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While conversion of stable renal transplant recipients (RTR) from calcineurin inhibitors (CNI) to sirolimus (SRL) is safe and effective, it is still under investigation for recent, high-risk cases. We studied the long-term effects of conversion of high-risk subjects maintained on a CNI, mycophenolate mofetil, plus steroid regimen to SRL, mycophenolate mofetil, plus steroid on graft and patient outcomes. We retrospectively reviewed the first 100 RTR converted to SRL treatment over approximately 5 years. The main indications for conversion were biopsy-proven acute rejection (BPAR), CNI toxicity, CNI elimination, and acute-tubular necrosis (ATN). Exclusion criteria were limited to bone marrow suppression. The overall mean +/- SD age was 38.5 +/- 15.6 years, including pediatric and geriatric age groups. Mean +/- SD body mass index (BMI) was 28.99 +/- 8.0 and 40% had a BMI30. There were 40% RTR from deceased donors and 60% showed 4 to 6 HLA mismatches. Preconversion total BPAR and steroid-resistant rejection incidences were 35% and 14%, respectively. Mean +/- SD time to start of SRL was 11.9 +/- 22.8 months posttransplantation. Proteinuria2 g/d, leukopenia, and hyperlipidemia increased significantly after conversion (P = .001, P = .0003, and P = .0001, respectively). Patient and graft survivals were 95% and 90%, respectively. There was significant improvement in graft function postconversion (P.0001). There was a high incidence of side effects and cases of SRL discontinuation. Multivariate analysis demonstrated the influence of bone marrow suppression, obesity, hyperlipidemia, nutritional status, proteinuria, and graft function on graft and patient outcomes. We concluded that conversion from CNI to SRL was effective among high-risk RTR, but with a high incidence of adverse events during long-term follow-up.

Introduction Invasive fungal sinusitis is a rare but often fatal infection in immunocompromised patients. Aggressive antifungal treatment is mandatory, but is not without risk. Caspofungin, an antifungal agent that is a member of the echinocandin family, an inhibitor of glucan synthesis in the fungal wall, is active against Aspergillus and Candidae infections. Although it works on the fungal wall, it does not affect mammalian cells; hence, its toxicity is minimal. Case Summary This report describes a case of invasive Aspergillus sinusitis in a kidney transplant recipient with diabetes mellitus. The infection involved the apex of the right orbit causing optic nerve compression. The patient was treated with transnasal endoscopic decompression of the optic nerve and intravenous AmBisome (liposomal amphotericin B) for 2 weeks without clinical improvement. The combination of caspofungin and AmBisome administered for another 2 weeks yielded partial improvement. The AmBisome had to be discontinued due to deterioration of renal and hepatic function, but the patient completed a further 7-week course of caspofungin alone. Retro-orbital biopsy confirmed a complete response to treatment; the patient’s renal and hepatic function returned to normal. Conclusion This case indicates that caspofungin is effective to treat invasive Aspergillus sinusitis in kidney transplant recipients. This agent is well tolerated and safe with respect to renal and hepatic function.

Objective. The area under the concentration-time curve of cyclosporine microemulsion is the best measure of the absorption and beneficial effects in renal transplant recipients. We sought to determine the best method of monitoring cyclosporine levels in these patients. Methods. Prospective evaluation of peak cyclosporine blood levels and area under the curve monitoring were performed for 1 year in 65 renal transplant recipients (study group). Cyclosporine trough levels and peak cyclosporine blood levels were correlated with the calculated area under the curve. Cyclosporine trough levels were monitored in equal numbers of matched controls. Results. There were no significant differences in the incidence of acute rejection, cyclosporine nephrotoxicity, proteinuria, serum creatinine levels, or graft and patient outcomes between the groups (P = .1). Peak cyclosporine blood levels guided by calculating the area under the curve were found to be 27% to 32% lower than previously reported. The correlation coefficient was 90% for peak cyclosporine blood levels (P

