Mohamed A. Bakr

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.

An investigation to assess the potential of CD25highCD4+ T cells to regulate responses to donor alloantigens in clinically stable renal transplant recipients

Regulatory T cells are enriched within CD25highCD4+ leukocytes, however their role in renal transplant recipients with stable function vs. recipients with biopsy‐proven chronic allograft dysfunction remains unclear. We therefore studied the number, phenotype, and function of CD25highCD4+ cells in the peripheral blood of 30 renal transplant recipients of living‐related grafts, comprising 15 rejection‐free recipients with stable graft function (Group A) and 15 with biopsy‐proven chronic graft dysfunction (Group B). A higher absolute number of CD25highCD4+ cells were present in the peripheral blood of rejection‐free recipients (Group A) vs. those recipients with chronic graft dysfunction (Group B) (P = 0.019); but there was no significant difference with healthy volunteers (P = 0.084). In carboxyfluorescein diacetate succinimidyl ester‐mixed leukocyte culture assays, depletion of CD25highCD4+ revealed active regulation in 11 (74%) of 15 rejection‐free recipient samples (Group A) in response to donor‐ but not third party‐leukocytes, whereas no regulatory activity was observed in any samples from recipients with chronic graft dysfunction (Group B). In conclusion, these data provide evidence for the presence of an increased number of CD25highCD4+ T cells with donor‐specific regulatory activity in the peripheral blood of renal transplant recipients with stable graft function compared with recipients with chronic graft dysfunction.

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.

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.

Glutathione peroxidase activity in patients with renal disorders

BackgroundGlutathione 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.MethodsThe 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.ResultsCompared 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.ConclusionsP-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.

KDIGO Clinical Practice Guideline on the Evaluation and Care of Living Kidney Donors

Abstract The 2017 Kidney Disease: Improving Global Outcomes (KDIGO) Clinical Practice Guideline on the Evaluation and Care of Living Kidney Donors is intended to assist medical professionals who evaluate living kidney donor candidates and provide care before, during and after donation. The guideline development process followed the Grades of Recommendation Assessment, Development, and Evaluation (GRADE) approach and guideline recommendations are based on systematic reviews of relevant studies that included critical appraisal of the quality of the evidence and the strength of recommendations. However, many recommendations, for which there was no evidence or no systematic search for evidence was undertaken by the Evidence Review Team, were issued as ungraded expert opinion recommendations. The guideline work group concluded that a comprehensive approach to risk assessment should replace decisions based on assessments of single risk factors in isolation. Original data analyses were undertaken to produce a “proof-in-concept” risk-prediction model for kidney failure to support a framework for quantitative risk assessment in the donor candidate evaluation and defensible shared decision making. This framework is grounded in the simultaneous consideration of each candidates profile of demographic and health characteristics. The processes and framework for the donor candidate evaluation are presented, along with recommendations for optimal care before, during, and after donation. Limitations of the evidence are discussed, especially regarding the lack of definitive prospective studies and clinical outcome trials. Suggestions for future research, including the need for continued refinement of long-term risk prediction and novel approaches to estimating donation-attributable risks, are also provided. In citing this document, the following format should be used: Kidney Disease: Improving Global Outcomes (KDIGO) Living Kidney Donor Work Group. KDIGO Clinical Practice Guideline on the Evaluation and Care of Living Kidney Donors. Transplantation. 2017;101(Suppl 8S):S1–S109.

Living-donor kidney retransplantation: risk factors and outcome

Authors from Mansoura in Egypt present a study of risk factors and outcome from living‐donor renal re‐transplantation. This is sometimes avoided as being unlikely to have a good outcome, but it is shown here to be the treatment of choice in patients who have lost the primary graft.

Ketoconazole-Tacrolimus Coadministration in Kidney Transplant Recipients: Two-Year Results of a Prospective Randomized Study

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.

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 1,400 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.

Nail changes in kidney transplant recipients

BACKGROUND Nail changes are common complications of end-stage renal disease, and reports of nail changes in kidney transplant recipients (KTR) are rare. Few reports have documented a higher prevalence of onychomycosis in KTR compared with controls, while others found no significant differences. In this study, we investigated the prevalence and nature of nail changes in a large series of KTR. METHODS Three hundred and two KTR (216 males and 86 females) were included in this study, and the mean transplant duration was 6.57 years (range 1.5 month-23 years). They were screened for the presence of nail changes. Nail clippings were collected when indicated and cultures were performed for patients with suspected onychomycosis. The patients were compared with 302 age- and sex-matched healthy controls (220 males and 82 females). RESULTS One hundred and twenty-one KTR (40.1%) had nail changes compared with 104 (34.4%) in controls. Onychomycosis, Muehrckes nail and leuconychia were significantly more common in KTR [23 (7.6%), 13.3 (4.3%), 11 (3.6%), respectively] compared with controls [7 (2.3%), 1(0.3%), 2 (0.66%), P = 0.002, 0.001 and 0.02, respectively]. However, the most frequent nail change among KTR and controls was absent lunula, 90 (29.8%) and 80 (26.5%), respectively P = 0.36. Longitudinal ridging was also a frequent nail pathology among KTR and controls, 21 (6.9%) and 19 (6.3%), respectively, P = 0.74. CONCLUSION KTR have higher prevalence rates of onychomycosis, Muehrckes nail and leuconychia than the healthy population. On the other hand, absent lunula could be a normal variation among Egyptian people.