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Biomedical subjects

Mohamed A Bakr

Publications and source records attributed to Mohamed A Bakr.

13 recordsLinked to original sources

Histologic and clinical findings in living donor allografts with long-term stable function.

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.

Adult↗

Pediatric live-donor kidney transplantation in Mansoura Urology & Nephrology Center: a 28-year perspective.

Our objective was to evaluate our overall experience in pediatric renal transplantation. Between March 1976 and March 2004, 1,600 live-donor kidney transplantations were carried out in our center; 216 of the patients were 18 years old or younger (mean age 12.9 years). There were 136 male patients and 80 female patients. The commonest causes of end-stage renal disease (ESRD) were renal dysplasia (22%), nephrotic syndrome (20%), hereditary nephritis (16%), and obstructive uropathy (16%). Of the donors, 94% were one-haplotype matched and the rest were identical. Pre-emptive transplantation was performed in 51 (23%) patients. Triple-therapy immunosuppression (prednisone + cyclosporine + azathioprine) was used in 78.2% of transplants. Rejection-free recipients constituted 47.7%. Hypertension (62%) was the commonest complication. A substantial proportion of patients (48%) were short, with height standard deviation score (SDS) less than -1.88. The overall infection rate was high, and the majority (53%) of infections were bacterial. The graft survival at 1 year, 5 years and 10 years were 93.4%, 73.3% and 48.2%, respectively, while the patients' survival at 1, 5 and 10 years were 97.6%, 87.8% and 75.3%, respectively. Despite long-term success results of pediatric renal transplantation in a developing country, there is a risk of significant morbidity.

Adolescent↗

Long-term evaluation of basiliximab induction therapy in live donor kidney transplantation: a five-year prospective randomized study.

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.

Acute Disease↗

Glutathione peroxidase activity in patients with renal disorders.

BACKGROUND: Glutathione peroxidase (GPx) protects cells from oxidative damage by catalyzing the reduction of both organic and hydrogen peroxides, using glutathione as a reducing agent. Both plasma GPx (P-GPx) and erythrocyte GPx (E-GPx) have been identified in human blood. Kidney proximal tubular cells are the main source of GPx activity in the plasma. Oxidative damage has been reported to participate in the progression and complications of renal diseases. METHODS: The activities of both E-GPx and P-GPx were determined, using Randox commercial kits, in 12 patients with nephrotic syndrome (NS), 48 patients with renal impairment (RI), and 50 patients with chronic renal failure on maintenance hemodialysis (HD; before as well as immediately after dialysis), and in 50 healthy volunteers who served as controls. RESULTS: Compared to the results in healthy controls, P-GPx activity was reduced in the HD group and the RI group, whereas the NS group showed no significant difference from the control. The HD group showed a higher drop in P-GPx (reduced to 36.6% of the mean control value) than the RI group (reduced to 61.8% of the mean control value). Further analysis of the RI group showed a highly significant negative correlation between P-GPx activity and serum creatinine level (r = -0.691; P < 0.001). Also, a highly significant negative correlation was found between P-GPx and blood urea nitrogen (r = -0.792; P < 0.001). However, E-GPx activity showed no significant correlation with either serum creatinine or blood urea nitrogen. E-GPx was reduced to 55.2% and 68.9% of the mean control 1 value in the NS group and the RI group respectively, while the HD group showed no significant change. Further analysis of the RI group found that E-GPx activity showed no significant correlation with either serum creatinine or blood urea nitrogen. In HD patients, GPx activity was measured before and immediately after hemodialysis. E-GPx activity was similar before and after dialysis, without a significant difference (pre-dialysis, 37.7 +/- 13.5 U/g hemoglobin [Hb]; post-dialysis, 38.72 +/- 12.31 U/g Hb). However, P-GPx activity was significantly increased (pre-dialysis, 254.4 +/- 62.6 U/ml; post-dialysis, 296.98 +/- 74.04 U/ml; P < 0.001), but it was still significantly lower when compared to that in the healthy controls. CONCLUSIONS: P-GPx activity is an important test to assess the oxidative damage in patients with kidney diseases. The progression of renal disorders is accompanied by a decrease in P-GPx activity, but not by a decrease in E-GPx activity. Thus, we conclude that P-GPx activity largely depends on physiological renal function, whereas E-GPx activity does not.

Adolescent↗

Comparison of sirolimus with low-dose tacrolimus versus sirolimus-based calcineurin inhibitor-free regimen in live donor renal transplantation.

UNLABELLED: 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.

Adult↗

Induction therapy.

