Hepatitis C Treatment With Direct-Acting Antivirals in Kidney Transplant: Preliminary Results From a Multicenter Study.

Hepatitis C (HC) is a very relevant negative prognosis factor for graft and transplant recipient survival. New direct-acting antivirals (DAAs) allow us to solve this problem in an effective way. It is crucial to understand their real impact in our daily practice. We analyzed treatment results with DAA, free of interferon, in kidney transplant recipients (KTRs) from 15 Spanish hospitals (Grupo Español de Actualización en Trasplante), regarding effectiveness, tolerance, and impact on immunosuppression, renal function-proteinuria, and diabetes. One hundred nineteen KTRs were included (9 combined liver-kidney transplants). The main DAA used was sofobusvir (91%) combined with ledipasvir (55%), simeprevir (14%), or daclatasvir (13%); in 9 cases (7%), a paritaprevir-ritonavir-ombitasvir-dasabuvir combination (3D) was used; Ribavirin was used as a coadjuvant in 18%. Side effects were limited (23.5%) and without relevance in general, except in 7 patients for whom we needed to interrupt the treatment due to neurotoxicity (1) caused by drug interaction (3D and tacrolimus) or anemia (3) by Ribavirin or others. Ninety-four patients had completed the treatment when data were analyzed: virological response was seen in 97.8% % of cases. Liver function analysis improved: 84% normal versus 21% before starting the treatment (P < .001). Renal function and proteinuria did not change. Tacrolimus level at the end of DAA-treatment was significantly lower with respect to the beginning (5.8 ± 2.1 ng/mL vs. 7.4 ± 1.8 ng/mL, P = .03), despite a slight increase in the dose (2.6 mg/d vs. 2.3 mg/d, P = .17). DAA are highly effective in the treatment of hepatitis C in KTRs with good tolerance in general, making it possible to solve the problem and have a good chance to improve the prognosis in our transplantation patients. The use of these therapies in KTRs requires special control and coordination with digestive professionals, especially if 3D or Ribavirin is used.

Kidney transplantation with organs from donors after circulatory death type 3: a prospective multicentric Spanish study (GEODAS 3).

To increase the number of kidney donors, new strategies are needed such as living donor programs, expanded criteria donors, or donors after circulatory death (DCD) kidney transplantation programs. The GEODAS group has started an observational, prospective, multicenter clinical study, collecting data from all DCD type-3 kidney transplantations performed in seven Spanish hospitals from January 2012 to January 2014. The preliminary results have shown a delayed graft function of 40.4% and graft survival of 93.7% with a nadir creatinine of 1.3 mg/dL. From all 33 potential donors included in the study, 32 were effective and 63 kidney grafts were transplanted with a utilization rate of 98.5%. Creatinine evolution (median [range]) was in the first month: 2.1 [0.6-5.6]; third month: 1.6 [0.8, 4.2]; first year: 1.6 [0.9-2.2]. These results are similar to kidney transplantation from donors after brain death as shown in the literature, especially in the graft and recipient survival rates. In addition, the controlled programs are easier and less expensive than uncontrolled DCD programs with a higher rate of graft use.

Utilization of advanced-age donors in renal transplantation.

The shortage of organ availability in recent years has made it necessary to use grafts from advanced-aged donors to maintain the rate of renal transplantation in our country. The objective of this study was to evaluate the graft function and patient survival using kidneys from deceased donors of over 65 year of age. From 2005 until 2010, we compared the outcomes of patients who received grafts from donors over 65 years old vs less than 65 years. We observed no significant difference in sex, time on dialysis, or cold ischemia time between the groups. As expected the recipient age was significantly different. For the analysis of survival, we used the Tablecloth-Haenzel test and the Kaplan-Meier survival estimator. Actuarial survivals at 3 years after transplantation showed 84.8% among patients transplanted with kidneys from donors over 65 years old versus 97.5% in the control group. The graft survival was 78.8% among expanded criteria versus 86.85% in the control group. When we analyzed graft survival using an "exitus-censured" analysis, we obtained graft survivals of 89.1% in the expanded criteria kidney group versus 88.6% among the controls. We concluded that the use of kidney from donors over 65 years of age allows us to increase the rate of renal transplantation to about 15 to 20 per million population, with good graft and patient survivals provided that the protocol for expanded criteria organs ensured proper macroscopic and microscopic evaluation of the organ for transplantation.

Efficacy and safety of conversion from twice-daily to once-daily tacrolimus in a large cohort of stable kidney transplant recipients.