Introduction Calcineurin inhibitor (CNI) induced HUS, although rare, can be a serious complication of renal transplantation. Classical syndrome of microangiopathic hemolytic anemia, thrombocytopenia, and acute renal injury may not be fully manifested. Methods We retrospectively analyzed our data in 950 kidney recipients under follow-up in our center (1994 – 2008). We reviewed the kidney biopsies performed for these patients to exclude conflicting diagnoses like antibody mediated rejection. Results HUS was diagnosed in 12 patients (1.26%). None of them had HUS as the original kidney disease. Cyclosporine was the primary immunosuppression in 9 and tacrolimus in 3 patients. The median day of onset was 7 days. Manifestations were anemia (100%), thrombocytopenia (75%), elevated reticulocyte count (62.5%), fragmented red blood cells (8.3%), elevated lactate dehydrogenase (LDH) enzyme (83.3%), increased fibrin degradation product (FDP) (83.3%), reduced haptoglobin level (42.9%) and hyperbilirubinemia (25%). CNI elimination was the first step in the management. Transfusion of fresh frozen plasma (FFP) was used in 10 patients and plasma exchange with FFP in the other two. All grafts recovered function. Cyclosporine or tacrolimus were reintroduction in two patients after complete clinical and laboratory recovery. Both patients developed recurrence of HUS. While the former did not the latter did recover on further treatment of HUS. Conclusion Anemia, thrombocytopenia, elevated LDH and FDP are the most frequent manifestations of HUS. Early CNI elimination and fresh plasma transfusion can revert CNI induced HUS and save the graft. Reintroduction of CNI may be deleterious to the graft and should be avoided.

Background. High levels of soluble CD30 (sCD30), a marker for T-helper 2-type cytokine-producing T cells, pre or post-renal transplantation serves as a useful predictor of acute rejection episodes. Over the course of 1-year, we evaluated the accuracy of serial sCD30 tests to predict acute rejection episodes versus other pathologies that affect graft outcomes. Patients and methods. Fifty renal transplant recipients were randomly selected to examine sCD30 on days 0, 3, 5, 7, 14, and 21 followed by 1, 3, 6, and 12 months. The results were analyzed for development of an acute rejection episode, acute tubular necrosis (ATN), or other pathology as well as the graft outcome at 1 year. Results. Compared with pretransplantation sCD30, there was a significant reduction in the average sCD30 immediately posttransplantation from day 3 onward (P < .0001). Patients were divided into four groups: (1) uncomplicated courses (56%); (2) acute rejection episodes (18%); (3) ATN (16%); and (4) other diagnoses (10%). There was a significant reduction in sCD30 immediately posttransplantation for groups 1, 2, and 3 (P < .0001, .004, and .002 respectively) unlike group 4 (P = .387). Patients who developed an acute rejection episode after 1 month showed higher pretransplantation sCD30 values than these who displayed rejection before 1 month (P = .019). All groups experienced significant improvement in graft function over 1-year follow-up without any significant differences. Conclusion. Though a significant drop of sCD30 posttransplantation was recorded, serial measurements of sCD30 did not show a difference among subjects who displayed acute rejection episodes, ATN, or other diagnoses.

Background. We studied early sirolimus (SRL) therapy in renal transplant recipients at high risk after administration of antithymocyte globulin or interleukin-2 receptor blockade induction. Patients and Methods. In 45 patients, SRL therapy was started within 1 month after transplantation. The primary indications for conversion of treatment from calcineurin inhibitors (CNIs)―mycophenolate mofetil (MMF)-steroid to SRL-MMF-steroid were biopsy-proved rejection (after treatment), CNI toxicity, CNI elimination, and acute tubular necrosis. Pediatric, geriatric, and other patients with medical comorbidities were not excluded. Results. Post-SRL rejection episodes were reported in 22.2% of recipients including 15.6% who were resistant to steroid therapy. Mean (SD) follow-up after SRL therapy was 59.9 (8.1) months. Proteinuria greater than 2 g/d (P = .001), leukopenia (P < .001), hyperlipidemia (P < .001), and transaminases values (P = .02) increased significantly after SRL therapy. Graft survival was 88.8%, and patient survival was 93.3%. There was significant improvement in serum creatinine concentration and estimated creatinine clearance by the end of the study (P < .001). A high incidence of adverse effects and infections was noted post-SRL therapy, and the drug was discontinued in 31% of patients because of multiple adverse effects. At multivariate analysis, age, hypertension, nutritional status, bone marrow suppression, hyperlipidemia, and graft dysfunction were identified as risk factors for worse graft and patient outcome. Conclusion. Early treatment with combined SRL-MMF-steroid may be effective as a CNI-free immunosuppression regimen in patients at high risk; however, there is a high rate of adverse effects during long-term follow-up.

