Efficacy and safety of early tacrolimus conversion to sirolimus after kidney transplantation: Long-term results of a prospective randomized study.

We report a prospective, open-label, randomized study to evaluate the safety and efficacy of converting patients with a stable renal function from tacrolimus (Tac)-based regimen to a sirolimus (SRL)-based regimen after kidney transplantation. Fifty-eight low-risk renal allograft recipients who receiving Tac 6 months posttransplant, were randomly assigned to continue Tac (n = 29) or convert to SRL (n = 29). We evaluated the 3-year outcomes including patient and graft survival, graft function, and safety profile. Three-year patient and graft survival in SRL and Tac groups were 93.1% versus 100% (P = 0.32), and 89.7% versus 100% (P = 0.11), respectively. However, the SRL group had a significantly better renal function, from the 2nd year posttransplant until the last follow-up. Four (13.8%) patients in the SRL group and 3 (10.3%) in the Tac group (P = 0.5) developed biopsy-proven acute rejection. Mean urinary protein excretion increased significantly after SRL conversion. Diastolic blood pressure was significantly lower at the end of the study in patients who eliminated Tac (80.4 vs. 75.6 mmHg in Tac and SRL group, respectively) (P = 0.03). Mean hemoglobin concentrations decreased after SRL conversion and remained significantly lower from 12 months to 36 months (P = 0.01). The mean serum cholesterol (540 ± 44 mg/dl) and triglyceride (177 ± 27 mg/dl) increased significantly in the SRL group, compared to Tac group (487 ± 62 mg/dl) (P = 0.03) and (141 ± 26 mg/dl) (P = 0.04). Our experience demonstrates that conversion to SRL from calcineurin inhibitors-based therapy may result in better renal function and blood pressure control in renal transplant recipients without an increased risk of acute rejection. However, these benefits have not resulted in a growing advantage in graft or patient survival.

Bone loss in pediatric renal transplant recipients.

The factors that affect bone mineral density (BMD) and the long term progress of BMD after transplantation in children is still unknown. Therefore we performed a cross-sectional study to determine BMD in 83 recipients who received living renal allotransplants in Mansoura Urology & Nephrology Center between 1981 and 2001 (mean age at transplantation 13.2 +/- 3.1 years) by dual energy x-ray absorptiometry at various time intervals up to 16 years after transplantation (mean duration after transplantation was 48 +/- 34 months, range 6-192 months). The Z-score for lumbar spine was -2.28 +/- 2.06 and -1.44 +/- 1.44 for the total body. Osteopenia/osteoporosis were present in about two thirds of our kidney transplant recipients. The significant predictors for osteopenia/osteoporosis by univariate analysis were cyclosporine based immunosuppression, the cumulative steroid dose/m2 surface area, graft dysfunction and the urinary deoxypyridinoline. Using logistic regression analysis the cumulative steroid dose/m2 surface area and the urinary deoxypyridinoline were the major significant predictors for bone loss.

Impact of clinical and histopathological factors on outcome of Egyptian patients with crescentic glomerulonephritis.

This study included 128 patients with crescentic glomerulonephritis (CGN) having sufficient clinical and histopathological data and were followed up in our institute for a mean period of 34 +/- 28 months. There were 49 males and 79 females with mean age 22.7 +/- 14 years. We studied the effect of clinical, laboratory and histopathological parameters on kidney function and patient survival at the end point of the study. The multivariate analysis revealed that serum creatinine at presentation, nephrotic range proteinuria during the follow up period, percentage of glomeruli affected by crescents, percentage of fibrous crescents and absence of cellular infiltration were significant risk factors affecting the kidney function at termination of the study. The only risk factor which correlated significantly with the patient mortality was the serum creatinine at last follows up.

Impact of schistosomiasis on patient and graft outcome after renal transplantation: 10 years' follow-up.

