The previously common post-kidney transplant Kaposi sarcoma has become non-existent for a decade: an Egyptian experience.

BACKGROUND: De novo malignancy is a worrying complication after kidney transplantation; the type of which may vary due to factors such as the prevalence of viral infection and race. Kaposi sarcoma used to be the most common malignancy among our patients constituting more than one-third of cancers. Nevertheless, we noticed that Kaposi sarcoma has not been observed for a long period. Therefore, we conducted this study to explore such observation. METHODS: Data of all kidney transplant recipients were retrieved and retrospectively analyzed. Their total number was 3126 patients. Their mean age was 28.71 ± 10.97 years and of them, 823 (26.3%) were females. The pattern of Kaposi sarcoma throughout the last decade as well as the preceding three decades was studied. The possible relation between the disappearance of Kaposi sarcoma and three paradigm shifts in our practice, namely the use of mTOR inhibitors, steroid-free regimen and CMV prophylaxis was explored. RESULTS: Since 2010, no new cases of Kaposi sarcoma have been observed. In addition, patients who have been transplanted after 2006 did not develop such malignancy. Patients who received CMV prophylaxis and/or were maintained on mTOR inhibitor or steroid-free regimens have not developed Kaposi sarcoma. Moreover, CMV prophylaxis had a statistically significant difference when compared to a homogenous group without CMV prophylaxis. However, Kaplan-Meier analysis of patients of the three policies and their counterpart groups showed comparable results. CONCLUSION: Kaposi sarcoma, which was previously the most common malignancy, is no longer observed for almost a decade among our kidney transplant recipients. m-TOR inhibitors, steroid-free regimen and CMV prophylaxis policy are possible contributing factors. Nevertheless, only CMV prophylaxis policy had a statistically significant relation to the disappearance of Kaposi sarcoma.

Conversion From Twice-Daily to Once-Daily Tacrolimus Among Egyptian Living-Donor Kidney Allograft Recipients: A Single-Center Experience.

OBJECTIVES: Adherence to immunosuppression and minimization of drug exposure are important con-siderations in preventing rejection and maximizing transplant outcomes. The once-daily tacrolimus protocol confers potential benefit by simplifying immunosuppressive regimens, thereby improving adherence among transplant recipients. Studies of stable transplant recipients have suggested that once-daily tacrolimus is bioequivalent to twice-daily tacrolimus and is noninferior to twice-daily tacrolimus with a concentration-dependent rejection risk. Our aim was to evaluate the safety and efficacy of conversion from twice-daily tacrolimus formulation to a once-daily formulation among a cohort of adult living related-donor renal transplant patients as a single-center experience. MATERIALS AND METHODS: This prospective, one arm, single-center study included 238 patients with at least 12 months posttransplant follow-up and no rejection episodes in the last 3 months. Conversion from twice-daily to once-daily formulation was based on a 1:1 ratio. RESULTS: The mean tacrolimus dose was 4.7 ± 2.7 mg/day preconversion versus 4.9 ± 3.2 mg/day postconversion (P = .8). The mean tacrolimus level was 7.4 ± 3.4 versus 6.1 ± 2.8 ng/mL (P = .75). Of total patients, 45% were maintained on a tacrolimus dose of less than 2 ng/dL. Renal function was comparable before and after conversion (mean serum creatinine was 1.25 ± 0.88 vs 1.23 ± 0.78 mg/dL; P = .9). The incidence of biopsy-proven acute rejection was 19.7% preconversion versus 4.2% postconversion. Graft and patient survival rates were comparable between the 2 tacrolimus formulations. Once-daily tacrolimus also had favorable effects on blood pressure, lipid profile, and glucose tolerance. CONCLUSIONS: Conversion from conventional tacrolimus (twice daily) to once-daily tacrolimus may be a valuable option with comparable patient and graft survival and may lead to improved adherence that may be reflective of better long-term results. It should be considered for de novo immunosuppression among living-donor renal allotransplant recipients.

Treatment of Chronic Hepatitis C Infection Among Egyptian Kidney Transplant Recipients: A Pilot Study.