Transplantation is a suitable option for patients with end-stage organ failure. Many immunosuppressive agents are available, and this may pose difficulty in choosing an appropriate combination for maintenance therapy, treating episodes of acute rejection of varying severities, and tailoring therapies for specific patients. Induction therapy strategies are accomplished either by relatively high doses of conventional immunosuppressants or by using poly- or monoclonal antibodies. These antibodies are an integral part of transplant medicine today. The rationale for antibody therapy aims at augmenting immunosuppression, ensuring that delayed introduction of calcineurin inhibitors is safe, encouraging steroid withdrawal, and facilitating treatment of patients sensitized to human leukocytic antigens in addition to its crucial role in immunologic conditioning either by tolerance induction or alternatively minimizing the immunosuppressive drugs. Different trends in induction therapy initially consisted of anti-thymocyte globulin, then anti- CD3 Orthoclone, and finally anti-CD20, 25, and 52 agents. Induction therapy is associated with beneficial short- and long-term outcomes when increased risk of adverse effects related to immune system suppression are an issue, especially from cytomegalovirus and lymphomas.

Alemtuzumab↗

Impact of Rh(D) blood group system on graft function and survival in live-donor kidney transplantation: a single-institution experience.

One thousand five hundred consecutive live-donor renal transplants were performed in a single institution. Among these patients, 1,372 patients (group I) received Rh-identical allografts and 128 (group II) received Rh-nonidentical allografts. The two groups were homogenous apart from the prevalence of the Rh nonidentity among unrelated donor-recipient pairs. The rate of acute and chronic rejection was comparable in both groups (P = 0.33 for acute rejection and P = 0.66 for chronic rejection). The mean serum creatinine at 5 years was 1.8 +/- 1 mg/dL for group I and 1.7 +/- 0.9 mg/dL for group II (P = 0.5). The 1-, 5-, and 10-year graft survival rates were 94%, 78%, and 54% for group I and 95%, 82%, and 57% for group II. We found that the Rh(D) blood group system is not likely to be a clinically relevant histocompatibility barrier to live-donor renal transplantation.

Adolescent↗

Preemptive living-donor kidney transplantation: clinical course and outcome.

BACKGROUND: Dialysis is not only associated with morbidity, it is also expensive. In developing countries, preemptive renal transplantation (Tx) may be a cost-effective option, offering an additional benefit to conventional renal Tx. MATERIALS: Between March 1976 and March 2001, 1,279 first living-donor Txs were performed in our center. The 82 patients (6.4%) who underwent Tx without prior dialysis were compared with 1,197 patients who had been dialyzed before Tx. RESULTS: The dialysis-dependent group received more blood transfusions (65% vs. 30%) before Tx. Actuarial graft and patient survival at 5 years was comparable in both groups (P =0.2 and P =0.8, respectively). The incidence of acute and chronic rejection was not different between the two groups. Mortality rate was also similar in the two groups. The main cause of death with a functioning graft was cardiovascular in the preemptive Tx group and chronic liver disease and infection in the control group. CONCLUSION: In the context of a developing country, preemptive Tx offers comparable patient and graft survival to conventional renal Tx and eliminates the complications, inconvenience, and cost of dialysis.

Adult↗

Living-donor kidney retransplantation: risk factors and outcome.

OBJECTIVE: To review the results of kidney retransplantation at our centre. PATIENTS AND METHODS: Between March 1976 and January 2002, 1406 kidneys were transplanted; among these, 54 patients received a second graft (39 men, mean age 32.1 years, sd 8.6). The donors were 48 relatives (mean age 35.4 years, sd 10.1). RESULTS: The mean (sd, range) duration of the first graft was 49.1 (45.9, 1-192) months and the main cause of these grafts failing was immunological. The mean duration of graft failure was 17.3 (10.5, 5-62) months. The rate of histocompatibility leukocyte antigen (HLA)-A, -B >3 was 16.7% and of haplotype DR matching was 11%. The immunosuppression regimen was mainly based on cyclosporin (75%). There were 33 episodes of acute rejection in 23 patients. The major complications were hypertension (70%), infections (30%) and hepatitis (11%). The overall graft and patient survival was good; 15 grafts (27%) were lost during the follow-up of 1-17 years. Ten patients died, five with a functioning graft. Multivariate analysis showed that donor relationship, primary immunosuppression, duration of first graft and serum creatinine level at 1 year were predictors of graft survival. CONCLUSION: Renal retransplantation is the treatment of choice in patients who have lost their graft. The use of related living-donors and potent immunosuppression could help to improve the outcome.

Adult↗

Effect of donor/recipient body weight mismatch on patient and graft outcome in living-donor kidney transplantation.

BACKGROUND/AIMS: There have been conflicting reports showing that kidneys from small donors may be at risk for graft loss if they are transplanted into large recipients. The aim of this work was to examine the donor/recipient body weight ratio (D/RBWR) on patient and graft outcome. METHODS: During the period from January 1990 to January 2002, 856 kidney transplants were performed. Of these, 776 kidney transplant recipients were selected after exclusion of pediatric, second transplant patients and those with a body mass index of 35. All patients achieved a minimum follow-up of 1-year. According to D/RBWR, patients were divided into 3 groups: low (0.9), medium (0.91-1.2) and high (1.2). Data were collected on graft function, acute and chronic rejection, post-transplant complications, and 1- and 5-year graft and patient survival. RESULTS: There was a statistically significant increase in the incidence of chronic rejection, post-transplant hypertension and diabetes mellitus in the low group. The incidence and frequency of acute rejection episodes were nearly the same in the 3 groups. Graft function, estimated by serum creatinine at 1 year, was significantly lower in the low group. The 5-year graft and patient survival was 71, 80, 88 and 81, 85 and 92%, in the low, medium and high groups, respectively. CONCLUSIONS: We conclude that a low D/RBWR may contribute to inferior long-term renal allograft survival. The hyperfiltration hypothesis due to low nephron mass in the low D/RBWR group may explain these findings.

