Conversion from Prograf to Advagraf in stable kidney transplant recipients: better renal function after 3-year follow-up.

BACKGROUND: The complexity of treatment after solid organ transplantation has been related to non-adherence to therapy prescriptions and to reduced graft survival. The aim of this study was to evaluate the middle-term effects of the conversion from Prograf (TAC), to extended-release tacrolimus (Advagraf) (ADV) in stable kidney transplant recipients. METHODS: Conversion from TAC to ADV (dose, 1:1 mg/mg) was planned in 78 kidney transplant patients with stable renal function 71±48 months after renal transplantation. Before conversion, 1 week after conversion, and every 6 months up to 3 years, patients were evaluated clinically and by means of the usual blood chemistry and pharmacologic parameters. RESULTS: Twenty patients (26%) refused to change their pre-existing immunosuppressive therapy; therefore, 58 patients entered the study and 45 (77%) completed the 3-year follow-up. Patient survival was 98% and allograft survival was 96%. Significant reduction in serum creatinine levels and increased glomerular filtration rate were observed after conversion (3-year creatinine: before TAC 1.67±0.47 mg/dL vs after ADV 1.47±0.62 mg/dL, P<.001; glomerular filtration rate, MDRD abbreviated: before TAC 49±15 mL/min vs after ADV 59±24 mL/min, P<.001). The daily dose and C0 blood levels of tacrolimus were stable before and after conversion (dose before vs 3 years after conversion: TAC 3.79±1.81 mg/day vs ADV 3.54±1.86 mg/day, P=ns; C0 tacrolimus blood levels, before vs 3 years after conversion: TAC 6.03±1.75 ng/mL vs ADV: 5.58±1.38 ng/mL, P = NS). One patient in the ADV group had an episode of acute rejection (2%). CONCLUSIONS: Our data support the safety and efficacy of converting from Prograf to Advagraf in stable kidney transplant patients in the middle term. We suggest that the observed improvement in renal function after conversion to ADV is related to the reduction of the 24-hour tacrolimus area under the curve exposure.

Do patients who participate in a clinic experimental protocol have the same probability of success from that who were not selected or refused to participate? Outcome surveillance, safety, and bioethical considerations in kidney transplant clinical research.

INTRODUCTION: Safety in conducting a clinical trial is a prerequisite for patients who will be enrolled into that study. The aim of the present study was to evaluate retrospectively if patient and graft survival were similar among patients who participated in clinical trials versus those who did not. PATIENTS AND METHODS: We evaluated pretransplant and posttransplant characteristics of 245 kidney transplant (KT) patients who were selected to participate in at least one Phase II/Phase III clinical trial. We compared them with 361 KT patients who were not enrolled or refused to participate in those clinical trials; all studies were conducted at a single transplant center. Inclusion/exclusion criteria were as noted for each individual protocol. Only studies with enrollment at time of graft implant were considered. RESULTS: Selection of patients participating in clinical trials in general exclude high-risk patients. In our experience, only 36% of transplanted patients were selected for a multicenter, prospective, randomized, international study that included changes to the strategies in the administration of immunosuppressive drugs already on the market or development of a new immunosuppressant. After 5 years, graft and patient survival rates were similar between those who participated and those who did not participate in a clinical study. Although our data were collected retrospectively, an alternative design to achieve these conclusions would be a noninferiority study. CONCLUSIONS: Our results demonstrated similar rates of graft and patient survival among enrolled patients versus nonenrolled patients. Outcome surveillance offers safety in participating in clinical trials that involve changes in standard immunosuppression therapy and are part of the research necessary to develop patient-centered medical interventions.

Elderly kidney transplant recipient with intermittent fever: a case report of leishmaniasis with acute kidney injury during liposomal amphotericin B therapy.

We present a case report of visceral leishmaniasis in an elderly kidney transplant recipient (age, 73 years) with high intermittent fever in the 2 months before admission. Symptoms started 16 years after transplant. The patient received appropriate treatment with liposomal amphotericin and experienced transient increases in serum creatinine levels. Progression to dialysis was avoided with short duration of therapy (5 consecutive days, plus 1 more dose 1 week apart, a schedule alternative to 15-21 days [supported by the literature]) and a temporary reduction in tacrolimus exposure. After 4 months, recurrence of symptoms without other explanation required a second bone marrow aspirate; it revealed the persistence of amastigote forms. Visceral leishmaniasis is a potentially life-threatening infection; to the best of our knowledge, this is the oldest transplanted patient with a case of leishmaniasis described in the literature.

Posttransplant encapsulating peritoneal sclerosis, long-term success with everolimus and low-dose CNI: a case report.

Encapsulating peritoneal sclerosis is a serious complication of peritoneal dialysis and can occur even after transplant. The gut is partially or totally enveloped by a thick fibrous membrane that leads to the formation of multiple sections containing intestinal loops contracted and reduced in volume. Exacerbation after renal transplantation is a very rare but sometimes dramatic condition. We report a patient who developed intestinal obstruction due to encapsulating peritoneal sclerosis 1 year after a deceased-donor kidney transplant. Treatment included laparotomy, small-bowel lengthening by release of adhesions, and high doses of corticosteroids. The patient received immunosuppressive therapy with a combination of low-dose cyclosporine, everolimus, and prednisone, unchanged except for a temporary steroid increase in the postoperative period. We report success with this combined surgical plus medical therapy, with no recurrence after 81 months of follow-up.

Expanding the living donor pool, "Ist Act": analysis of the causes of exclusion of potential kidney donors.