OBJECTIVES: Chronic hepatitis C infection incidence and prevalence are high in Egypt and represent a major health burden. Hepatitis C virus infection can affect graft outcomes in kidney transplant recipients. Treatment of hepatitis C virus infection among this special group was difficult during the interferon era; however, with advances in direct-acting antivirals, treatment outcomes have become more promising. MATERIALS AND METHODS: This is a pilot, observational, single-center, one arm study that included 50 kidney transplant recipients seen at the Mansoura (Egypt) Urology and Nephrology Center. Patients were consented to receive a sofosbuvir-based regimen as all had creatinine clearance of greater than 30 mL/min/1.73 m2. RESULTS: All patients achieved rapid virologic responses 4 weeks after starting treatment. Forty-nine of 50 patients achieved 12-week and 24-week sustained viral responses. Six patients had increased serum creatinine levels. Four graft biopsies were performed. Anemia was the most common adverse effect among the patients who were maintained on ribavirin. CONCLUSIONS: Treatment of chronic hepatitis C infection has become easier and safe with the advance of new direct-acting antivirals.

Comparative analysis for optimizing the modified release tacrolimus (Advagraf) after kidney transplantation: A prospective randomized trial.

Immunosuppression management in clinical transplantation aims to balance delivery of efficacy against adverse reactions using therapeutic drug monitoring. Adherence to posttransplant immunosuppressive medications and minimizing variability in drug exposure are important considerations in preventing rejection and maximizing overall transplant outcomes. The availability of once-daily tacrolimus may add a potential benefit by simplifying immunosuppressive regimens, though improving compliance among transplant recipients. The aim of our study is to investigate the safety and efficacy of the once-daily formulation of tacrolimus (Advagraf) against the usually used twice daily tablets (Prograf). A prospective randomized trial 1:2 was designed for 99 consecutive live-related renal transplant recipients who received their grafts at a single center (study group, Advagraf, 33 recipients and control group, Prograf, 66 recipients). The demographic data were homogeneous among both groups regarding donors and patients' characteristics. Posttransplant hypertension, infection, malignancy, and diabetes mellitus were comparable among both groups. Renal function and rejection episodes showed no statistical significance among recipients of both groups. Despite slight higher Advagraf unit doses, there was no statistical difference regarding the tacrolimus trough levels, between the two groups. Our singlecenter experience revealed that the availability of once-daily tacrolimus formulation could give potential benefit of improved medication compliance and better allograft outcomes by decreasing pill burden and thereby simplifying dosing schedule, Advagraf was non-inferior to twice-daily tacrolimus regarding safety and efficacy. Although being nonsignificant, a trend for better kidney function was noted in this short-term study in the Advagraf group, so long-term follow-up is needed to verify this.

Postrenal transplant malignancy: Incidence, risk factors, and prognosis.

The newer and potent immunosuppressive agents have successfully reduced the risk of rejection after kidney transplantation, but the development of cardiovascular diseases, infections, and malignancy is major factors limiting their success. Posttransplantation malignancy is the second most common cause of death in renal transplant recipients after cardiovascular disease; it is expected that mortality due to malignancy may become the most common cause of death within the next two decades. This study is designed to evaluate the incidence, risk factors, and types of malignancies occurring after renal transplantation and their impact on patient and graft survival. A total of 2288 patients underwent living donor renal allotransplantation in the Urology and Nephrology Center, Mansoura University, during the period between 1975 and 2011. Among these patients, 100 patients developed posttransplantation malignancy. Patients were categorized into five major groups according to their type of malignancy; Kaposi's sarcoma (KS), non-Kaposi's skin tumors (non-KS), posttransplant lymphoproliferative disorders (PTLD), solid tumors, and genitourinary and reproductive system (GU and RS). Overall, the incidence of cancer in renal transplant recipients was 4%. There were 83 male (83%) and 17 female patients (17%). The most frequent cancer was KS seen in 33 patients (33%). The lowest median time to development of cancer was observed in KS (35 months). The highest median time to development of cancer was observed in PTLD (133 months). The best graft survival was observed in PTLD and the worst in non-KS tumors. The best patient survival was observed in KS and the worst in GU and RS tumors. Azathioprine-based regimen was associated with a higher rate of cancer. The number of patients who died was 65 (65%). Our results indicate that the occurrence of malignancy has an important impact on short- and long-term graft and patient survival.

