Başkent Üniversitesi Yayınları
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Item Alemtuzumab Preconditioning Allows Steroid-calcineurin Inhibitor-free Regimen in Live-donor Kidney Transplant(Başkent Üniversitesi, 2011-10) Refaie, Ayman F.; Ghoneim, Mohamed A.; Kamal, Ahmed I.; Sheashaa, Hussein A.; Ismail, Amani M.; Mahmoud, Khaled M.Objectives: This prospective study was designed to develop a steroid and calcineurin inhibitor-free regimen for kidney transplants using alemtuzumab. Materials and Methods: A single dose of alemtuzumab (30 mg) was given preoperatively. Phase 1: Twenty-one patients were randomized into 2 groups; the tacrolimus (n=11) and the sirolimus groups (n=10). Steroids were given for 5 days. Azathioprine (1 mg/kg) was added when white blood cells ≥ 4000 cells/cm3. Mean follow-up was 48 ± 2.8 and 48.2 ± 1.6 months for the tacrolimus and sirolimus groups. Phase 2: Twenty patients were included and the study design was modified. Tacrolimus was given for 2 months, and was replaced by sirolimus thereafter. The mean follow-up was 28.3 ± 2.1 months. Results: Phase 1: Acute rejection episodes were encountered in 5 patients of the tacrolimus versus 2 cases in the sirolimus group (P = .44). Antibody-mediated rejection was diagnosed in 2 recipients in each group. Four patients were switched from sirolimus to tacrolimus owing to resistant rejection, significant proteinuria, persistent thrombocytopenia, lymphocele, and urinary leakage. One patient was shifted from tacrolimus to sirolimus owing to Kaposi sarcoma. Glomerular filtration rate was significantly higher in the sirolimus group. Currently, 14 patients (8 tacrolimus, and 6 sirolimus) are steroid-free. One patient died from the tacrolimus group owing to fulminant hepatitis. Two grafts were lost in the sirolimus group versus 1 graft in the tacrolimus group. Phase 2: Five patients developed successfully treated borderline changes with no antibody-mediated rejection. Mean serum creatinine was 114.9 ± 17.7 µmol/L. Currently, 17 patients are steroid-free and 15 of them are calcineurin inhibitor-free as well. In this phase, only 1 patient died with a functioning graft. Conclusions: This clinical trial provides a good insight into a potentially effective steroid and calcineurin inhibitor-free protocol with the use of alemtuzumab induction in combination with sirolimus.Item Ten-year Follow-up of Basiliximab Induction Therapy for Live-donor Kidney Transplant: A Prospective Randomized Controlled Study(Başkent Üniversitesi, 2011-08) Sheashaa, Hussein A.; Ghoneim, Mohamed A.; Sobh, Mohamed A.; Ismail, Amani M.; Rashad, Rashad H.; Bakr, Mohamed A.Objectives: The effect of basiliximab induction therapy on long-term patient and graft survival is not clear. We sought to evaluate if there is any advantage to routine basiliximab induction on the long-term outcome of living-related donor kidney transplants. Materials and Methods: One hundred adult recipients with their first kidney allograft were randomized into 2 treatment groups; 1 group received basiliximab, and the second served as a control. All patients received a maintenance triple immunosuppressive therapy (steroids, cyclosporine, microemulsion, and azathioprine). We followed them for 10 years. Results: Basiliximab reduced the proportion of patients who experienced an acute rejection in the first year (18/50) when compared with the control group (31/50) (P = .009), and in 10 years (28/50) when compared with controls (37/50) (P = .059). The cumulative steroid dosage used throughout the study was significantly lower in the basiliximab group. The overall incidence of posttransplant complications was comparable among the 2 groups. There was no significant difference in patient and graft survival; 10-year patient and graft survival were 92% and 76% for basiliximab and 90% and 68% for the control group. Conclusions: Routine basiliximab induction significantly reduces the incidence of acute rejection without any noticeable effects on the long-term renal transplant outcome.Item Steroid Avoidance Reduce the Cost of Morbidities After Live-donor Renal Allotransplants: A Prospective, Randomized, Controlled Study(Başkent Üniversitesi, 2011-04) Gheith, Osama A.; Ghoneim, Mohamed A.; Shokeir, Ahmed A.; Refaie, Ayman; Bakr, Mohamed A.; Nematalla, Ahmed H.Objectives: Steroids have had the main role in renal transplant for more than 4 decades. However, chronic use of steroids is