The effect of anemia on the efficacy and safety of treating chronic hepatitis C infection with direct-acting antivirals in patients with chronic kidney disease.

BACKGROUND/AIM: Chronic hepatitis-C infection is a great health burden in Egypt. The effect of anemia on the efficacy and safety of direct-acting anti-viral (DAA) therapies for those with chronic-kidney disease (CKD) has not been evaluated. PATIENTS/METHODS: This single-center retrospective study included 235 renal patients: i.e., 70-CKD patients not on hemodialysis (42 with anemia, 28 without); 40 hemodialysis patients (16 anemic; 24 non-anemic), and 125 kidney-transplant (KTx) recipients (40 anemic; 85 non-anemic). Anemia was defined by a hemoglobin level < 10.5 g/dL. Hemodialysis patients received ritonavir-boosted paritaprevir/ombitasvir. KTx patients received sofosbuvir/daclatasvir. CKD patients with eGFR > 30 mL/min/1.73 m2 received sofosbuvir/daclatasvir. Those with eGFR < 30 mL/min/1.73 m2 received ritonavir-boosted paritaprevir/ombitasvir; 64 non-anemic patients also received ribavirin therapy. RESULTS: Mean age of CKDs was 49.1 years, 43.2 years for HDs, and 45.2 years for KTx patients. Most were male; body-mass index was ~ 23.8. Anemia did not affect the efficacy of DAAs in hemodialysis, CKD, or KTx patients. Most patients achieved a rapid virologic response (RVR), and a 12- and 24-week sustained viral response. Worsening of anemia among the non-anemic group was mostly related to ribavirin therapy in hemodialysis patients (11/16 patients). Acute kidney injury in CKDs occurred more frequently within the anemic group (59.5%) compared to the non-anemic group (32.1%). For KTx, graft impairment was more common among the anemic group (7/40) compared to the non-anemic group (2/85). CONCLUSION: Hemoglobin levels of < 10.5 g/dL prior to DAA treatment did not affect the virological response in renal patients but was associated with increased serum creatinine among KTx and those with CKD.

Legislative proposal in Italy to facilitate contacts between deceased organ donor families and transplant recipients.

Contacts between organ donors and recipients might be possible in the near future in Italy. As suggested by The Italian Committee of Bioethics "anonymity is requested by the Italian National Transplant Centre" before transplantation anonymity shall be strict in order to grant privacy, gratuity, justice, solidarity and benefits and avoids organ trafficking. Following a period that is ethically correct and justifiable, organ donor families and recipients can meet after signing a valid declaration of consent, expressed on a template valid for the whole country. A third party within the body of the National Health Systems shall control the validity of the consent. The opinion stresses that contacts are not a right but a possibility justifiable on ethical grounds if the procedure is followed appropriately. A legislative proposal has been presented before the Chamber of deputies incorporating all suggestions made by the National Committee of Bioethics. The agreement between parties might be signed a year after transplantation. This is a long enough period of time for the recipients to fully appreciate the benefits of the procedure and for the donor families to see the effects of their decision (the opinion and the Law proposal hit the Zeitgeist, and keep Italy in the regulation of European Union).

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.

Detection of Hepatis C Virus-Related Immunologic Markers and Their Impact on Outcomes of Living-Donor Kidney Transplant Recipients.

OBJECTIVES: Liver disease is an important cause of morbidity and mortality among recipients of transplanted organs. In addition to the liver, hepatitis C virus infection has a significant prevalence among recipients of kidney transplant and is related to worse graft and recipient survival as the kidney is an important component of the hepatitis C virus clinical syndrome. MATERIALS AND METHODS: This retrospective single center study included 336 patients with end-stage renal disease who received a kidney transplant at the Mansoura Urology and Nephrology Center from January 1992 to December 1995. Of 336 patients, 63 were excluded, and the remaining 273 patients were divided into 3 groups: viremic active (72 patients), viremic inactive (108 patients), and nonviremic (93 patients). Division of patients was based on hepatitis C virus RNA complement level (C3 and/or C4 consumption), circulating cryoglobulins, and rheumatoid factor detection. RESULTS: Our study showed insignificant differences regarding patient characteristics and demographic data among the study groups but significantly higher incidence of transaminitis in viremic (active and inactive) patients. Nonsignificant differences were found regarding proteinuria among the 3 groups, including among those who had levels in either nephrotic or nonnephrotic ranges. Biopsy-proven acute rejection episodes among the 3 groups of recipients were statistically comparable, with significantly higher frequency of chronic rejection episodes among viremic active patients. Nonviremic recipients had significantly lower serum creatinine levels than viremic (active and inactive) recipients. Patient and graft survival results were comparable among the groups. CONCLUSIONS: Presence of hepatitis C virus immunologic markers does not have a significant effect on patient and graft survival; however, it may be a clue for long-term incidence of chronic rejection.

