE and the controls (P=0.002 for R/R131 vs R/H131 and H/H131, OR 2.5 (95% Cl 1.4-4.5), but not in FcgammaRIIIa genotypes. FcgammaRIIa-R allele was a significant predictor of lupus nephritis, as compared with SLE patients without nephritis (P=0.034 for R131 vs H131, OR 1.4 (95% Cl 1.03-1.9)), but proliferative nephritis (WHO class III and IV) was less common in patients with FcgammaRlla-R/R131 and in FcgammaRIIa-R allele. In 300 SLE patients, high binding allele combination H131/V176 was less common in SLE with nephritis than in SLE without nephritis. Hemolytic anemia was less common in R131/F176 allele combination among four FcgammaRIIa/FcgammaRIIIa allelic combinations. Male SLE patients showed a higher frequency of renal involvement, serositis, thrombocytopenia, malar rash and discoid rash than female SLE, and male SLE had a higher frequency of FcgammaRIIa-R/R131 or R131-allele than male controls, but FcgammaRIIa or FcgammaRIIIa genotypes had no association with renal involvement in male SLE patients. FcgammaRIIa-H/H131 showed a higher frequency of hemolytic anemia and less pulmonary complications in male SLE. Female SLE patients showed higher frequency of any hematologic abnormality, lymphopenia, anticardiolipin antibody (+) and anti-Ro antibody (+) than male SLE, and had earlier onset of first symptoms. There was no skewing in FcgammaRIIa or FcgammaRIIIa genotypes between female SLE and female controls, but FcgammaRIIa-R131 allele showed skewing between female SLE with nephritis and female SLE without nephritis. The age at onset of thrombocytopenia was earlier in FcgammaRIIa R/R131 among three FcgammaRIIa genotypes, and serositis in FcgammaRIIIa-F/F176 among three FcgammaRIIIa genotypes. FcgammaRIIa-R131 homozygote was a major predisposing factor to the development of SLE and FcgammaRIIa-RI31 homozygote and R131 allele were a predisposing factor, and H131/V176 was a protective allele combination in lupus nephritis. In contrast to other ethnic patients, in our study cohort, clinical manifestation was different between male and female, and FcgammaRIIa and FcgammaRIIIa showed somewhat different clinical associations between the genders.

To better define the relationships between circulating autoantibodies and renal involvement in systemic lupus erythematosus (SLE), antibodies to both dsDNA and soluble cellular antigens were detected in sera from a large series of SLE patients. Significantly higher dsDNA binding activities and lower complement levels at onset were found in patients with renal disease; however, this was uniquely due to subjects with diffuse or focal proliferative glomerulonephritis. Patients with membranous nephropathy (MGN) showed very low dsDNA binding activities (6/9 of them being negative for dsDNA antibodies) and normal mean C3 and C4 levels. A comparison between patients with proliferative nephritis and patients without renal involvement with high dsDNA binding activities revealed significantly lower complement levels in the former group. No significant difference was observed in the prevalence of antibodies to soluble cellular antigens between patients with or without renal disease; however, nRNP antibody was two-fold more frequent in patients with MGN than in all other subgroups. This study highlights the close relationship between concurrently high anti-dsDNA and low complement levels and proliferative glomerulonephritis in SLE, and suggests that subjects with MGN may represent a subgroup of SLE patients showing peculiar serological features. Different mechanisms possibly involved in the pathogenesis of MGN in SLE are discussed.

Proliferaiive nephritis is an old term and one often used loosely to mean glomerular hypercellularity. It has featured prominenlly in pathological classifications of nephritis since the systematic studies of Volhard and Farr.1 Individual types of proliferative nephritis are described in detail elsewhere in this series, and it is not the purpose of this chapter to reiterate these discussions; but rather to consider glomerular proliferation more generally. This is especially pertinent now for two reasons: first because recent clinical and experimental studies have defined the cellular composition of glomeruli much more accurately than has previously been possible; and secondly because of the wealth of information about the control of cell proliferation that has emerged from in vitro studies over the past 5 years. These emphasize the close links between factors controlling cell proliferation, acute inflammaiion and synthesis of the extracellular matrix (i.e. scarring).2,3

Tissue culture of isolated glomeruli from patients with glomerulonephritis. To study aspects of glomerular cell response in varying types of glomerulonephritis, we evaluated isolated glomeruli from 101 normal and diseased adult human renal biopsy specimens in tissue culture. Glomerular cell outgrowths from normal glomeruli consisted of large stellate cells (type I) and smaller fusiform cells (type II). A very occasional cell (type III), which had the features of a macrophage, was seen. The cellular outgrowth from isolated glomeruli reflected the numbers and types of cells present in the diseased glomeruli. Reduced numbers of cells were found in the outgrowth of sclerotic, hypocellular glomeruli. Glomeruli from biopsy specimens with altered morphologic appearances but no increase in cellularity (minimal change nephropathy, membranous nephropathy) produced the same growth pattern as from glomeruli isolated from normal kidneys. In mesangial proliferative nephritis, increased numbers of type II cells were detected in the outgrowth. Large numbers of macrophages were found in the glomerular outgrowth of patients with crescentic glomerulonephritis. Macrophages were absent when crescentic glomeruli were sclerosed, indicating the importance of macrophages in the acute hypercellular phase of crescent formation. Cultures tissulaires de glomerules isoles de malades atteints de glomerulonephrite. Afin d'evaluer les aspects de la reponse des cellules glomerulaires dans differents types de glomerulonephrites, des glomerules isoles de 101 biopsies d'adultes normaux ou malades ont ete etudies en culture de tissu. Les cellules glomerulaires cultivees a partir de glomerules normaux etaient de grandes cellules etoilees (type I) et des cellules fusiformes plus petites (type II). Plus rarement des cellules ayant les caracteres de macrophages (type III) ont ete observees. Pour les glomerules pathologiques, la culture cellulaire a reflete le nombre et le type des cellules initialement presentes. Le nombre de cellules etait diminue dans les cultures de glomerules sclerotiques. Les glomerules modifies mais sans hypercellularite (modifications minimes, extra-membraneuses) donnent issue aux memes cultures cellulaires que les glomerules normaux. Les glomerules de nephrite mesangiale proliferative donnent un nombre accru de cellules de type II. Les macrophages en grand nombre ne sont observes qu'a partir de glomerules obtenus chez des malades atteints de glomerulonephrites proliferatives. Les macrophages sont absents quand les glomerules avec des croissants sont scleroses, ce qui indique l'importance des macrophages dans la phase hypercellulaire aigue de la formation des croissants.

In Reply.— Dr Sporn's well-documented recent observation of renal cortical necrosis following streptococcal infection lends support to our impression both from the older literature and from our case that such an association should be recognized. A causal connection also seems implied by the apparent absence in Dr Sporn's patient of any other known cause of cortical necrosis. Evidently the differentiation of poststreptococcal glomerulonephritis from cortical necrosis or from combined cortical necrosis with proliferative nephritis has prognostic importance and thus requires our consideration in appropriate circumstances.