associated with many comorbidities, owing to a lack of assessing cost-benefit of steroid avoidance in live-donor renal allotransplants. In this prospective, randomized, controlled study, we aimed to assess the cost-benefit of a steroid-free immunosuppression regimen among Egyptian live-donor renal transplants. Materials and Methods: One hundred patients were randomly allocated to receive tacrolimus, mycophenolate mofetil, and steroids for only 3 days (n=50 patients; study group) or tacrolimus, mycophenolate mofetil, and steroids on a maintenance basis (n=50 patients; control group). All patients received basiliximab (Simulect) induction, with median follow-up of 12 months. Results: Both groups showed comparable graft and patient survivals, rejection episodes, and graft functioning. Posttransplant comorbidities were significantly more prevalent in the steroid-maintenance group. Hypertension was detected in 4% of steroid-free group versus 24% in the steroid-maintenance group (P = .0009). Posttransplant diabetes mellitus, serious infections, and hyperlipidemia were significantly more prevalent in the steroid-maintenance group (P < .05). Associated hospitalization costs were 2.2-fold higher in the steroid-maintenance group than they were in the steroid-free group. One year after transplant, the cost of managing posttransplant comorbidities was significantly higher in steroid-maintenance group, despite comparable costs of immunosuppression. Conclusions: In low, immunologic risk recipients of live-donor renal transplants, using basiliximab induction and maintenance with tacrolimus, mycophenolate mofetil, steroid avoidance was associated with lower first annual total costs despite comparable immunosuppression costs, which was attributed to lower costs of associated morbidities.Item End-stage Renal Disease Among Living-Kidney Donors: Single-center Experience(Başkent Üniversitesi, 2011-02) Wafa, Ehab W.; Ghoneim, Mohamed A.; Ghar, Mohamed I. Abo El; Mostafa, Amani; Sheashaa, Hussein A.; Fouda, Mohamed A.; Abbas, Tarek M.; Refaie, Ayman F.Objectives: Renal transplant from living donors is widely accepted as a highly effective treatment for end-stage renal disease. Donors undergo a major operation with considerable perioperative risks of morbidity and mortality. Living with a single kidney also confers long-term risks. This study sought the incidence and causes of end-stage renal disease among living kidney donors. Materials and Methods: This study included all donors who had reached end-stage renal disease among 2000 consecutive living-kidney donors. All operations and follow-up were performed in a single center. We studied the onset of renal disease, cause of end-stage renal disease, date of replacement therapy, and outcome. We also revised the donor’s medical records related to their corresponding recipients. Results: Of 2000 living donors, 8 developed end-stage renal disease; 6 were men (mean age, 30.87 ± 5.84 years. Renal failure occurred 5 to 27 years after donation. Renal transplant was done in 1 donor. Medical complications were proteinuria (6 patients), hypertension (7 patients), diabetes (3 patients), gout (3 patients), ischemic heart disease (5 patients), and hepatitis viral infection (4 patients). The causes of end-stage renal disease were diabetic nephropathy in 3 patients. Other possible causes included toxic nephropathy, chronic pyelonephritis, and preeclampsia. Conclusions: Living kidney donation is safe, and development of renal failure after donation is caused by the same causes as in the general population.Item Proteinuria Among Primarily Sirolimus Treated Live-donor Renal Transplant Recipients' Long-term Experience(Başkent Üniversitesi, 2010-12) Hamdy, Ahmed F.; Ghoneim, Mohamed A.; Bakr, Mohamed A.Objectives: Recent evidence of a high incidence of proteinuria among de novo sirolimus-based regimens has been reported among renal transplant patients at short-term follow-up. We report on long-term evaluation of proteinuria among patients maintained on such regimen. Materials and Methods: Between May 2001 and January 2003, 132 patients received a renal allograft from a living donor and were randomized to 2 groups (steroids/sirolimus/tacrolimus, n=65) and (steroids/sirolimus/mycophenolate mofetil, n=67): Both received basiliximab induction. Retrospective review of those patients was performed, 5 years posttransplant with particular emphasis on the incidence of