Abstract. The currently used classification reflects our understanding of the pathogenesis of the various forms of lupus nephritis, but clinicopathologic studies have revealed the need for improved categorization and terminology. Based on the 1982 classification published under the auspices of the World Health Organization (WHO) and subsequent clinicopathologic data, we propose that class I and II be used for purely mesangial involvement (I, mesangial immune deposits without mesangial hypercellularity; II, mesangial immune deposits with mesangial hypercellularity); class III for focal glomerulonephritis (involving Ͻ50% of total number of glomeruli) with subdivisions for active and sclerotic lesions; class IV for diffuse glomerulonephritis (involving Ն50% of total number of glomeruli) either with segmental (class IV-S) or global (class IV-G) involvement, and also with subdivisions for active and sclerotic lesions; class V for membranous lupus nephritis; and class VI for advanced sclerosing lesions]. Combinations of membranous and proliferative glomerulonephritis (i.e., class III and V or class IV and V) should be reported individually in the diagnostic line. The diagnosis should also include entries for any concomitant vascular or tubulointerstitial lesions. One of the main advantages of the current revised classification is that it provides a clear and unequivocal description of the various lesions and classes of lupus nephritis, allowing a better standardization and lending a basis for further clinicopathologic studies. We hope that this revision, which evolved under the auspices of the International Society of Nephrology and the Renal Pathology Society, will contribute to further advancement of the WHO classification.The morphologic changes in a renal biopsy from a patient with systemic lupus erythematosus (SLE) comprise a spectrum of vascular, glomerular, and tubulointerstitial lesions. The classification of SLE nephritis has evolved over the past 40 years as more lesions were identified and defined. It has been an increasing challenge to apply new pathogenetic insights to the interpretation of the renal biopsy in SLE and to correlate pathologic findings with clinical symptoms, choice of treatment, and prognosis. The current classification, which was advanced in 1982 (1) and revised in 1995 (2), reflects our understanding of the pathogenesis of the various forms of renal injury in SLE nephritis. However, subsequent clinicopathologic studies have revealed the need for clarification of the different categories and the diagnostic terminology. The clas-

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The currently used classification reflects our understanding of the pathogenesis of the various forms of lupus nephritis, but clinicopathologic studies have revealed the need for improved categorization and terminology. Based on the 1982 classification published under the auspices of the World Health Organization (WHO) and subsequent clinicopathologic data, we propose that class I and II be used for purely mesangial involvement (I, mesangial immune deposits without mesangial hypercellularity; II, mesangial immune deposits with mesangial hypercellularity); class III for focal glomerulonephritis (involving <50% of total number of glomeruli) with subdivisions for active and sclerotic lesions; class IV for diffuse glomerulonephritis (involving > or =50% of total number of glomeruli) either with segmental (class IV-S) or global (class IV-G) involvement, and also with subdivisions for active and sclerotic lesions; class V for membranous lupus nephritis; and class VI for advanced sclerosing lesions. Combinations of membranous and proliferative glomerulonephritis (i.e., class III and V or class IV and V) should be reported individually in the diagnostic line. The diagnosis should also include entries for any concomitant vascular or tubulointerstitial lesions. One of the main advantages of the current revised classification is that it provides a clear and unequivocal description of the various lesions and classes of lupus nephritis, allowing a better standardization and lending a basis for further clinicopathologic studies. We hope that this revision, which evolved under the auspices of the International Society of Nephrology and the Renal Pathology Society, will contribute to further advancement of the WHO classification.