Adolescent↗

Death with functioning graft in living donor kidney transplantation: analysis of risk factors.

BACKGROUND: Death with a functioning graft (DWF) has been reported as a major cause of graft loss after renal transplantation. It has been reported to occur in 9-30%. METHODS: From March 1976 to January 2002, a total of 1400 living donor renal transplants were performed in our center. Out of 257 reported deaths among our patients, 131 recipients died with functioning grafts after a mean period of 53.4 +/- 53.2 months. RESULTS: DWF patients account for 27% of all graft losses in our series. The mean age was 34.9 + 10.6 (range 8-62 years), 98 of them were male and 33 were female. The original kidney disease was GN in 9, PN in 24, PCK in 5 and nephrosclerosis in 8 patients. Acute rejection episodes were diagnosed in 84 patients (63.1). The post-transplant complications encountered were hypertension in 78 patients (59.5%), diabetes mellitus in 30 patients (22.9%), medical infections in 68 (51.5%), hepatic complications in 30 (22.9%) and malignancy in 17 patients (13%). The main causes of death in these patients were infections in 46 (35.6%), cardiovascular in 23 (17.6%), liver cell failure in 15 patients (11.4%) and malignancy in 8 (6.1%). The mean serum creatinine was 2 +/- 0.6 mg/dl at last follow-up before death. CONCLUSION: We conclude that the relatively higher mortality in renal transplantation is, in part, due to co-morbid medical illness, pre-transplant dialysis treatment, and factors uniquely related to transplantation, including immunosuppression and other drug effects. DWF must be in consideration when calculating graft survival.

Adolescent↗

Characteristics of long-term live-donor renal allograft survivors.

BACKGROUND/AIMS: Despite the high rate of rejection, allograft failure and patient mortality in the early years of renal allotransplantation, some patients have done-remarkably well. We report here on 62 renal transplant recipients out of 144 patients (43%) who had functioning grafts for more than 15 years (range 15-24 years). MATERIALS: Demographic and follow-up data for patients fulfilling the criteria were reviewed. These patients include 43 males and 19 females, with a mean age at transplantation of 27.5 +/- 6.6 years (range 9-43 years), and mean donor age of 30 +/- 8.6 years. The donor source was 8 parents, 49 siblings and 5 unrelated. The main causes of end-stage renal disease were chronic pyelonephritis and chronic glomerulonephritis. Twenty-nine patients were treated with cyclosporine (CsA) while 33 patients were primarily immunosuppressed by steroids and azathioprine. RESULTS: Acute rejection episodes occurred in 40 patients (64.3%), out of them 19 patients experienced two or more acute rejection episodes. Univariate analysis showed that recipient and donor age, HLA-DR matching, pre- and post-transplant hypertension, ATN, delayed diuresis and chronic allograft nephropathy are significant risk factors; while recipient age, delayed diuresis and post-transplant hypertension were still significant by multivariate analysis. CONCLUSIONS: We concluded that renal transplantation, even in its earliest years and despite the numerous complications, has provided 15 or more years of near-normal life to patients with end-stage renal disease. Certain characteristics of long-term renal allograft survivors include young donor/recipient pairs, good DR matching with less pre- and post-transplantation prevalence of hypertension.

Adult↗

Basiliximab reduces the incidence of acute cellular rejection in live-related-donor kidney transplantation: a three-year prospective randomized trial.

BACKGROUND: The aim of this work was to investigate the benefit of basiliximab induction therapy in living-related-donor kidney transplantation. METHODS: One hundred adult recipients of a first kidney allograft were randomized into two treatment groups, one to receive basiliximab and the second as a control. All patients received maintenance triple immunosuppressive therapy (steroids, cyclosporine microemulsion and azathioprine). The patients were followed up for a minimum of three years. The end points for evaluation included the incidence of acute rejection episodes, severity of rejection, cumulative steroid dose, patients' and graft survival. RESULTS: Basiliximab significantly reduced the proportion of patients who experienced an acute rejection in the first year (18/50) compared to the control group (31/50). At three years there were 26 acute rejections in the basiliximab group and 36 in control group. The cumulative steroid dose at three and 12 months was significantly lower in the basiliximab group. The overall incidence of post-transplant complications was comparable in the two groups. CONCLUSIONS: Prophylactic basiliximab is well tolerated and significantly reduces the incidence of acute rejection episodes in living-related-donor kidney transplantation.

Acute Disease↗