Posttransplant Erythrocytosis Among Egyptian Living-Donor Kidney Transplant Recipients.

OBJECTIVES: The goal when treating patients with end-stage renal disease is to increase patient survival and to provide a better quality of life, both of which can be achieved by kidney transplant. Identifying problems associated with kidney transplant is an essential step toward improved graft function. Here, we evaluated posttransplant erythrocytosis, a frequent complication among kidney transplant recipients. MATERIALS AND METHODS: In this single-center retro-spective study, we identified 1850 kidney transplant recipients who were transplanted at the Mansoura Urology and Nephrology Center (Mansoura University, Mansoura, Egypt) from 1990 and 2013. From these patients, we identified 174 transplant recipients with posttransplant erythrocytosis and another 174 recipients without posttransplant erythrocytosis (control group). All recipients were evaluated retrospectively regarding incidence and risk factors for posttransplant erythrocytosis occurrence, graft function and survival, and patient survival. RESULTS: Both patient groups were comparable regarding age and sex (mean age of 32 years and higher percentage of male recipients in both groups). Degree of HLA class I and class II matching was not significantly different between groups. There were also no significant differences in immunosuppression protocols, although most patients were on steroid and cyclosporine therapy. Prevalence of acute and chronic rejection episodes was comparable between groups. Graft function was better in the posttransplant erythrocytosis group than in the control group, and higher patient survival was noted in patients with posttransplant erythrocytosis (P < .001). CONCLUSIONS: Posttransplant erythrocytosis was correlated with good graft function. In our study patients, those with posttransplant erythrocytosis had better graft and patient survival.

Impact of Sex Disparities on Outcomes of Living-Donor Kidney Transplant in Egypt: Data of 979 Patients.

OBJECTIVES: Renal transplant is the criterion standard for treatment of end-stage renal disease. The effects of disparities between men and women on renal transplant outcomes have been evaluated in many studies but with debatable results. It has been suggested that female kidney donors have poor outcomes after transplant compared with male kidney donors, especially when implanted in a male recipient. The aim of the study was to evaluate the effects of sex on living-donor kidney transplant outcome. MATERIALS AND METHODS: The data of 979 patients who underwent living-donor kidney transplant from January 2000 to December 2010 at a single center were reviewed retrospectively. The patients were divided into 4 groups according to recipient and donor sex: male donor-to-male recipient (n = 307), male donor-to-female recipient (n = 132), female donor-to-male recipient (n = 411), and female donor-to-female recipient (n = 129). We compared the demographic characteristics, posttransplant rejection and complications, and graft and patient survival rates among the groups. RESULTS: Male recipients were older than female recipients, whereas male donors were younger than female donors (P < .001). No statistically significant differences were shown regarding recipient body mass index, ischemia time and time to diuresis, and acute and chronic rejection rates between the groups. Graft (P = .947) and patient (P = .421) survival rates were comparable between groups. CONCLUSIONS: Donor and recipient sex had no significant effect on outcomes of living-donor renal allograft recipients.

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.

Challenges for Renal Retransplant: An Overview.

Despite many achievements in renal transplant in the past few years regarding immunosuppression and tissue matching, the rates of early and late graft loss and return to dialysis are still high. Many of those with primary graft failure will be listed for a kidney retransplant, as this allows for better quality of life than dialysis. Many challenges face those requiring renal retransplant, including first graft nephrectomy and whether site of retransplant should be ipsilateral or contralateral, whether to conduct preemptive retransplant or wait while on dialysis, additional immunologic factors, immunosuppression after retransplant, cancer risk, BK virus infection, and retransplant in pediatrics. Despite the increased relative risks associated with retransplant, patients receive a significant survival benefit, better quality of life, and low health care costs versus remaining on dialysis after a failed transplant.

Impact of Donor Source on the Outcome of Live Donor Kidney Transplantation: A Single Center Experience.

