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Background/Aims: Protocol biopsy is an important strategy which assesses the histological changes that can occur in the renal allograft and adversely affect its outcome. We aimed to evaluate histological changes in long-term living donor transplants. Methods: Elective biopsies were done for 120 live donor renal transplant recipients with well-functioning grafts and no rejection history at least 1 year or more after transplant. All patients had serum creatinine levels <2 mg/dl. The histopathological findings using the chronic allograft damage index score were correlated with different clinical and immunological parameters. Results: Chronic tubulointerstitial fibrosis was the most prevalent finding (85% of cases), mostly of mild degree. Normal biopsies were reported in only 7.5% of cases, whereas chronic cyclosporine nephrotoxicity was detected in 5.8% of biopsies. Posttransplant hypertension was significantly correlated with glomerulosclerosis, and posttransplant diabetes with glomerulosclerosis, mesangial matrix increase, tubular atrophy and interstitial fibrosis. The main risk factors associated with a high chronic allograft damage index score were DR mismatching, posttransplant diabetes and time of biopsy. All histopathological changes increased with advancing donor age and declining graft function. Conclusion: Elective biopsies showed that histopathological findings do exist even with stable renal function that may pave the way for predicting long-term graft outcome. Copyright © 2006 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background/Aims: In developing countries, kidney transplantation is greatly hindered by financial problems, especially due to costly newer immunosuppressive medications. Ketoconazole increases blood levels of tacrolimus and cyclosporine through inhibition of cytochrome P450 microsomal enzymes. We previously reported on the 6-month safety and the outstanding impact on treatment costs of the ketoconazole-tacrolimus combination in kidney transplant recipients. Data of this combination are still lacking in the literature. We hereby report on the 2-year results of our trial. Methods: This prospective, randomized study included 70 live-donor kidney transplant recipients receiving tacrolimus (age 16–45 years, 54 males and 16 females). Patients were randomized into two equal groups: group 1, where ketoconazole 100 mg/day was added, and group 2 (control group). Results: After 2 years, group 1 (ketoconazole) patients still showed a highly significant reduction of the tacrolimus dose (by 53.8%) and cost (by 52.9%) compared with the control group (p < 0.001) and a significant improvement in graft function in comparison to their own initial graft function (p = 0.002). Throughout the 2 years, no side effects of ketoconazole were noted. Conclusion: We conclude that the long-term ketoconazole-tacrolimus combination therapy in kidney transplant recipients during the 2 years is safe, has an outstanding impact on treatment costs and improves graft outcome. Copyright © 2006 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: The potential benefit of pre-transplant treatment of chronic hepatitis C on long-term evolution after renal transplantation is not clear. Methods: Fifty successive renal transplant candidates had their sera positive for HCV RNA and a biopsy-proven chronic hepatitis. Out of these, 18 patients received a standard course of interferon-α2b (IFN; 3 MU three times weekly after hemodialysis sessions for 6 months). Results: IFN was discontinued in 2 patients (11%) due to persistent leukopenia. HCV RNA turned negative in 10 patients of the treatment group and in none of the control group. Two patients of the IFN group had a virological relapse post-transplantation. Post-transplant follow-up periods were 41.5 ± 15 and 50 ± 16 months for the treated and control groups respectively. Transaminases remained normal in all patients of the IFN group after transplantation. In contrast, biochemical evidence of acute and chronic hepatitis was observed in 5 (p = 0.03) and 13 (p = 0.002) patients, respectively, of the control group. Logistic regression analysis identified non-receiving IFN before transplantation as a risk factor for post-transplant hepatic dysfunction (odds ratio = 11.7, p = 0.003) and for chronic allograft nephropathy (odds ratio = 11.6, p = 0.02). Conclusions: IFN-treated patients had a significantly better post-transplant hepatic function and significantly lower rates of chronic allograft nephropathy. Copyright © 2005 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background/Aims: The use of cyclosporine A (CsA) in the treatment of