Variances in the Use of Everolimus in Kidney Transplantation: A 2-Year Registry of Everyday Practice.

BACKGROUND: Everolimus (EVL)-based immunosuppressive strategies may permit the reduction of calcineurin inhibitors (CNI) and their side effects, while offering a safe and efficient treatment. Our aim was to describe our experience with EVL in everyday practice and provide information for its optimal utilization. METHODS: Prospective, multicenter study of 181 kidney transplant recipients treated with EVL as part of their immunosuppressive regimen, with a follow-up of 24 months. We studied demographic data, transplant characteristics, clinical information, drugs used, serum creatinine, estimated glomerular filtration rate (eGFR), rejection episodes, and adverse events. RESULTS: In total, 181 renal transplant recipients were included. Of these, 30 (16.6%) received EVL de novo and 151 (83.4%) were converted; median time from transplantation to conversion was 10 (range, 1-312) months. Main reasons for conversion were prevention of interstitial fibrosis and tubular atrophy (23.9%), intolerance to immunosuppressants (11.1%), neoplasia (13.9%), nephrotoxicity (8.9%), and cytomegalovirus infections (8.3%). The eGFR values at baseline, months 12, and 24 were 46.4 ± 27.4 mL/min, 54.8 ± 22.9 mL/min, and 55.9 ± 26.5 ml/min, respectively. Two of 181 (1.1%) patients died, 5 of 181 (2.8%) lost their grafts, 12 of 181 (6.6%) had an episode of acute rejection, 13 of 181 (7.2%) had ≥1 serious event and infection, and 85 of 181 (49.9%) had ≥1 nonserious adverse event or infection. Multivariate analysis showed that increased eGFR at month 24 was associated with lower donor age, shorter time from transplant to EVL introduction, and a baseline eGFR ≥40 mL/min. CONCLUSION: Through different strategies among centers, the inclusion of EVL improved renal function during the first 12 months.

Use of everolimus in renal transplant recipients: data from a national registry.

Proliferation signal inhibitors, such as everolimus, offer immunosuppression without the toxicity of calcineurin inhibitors. This descriptive and prospective study reports outcomes at 1 year and predictors of improved estimated glomerular filtration rate (eGFR) in 174 renal transplant recipients from a national registry of the use of everolimus. At 1 year after conversion, 48.85% of patients had improved eGFR compared with baseline. The mean time from transplantation to initiation of treatment with everolimus was 47.97 months, the median 22 (range, 0-312) months. The kidneys were from deceased donors in 120 patients (68.79%) and from living donors in 54 (31.21%); 35 (20.83%) were expanded-criteria donors. When comparing the baseline versus 12-month values of laboratory results, total cholesterol levels and platelet counts differed significantly-191.55 ± 43.92 mg/dL versus 204.52 ± 41.29 mg/dL (P < .05) and 213,411 ± 63,231/mm(3) vs 255,571 ± 59,153/mm(3), respectively (P < .05)-but remained within clinically controllable ranges. Glycemia, triglycerides, hematocrit, hemoglobin, and leukocytes remained stable. Logistic regression analysis of baseline variables showed that the only independent prognostic factor for improved eGFR at 1 year was the conversion of patients to everolimus within the first 12 months after transplantation (odds ratio, 2.17; 95% confidence interval, 1.15-4.10). In conclusion, regarding the effectiveness of everolimus in our subjects, the only predictor of improved eGFR identified at 1 year was conversion within 12 months after transplantation.

First epidemiologic study in Argentina of the prevalence of BK viruria in kidney transplant patients.

BACKGROUND: The worldwide seroprevalence of human BK polyomavirus (BKV) in adults is 80%. About 10%-60% of renal transplant recipients experience BKV infection, nephropathy of the graft may occur in 5% of the cases, and up to 45% lose the graft. The aim of this work was to describe the prevalence of BK viruria during the 1st year after transplantation. METHODS: An epidemiologic multicenter cross-sectional study was carried out in consecutive patients at each site with kidney transplantation from August 2011 to July 2012. Clinically significant viruria was defined as >10(7) copies/mL. Viral DNA was extracted with the use of silica columns. Quantification was performed with the use of real-time polymerase chain reaction with primers that amplify a fragment of the large T-antigen gene and with a specific Taqman-MGB probe for BKV. For each assay, a standard curve with a quantified plasmid was included. RESULTS: Of 402 renal transplant recipients at 18 renal transplant sites, we analyzed 382; median age was 46.33 years, and 46.40% were female. The median of the temporal distribution for urine samples was 153 days. BK virus was detected in 50/382 samples (13%), 18 with values >10(7) copies/mL (4.7%). The median of the distribution of positive values was 123 days and the highest frequency of positive values was in months 3-7. The conditions of recipient older than 34 years and donor older than 41 years were the only ones that showed statistically significant association with BK viruria. No association with any specific immunosuppressive drug was observed. CONCLUSIONS: This is the first multicenter study conducted in Argentina to determine the prevalence of BK viruria in renal transplant recipients. Because of the growing number of the population susceptible to this infection, it is important to register and describe data about its epidemiology and associated risk factors.

Outpatient renal needle biopsy of the transplanted kidney: safety profile.