Optimizing Immunosuppressive Regimens Among Living-Donor Renal Transplant Recipients.

OBJECTIVES: We review different immunosuppressant protocols used for living-donor kidney transplant recipients at our center. MATERIALS AND METHODS: Many prospective randomized studies from our center have been reported between March 1976 and 2016, with more than 2700 renal transplant procedures conducted. The first study was a prospective randomized trial of azathioprine versus cyclosporine. The second study compared triple therapy (prednisolone + azathioprine + cyclosporine) versus conventional therapy (prednisolone + azathioprine). The third study was a cost-saving study, in which 100 patients received ketoconazole along with the triple regimen. Another trial demonstrated the advantages of a microemulsion form of cyclosporine. A subsequent trial compared calcineurin inhibitor minimization versus avoidance protocols. Rescue therapies were carried out to intensify immunosuppressive regimens after repeated rejection. In addition, steroid-free regimens were evaluated during both short- and long-term treatment. A recent trial reported a step-forward avoidance protocol with a calcineurin inhibitor and a steroid-free regimen, whereas another current study is the TRANSFORM one. The rationale behind antibody therapy was tho roughly evaluated among living-donor renal trans plant recipients with different agents, including basiliximab, daclizumab, antithymocyte globulin, and alemtuzumab. RESULTS: Earlier studies have demonstrated the efficacy of conventional regimens without induction therapy, especially in longer follow-up. The standard triple therapy has emerged with intensified immunosuppressive and lowered dose of each drug, especially cyclosporine. In minimization studies, no significant differences were encountered regarding patient and graft survival, even in the long-term. Steroid avoidance was safe and effective. Calcineurin inhibitors and steroid-free regimens have shown comparable patient and graft survival. Induction therapy has lowered the incidence and severity of acute rejection. CONCLUSIONS: A better 5-year graft survival and less posttransplant complications have been achieved with steroid avoidance after induction with basiliximab. Induction therapy did not affect graft and patient survival rates despite lowered incidence and severity of acute rejections.

Study of depression and quality of life among hemodialysis patients: an Egyptian experience.

PURPOSE: Depression is common among hemodialysis patients. Even in developed countries, the prevalence of depression and its relation to health-related quality of life (HRQOL) in dialysis patients has only been poorly investigated. Furthermore, similar reports from many developing countries such as Egypt are scarce. This might be due to cultural and social concerns. This study is intended to address this important issue. METHODS: This cross-sectional study was conducted at the dialysis unit of the Urology and Nephrology Center, Mansoura University, Egypt. Data of 76 chronic hemodialysis patients (mean age 43.2 ± 15 years; 54 males and 22 females) were retrieved. Psychiatric interview and psychometric assessment of depression and HRQOL (using an Arabic-adapted Beck Depression Inventory II and Short Form scale, respectively) were performed. RESULTS: Depression was diagnosed in 58 patients (76.3 %). Of them, 18 (23.7 %), 15 (19.7 %) and 25 patients (32.9 %) were suffering from mild, moderate and severe depression, respectively. Depressed dialysis patients group was comparable to the non-depressed group except for a higher prevalence of peripheral neuropathy (46.7 vs. 11.5 %; p = 0.034) and a less frequent use of iron therapy (52.7 vs. 86.7 %; p = 0.017). Except for role limitation due to physical problems, all HRQOL aspects were significantly worse among the whole group of depressed patients compared to the non-depressed group. CONCLUSION: Depression is common among our Egyptian hemodialysis patients. It seems to adversely affect almost all aspects of HRQOL. Therefore, a regular combined nephrology/psychiatry approach should be central to the medical care of hemodialysis patients in order to accurately assess for depression among them. Moreover, large national studies to delineate the prevalence and impact of depression among Egyptian hemodialysis patients are needed.