BACKGROUND: Renal transplantation is the ideal method for management of end-stage renal disease. The use of living donors for renal transplantation was critical for early development in the field and preceded the use of cadaveric donors. Most donors are related genetically to the recipients, like a parent, a child, or a sibling of the recipient, but there are an increasing percentage of cases where donors are genetically unrelated like spouses, friends, or altruistic individuals. Donor shortages constitute the major barrier for kidney transplantation, and much effort has been made to increase the supply of living donors. The impact of donor source on the outcome of renal transplantation is not adequately studied in our country. OBJECTIVES: The aim of the study was to evaluate the impact of donor source on the outcome of live donor kidney transplantation. PATIENTS AND METHODS: From March 1976 to December 2013, the number of patients that underwent living renal transplantation sharing at least one HLA haplotype with their donors was 2,485. We divided these patients into two groups: (1) 2,075 kidney transplant recipients (1,554 or 74.9% male and 521 or 25.1% female) for whom the donors were living related, (2) 410 kidney transplant recipients (297 or 72.4% male and 113 or 27.6% female) for whom the donors were living unrelated. All patients received immunosuppressive therapy, consisting of a calcineurin inhibitor, mycophenolate mofetil, or azathioprine and prednisolone. We compared acute rejection and complication rates, as well as long-term graft and patient survival of both groups. Demographic characteristics were compared using the chi-square test. Graft survival and patient survival were calculated using the Kaplan-Meier method. RESULTS: The percentages of patients with acute vascular rejection were significantly higher in the unrelated group, while percentages of patients with no rejection were significantly higher in the related group, but there were no significant differences regarding patient and graft survivals between both groups. CONCLUSIONS: Kidney transplant recipients who received their grafts either from live related donors or live unrelated donors had comparable patient and graft survival outcomes.

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.

Apelin and New-Onset Diabetes After Transplant in Living Kidney Allograft Recipients.

OBJECTIVES: Apelin, a cytokine mainly secreted by adipocytes and several tissues, includes the gastrointestinal tract, adipose, brain, kidney, liver, lung, and various sites within the cardiovascular system. Apelin is closely related to glucose metabolism, and has been proposed to be a promising therapeutic agent in treating insulin resistance. Apelin and orphaned G-protein-coupled apelin exhibit roles in regulating fluid homeostasis. Circulating serum apelin suppresses insulin secretion by binding to the G-protein-coupled apelin receptor on B cells of islets of Langerhans. Several studies also have documented the altered level of serum apelin in type 2 diabetic patients, but the results remain controversial. This study sought to analyze apelin levels in new-onset diabetes after transplant. MATERIALS AND METHODS: Forty-seven diabetic renal transplant recipients were compared with 40 nondiabetic renal transplant recipients. Data were collected for positive family history of diabetes, body weight, body mass index, blood pressure, and blood chemistry including apelin level. Logistic multiple analysis were made for statistically significant data on univariate analysis. RESULTS: Apelin levels were significantly higher among obese, hypercholesterolemia new-onset diabetes after transplant patients, 428.7 ± 193.29, 256.8 ± 128 (P > .001). There was appositive correlation between serum apelin and proteinuria. CONCLUSIONS: Serum apelin has a high level in new-onset diabetes after transplant, than nondiabetic patients, and they positively correlate with proteuria in new-onset diabetes after transplant patients.

The Long-Term Effect of Hepatitis C Virus on the Outcome of Live-Donor Kidney Transplant Recipients. A Retrospective Study.

OBJECTIVES: Hepatitis C virus infection occurs frequently among end-stage renal disease patients. Moreover, its effect on long-term patient and renal graft survival is controversial. This study was performed to assess the long-term effect of hepatitis C virus on the outcome of kidney allografts. MATERIALS AND METHODS: We retrospectively analyzed 273 hepatitis B negative renal transplant recipients who were transplanted at Mansoura Urology and Nephrology Center, for whom hepatitis C virus RNA polymerase chain reaction results were available before transplant, and followed them for at least 17 years after transplant. We compared graft and patient survival rates between viremic group (study group) and nonviremic group (control group). We also studied posttransplant hepatic function, graft performance, and incidence of posttransplant diabetes mellitus. RESULTS: Hepatitis C virus was detected in sera of 195 patients (71%). No statistically significant increased risk for graft failure (P = .29) or patient death (P = .47) was found among the groups. Hepatitis C virus viremic transplant recipients had significantly greater frequencies of biochemical chronic liver disease (P = .01). However, we did not report significant differences regarding incidence, quantity of proteinuria, biopsy-proven acute rejection, chronic allograft nephropathy, and incidence of posttransplant diabetes mellitus between the studied groups. CONCLUSIONS: Hepatitis C virus infection was shown to increase the incidence of chronic hepatitis posttransplant. However, no statistically significant adverse effect on long-term renal graft and patient survival was noted.