Status In Renal Transplant Recipients Research Articles

Preliminary Results of the Effect of Treatment of Hyperhomocysteinemia and Its Relationship With Inflammation, Coagulation Status, and Endothelial Function After Renal Transplantation

The aim of this study was to assess the relationship between total plasma homocysteine (tHC) and several markers of endothelial function, coagulation, and pro-inflammatory status in renal transplant recipients. Our own previous study demonstrated the efficacy of folic acid (FA) and vitamin B 12 (B 12) treatment to reduce tHC. Using 70 stable recipients, 56 of whom showed hyperhomocisteinemia (HHC) (tHC ≥ 14 μmol/L) and a control group (n = 14, tHC < 14 μmol/L), we treated 29 patients in the HHC group (10 mg FA and 500 mg B 12 daily) and determined their endothelial function, inflammatory activity, and coagulation status. We assessed plasma levels of von Willebrand Factor and fibrinogen as the prothrombotic profile and C-reactive protein and plasma albumin as inflammation markers. We performed Doppler sonography of the brachial artery to assess endothelial function. The mean value of plasma tHC of 19.05 ± 3.70 μmol/L before treatment decreased to 13.45 ± 3.25 μmol/L after 3 months of treatment ( P < .001). The vWF was significantly correlated with tHC ( P < .05) and was higher in the HHC patients ( P < .05). The fibrinogen mean level was also significantly higher in HHC patients ( P < .05). The C-reactive protein level was significantly higher and the albumin level was lower among patients with HHC. The endothelium-dependent dilation (EDD) correlated with baseline tHC ( P < .05). In preliminary data we observed that homocysteine-lowering therapy may provide cardiovascular protection by enhancing endothelial function, limiting oxidative stress, and reducing procoagulation status.

EVALUATION OF P-GLYCOPROTEIN EXPRESSION AND FUNCTION IN PERIPHERAL-LYMPHOCYTES OF RENAL TRANSPLANT RECIPIENTS: RELATIONSHIP WITH LYMPHOCYTE-SENSITIVITY TO IMMUNOSUPPRESSIVE DRUGS AND CLINICAL STATUS.

P719 Aims: P-glycoprotein (P-gp) is reported to mediate the efflux of several lipophilic drugs from mammalian cells. Overexpression of P-gp in immune cells may result in the insufficient efficacy of immunosuppressive drugs in renal transplantation patients. With this in mind, we evaluated P-gp expression and function in peripheral-blood mononuclear cells (PBMCs) to examine their influence on PBMC-sensitivity to immunosuppressive drugs and the clinical status of renal transplant recipients. Methods: Seventeen renal transplant recipients, nine patients with chronic renal failure, and 16 healthy subjects were included in the study. The basic characteristics of these subject groups did not differ significantly. Out of the 17 transplant recipients, 14 had received cyclosporine-based immunosuppressive therapy, while two patients received tacrolimus and one a steroid without calcineurin inhibitors. P-gp expressed in PBMCs was stained with FITC-labeled anti-P-gp monoclonal antibodies and subsequently analyzed with flow cytometry. P-gp function was evaluated with incorporation and efflux of rhodamine 123 (R123) in the presence or absence of cyclosporine, followed by flow cytometry analysis. PBMC-sensitivity to the suppressive effects of prednisolone, methylprednisolone, cyclosporine or tacrolimus was evaluated by measuring the IC50s (ng/ml) of these agents against concanavalin A-induced blastogenesis of PBMCs in vitro. Results: The incidence of transplant recipients with PBMCs exhibiting high-rates of P-gp expression was significantly higher than that of the healthy subjects (p=0.0035). However, percentages of P-gp expressing PBMCs and P-gp function evaluated by R123-efflux ability of the cells did not correlate significantly in either of the subject groups. The IC50s of the immunosuppressive drugs did not correlate with the percentage of cells expressing P-gp or P-gp function in the PBMCs of the transplant recipients. In addition, we found no statistically significant correlation between these P-gp parameters and other clinical characteristics of the recipients such as the incidence of rejection episodes or adverse effects of the immunosuppressive drugs administered. In contrast, the amount of R123 incorporated and retained in the PBMCs significantly correlated with either serum creatinine or blood urea nitrogen (BUN) concentrations in transplant recipients (p=0.021 and p=0.0014, respectively). Conclusions: We conclude that P-gp expression and its function in PBMCs had little influence on the cellular and clinical pharmacodynamics of immunosuppressive drugs in the renal transplant recipients. Increases in concentrations of serum creatinine, BUN, and/or possibly other uremic toxin(s) due to the impairment of renal graft function results from chronic allograft rejection or cyclosporine side effects may have suppressed the P-gp function in the PBMCs of these recipients.