Exploring the opinion of hemodialysis patients about their dialysis unit.

Hemodialysis (HD) patients are subjected to a number of physical and mental stresses. Physicians might be unaware of some of these problems. We assessed our patients' opinion about the service provided at the dialysis unit. Our unit has 89 patients on HD. A questionnaire exploring our patients' opinion relative to the service provided was prepared. The patients were asked to fill-in the questionnaire in a confidential manner. Questionnaires were then collected and examined while unaware of patient identities. Sixty-nine patients (77.5%) responded to the questionnaire. Eight patients (11.6%) revealed their names on the questionnaire. According to the questionnaire, the patients were asked to assess the service of each service by choosing one of the following grades: "excellent," "mediocre" or "bad." For the whole group of contributing patients, there were 563 "excellent," 85 "mediocre" and five "bad" choices in addition to 37 blank "no comment" choices. Food service had the least percentage (68%) of evaluation as "excellent," while doctor' performance got the highest excellent evaluation (85.5%). Thirty-five patients (50.7%) added further comment(s). An audit meeting was conducted to discuss these results. Exploring the opinion of patients on HD might uncover some areas of dissatisfaction and help in improving the provided service. We recommend widespread usage of questionnaires to assess patient satisfaction as well as to assess other health-care aspects.

Induction immunosuppressive therapy in kidney transplantation.

Induction therapy after kidney transplantation is intensive immunosuppression in the initial days after transplant when the immune system of the recipient has the first contact with donor antigens. Initial intensive immunosuppression may be required to prevent acute rejection and graft loss, and subsequent immunosuppression may be decreased to minimize adverse events associated with immunosuppressive drugs. Induction agents include lymphocyte-depleting antibodies such as rabbit antithymocyte globulin, alemtuzumab, muromonab-CD3, rituximab, and bortezomib; lymphocyte-nondepleting antibodies such as interleukin 2 receptor antibodies; and other discontinued or investigational agents such as efalizumab and alefacept. Induction therapy may be adjusted for special situations such as living-donor kidney transplant, pediatric transplant, hepatitis C virus-seropositive recipients, recipients who require desensitization, patients who are at risk for developing delayed graft function, and old donors. The optimal immunosuppressive regimen may vary, and clinical practice guidelines are available.

Evaluation of growth in low-body-weight kidney transplant Egyptian children: 25-year experience.

BACKGROUND: Identification of problems associated with kidney transplantation in low-body-weight children is an essential step toward improving graft function and patient survival as well as quality of life. PATIENTS AND METHODS: This study comprised 63 renal transplant children weighing 25 kg or less at time of renal transplantation. All children received a living donor renal allotransplant between December 1984 and March 2009. These children were retrospectively evaluated regarding their survival, graft survival as well as physical growth. RESULTS: Our patient and graft survival rates at 1, 5 and 10 years were 98.4%, 96.8% and 96.8%, and 94.9%, 82.6% and 58.4%, respectively. Significant risk factors for growth retardation post renal transplant were identified and included older age at time of transplant (p=0.019), female sex (p=0.010), retarded growth at time of transplant (p=0.011, by univariate analysis, and p=0.028, by multivariate analysis), incidence of chronic rejection (p=0.012), higher steroid cumulative dose (p=0.013) and graft dysfunction (p=0.009, by multivariate analysis). CONCLUSION: The current final height of low-body-weight transplant Egyptian children has remained suboptimal. The management of growth retardation posttransplant is multifactorial and should start early before transplantation, with optimal care of growth in children with chronic kidney disease. Moreover, expedited transplantation, whenever indicated, and optimization of posttransplant graft function with minimal steroid exposure are essential factors which were shown to be possible using immunosuppression based on tacrolimus plus mycophenolate mofetil, after basiliximab induction.

HLA class I typing in Egyptian childhood minimal change nephrotic syndrome.

