Browsing by Author "Refaie, Ayman F."

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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.
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.
Transplantation of Insulin-Producing Clusters Derived From Adult Bone Marrow Stem Cells to Treat Diabetes in Rats
(Başkent Üniversitesi, 2008-09) Gabr, Mahmoud M.; Ghoneim, Mohamed A.; Refaie, Ayman F.; Zakaria, Mahmoud M.; Sobh, Mohamed M.
Objectives: Recent findings suggest that bone marrow stem cells can differentiate into numerous cell types. This would provide a potentially unlimited source of isletlike cells for transplantation and a promising therapy for diabetes mellitus. Here, we studied the differentiation ability of adult bone marrow hematopoietic-rich stem cells to form glucose-regulating insulin-producing cells. Their ability to treat chemically induced diabetes in rats was then tested. Materials and Methods: Hematopoietic-rich stem cells were obtained from the long bones of rats and cultured in a serum-free medium containing 1% dimethyl sulfoxide for 3 days. The cells were cultured for 7 days in a glucose-rich medium supplemented with pancreatic extract. Thereafter, cultures were done in a medium (low concentration of glucose and 5% fetal bovine serum) supplemented with nicotinamide and exendin-4 for 7 more days. Results: At day 17 of culture, the cells formed isletlike clusters. These were distinctly stained crimson red by diphenylthiocarbazone and expressed insulin and endocrine-specific transcription genes. Insulin was secreted in a dose-response manner as a function of increasing glucose concentrations. When transplanted in the testes of diabetic rats, the differentiated cells could normalize blood glucose levels for 3 months in 80% of the treated rats. The therapeutic benefits were reversed after orchidectomy. Conclusions: Hematopoietic-rich stem cells may include pancreatic progenitor cells capable of differentiating into functioning endocrine hormone-producing cells. This finding suggests a possible means of treating diabetes mellitus.