Immune status in renal transplant recipients with hepatitis C virus infection

Immune status in renal transplant recipients with hepatitis C virus infection

Nutritional status in renal transplant recipients, evaluated by means of body composition analysis

Nutritional status in renal transplant recipients, evaluated by means of body composition analysis

Long term cyclosporine kinetiks and its influence on lipid status in renal transplant recipients

LONG TERM CYCLOSPORINE KINETIKS AND ITS INFLUENCE ON LIPID STATUS IN RENAL TRANSPLANT RECIPIENTS. F. K. Matzkies, W. Keuthage, U. Gerhardt, B. Suwelack, and H. Hohage. University of Muenster, Medical Department, Mnenster, Germany We retrospectively investigated the influence of cyclosporine A treatment on cholesterol levels in 261 patients with stable renal function over a time period of 60 months. Patients were eligible if fasting serum-chnlesterul values and baseline CYA levels were available at 1, 3, 9, 12, 24, 36, 48, 60 months after transplantation. Correlation and regression analysis was perfomed on creatinine (SCr), total cholesterol, total CYA dosage (CYA d), CYA baseline values (CYA b) relation of CYA dosage and bodyweight (CYA d/w) and relation of CYA dosage to CYA baseline values (CYA d/b). Mean age was 42--12 years, mean body weight showed an increase from 64± 11 kg after transplantation to 69± 12 kg after nine months remaining stable at 60 months. CYA d was 323:~105 mg at first month with a linear reduction over time to 247±87 mg at 60 mouth (23%). CYA b showed a comparable reduction from 290~252 to 121,~63 ng/ml, respectively. CYA d/w reduced from 5,1±1.6 to 3.5±1.3 mg/kg/d over the time period of 60 months. The correlation of CYA d/b showed a slight increase from baseline 52±39 to 61±48 (9 months) and a continous decrease to 35±25 g/1. SCr was 2.0±2.5 mg/dl at baseline and fell to 1.7±1.5 mg/dl at three month with a contiuons increase to 2,0:~ 1.4 mg/dl after 60 months. Cholesterol values were 254±50 mg/dl at baseline with a slight linear increase over the time to 276±59 rag/d1 at 60 months. There was no significant correlation between CYA d, CYA h, CYA d/b, CYA d/w and cholesterol. Stratification of patients according to age, sex, time from transplantation and cholesterol value did not identify subgroups of patients with correlation to CYA values. Multiple regression analysis showed no correlation between cholesterol values and creatinine or CYA values. According to these findings We conclude: The influence of CYA on cholesterol levels is not dose dependent. Even so CYA b values were reduced by half over the entire time period, a slight increase in cholesterol values occurred. Therefore, mechanisms independent from CYA may contribute to cholesterol values. 55

Colchicine myopathy in renal transplant recipients on cyclosporin.

Few data are available about the muscle status in renal transplant recipients. Moreover, the list of myotoxic drugs is growing longer and some of them are likely to be prescribed in renal transplant patients. These conditions may act as confounding factors in case reports of both cyclosporin and colchicine myopathies. Moreover no study has evaluated the frequency of myopathy in patients on both colchicine and cyclosporin. We conducted a retrospective study including all renal transplant recipients followed in our unit in whom colchicine was prescribed since January 1994. Clinical and biological data of patients on both colchicine and cyclosporin were analysed. Secondly case subjects were compared with matched controls not receiving colchicine but cyclosporin. Ten patients received colchicine in association with cyclosporin. Five patients (50%) experienced muscular symptoms and when performed, muscular histology showed vacuolar myopathy. All five patients improved after colchicine withdrawal. Cases with and without muscular symptoms did not differ in age, transplant duration, and serum creatinine level. Mean duration of colchicine therapy was 12.2 +/- 4.4 months in cases with muscular symptoms and 6.8 +/- 4.6 months in cases without muscular symptoms (P < 0.05). No control complained of either muscular pain nor weakness (P < 0.0005). Only one patient (3.3%) had elevated serum creatine phosphokinase concentration (P < 0.0005). We conclude that myopathy is very frequent in patient on both colchicine and cyclosporin. Muscular symptoms improve in all patients after colchicine withdrawal.