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Aim: Tacrolimus is a calcineurin inhibitor that has been increasingly used in transplant medicine. However, the efficacy and safety of combined therapy of low-dose tacrolimus and prednisone in the treatment of nephrotic syndrome (NS) with slight mesangial proliferation has not been reported. Patients and Methods: Sixty patients with NS with slight mesangial proliferation were randomly divided into a prednisone therapy group (control), a combined low-dose tacrolimus (2 mg/day) and a prednisone therapy group (tacrolimus group). The efficacy and safety of tacrolimus was analysed. The initial dose of prednisone was 1 mg/kg per day and 30 mg/day in the control group and tacrolimus group, respectively. The duration of treatment was 6 months. Results: After a 6-month trial of combined low-dose tacrolimus and prednisone, complete remission was achieved in 29 patients (96.66%) and partial remission in one patient (3.33%). In the control group, complete remission was achieved in 27 patients (90%) and partial remission in three patients (10%). A significant improvement in proteinuria levels was observed in the tacrolimus group compared with the control group, starting at the second week and remaining throughout the study period. Furthermore, a significant improvement in serum albumin levels was observed in the tacrolimus group compared with the control group, starting at the first month and remaining until the third month. The main side-effect was obesity (100%) and acne (46.66%) in the control group. However, these adverse events were not observed in the tacrolimus group. Conclusion: The results demonstrated that combined therapy of low-dose tacrolimus and prednisone is an effective and safe therapeutic method for NS with slight mesangial proliferation. [ABSTRACT FROM AUTHOR]

The aim of the present study was to find out if specific IgM (M) antibody (directed against rat kidney fraction 3 (rKF3)) or rKF3 antigen were able to influence disease progression in an experimental autoimmune kidney disease called slowly progressive Heymann nephritis (SPHN). The level of circulating autoantibodies (aabs) and the morphological and functional changes to the kidney were studied in six groups of rats. All of the treatment components (except post-treatment with M) used in the SPHN pre- and post-treated rats and post-treated-only rats had measurable beneficial effects (even during restimulation with the chemically modified renal antigen, 22 weeks after the induction of the disease) as demonstrated by diminished pathogenic IgG aab production, less severe kidney lesions, and proteinuria reductions. The injected rKF3 minimized progression best in this experiment, especially when administered in a pre- and post-treatment regimen. It is thought that the effect of rKF3 in the reduced progression of SPHN was due to increased production of specific IgM aabs, which in turn limited pathogenic aab production and continuous buildup of immune complexes in the glomeruli by facilitating removal or blockage of nephritogenic autoantigens from the circulation. [ABSTRACT FROM AUTHOR]

The purpose of the study was to find out if a new modified vaccination technique would be effective in downregulating immunopathological events during the course of an experimental autoimmune kidney disease (which is morphologically and functionally similar to Heymann nephritis) called ‘slowly progressive Heymann nephritis’ (SPHN). We have shown that the pathogenic IgG autoantibody (aab)-induced experimental autoimmune kidney disease process can be downregulated early on as well as during the chronic progressive phase, when rats were restimulated. The IgM aab, resulting from stimulation by immune complexes made up of rat kidney fraction 3 (rKF3) antigen and rat anti-rKF3 IgM antibody in antigen excess (MIC), can greatly diminish pathogenic aab production by removing or blocking nephritogenic antigens. Reduced IgG aab production limits the formation of damaging immune complexes (IC) in the glomeruli and development of proteinuria. At the end of the experiment 60% and 80% of the MIC-treated groups had no pathogenic IgG aab in their circulation, while all the untreated SPHN rats had high levels of IgG aab associated with disease progression manifesting in increased proteinuria and severe immune complex glomerulonephritis. [ABSTRACT FROM AUTHOR]

A slowly progressive Heymann nephritis (SPHN) was induced in three groups of rats by weekly injections of a chemically modified renal tubular antigen in an aqueous medium. A control group of rats received the chemically unmodified version of the antigen in an aqueous solution. One group of SPHN rats were pre- and post-treated with weekly injections of IC made up of rKF3 and rarKF3 IgM antibody at antigen excess (MIC) (immune complexes [ICs] containing sonicated ultracentrifuged [u/c] rat kidney fraction 3 [rKF3] antigen and IgM antibodies specific against the antigen, at slight antigen excess). One group of SPHN rats were post-treated with MIC 3 weeks after the induction of the disease and one group of SPHN animals received no treatment. The control group of rats received pre- and post-treatment with sonicated u/c rKF3. The incidence of immune-complex glomerulonephritis (ICGN) in the untreated SPHN rats was 87%, in the pre- and post-treated animals 13%, and in the post-treated-only rats 20%. Rats receiving sonicated ultracentrifuged rKF3 antigen did not develop ICGN. The present experiment demonstrates that the development of SPHN can be not only prevented but also effectively terminated by our newly developed modified vaccination technique. [ABSTRACT FROM AUTHOR]