idiopathic nephrotic syndrome was firstly reported in 1986. On the other hand, many studies have documented the benefit of ketoconazole (keto) administration in renal and cardiac transplant adults treated with CsA, but this co-administration has not been reported in children with minimal change disease (MCD). Thus, deliberate use of keto to reduce the need for cyclosporine is not new, but it is particularly relevant because of the high cost of cyclosporine. Methods: This study included 46 children with MCD who were steroid resistant or dependent and received CsA. Among them, 31 received daily keto therapy (keto group) in a dose of 50 mg with concomitant decrease of the CsA dose by one third while 15 patients received CsA alone (non-keto group). Results: The mean (±SD) duration of CsA treatment was 25.7 ± 13.7 months. The characteristics of both groups were comparable. Co-administration of keto significantly improved the response to CsA therapy (from 60 to 94%) and decreased the frequency of renal impairment (from 27 to 3%). Hepatic function remained within the normal range in both groups. Co-administration of keto significantly reduced mean doses of CsA with overall net cost savings of about 34%. Conclusion: From this study, we may conclude that co-administration of low dose ketoconazole to cyclosporine in children with idiopathic MCD is safe. This combination significantly reduces CsA cost and, moreover, keto may improve the response to cyclosporine and may have a favorable effect on the kidney function. Copyright © 2005 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background/aims: The long-term evaluation of basiliximab induction therapy has not been addressed yet. We aim to evaluate its long-term effects in living related donor kidney transplantation.Methods: 100 adult recipients with their first kidney allograft were randomized into two treatment groups--one group received basiliximab and the second served as a control. All patients received a maintenance triple immunosuppressive therapy (steroids, cyclosporine microemulsion and azathioprine) and were closely followed for 5 years.Results: Basiliximab significantly reduced the proportion of patients who experienced an acute rejection in the first year (18/50) when compared to the control group (31/50) and in 5 years (27/50) when compared to (36/50) the controls. The cumulative steroid dose used throughout the study was significantly lower in the basiliximab group. The overall incidence of post-transplant complications was comparable between the two treatment groups. There was no significant difference in patients and graft survival; 5-year patient and graft survival were 100 and 86% for basiliximab, and 96 and 88% for the control group respectively.Conclusion: Although routine basiliximab induction significantly reduces the incidence of acute rejection, its beneficial long-term effects on graft function and patient and graft survival are not yet evident. [ABSTRACT FROM AUTHOR]

Background/Aims: Use of androgen as an adjuvant therapy to treat anemia in patients on hemodialysis is debated. Our target is to assess the safety and the efficacy of nandrolone decanoate (ND) as an effective adjunctive therapy to treat such anemia. Methods: This study included 32 anemic adult hemodialysis patients who had adequate iron stores. They were randomized into two equal groups: the first group received subcutaneously a low dose of erythropoietin (EPO) 1,000 U three times weekly combined with ND, 50 mg intramuscularly twice weekly, and the second group received only the same low dose of EPO for the 6-month study period. All patients were subjected to a serial follow-up of hemoglobin (Hb), hematocrit % (Hct%), iron store indices, serum insulin-like growth factor-1 (IGF-1) concentration and liver function tests. Results: A significant rise of both Hb and Hct in both groups was found at the end of the study (p < 0.001). Although the rise of both Hb and Hct was higher in the androgen group, it was not rated as being statistically significant. Both groups showed a significant rise of serum IGF-1 concentration at the end of the study in comparison to its initial value. Moreover, the androgen group attained a more statistically significant rise of IGF-1 serum concentration. Four female patients discontinued ND because of related adverse effects, principally distressing hirsutism and hepatic dysfunction. Conclusion: Addition of ND to a low-dose EPO regimen does not offer a significant benefit. Androgen-related side effects limit its use in female patients. Copyright © 2005 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Anemia in hemodialysis patients is a complex syndrome. The impetus