The absence of cANCA, anti-PR3, and anti-MPO shows that with appropriate assay conditions, ANCA testing assists in the differentiation between SLE and the ANCA-associated vasculitides. The lack of a correlation between pANCA or any ANCA subspecificity and clinical manifestations suggests that ANCA do not identify particular clinical subsets among SLE patients, including those with lupus vasculitis.

Inflammatory systemic disorders with renal tissue damage require the adherence of polymorphonuclear leukocytes to the endothelium, which is mediated by cell surface adhesion molecules. This study measured the serum concentrations of circulating adhesion molecules [intercellular adhesion molecule 1 (cICAM-1), vascular cell adhesion molecule 1 (cVCAM-1), cE-selectin] by sandwich enzyme-linked immunosorbent assay in Wegener's granulomatosis (n = 25) and systemic lupus erythematosus (n = 50). Active Wegener's granulomatosis with cellular crescent formation was associated with significantly raised cICAM-1 levels, an elevated histological activity index, and a high rate of hemodialysis in comparison to Wegener's granulomatosis with fibrocellular crescents or lupus nephritis. The activity index and cICAM-1 levels can be used as parameters to predict renal outcome in Wegener's granulomatosis. cVCAM-1 levels in Wegener's granulomatosis were significantly higher in patients with hemodialysis compared to those without hemodialysis. In lupus nephritis only cVCAM-1, not cICAM-1 or cE-selectin, were significantly higher (P < 0.01) than controls. cVCAM-1 levels in both diseases were significantly higher than in controls. Only in Wegener's granulomatosis did cICAM-1 and cVCAM-1 levels decrease with clinical remission; in systemic lupus erythematosus the levels remained unchanged. cE-selectin levels were not significantly elevated in systemic vasculitis or collagen disease although individual patients revealed high serum concentrations. These data suggest that levels of circulating adhesion molecules reflect different pathophysiological processes in systemic vasculitis and collagen disease and may be used as markers of disease activity and renal outcome.

The tissue expressions of vascular cell adhesion molecule 1 (VCAM-1), intercellular adhesion molecule 1 (ICAM-1) and endothelial leukocyte adhesion molecule 1 (E-selectin-1) were investigated in biopsy specimens from 28 patients with different stages of IgA nephropathy (IgAN) and 20 patients with acute renal failure (ARF) or chronic renal diseases (amyloidosis, Alport’s glomerulopathy) by immunohistochemistry. The results were compared with the serum levels of the three adhesion molecules. VCAM-1 expression was significantly increased on parietal/tubular epithelial cells in IgAN and ARF. Significantly elevated circulating VCAM-1 levels were measured in IgAN and amyloidosis, but did not correlate with renal function (creatinine clearance). Significantly increased glomerular endothelial/epithelial ICAM-1 expression was found in IgAN and ARF. Intense mesangial ICAM-1 expression was found in mild stages of IgAN and in Schönlein-Henoch syndrome. Circulating ICAM-1 was not significantly elevated in IgAN and different renal diseases. VCAM-1 and ICAM-1 expressions of interstitial infiltrating cells were significantly higher in severe than in mild IgAN and associated with an increased infiltration of inflammatory leukocytes. Patients with IgAN and different renal diseases had decreased mesangial and almost absent interstitial E-selectin expression as compared with controls. The circulating E-selectin levels were significantly elevated in ARF. In conclusion, the tissue expression of adhesion molecules in IgAN reflects a continuous inflammatory renal activity. However, only increased circulating VCAM-1 serum levels correlated significantly with the histological state of renal inflammation and could be used as a disease marker.

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Heparan sulfate proteoglycans are major components of the glomerular basement membrane and play a key role in the molecular organization and function of the basement membrane. Moreover, their presence is essential for maintenance of the selective permeability of the glomerular basement membrane. Recently, we isolated and characterized a novel small basement membrane-associated heparan sulfate proteoglycan from human aorta and kidney. Partial amino acid sequence data clearly show that this heparan sulfate proteoglycan is distinct from the large basement membrane-associated heparan sulfate proteoglycan (perlecan). Using specific monoclonal antibodies, we have shown that the novel heparan sulfate proteoglycan is located predominantly in the glomerular basement membrane and, to a lesser extent, in the basement membrane of tubuli. Turnover or, in the course of kidney diseases, degradation of heparan sulfate proteoglycan from glomerular basement membranes may lead to urinary excretion of heparan sulfate proteoglycan, which can be measured by a sensitive enzyme immunoassay. The aim of the present study was to analyze whether changes in the structure and function of glomerular basement membranes can be directly detected by measurement of the excretion of a component of this basement membrane, eg, heparan sulfate proteoglycan into urine. The excretion of this small heparan sulfate proteoglycan was compared after physical exercise in normotensive and hypertensive subjects. Normotensive subjects and treated, essential hypertensive patients underwent a standardized workload on a bicycle ergometer. Biochemical characterization of the urinary proteins and heparan sulfate proteoglycan was performed before and 15 and 45 minutes after exercises.(ABSTRACT TRUNCATED AT 250 WORDS)

The grafting of immunocompetent allogeneic cells into MHC-discordant, genetically nonresponsive F1 hybrids of inbred rat strains consistently leads to an acute, lethal graft-versus-host disease (GVHD). The novel immunomodulating drug leflunomide, which has been shown to be efficacious in animal models of autoimmunity and adverse transplantation reactions, was studied in a rat model of GVHD. It was found that this drug not only was a powerful agent to prevent this otherwise terminal disorder, but was also proficient when used as a therapy of an established GVHD. Since leflunomide has been shown to be efficacious and safe in patients with chronic rheumatoid arthritis, it would also be reasonable to investigate this drug in clinical trials for bone marrow transplantation and GVHD in human beings.

A case of cerebral tuberculoma in a 39-year-old patient who had received a renal graft from a living related donor 11 years previously is reported. The patient had a major seizure, progressive psychiatric signs and fever 5 days prior to admission. The clinical history suggested a neurological cause and rapid diagnosis of a cerebral tuberculoma was made by a computed tomography-guided stereotactic puncture of a space-occupying cerebral lesion. The aspirated pus contained Mycobacterium tuberculosis. Anti-tuberculous therapy with isoniacid, rifampicin, ethambutol and pyracinamide was administered. Transplant function deteriorated and the patient died due to intractable septicemia with multiorgan failure from pulmonary infection dissemination and additional urinary tract infection with atypical mycobacteria. The chance for a benign clinical course necessitates vigorous procedures for an early diagnosis of cerebral infections in renal transplant recipients with neurological/psychiatric signs.

Abstract.Normal development of the kidney is a highly complex process that requires precise orchestration of proliferation, differentiation, and apoptosis. In the past few years, a number of genes that regulate these processes, and hence play pivotal roles in kidney development, have been identified. The Wilms' tumor suppressor geneWT1has been shown to be one of these essential regulators of kidney development, and mutations in this gene result in the formation of tumors and developmental abnormalities such as the Denys-Drash and Frasier syndromes. A fascinating aspect of theWT1gene is the multitude of isoforms produced from its genomic locus. In this review, our current understanding of the structural features ofWT1, how they modulate the transcriptional and post-transcriptional activities of the protein, and how mutations affecting individual isoforms can lead to diseased kidneys is summarized. In addition, results from transgenic experiments, which have yielded important findings regarding the function of WT1in vivo, are discussed. Finally, data on the unusual feature of RNA editing ofWT1transcripts are presented, and the relevance of RNA editing for the normal functioning of the WT1 protein in the kidney is discussed.