An autoimmune kidney disease morphologically and functionally similar to Heymann nephritis (HN) was induced in mature male Sprague Dawley rats by repeated weekly IP injections of a chemically modified azo sonicated ultracentrifuged (u/c) rat kidney fraction 3 (rKF3) antigen in an aqueous medium. The experiment was terminated 15 weeks after the first injection of the chemically altered antigen. Serum samples collected and analysed by an indirect fluorescent antibody test on normal rat kidney sections during the course of the experiment showed a gradual rise in circulating pathogenic autoantibodies directed against the proximal tubular brush border regions. Proteinuria was present and significantly increased in the urine of two of eight rats. The arising immune-complex glomerulonephritis (ICGN) revealed typical HN kidney disease lesions in 70% of the rats in histological, direct fluorescent antibody and electron-microscopical examinations. Control rats injected similarly with the an unmodified version of the same antigen did not develop the HN-characteristic morphological and functional changes. To our knowledge, this is the first time that the autoimmune kidney disease designated as an active HN has been produced by the administration of a chemically altered renal antigen in an aqueous solution and not by the usual presentation of the nephritogenic renal antigen in an adjuvant. [ABSTRACT FROM AUTHOR]

Diffuse distribution of small, faintly staining, beaded deposits of rat immunoglobulin M (IgM) around the glomerular capillary blood vessels, and a more intensely staining larger deposition in the mesangium, were observed on the kidney sections of normal rats. As glomerular-fixed nephritogenic antigens are known to be present on the epithelial aspect of the glomerular basement membrane (GBM), especially at the soles of foot processes and at the slit pores, it was assumed that the IgM antibodies were directed against these antigens. Investigation by immunofluorescent antibody double-staining techniques of rat kidney sections obtained from normal and rabbit anti-FX1A-injected rats stained for the nephritogenic antigen showed that a number of antigenic sites in the glomeruli and in the mesangium shared antibody hits by heterologous rabbit IgG and autologous rat IgM antibodies. Most sites in the glomeruli stained specifically for rat IgM or rabbit IgG, but preferentially for the latter. The intensely fluorescent mesangial deposits stained mainly for rat IgM, indicating that at these sites the antigenic material was virtually saturated, while areas at the entry to the mesangial space also stained for rabbit IgG, indicating that at these locations free nephritogenic epitopes were still available for reaction with the anti-FX1A antibody. Western blot analysis have shown that the rabbit anti-rat FX1A IgG and the rat anti-rat KF3 IgM antibodies are directed against the same renal tubular-derived antigen with a molecular weight of 70,000. These experimental findings collectively demonstrate that the heterologous IgG and autologous IgM antibodies are directed against the same nephritogenic antigen, which is found in the glomeruli, the mesangium and the proximal convoluted tubules. Thus, the IgM autoantibody has a possible physiological role but, in addition, there is evidence of active immunophagocytic events, manifested in a rapid and continuous entrapment and expulsion of macromolecules after their processing by the mesangial cells of normal and passive Heymann nephritis rats. [ABSTRACT FROM AUTHOR]

A slowly progressive autoimmune kidney disease was induced in Sprague Dawley rats by subcutaneous injection of a chemically modified kidney antigen (rKF3), incorporated into Alum and Distemper complex vaccine, followed by subcutaneous injections of an aqueous preparation of the same antigen. Pathogenic autoantibodies developed, which reacted with fixed glomerular nephritogenic antigen. Subsequently, immunopathological events lead to chronic progressive immune complex glomerulonephritis and proteinuria. The slowly developing disease was morphologically and functionally similar to Heymann nephritis (HN). The damage observed in the kidneys of experimental animals at 8 weeks and at the end of the experiment was examined by direct fluorescent antibody test, histology and electron microscopy. The changes were similar to the typical lesions found in HN rat kidneys, but less severe. Animals became proteinuric from 17 weeks onward (instead of the usual 4–8 weeks). By the end of the experiment, at 8 months, 100% of the rats were proteinuric. This new experimental model of autoimmune kidney disease, which is not complicated by intraperitoneal deposition and retention of Freund's complete adjuvant and renal tubular antigens, allowed us to investigate the pathogenesis of the disease processes from a different aspect, and promises to be a useful and improved model for the investigation of future treatment options. [ABSTRACT FROM AUTHOR]

Presents case reports on a 31-year-old male with relapsing idiopathic membranous glomerulonephritis complicated with renal vein thrombosis. Diagnosis of recurrent renal vein thrombosis; Details on the treatment of primary membranous nephropathy.

The hormone lα, 25 dihydroxyvitamin D3 (l,25(OH)2D3) has potent immunosuppressive effects in vitro. Recent publications also described a protective effect of the hormone in various animal models of immune-mediated diseases. To test its in vivo activity we induced active Heymann nephritis in Lewis rats that were either untreated or treated with l.25(OH) 2D3 or its synthetic 20-epi analogue, KH1060. Treatment with cyclosporine A (CsA) was used as an immunosuppressive control. In this nephrotic model the administration of l,25(OH) 2D3 (0.5μg,/kg body weight) given on alternate days during the first 13 days after active immunization significantly reduced the proteinuria as measured by weeks 7-9. This reduction was comparable to the reduction observed in rats treated with CsA (20 mg/kg) on alternate days. A second series of experiments with 1,25(OH) 2D3 confirmed these findings. The level of autoantibodies was found to be significantly suppressed during the treatment time in the CsA (20 mg/kg) group, whereas the limit of significance (P=0.06) was reached in the 1,25(OH) 2D3(0.5 μg/kg) group. The size of the immune deposits also was found to be substantially smaller in the groups that developed less proteinuria. The administration of 1,25(OH) 2D3 transiently increased the mean serum calcium concentration with 2.5 mg/dl above the pretreatment values, and the urinary calcium excretion by a factor of 3-5 during the short treatment time. Treatment with the analogue KH1060 did not reduce the proteinuria significantly. Our experiments add evidence to the hypothesis that 1,25(OH) 2D3 in pharmacological doses has immunosuppressive potency. [ABSTRACT FROM AUTHOR]