Since May 2005, we began performing renal graft biopsies as outpatient procedures when the patient's condition did not require hospitalization. To evaluate the safety profile of the 137 procedures performed in 111 patients, we performed a retrospective analysis of complications after all biopsies between 4 May 2005 and 6 January 6, 2011. The analysis focused on types of complications as well as needs for hospitalization with length of stay, for blood transfusion or for a further intervention. There were complications in 10.9% of procedures (n = 15) with 8% requiring hospitalization (n = 11). The complications were: gross hematuria (n = 10) including blockage of urinary flow (n = 2) with one subject requiring urologic intervention, and one patient experienced severe pain at the puncture site. Neither renal graft nor patient survival was threatened; there was no hemodynamic decompensation needing blood transfusions. The average hospital stay was 2.27 days (range = 1-8). Outpatient renal biopsies in 111 patients (137 procedures) had an 8% incidence of complications requiring admission and an average length of hospitalization of 2.27 days. Gross hematuria the most frequent problem, in no way compromised patient or graft survival showing it to be a safe outpatient procedure.

Results of the conversion to everolimus in renal transplant recipients with posttransplantation malignancies.

Management of posttransplantation malignancies should include control of the neoplasia and preservation of renal function. Conversion to everolimus (EVL) would potentially have both effects. Twenty-one patients were converted to EVL due to posttransplantation neoplasms. We have presented herein descriptive data and postconversion (PC) outcomes among subjects of mean age 53.6 +/- 10.1 years (range, 36-69), 57.1% were males, undergoing conversion at 108.2 +/- 74.7 (range, 5-316) months after transplantation. All patients received standard immunosuppressive therapy and 9.5% had been induced with thymoglobulin. Malignant neoplasms were as follows: skin (n = 7), gynecological (n = 3), gastrointestinal (n = 3), PTLD (n = 2), renal (n = 2), CNS (n = 1), seminoma (n = 1), Kaposi's sarcoma (n = 1), and prostate cancer (n = 1). PC to EVL, calcineurin inhibitors (CNIs) were discontinued in 18 of 19 patients, mycophenolate in 9/12, and azathioprine in 5/7; all patients continued to receive steroids. In 16 patients (79%) tumors were removed. Chemotherapy was performed in 2 patients with PTLD and radiotherapy was performed in 1 patient with prostate cancer. Mean follow-up was 505 days (range, 59-1151); baseline glomerular filtration rate (GFR) was 53.5 +/- 21.6 mL/min versus 48.5 +/- 25.7 mL/min (P = not significant [NS]) at the last control. One patient experienced graft loss at day 744 after conversion due to chronic rejection. Adverse events were observed in 57% of patients and 28% displayed infections; no patient discontinued EVL. There were 2 deaths: 1 due to an infection and the other due to postsurgical complication. No deaths due to cancer progression were observed. The results observed in this series suggested that conversion to EVL for a posttransplantation neoplasm is a valid therapeutic alternative to preserve graft function and control disease progression.

National survey of anemia prevalence after kidney transplantation in Argentina.

Anemia is prevalent in kidney transplant recipients and likely contributes to morbidity and mortality. The definition of anemia as established by the World Health Organization and subsequently adopted by the American Society of Transplantation is a hemoglobin concentration of 12 g/dL or less in women and 13 g/dL or less in men. Using this definition, the prevalence of anemia is nearly 30%. The National Survey of Post Transplant Anemia (PTA) in kidney transplant recipients in Argentina was conducted to evaluate the incidence of PTA at 1 year and its relationship to variables that influence transplantation outcome. At 1 year posttransplantation, mean (SD) hemoglobin concentration was 12.43 (1.77) g/dL (n = 379), hematocrit concentration was 38.26% (5.59%) (n = 379), serum creatinine concentration was 1.51 (0.72) mg/dL (n = 380), and creatinine clearance was 60.8 (22.47) mL/min (n = 334). The prevalence of PTA in Argentina at 1 year posttransplantation was 42.25%. At univariate analysis, female sex, immunosuppression regimen (mycophenolate mofetil plus mammalian target of rapamycin), and pediatric age group were associated with anemia. At multivariate analysis, only renal function and pediatric age group were associated with anemia. The mean hemoglobin level at year of transplant was 12.43 g/dL +/-1.77 and the prevalence of PTA in Argentina at year of transplant is 42.25%. Results of our survey show a correlation between Hb levels and graft function and pediatric recipient.

Parathyroidectomy for parathyroid carcinoma in renal transplantation.

INTRODUCTION: Hyperparathyroidism (HPT) is a highly prevalent pathology in the chronic renal disease population, which is associated with considerable morbidity, and mortality. The histopathological findings most often reported are solitary adenoma, diffuse hyperplasia, and autonomous hyperplasia. Carcinoma is an unusual cause of primary parathyroid hyperfunction (0.5% to 4% according to data); in renal transplanted patients it is exceptional. We sought to analyze parathyroid gland histology from renal transplant patients in comparison with nontransplanted patients and to report a parathyroid carcinoma case in a renal transplant patient. METHODS: We retrospectively analyzed parathyroidectomies (PTX) and histopathological reports between March 1989 and December 2003. RESULTS: Among 72 PTXs 41 were performed because of primary HPT; 26, secondary HPT; and five, tertiary HPT. Among the 41 primary HPT cases there were two carcinomas (4.88% primary HPT operated patients), one of whom was in a kidney transplant recipient. Among the total number of surgeries, seven were performed in six renal transplant patients, including five diffuse hyperplasia cases; one, nodular hyperplasia with an adenoma focus; and one, parathyroid carcinoma. CONCLUSIONS: Parathyroidectomy indications in the renal transplant population are usually associated with the clinical picture of tertiary HPT, which does not resolve after a functional renal transplant. In spite of this, diffuse hyperplasia, which is associated with secondary HPT, was the most frequent hystological finding. Two carcinomas were observed: one in a renal transplant patient (16.6% parathyroidectomies) and the other in a patient who did not show renal failure. These data coincide with international records.