Background Hyperinfection strongyloidiasis is a potentially fatal syndrome associated with conditions of depressed host cellular immunity. A high degree of suspicion is required to detect cases early and thereby avoid a fatal outcome. Patients and Methods Three consecutive cadaveric kidney transplant recipients died within 2 months from hyperinfections with strongyloides. All members of the transplant team were involved in a campaign to localize the source of infection, identify and treat affected patients, and provide adequate prophylaxis to other transplant recipients. We reviewed cadaveric donor files and screened 61 hospital personnel, 27 hospital inpatients, and the 87 hospital outpatients transplanted in a year’s time before that event for a possible source. The screening test included analysis of fresh stool samples on 3 consecutive days for strongyloides larvae. The anti-helminthic drug albendazol was administered to all patients during screening. They were followed for possible development of the disease during the infectivity period. Results The first 2 recipients received their kidneys from 1 cadaveric donor, while the third received it from a different donor. Both donors came from areas endemic for strongyloidiasis. The 3 recipients were on tacrolimus-based immunosuppression. The twin recipient of the second kidney was on cyclosporine and did not manifest a disease. All stool samples taken for screening were negative for the infective larvae. None of the other recipients developed the disease. Conclusions Cadaveric donors were the possible source for this outbreak. Cyclosporine probably has a protective effect against strongyloides. In our setting, screening of cadaveric donors for strongyloides is mandatory before accepting them for donation, and oral prophylaxis is required for all recipients.

Cyclosporine (CsA) microemulsion has been the mainstay immunosuppressive agent for renal transplant recipients for years. A single daily dosing of cyclosporine (SD) is rarely used. The objective of this study was to evaluate the efficacy of SD versus twice daily dosing of CsA. Retrospective evaluation of SD use was conducted for 44 renal transplant recipients for 12 months (study group). Equal numbers of matched recipients were selected for age, sex, HLA mismatch, donor type, and immunosuppressive regimen (control group). We measured CsA trough (C0) and peak (C2) blood levels, 12-hour CsA profile, and the area under the concentration-time curve (AUC). There were significant differences in C0, C2, and calculated AUC after shifting to SD. In the study group, the mean AUC was 4619 ng/mL/h before versus 6567 ng/mL/h after shifting to SD (P=.004). This became more therapeutic and identical to the mean AUC in the control group, which was 6551 ng/mL/h. Total daily CsA dose was significantly lower in the study group compared with the control group (P

Introduction BK virus nephropathy (BKVN) is a significant cause of graft loss among renal transplant recipients. The treatment outcomes of BKVN have been variably reported in the literature. Patients and methods We prospectively investigated BKV infection and BKVN among a population of renal transplant recipients with suspected BKV infection. The 42 subjects who all had acute allograft dysfunction, were categorized in three groups: those with clinical, laboratory, and histological findings that did not suggest acute rejection, drug toxicity, or obstruction (group 1, n = 24); those with findings that suggested probable acute cellular rejection but did not respond to antirejection treatment (group 2, n = 10); and those whose renal histology suggested BKVN (group 3, n = 8). Polymerase chain reaction analysis was done to detect BKV DNA in urine and blood samples from each subject. BKV DNA was detected in 19 (45%) urine samples with 11 of these subjects (26.1% of total) having BK viremia as well. Results No evidence of BKVN was detected histologically in seven subjects with isolated BK viruria, while the others proved to be JC virus infections. Among the 11 subjects with BK viremia, eight had BKVN based on renal histology at the time of diagnosis with BKV infection, while the other three subsequently developed histological features of BKVN. BKVN developed after 5.3 ± 2.5 (2 to 44) months after transplantation. The serum creatinine at time of BKVN diagnosis was 158.9 ± 58 (87 to 285) μmol/L. All subjects were initially treated with a 50% reduction in immunosuppressive drug doses. Further decreases in immunosuppression were performed in all patients with close monitoring of renal function. All subjects were followed up for a of 18.2 ± 5 (12 to 26) months. Two grafts were lost not due to BKVN, and one patient was lost to follow-up during this period. The latest serum creatinine in eight recipients is 113 + 20 (81 to 138) μmol/L, which is better than the renal function at diagnosis. Conclusion The prevalence of BKVN in suspected BKV infection was 26%. Although the study period was short (30 months), BK viremia strongly correlated with BKVN, which seemed to be successfully treated with reduction in immunosuppression.

