M.A. Halim

Posttransplantation Calcineurin Inhibitor–Induced Hemolytic Uremic Syndrome: Single-Center Experience

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.

Serial soluble CD30 measurements as a predictor of kidney graft outcome.

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.

Renal transplantation in children

OBJECTIVE Renal transplantation is the preferred method for the treatment of children in end-stage renal disease (ESRD). In this retrospective study, we analyzed the results at our center. PATIENTS AND METHODS Between November 1993 and June 2006, 86 children (50 boys and 36 girls) received organs from 50 living donors (LDTx) and 36 cadaveric donors (CDTx). Twenty children were <10 years. In addition to ESRD, some patients had one or more other high-risk factors, eg, abnormal lower urinary tract in 36 recipients (42%). The procedure was a preemptive transplantation in 28, and a retransplantation in 9 recipients. Induction immunosuppression used either antithymocyte globulin (43 cases) or anti-interleukin-2 receptor antibodies (20 cases). RESULTS Patients were followed for 6 to 150 months. There were 24 surgical complications (28%), 26 acute rejection episodes (33%), and 17 of systemic bacterial or viral infections. Two recipients died at 1 and 21 months. The 14 grafts were lost at 1 day to 87 months. The 1- and 10-year actuarial survival rates were 99% and 98%, respectively, for the recipients, and 88% and 84%, respectively, for the grafts. The 10-year actuarial graft survival rates were 98% in LDTx and 64% in CDTx; 86% in recipients >10 years old and 75% in recipients <10 years old. Abnormal urinary tract, pretransplantation dialysis, and transplant number showed no effect on graft survival. All pediatric recipients with functioning grafts are fully rehabilitated. CONCLUSION Renal transplantation is the preferred method of treatment for children in ESRD. Higher graft survival rates were achieved in older children and following LDTx.

Long-Term Follow-up of 100 High-Risk Renal Transplant Recipients Converted From Calcineurin Inhibitors to Sirolimus: A Single Center Experience

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 BMI > 30. 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. Proteinuria > 2 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.

Active management of post-renal transplantation BK virus nephropathy: preliminary report.

OBJECTIVE To assess the efficacy of leflunomide, intravenous immunoglobulins, and ciprofloxacin as active treatment of postrenal transplant BK virus nephropathy (BKVN) in graft outcome at 1 year. PATIENTS AND METHODS Renal transplant recipients with positive results of 2 BK virus polymerase chain reaction tests of urine and blood underwent graft biopsy to confirm BKVN. If BKVN was diagnosed, antimetabolite therapy (mycophenolate mofetil or azathioprine) was changed to leflunomide therapy accompanied by a course of immunoglobulin and oral ciproflxacin. RESULTS Of 18 patients evaluated, 72% were men. Nine patients received cadaveric organs, with a mean of 3.6 HLA mismatches. All patients received induction thereapy (61% thymoglobulin), and 61% received antirejection therapy before BKVN was diagnosed. Maintenance immunosuppression therapy was primarily with prednisolone (94%); mycophenolate mofetil, 2 g/d (94%); and tacrolimus (61%). At baseline, mean (SD) creatinine clearance was 35.6 (11.5) mL/min/1.73(2), which decreased to 29.3 (17.3) mL/min/1.73(2) at 1 year (P = .01). Patients were divided into 2 groups of 9 each according to creatinine clearance values. In group 1, baseline value was 44.5 (6.6) mL/min/1.73(2), compared with 25.36 (7.8) mL/min/1.73(2) in group 2, which decreased to 42.66 (12.8) mL/min/1.73(2) (P = .23) and 16.76 (9.0) mL/min/1.73(2) (P = .009), respectively, at 1 year. Three grafts (16.7%) were lost by the end of the study, all in group 2 (P = .03). CONCLUSION Late diagnosis and intensive immunosuppression predispose to BKVN. Early active treatment of BKVN may improve graft outcome at 1 year posttransplantation.

Early sirolimus therapy in renal transplant recipients at high risk: is it justified?

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.