Ahmed F. Hamdy

Comparison of Sirolimus with Low‐Dose Tacrolimus Versus Sirolimus‐based Calcineurin Inhibitor‐Free Regimen in Live Donor Renal Transplantation

Between May 2001 and January 2003, 132 live donor renal allotransplant recipients were included in a prospective, randomized controlled trial where they were divided into two groups. All patients received steroids and basiliximab induction therapy. For maintenance immunosuppression, tacrolimus and sirolimus were used in group A. In group B, mycophenolate mofetil (MMF) and sirolimus were utilized. Patients were followed up for a minimum of 24 months. One‐year patient and graft survival rates were not significantly different between group A (96.9%, 92.3%) and group B (100%, 98.4%), respectively. However, the incidence of biopsy‐proven acute rejection was less in group B but the difference was not statistically significant (13.5% vs. 18.5% in group A). Statistically significant better renal function was encountered among group B patients at two years post‐transplantation as measured by serum creatinine (1.25 vs. 1.43 mg/dl; P = 0.017) and calculated glomerular filtration rate (GFR) (94.9 vs. 79.6 ml/min; P = 0.005). One year protocol biopsies showed insignificant differences relative to chronic allograft damage index (CADI) between either group (Group A: 2.41 vs. Group B: 2.69; P = 0.436). Conclusion: Similar outcome was noted among patients in whom calcineurin inhibitors were not included in their immunosuppressive regimen. The long term impact of this observation on graft survival and function needs longer follow up.

Long-term Efficacy and Safety of a Calcineurin Inhibitor-free Regimen in Live-Donor Renal Transplant Recipients

Calcineurin inhibitor (CNI) nephrotoxicity is a major concern after renal transplantation. To investigate the safety and efficacy of a CNI-free immunosuppressive regimen, 132 live-donor renal transplant recipients were included in a prospective, randomized controlled trial. All patients received induction therapy with basiliximab and steroids. The patients were randomized to a maintenance immunosuppression regimen that included steroids, sirolimus, and either low-dose tacrolimus or mycophenolate mofetil (MMF). Over a mean follow-up period of approximately 5 yr, patient and graft survival did not significantly differ between the two maintenance regimens. Patient survival was 93.8% and 98.5% in the tacrolimus/sirolimus and MMF/sirolimus groups, respectively, and graft survival was 83% and 88%, respectively. However, the MMF/sirolimus group had significantly better renal function, calculated by Cockcroft-Gault, from the second year post-transplant until the last follow-up. In addition, this group was less likely to require a change in their primary immunosuppression regimen than the tacrolimus/sirolimus group (20.8% versus 53.8%, P = 0.001). The safety profile was similar between groups. In summary, after long-term follow-up, a CNI-free maintenance regimen consisting of sirolimus, MMF, and steroids was both safe and efficacious among low to moderate immunologic risk renal transplant recipients.

Long-term evaluation of single bolus high dose ATG induction therapy for prophylaxis of rejection in live donor kidney transplantation

Background/AimsThe long-term evaluation of single bolus high dose antithymocyte globulin (ATG) induction therapy has not been adequately studied. We aimed to evaluate its long-term effects in the living related donor kidney transplantation.MethodsEighty adult recipients with their first kidney allograft were randomized into two equal treatment groups, one group received intraoperative single bolus rabbit ATG in a dose of 9xa0mg/kg and the second group served as a control. All patients were maintained on triple immunosuppressive therapy (steroids, calcineurin inhibitor and antiproliferative agent). We followed them thoroughly for minimum of 5xa0years.ResultsATG significantly reduced the proportion of patients who experienced acute rejection episodes in the first year (9/40) when compared to the control group (26/40) and in 5xa0years (11/40) when compared to (30/40) in controls. The cumulative steroid dose used throughout the study was significantly lower in the ATG group. The overall incidence of post-transplant complications was comparable among the two treatment groups. There was no significant difference in patient and graft survival: 5 year survival was 100% and 85% for the ATG group, and 95% and 92.5% in the control group, respectively.ConclusionAlthough routine single bolus ATG induction significantly reduces the incidence of acute rejection, its long-term beneficial effects on graft function and patient and graft survival are not evident.