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Abstract. Proteinuria is a poorly understood feature of many acquired renal diseases. Recent studies concerning congenital nephrotic syndromes and findings in genetically modified mice have demonstrated that podocyte molecules make a pivotal contribution to the maintenance of the selective filtration barrier of the normal glomerulus. However, it is unclear what role podocyte molecules play in proteinuria of acquired renal diseases. This study investigated the mRNA and protein expression of several podocyte-associated molecules in acquired renal diseases. Forty-eight patients with various renal diseases were studied, including minimal change nephropathy, focal segmental glomerulosclerosis, IgA nephropathy, lupus nephritis, and diabetic nephropathy, together with 13 kidneys with normal glomerular function. Protein levels of nephrin, podocin, CD2-associated protein, and podocalyxin were investigated using quantitative immunohistochemical assays. Real-time PCR was used to determine the mRNA levels of nephrin, podocin, and podoplanin in microdissected glomeruli. The obtained molecular data were related to electron microscopic ultrastructural changes, in particular foot process width, and to clinical parameters. In most acquired renal diseases, except in IgA nephropathy, a marked reduction was observed at the protein levels of nephrin, podocin, and podocalyxin, whereas an increase of the glomerular mRNA levels of nephrin, podocin, and podoplanin was found, compared with controls. The mean width of the podocyte foot processes was inversely correlated with the protein levels of nephrin (r ϭ Ϫ0.443, P Ͻ 0.05), whereas it was positively correlated with podoplanin mRNA levels (r ϭ 0.468, P Ͻ 0.05) and proteinuria (r ϭ 0.585, P ϭ 0.001). In the diseases studied, the decrease of slit diaphragm proteins was related to the effacement of foot processes and coincided with a rise of the levels of the corresponding mRNA transcripts. This suggests that the alterations in the expression of podocyte-associated molecules represent a compensatory reaction of the podocyte that results from damage associated with proteinuria.

tion than glomerulonephritis in relation to WG. This difference Renal histology in ANCA-associated vasculitis: Differences may be due to a delayed establishment of diagnosis in patients between diagnostic and serologic subgroups.with MPA compared to patients with WG. Both active and Background. Differences in renal histopathology between chronic lesions are more abundantly present in MPO-ANCAmicroscopic polyangiitis (MPA) and Wegener's granulomatopositive patients than in patients with PR3-ANCA-positivity, sis (WG), and between anti-neutrophil cytoplasm autoantibody which suggests that the pathogenesis of renal disease in these (ANCA) test results in patients with ANCA-associated vasculi-ANCA subsets could be different. Our results also suggest tis may provide insight into the differences in pathogenesis that ANCA test results may be useful in classifying ANCAand raise the opportunity of classifying the vasculitides more associated vasculitides. accurately. The possible differences in histopathology are investigated in this study.Methods. We report an analysis of 173 patients with renal disease in microscopic polyangiitis or Wegener's granulomato-Rapidly progressive deterioration of renal function sis. A total of 173 renal biopsies, performed at diagnosis, were is a frequent but clinically unfavorable feature of antiscored by two observers separately, using a previously stanneutrophil cytoplasm autoantibody (ANCA)-associated dardized protocol. Consensus on each biopsy was achieved during a central review.vasculitis, including microscopic polyangiitis, Wegener's Results. Normal glomeruli were more common in WG than granulomatosis, and renal limited vasculitis [1]. Usually, in MPA (P Ͻ 0.001). Glomerulosclerosis was more prominent this rapidly progressive deterioration of renal function in MPA than in WG (P ϭ 0.003). Interstitial fibrosis (P Ͻ is histopathologically accompanied by a pauci-immune 0.001), tubular atrophy (P Ͻ 0.001), and tubular casts (P ϭ crescentic necrotizing glomerulonephritis. However, the 0.005) were more frequently present and more severe in MPA than in WG. Presence of glomerulosclerosis was more extensive histopathological features vary among patients from mild in patients with myeloperoxidase (MPO)-ANCA than with focal segmental extracapillary proliferation to diffuse proteinase 3 (PR3)-ANCA (P ϭ 0.022). Interstitial fibrosis crescentic necrotizing glomerulonephritis with granulo-(P ϭ 0.008), tubular necrosis (P ϭ 0.030), tubular atrophy (P ϭ mas and tubular intra-epithelial infiltrates. In some cases, 0.013), and intra-epithelial infiltrates (P ϭ 0.006) were more extensive glomerulosclerosis is found [2]. frequently present and more severe in MPO-ANCA than in PR3-ANCA. The differences between microscopic polyangiitis and Conclusions. Glomerulonephritis in relation to MPA hasWegener's granulomatosis have been described as folmore characteristics of chronic injury at the time of presentalows [3,4]. Microscopic polyangiitis is characterized by a non-granulomatous systemic vasculitis that is as...