BACKGROUND: Reports on the association between human leukocyte antigens (HLAs) and childhood minimal change nephrotic syndrome (MCNS) are variable. The association between HLA class I and MCNS has not been tested among Egyptian children. METHODS: We studied such associations in a group of steroid-responsive MCNS Egyptian children (n=37) in comparison to a group of healthy Egyptians (n=100). Typing was performed using standard lymphocytotoxicity assay. RESULTS: The frequency of HLA-B27 was remarkably higher among MCNS children (18.9%) compared with the control group (1%) (p<0.001, risk ratio [RR] = 3.76, 95% confidence interval [95% CI], 2.5-5.66). Additionally, MCNS children had a significantly higher frequency of HLA-A11 (16.2% vs. 3%) and HLA-B13 (13.5% vs. 2%) (p=0.012 and p=0.016; RR=2.75 and RR=2.9; 95% CI, 1.58-4.79 and 1.66-5.06; respectively). With multivariate analysis, the previous 3 loci were still significant in addition to HLA-B12 (p=0.001, p=0.005, p=0.013 and p=0.033, for HLA-B27, HLA-B13, HLA-A11 and HLA-B12, respectively). The frequency of HLA haplotypes was comparable in both groups. CONCLUSIONS: We concluded that associations of HLA class I with childhood MCNS in Egypt have both similarities and dissimilarities to those in other populations. HLA-B27, which has not been reported before, has the strongest association. However, similar to studies from other populations, HLA-A11, HLA-B13 and HLA-B12 loci were also associated with MCNS.

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.

Long-term results of two unconventional agents in steroid-dependent nephrotic children.

Children with steroid-dependent minimal change nephrotic syndrome are prone to serious steroid side effects. Alternative therapies, such as oral cyclophosphamide, may also have serious side effects. We conducted this novel prospective study to compare the long-term efficacies of levamisole and I.V. pulse cyclophosphamide as therapies with potentially fewer side effects. This study included 40 children with idiopathic steroid-dependent minimal change nephrotic syndrome (age 3-15 years; 31 boys and 9 girls). The patients were randomized into two equal groups. One group received levamisole 2.5 mg/kg on alternate days (levamisole group) while the other group received I.V. cyclophosphamide 500 mg/m2/month for six months (cyclophosphamide group). Prednisolone was gradually withdrawn. After stopping treatment, the number of patients that maintained remission was five (25%) in each group at six months, four (20%) versus two (10%) at one year and three (15%) versus one (5%) at two years in the levamisole and cyclophosphamide groups respectively, and one (5%) in each group at three and four years. The overall side effects were mild and both drugs were well tolerated. In view of the results, we recommend trial of levamisole before adopting other therapies with more serious side effects in such patients.

Co-administration of ketoconazole to tacrolimus-treated kidney transplant recipients: a prospective randomized study.

BACKGROUND: Since the introduction of calcineurin inhibitors, there has been a significant improvement in the results of solid organ transplantation, including graft and patient survival. However, high cost, chronic nephrotoxicity and other side effects stand as major challenges for long-term use of these drugs. The long-term safety and financial benefits of the combination ketoconazole-cyclosporine previously studied. However, data about the effect of the addition of ketoconazole addition to tacrolimus-treated patients are scarce. Therefore, this study was conducted to evaluate the safety and financial impact of that combination. METHODS: The subjects of this work included 70 live-donor stable kidney transplant recipients receiving tacrolimus. Their age ranged from 16 to 45 years. Among them, 54 were males and 16 were females. All of them were 6 months or more post-transplantation. Patients were randomly divided into two equal groups. Group I patients initially received ketoconazole 100 mg/day in addition to their usual treatment, while group II patients were considered a control. Patients were followed-up for 6 months. RESULTS: Concomitant ketoconazole-tacrolimus resulted in marked reduction of tacrolimus dose (by 58.7%) and cost (by 56.9%). It also resulted in significant improvement in graft function and fungal skin infection, in addition to a decrease of gastrointestinal episodes and hospitalization. CONCLUSION: We conclude that ketoconazole-tacrolimus combination in kidney transplant recipients is safe, has outstanding impact on treatment costs and improves patient and graft outcome.