BACKGROUND: Schistosomiasis is a major health problem in some areas of the world. Schistosomal-specific nephropathy is a well-known occurrence and eventually leads to end-stage renal failure. Patients with schistosomal infection were considered to be suitable recipients for renal transplantation. However, the long-term impact of schistosomiasis on kidney transplantation is not yet been reported. METHODS: The long-term impact of schistosomiasis on patient and graft outcomes was studied by comparing two groups of subjects from a total of 243 patients. Group I consisted of cases with schistosomal infections and group II consisted of schistosoma-free controls. Schistosomiasis was documented in group I by identifying schistosoma eggs in urine, stool or rectal mucosal biopsy. Also intra-operative biopsies from bladder mucosa of the graft recipients and from the lower end of the ureter of living donors were obtained to search for schistosoma eggs. RESULTS: Sixty-three cases of schistosomiasis were diagnosed in both recipients and donors, 65 cases in recipients only, and eight cases in donors only. Infected recipients and donors with active lesions were treated at least 1 month before transplantation by combined antischistosomal drugs (praziquantel and oxamniquine). The 243 patients (136 schistosoma-infected cases and 107 controls) were followed regularly for a period of 10 years after transplantation. We found that there was no significant difference in the incidence of acute and chronic rejection between the groups; however, higher cyclosporin doses were needed for the infected group with subsequent higher incidence of both acute and chronic cyclosporin nephrotoxicity. Moreover, the schistosomal group had a significantly higher incidence of urinary tract infection and urological complications with no evidence of schistosomal re-infection. CONCLUSIONS: Despite a higher incidence of schistosoma-related complications after renal transplantation, schistosomal infection is not a major risk factor for transplantation. Therefore, infected patients can be considered as suitable recipients if they have been properly treated before transplantation.

Coadministration of ketoconazole and cyclosporine for kidney transplant recipients: long-term follow-up and study of metabolic consequences.

In a prospective randomized study including 100 kidney transplant recipients, we previously reported on the safety and financial benefits of the coadministration of ketoconazole (keto) to cyclosporine (CsA)-treated kidney transplant recipients. In this study, we report on the long-term follow-up of these patients and their control group, as well as possible metabolic consequences of this drug combination. Evaluation of 51 keto-treated patients and their control group (49 patients) included graft function, lipogram, fasting blood glucose, liver function tests, serum calcium, phosphorus, and radiological and histopathologic assessments. Follow-up of these patients for 54 months showed that the CsA dose reduction was 72.9% at 12 months, decreased to 69.3% at the last follow-up. We also found that the mean keto dose required for CsA dose reduction decreased to 82.8 +/- 24.1 mg/d compared with the starting dose (100 mg/d). Diagnosis of acute rejection episodes was similar in both groups. However, in the control group, rejection episodes were more recurrent, with poorer response to treatment. Acute CsA nephrotoxicity was more common in the keto group, but this was encountered more at keto induction and was rapidly reversed on further reduction of CsA doses. Chronic graft dysfunction was statistically significantly less in the keto group during the first year. However, by the end of the study, the difference was not statistically significant. In this study, hepatotoxicity was similar in the two groups. On studying the metabolic consequences, we found that serum cholesterol, low-density lipoprotein, and triglyceride levels were lower in the keto group. Bone mineral contents in both groups were less than the mean values for age- and sex-matched healthy controls. From this study, we conclude that long-term use of low-dose keto in CsA-treated kidney transplant recipients is safe and cost-saving and may induce better graft function. Bone mineral contents, vitamin D blood levels, and lipid profiles are not affected by long-term keto coadministration in CsA-treated kidney transplant recipients.

Impact of schistosomiasis on patient and graft outcome after kidney transplantation.

In this work the impact of schistosomiasis on kidney transplantation was investigated by comparing two groups of patients, group 1 (Schistosoma-infected cases) and group 2 (control cases). In group 1, schistosomiasis was diagnosed in both donor and recipient in 63 cases, in recipient only in 65 cases, and in donor only in eight cases. Schistosomal infection among kidney transplant recipients was S. haematobium in 17 cases, S. mansoni in 58 cases, and mixed in 53 cases. Schistosomiasis was diagnosed by finding Schistosoma eggs in urine, stools, rectal mucosal biopsy, recipient bladder mucosal biopsy, or in the donor ureter obtained during surgery. Patients and donors with active lesions were treated at least 3 weeks before transplantation by the antischistosomal drugs praziquantel and oxamniquine. Follow-up after kidney transplantation showed no significant difference between the two groups regarding the incidence of acute and chronic rejection. Nevertheless, dose of cyclosporin, HBs antigenaemia, incidence of urinary tract infection, renal stones, ureteric stricture, and urinary leakage were significantly greater among schistosomal patients when compared to control cases. Schistosomal reinfection was observed in 23% of cases at high risk. Antischistosomal treatment did not affect the graft function. We have concluded that schistosomiasis may affect the outcome of kidney transplantation.