of this study was to assess the safety and efficacy of iron saccharate complex (ISC) and sodium ferric gluconate complex (SFGC) in treating anemia in hemodialysis patients. Methods: Forty-eight adult anemic patients of both genders (33 males and 15 females) who had an adequate level of both hemodialysis and nutrition status and received neither EPO nor parenteral iron therapy during the preceding 6 months were randomized to 2 groups. The first group comprised 22 patients who were treated with parenteral ISC, 100 mg twice weekly for 2 months and once weekly thereafter. The second group included 26 patients who received SFGC, 62.5 mg twice weekly for 2 months and once weekly thereafter. The patients were followed up for 6 months. Results: This head-to-head study showed that iron stores were adequately repleted by the use of both drugs. Repletion of iron stores was associated with a significant rise in both hemoglobin and hematocrit in both groups at the end of the follow-up period in comparison to their initial values at the start of the study (p < 0.001). Both parenteral iron therapy preparations were tolerated without a statistical difference between both groups. Conclusion: This head-to-head study confirmed that both parenteral iron preparations are effective for adequate repletion of iron stores and constituted a step forward in the management of anemic hemodialysis patients without noticeable adverse effects related to the administration of both iron preparations. Copyright © 2005 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

In this study 43 patients with idiopathic nephrotic syndrome were randomly distributed into 2 age- and sex-matched groups. The first group was given fluvastatin while the second was used as control. The cases in the 2 groups were evaluated clinically, biochemically (creatinine clearance, albumin, 24-hour proteinuria, and lipogram), neurologically, and histopathologically (examination of renal biopsies obtained basally and after 1 year of treatment with fluvastatin). In the fluvastatin-treated group but not in the control group, we observed a significant reduction in cholesterol, low-density lipoprotein, and triglyceride. Clinical and laboratory assessment showed satisfactory tolerance of the drug by the patients. Proteinuria, serum albumin and creatinine clearance values were significantly better in the statin-treated patients. There was no difference in glomerular sclerosis between the 2 groups while interstitial fibrosis and renal fat deposits were less in the statin-treated group. The reduction in renal fat deposits in the statin-treated group was highly significant, while that of interstitial fibrosis was not. We conclude that: (1) statin can be safely and effectively used in the treatment of dyslipidemia in patients with persistent idiopathic nephrotic syndrome; (2) control of dyslipidemia in nephrotic patients is associated with better control of proteinuria and creatinine clearance; (3) statin treatment may cause regression of renal fat deposits in patients with nephrotic syndrome, and (4) longer term studies are still required to study further possible beneficial effects on renal histology and disease progression.Copyright © 2002 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Thirty male Sprague-Dawley rats were given ciclosporin (Cs) orally, 15 mg/kg daily for 80 days. Fifteen served as positive controls, while the other 15 were given daily colchicine at a dose of 30 µg/kg in addition to Cs. Additional 15 rats were given olive oil only and served as negative controls. The animals were subjected every other week to laboratory assessment of serum creatinine, sodium, potassium, and Cs whole-blood trough levels; also urine samples were examined for creatinine, sodium, potassium, and protein concentrations. At the end point, the animals were sacrificed, and kidney tissue was examined for histopathological changes. Comparing negative control versus Cs-treated and Cs-plus-colchicine-treated rats, there were no significant differences in serum creatinine, creatinine clearance, and serum and urine values of sodium and potassium as well as urinary protein/creatinine ratios. Yet histopathological examination of kidney tissues showed focal tubular atrophy and interstitial fibrosis in inner medulla and inner stripe of the outer medulla in all Cs-treated animals and in only 1 of the colchicine-treated group, but in none of the negative controls. Histological changes in other kidney zones in different animal groups were minor and not different. From this study, we may conclude that colchicine is of protective value against chronic Cs nephrotoxicity in Sprague-Dawley rats. [ABSTRACT FROM AUTHOR]