Continuous ambulatory peritoneal dialysis in Egypt: progression despite handicaps.

♦ Background: Despite the well-known advantages of continuous ambulatory peritoneal dialysis (CAPD), it continues to be grossly underutilized in many developing countries. However, some developing countries, such as Mexico, use the modality very effectively. In view of this, we started the first CAPD program in Egypt. ♦ Methods: Since its start in 1997, our program has treated 33 patients. Straight double-cuffed Tenckhoff catheters were surgically placed in all patients. Twin-bag systems were used. All patients underwent monthly clinical and biochemical assessment and measurement of Kt/V urea. Peritonitis and exit-site infection rates were monitored. ♦ Results: Most treated patients were adult and female. Mean age was 31.7 years and mean follow-up duration was 18 months. Peritonitis rate was 1 episode /21.3 months and was easily managed in most patients. Staphylococcus aureus was the most commonly isolated organism (24%) but 49% of cases were culture negative. There were no exit-site infections. Mean weekly Kt/V urea was 1.78 ± 0.23. ♦ Conclusion: We report the successful development of a small CAPD program in Egypt, made possible by well-established financial support, a motivated team of doctors and nurses, and good patient selection and training.

Long Term Prospective Assessment of Living Kidney Donors: Single Center Experience

Virtually, all studies reporting the outcomes of living kidney donation beyond the first year from donation were retrospective. In this prospective study, the outcome of 81 consecutive living kidney donors was thoroughly evaluated. Clinical, laboratory, and radiological assessments were carried out at predonation (basal), 3, 6, 12, and 24 months after donation. The mean age at time of donation was 37.8 ± 9.8 years and the majority was females (75.3%). The mean BMI increased significantly after donation (P < 0.04). The mean serum creatinine levels (mg/dl) were 0.75 ± 0.14, 1.01 ± 0.22, 0.99 ± 0.21, 0.98 ± 0.20, and 0.94 ± 0.20 (P < 0.0001). Likewise, the mean levels of measured creatinine clearance (mL/min) were 148.8 ± 35.7, 94.7 ± 26.6, 95.5 ± 24.6, 96.7 ± 20.2, and 101.6 ± 26.2 (P < 0.0001). The mean 24 hours urinary protein excretion (gm/dL) were 0.09 ± 0.03, 0.19 ± 0.18, 0.16 ± 0.09, 0.18 ± 0.25, and 0.17 ± 0.12 (P < 0.0001). There were significant increases in the means of the longitudinal and transverse diameters of the remaining kidney over time (P < 0.001). Out of 42 female donors, eleven female donors have got successful postdonation pregnancies. There were no reported surgical complications, either intra- or postoperative. Long-term follow-up is necessary for all living kidney donors through local institutional and world registries. This trial is registered with ClinicalTrials.gov NCT00813579.

Interleukin-10 gene polymorphism and graft outcome in live-donor kidney transplantation

Background Polymorphism has been described in many immunoregulatory molecules that play a role in the rejection process. It has offered a possible explanation for the individual difference in rejection susceptibility and renal graft survival independent of other risk factors. The aim of this work was to study the impact of the interleukin-10 (IL-10) cytokine gene polymorphism on the clinical course and outcome of a renal transplant. Materials and methods This work included 50 transplant recipients treated with a sirolimus-based immunosuppressive regimen for IL-10 cytokine gene polymorphisms. After transplantation, patients were classified into two groups: in group A, patients (12 patients) received sirolimus, tacrolimus, and steroid and in group B, patients (38 patients) received sirolimus, mycophenolate mofetil, and steroid. The results were correlated with rejections (acute and chronic) and patient and graft survival. Results In our study, we found no impact of IL-10 on the incidence and degree of acute rejection episodes, incidence of chronic allograft nephropathy, pathological changes in protocol biopsies, graft function, and graft and patient survivals. Conclusion On the basis of this work, we concluded that there is no impact of IL-10 cytokine gene polymorphisms on the clinical course and outcome of a renal transplant. Genes other than IL-10 could probably be involved as key molecules in graft function.