BACKGROUND: The evaluation of a potential living kidney donor (LKD) leads to exclusion of at least 50% of candidates. The aim of this study was to analyze the reasons for exclusion of potential LKDs referred to our center. METHODS: We retrospectively analyzed historic and clinical data of all potential LKDs who were evaluated over 7 years from January 2005 to March 2012. Data were obtained by review of an electronic database. RESULTS: Among 79 (50 female, 29 male) candidates, 24 (30.3%) successfully donated, comprising 22 related and 2 unrelated donors. We excluded 45 (56.9%), and 10 (12.6%) are actively undergoing evaluation. Reasons for exclusion were medical (n = 14; 31%), nonmedical (n = 18; 40%), positive cross-match (n = l7.7%), pregnancy (n = 2; 4.4%), and other reasons (n = 3; 6.6%). Of the 14 donors excluded for medical reasons, 75.8% were due to diabetes, cardiovascular disease, hypertension, or obesity and 21.5% to inadequate renal function, malignancy, or liver disease. Of the 18 (40%) excluded for nonmedical reasons, 6 (33.3%) were because the intended recipient received a deceased-donor transplantation before the evaluation could be completed, 5 (27.7%) because the recipient was no longer a candidate for transplantation, 5 (27.7%) because of donor withdrawal, and 2 (11.1%) for other reasons. CONCLUSIONS: Positive cross-match and deceased-donor transplantation during the evaluation process were the 2 most common reasons for LKD exclusion. Evaluation of potential LKDs is time consuming, requiring a remarkable amount of human and material resources. A dedicated pathway for the diagnostic work-up of LKDs may speed- the evaluation process and improve its efficiency, use of ABO-incompatible or paired-exchange donations may increase the yield of donor organs.

The reduction of left ventricular hypertrophy after renal transplantation is not influenced by the immunosuppressive regimen.

BACKGROUND: Cardiovascular (CV) disease is the first cause of death after kidney transplantation. Left ventricular hypertrophy (LVH) is one of the main CV risk factors. It has been reported that the antiproliferative properties of everolimus (EVE) treatment may decrease left ventricular mass. The aim of this study was to evaluate the evolution of LVH in two groups of kidney transplant recipients receiving immunosuppressive treatment with low-dose calcineurin inhibitor (CNI) + EVE or CNI + mycophenolate mofetil (MMF). METHODS: We evaluated 104 patients of mean age 47.5 ± 13.1 years who underwent kidney transplantation between January 2006 and December 2009 pretransplant by echocardiography, which was repeated every year for 3 years during which all patients continued the initial therapy. Over the 3-year period 76 subjects were treated with MMF, and 28 with EVE. We recorded left ventricular end-diastolic diameter (LVEDD), interventricular septum thickness in diastole (IVSTD), left ventricular posterior wall thickness in diastole (LVPWD), left ventricular end-diastolic volume and end-systolic volume during the follow-up echocardiographic evaluations. RESULTS: No differences in the evolution of the echocardiographic parameters were observed between the two groups-MMF versus EVE group: LVEDD, 50.3 ± 5.1 versus 51.2 ± 6.7 mm; IVSTD, 11.2 ± 1.9 versus 11.3 ± 2 mm; LVPWD, 10.2 ± 1.9 versus 10.5 ± 1.7 mm; relative wall thickness, 0.041 ± 0.08 versus 0.42 ± 0.08; ejection fraction, 63 ± 6% versus 61 ± 5%; and left ventricular mass index, 113 ± 28.9 versus 121.9 ± 39.4 g/m(2), respectively. Compared with pretransplant echocardiographic evaluations, similar reductions in left ventricular mass index were noted in both groups after transplantation. CONCLUSIONS: We observed that after renal transplantation there was a reduction of the LVH respect to the pretransplant dialytic status. The two immunosuppressive regimen did not influence the evolution of post-transplant LVH.

Quantitative analyses of kidney injury molecule-1 messenger RNA in kidney transplant recipients with graft dysfunction.

BACKGROUND: Kidney injury molecule-1 (KIM-1), a type I transmembrane protein that is not expressed in normal renal tissue, shows increased expression in dedifferentiated cells within damaged regions of the proximal tubule. We evaluated mRNA transcription of the KIM-1 gene in renal tissue of kidney transplant patients who were experiencing graft dysfunction searching for an accurate biomarker of kidney graft injury. PATIENTS AND METHODS: mRNA analysis was performed on 59 biopsies from kidney transplant patients who had been classified according to the Banff 1997 scheme. Biopsies were categorized in 5 diagnostic groups: acute tubular necrosis (ATN) with superimposed acute rejection episode (ARE), ATN; ARE; calcineurin inhibitor nephrotoxicity (CIN); or interstitial fibrosis and tubular atrophy (IFTA). Amplified tissue RNA was quantified by real-time polymerase chain reaction. RESULTS: Renal tissue evaluations showed significantly increased KIM-1 mRNA expression as shown by median values, 25-75 percentiles, and averages of the logarithmic transformation: namely, CIN group (50.6; 1.8-285, 1; 1.24) and IFTA group (7.5; 1.26-14.6; 0.62), displayed significant differences (P > .05). In contrast, expression was lower among the ATN (0.47; 0.28-1.06; -0.13); ARE (0.21; 0.11-0.78; -0.45), and ATN+ARE (0.46; 0.06-3.27; -0.25) cohorts. CONCLUSION: These preliminary data suggested that KIM-1 mRNA might be useful biomarker of tubular damage associated with CIN and IFTA.