Conversion of azathioprine to mycophenolate mofetil and chronic graft failure progression.

The purpose of the study was to evaluate the impact of conversion from azathioprine (AZA) to mycophenolate mofetil (MMF) on graft function in 35 renal transplant recipients with chronic allograft nephropathy (CAN). The immunosuppressive regimen originally consisted of AZA, cyclosporine (CsA), and prednisone (Pr). At the onset of the study (mean period = 39 posttransplant months), a graft biopsy was performed on all patients who were randomly divided into group 1 (n = 17) in whom MMF was introduced instead of AZA. The remaining 18 subjects (group 2) were maintained on the previous regimen. Two periods were analyzed: period I: 12 months before, and period II: 12 months after biopsy and therapy conversion. Graft function was assessed monthly by measurements of the 24-hour creatinine clearance (CCr). Analysis of variance (ANOVA) was used to compare the differences in CCr and proteinuria between the two groups. No difference was observed in the baseline characteristics, in the incidence of delayed graft function and acute rejection, or in the mean CsA dose. Pathohistological analysis revealed advanced CAN in the majority of patients in both groups. The morphological changes negatively correlated with graft function. The graft function showed parallel deterioration in the two groups; no significant difference was observed in the mean CCr values in the periods studied. Proteinuria was similar for both groups throughout the study. Conversion of AZA to MMF in recipients with CAN, albeit safe, was without significant benefit on the progression of chronic graft failure over the period of a year.

Relationship between IL-1beta and TNFalpha production by PBMC and clinical features of hemodialysis patients.

The relationship between production of IL-1beta and TNFalpha by peripheral blood mononuclear cells (PBMC) of hemodialysis (HD) patients and clinical disorders characteristic for HD patients was examined. The study included 28 HD patients divided in the 4 groups: group 1--6 patients with malnutrition; group 2--6 patients with secondary hyperparathyroidism; group 3--6 patients with eosinophilia; group 4--10 stable HD patients without clinical complication. The control group consisted of 9 healthy volunteers. All patients were dialyzed with cuprophane membrane more than one years. Blood samples were taken immediately before the beginning of hemodialysis and PBMC were isolated by centrifugation on the density gradient. Concentrations of IL-1beta and TNFalpha were measured in the supernatants of the cultures by ELISA tests. The results showed marked individual differences in cytokine production both in healthy controls and in HD patients. Spontaneous and LPS stimulated production of IL-1beta by PBMC of HD patients was significantly higher compared to PBMC of healthy controls. There were no significant differences between group of patients with different clinical complications in cytokine production. However, a positive correlation was found between IL-1beta concentration and body mass index for patients with malnutrition and between concentration of IL-1alpha and parathyroid hormone (PTH) for patients with secondary hyperparathyroidism. The results suggest that PBMC of HD patients are chronically stimulated to produce IL-1beta, which may contribute to the development of particular chronic complications.