proteinuria. Results: The 5-year incidence of proteinuria was 29.2% and 38.8% among sirolimus/tacrolimus and sirolimus/mycophenolate mofetil group. Single DR-matched patients (P = .016) and the incidence of acute rejection (P = .039) were associated with significantly higher incidence of proteinuria. Moreover, the presence of mesangial matrix increased (P = .015), and glomerulosclerosis (P = .014), in 1-year protocol biopsies, was found to have a positive predictive value for current and future incidences of proteinuria. Proteinuria was found to be associated with significant inferior graft outcome. Recurrent original kidney disease, de novo glomerulopathy, and acute transplant glomerulopathy were responsible for early cases of nephrotic range proteinuria (first 2 years), while cases presented later were attributed to chronic allograft nephropathy. Conclusions: Proteinuria has become a recognized, serious event of primarily sirolimus-treated renal transplants patients, which is most probably of glomerular origin. It has been shown that proteinuria exerts a bad prognostic effect upon graft function and subsequent graft survival at 5-year follow-up.Item Characteristics of Patients With Banff Borderline Changes in Renal Allograft Biopsies(Başkent Üniversitesi, 2009-12) Wafa, Ehab W.; Ghoneim, Mohamed A.; El-Agroudy, Amgad E.; El-Baz, Mahmoud; Gheith, Osama A.; El-Husseini, Amr; Abbas, Tarek M.Objectives: The aim of this retrospective study was to characterize the patients who experienced borderline rejection. Materials and Methods: Patients with a minimum follow-up of 2 years were enrolled in this study. Forty-seven patients out of 106 patients with borderline rejection (after exclusion of those with associated chronic interstitial fibrosis) were compared with patients with acute cellular rejection grade 1 (n=650), and patients free of rejection episodes (n=444) regarding the different characteristics. Results: Patients aged 20 years or younger were frequently in borderline rejection group than other groups (which was statistically significant) (P = .001). Significant differences were found in recipient and donor ages, consanguinity, pretransplant blood transfusion, and immunosuppression plan. Most patients in borderline rejection group received triple immunosuppression therapy than other groups (P = .001). Univariate and multivariate regression analysis of different variables on graft survival in borderline rejection patients revealed that none of them was statistically significant. Conclusions: Borderline rejection is a frequent finding in biopsy-proven acute rejection after kidney transplant. Time of occurrence, frequency, treatment or not, and response to therapy were not predictors to graft survival.Item Characteristics of Recipients Whose Kidney Allograft Has Functioned for More Than 20 Years(Başkent Üniversitesi, 2008-06) El-Agroudy, Amgad E.; Ghoneim, Mohamed A.; Shokeir, Ahmed A.; Ismail, Amani M.; Abbass, Tarek M.; El-Dahshan, KhaledObjectives: To study the characteristics of, and predictors for, survival in renal transplant recipients with an allograft functioning for more than 20 years. Materials and Methods: Of 144 renal transplants done between 1976 and 1985, 31 allografts were still functioning for more than 20 years (range, 21-28.5 years). The characteristics of the patients and determinants of the outcomes were obtained by reviewing the patients’ medical records. Results: Fourteen patients were treated with cyclosporine, while 17 patients had primary immunosuppression with azathioprine-based regimens. Episodes of acute rejection occurred in 17 patients (58%), 7 of these experienced 2 or more episodes. At most-recent follow-up, the mean serum creatinine level was 132 ± 44 µmol/L . Four patients were assessed by graft biopsy 15 or more years after the transplant, revealing 2 cases of mild glomerulosclerosis and 2 cases of moderate chronic allograft nephropathy. The most common complication was hypertension (54%). The independent determinants of long-term graft survival were donor age and source, hypertension both before and after renal transplant, and histopathological findings of chronic allograft nephropathy. Conclusions: Renal transplant offers a near-normal life to patients with end-stage renal disease soon after transplant and for upwards of 20 years and more. We found no significant benefit to cyclosporine-based immunosuppression on long-term graft survival.