Introduction Cyclosporine microemulsion has been the mainstay immunosuppressive agent in renal transplantation for years. Since single daily dosing of cyclosporine is rarely used, the objective of this investigation was to evaluate the efficacy of a single daily dose versus twice daily dosing of cyclosporine in renal transplant recipients. Methods Retrospective evaluation of single-dose cyclosporine use was conducted for 15 renal transplant recipients for 12 months (study group). Equal numbers of matched renal transplant recipients were selected for age, sex, human leukocyte antigen mismatch, donor type, and immunosuppressive regimen (control group). Cyclosporine trough level and peak cyclosporine blood levels, 12-hour cyclosporine profile, and the area under the concentration-time curve were measured. Results There was a significant difference in cyclosporine peak blood level and calculated area under the curve after shifting to single-dose cyclosporine (P = .001). In the study group, the mean area under the curve was significantly below the average therapeutic range before (3154 ng/mL/ho) versus 5532 ng/mL/h after shifting to the single-dose regimen (which was therapeutic). This value was 5749 ng/mL/h in the control group. Total daily cyclosporine dose was lower in the study group when compared with the control group at 6 and 12 months (P = .01). There were significantly fewer adverse effects in patients in the study group than in patients in the control group. Conclusion We conclude that although cyclosporine dose should be individualized in renal transplant recipients, a single dose of cyclosporine has the added advantage of decreasing dosages and cyclosporine-related adverse effects while maintaining optimal graft function.

Background Renal allograft transplantation with multiple arteries (MRA) was always avoided as much as possible as it is technically demanding and carries a higher MSK for complications. This was a single-center study to explore the graft outcomes of kidney transplantation with MRA. Patients and Methods We retrospectively reviewed the medical records of 35 patients who received kidney grafts with MRA for the surgical technique, surgical complications, graft function, and graft survival. The results were compared with those achieved in recipients of kidney grafts with a single renal artery (SRA). Results Of 35 grafts, there were 2 renal arteries in 30 grafts, and 3 renal arteries in 5 grafts. In the MRA group, there were 7 instances of surgical complications, the mean serum creatinine levels were 122, 139, and 156 μmol/L at 1 month, 1 year, and 5 years, respectively, and the actuarial graft survival rates were 94.3%, 88.6%, and 83% at 1, 5, and 10 years, respectively. In the SRA group, there were 56 instances of surgical complications, the mean serum creatinine levels were 115, 121, and 141 μmol/L at 1 month, 1 year, and 5 years, respectively, and the actuarial graft survival rates were 93.7%, 88.1%, and 84.4% at 1, 5, and 10 years, respectively. Conclusion Although transplantation of MRA grafts might carry a relatively higher risk for complications, it is justified because it gives results comparable with those achieved in SRA.

The prevalence of inflammatory bowel disease (IBD) after renal transplantation is affected by the immune tolerance and the modality of immunosuppression. Mycophenolate mofetil (MMF) may have a promoting effect on the development of posttransplantation erosive enterocolitis and a Crohn's disease-like pattern of colitis. We have presented a 40-year-old man with end-stage renal disease due to chronic glomerulonephritis who commenced hemodialysis for 2 months before receipt of a live unrelated renal transplant. He developed early posttransplantation diabetes mellitus and an anti graft rejection episode, which responded to a methylprednisolone pulse and OKT3 treatment. His immunosuppressive regimen included prednisolone, MMF, and tacrolimus. Three years after transplantation, he developed mild constitutional symptoms, mouth ulcerations, and chronic intermittent bloody diarrhea. Colonoscopy showed active segmental colitis with aphthous ulcers, involving the proximal descending colon and the splenic flexure. Colonic biopsies showed distended and branched crypts in the ascending colon, moderate active chronic colitis with regenerative atypia, skipping appearance, and ulceration in the splenic flexure and descending colon. The edematous crypts were associated with ulcerations in the sigmoid colon and rectum. The features were highly suggestive of Crohn's disease. He was successfully treated with high-dose steroids and 5-aminosalicylic acid. Subsequently, he developed chronic transplant glomerulopathy and restarted hemodialysis. We concluded that de novo Crohn's disease may develop in renal transplant recipients despite immunosuppressive therapy especially with MMF immunosuppression.