Prolonged-release tacrolimus was developed to provide a more convenient once-daily dosing that could improve patient adherence. We conducted a multicenter, prospective, observational, 12-month study to describe the efficacy, safety and patient preference of conversion from tacrolimus twice-daily to once-daily formulation in stable kidney transplant recipients in routine clinical practice. Conversion was made on a 1 mg: 1 mg basis (1 mg: 1.1 mg in patients with trough levels <6 ng/mL). The study included 1832 patients (mean age (± SD): 50.0 ± 13.4 years; 62.7% male). After conversion, a modest reduction in tacrolimus trough levels, necessitating an increase in daily dose, was observed (mean changes at 12 months of -9.1% and +1.24%, respectively; p < 0.0001). Mean glomerular filtration rate did not change significantly (56.5 ± 19.7 mL/min at conversion vs. 55.7 ± 20.6 mL/min at 12 months). Proteinuria, blood pressure, lipid, hepatic and glucose parameters remained stable. Eight patients (0.4%) had acute rejection and 34 patients (1.85%) discontinued treatment. Almost all patients (99.4%) preferred the once-daily formulation, because of less frequent dosing (66%) and improved adherence (34%). In conclusion, at similar doses to twice-daily tacrolimus, once-daily formulation provided stable renal function, a low acute rejection rate, and good tolerability in stable kidney transplant recipients in the routine clinical practice setting.

Prophylactic therapy with valganciclovir in high-risk (cytomegalovirus D+/R-) kidney transplant recipients: a single-center experience.

BACKGROUND: A prospective study was performed in kidney transplant patients at risk of developing cytomegalovirus (CMV) infection (CMV D+/R-). They were treated with valganciclovir (VGC) for 3 months as prophylactic therapy. The aim was to determine the safety and efficacy of prophylactic therapy with VGC. METHODS: Antigenemia and/or polymerase chain reaction CMV was routinely performed every 2 weeks up to month 3, monthly to month 6, and every other month until the end of the first year posttranplantation, as well as when clinically indicated. RESULTS: From July 2007 to April 2010, 366 renal transplantations were performed at our center, including 34 (9%) high-risk patients for CMV infection. The median age was 47 years; 19 were males and 15 females. Twelve (35%) patients developed CMV infections: 10 (34%) gastrointestinal disease and 3 viral syndromes. The timing of the clinical manifestations was 16% (3/12) between months 1 and 3, 75% (8/12) between months 4 and 6, and 8% (1/12) in month 9 posttransplantation. CONCLUSION: Treatment with intravenous ganciclovir followed by oral VGC was successful in all patients. No opportunistic infections or allograft rejection were observed; only 1 patient developed thrombocytopenia as an adverse event to VGC.

Combination of everolimus and tacrolimus in kidney transplant patients with intolerance to mycophenolate mofetil/mycophenolic acid.

OBJECTIVE: Most immunosuppressive protocols in de novo renal transplantation include tacrolimus in combination with mycophenolate mofetil/mycophenolic acid (MMF/MPA) and prednisone. A variable percentage of patients show intolerance to MMF/MPA needing a reduction, interruption, or suspension of the drug, thereby exposing the patient to a greater risk of a rejection episode. The association of everolimus and tacrolimus may prove to be an alternative option in such cases. The aim of this study was to present our clinical experience, evaluating the incidence of graft rejection. PATIENTS AND METHODS: We performed a descriptive study of 19 kidney transplant patients from 2001-2008 who were treated with tacrolimus, MMF/MPA, and prednisone and displayed gastrointestinal or hematological adverse events to MMF/MPA, which were addressed with everolimus. We analyzed parameters up to 2 years after the change. RESULTS: The doses and levels of everolimus were increased progressively. At the same time, we decreased the doses and levels of tacrolimus. Renal function remained stable during the period and there was no case of a rejection episode during the 2 years. Only 5 patients (26%) showed side effects which were attributable to everolimus; 36% of patients required starting and/or increasing the erythropoietin dose, 15% required iron supplements, 15% required diuretics, and 31% began or increased treatment with statins. CONCLUSION: Our experience suggested that a combination of tacrolimus and everolimus may be a safe, effective alternative for kidney transplant patients who show intolerance to MMF/MPA.

Conversion to everolimus in kidney transplant recipients with decreased renal function.

Whenever graft function is good and proteinuria is under control, many reports describe the efficacy and safety of the conversion to Everolimus (EVL) among stable kidney recepients, simultaneously withdrawing the calcineurin inhibitor (CNI). However, there are few publications that evaluate the role of EVL in patients with decreased renal function. We describe our experience with 22 stable renal transplant recipients whose serum creatinine concentrations were >2 mg/dL and proteinuria <1000 mg/24 h who underwent an abrupt switch from a CNI to EVL. Conversion was simple, well-tolerated, and safe using an initial dose of 1-3 mg/d that was sufficient to achieve the recommended levels of 3-8 ng/dL. The adverse events were expected; most of them were of medium intensity. Globally, over the 24 months follow-up, there was improved renal function despite the initial creatinine. The improvement was greater when the switch was performed during the first year after transplantation. Two patients lost their grafts after a dramatic evolution with development of nephrotic syndrome and increasing creatinine. In our experience, conversion to EVL is a safe alternative among patients with chronic allograft nephropathy or nephrotoxicity due to CNI, even in patients with significantly decreased renal function at the time of the switch.

Use of the new proliferation signal inhibitor everolimus in renal transplant patients in Spain: preliminary results of the EVERODATA registry.

Everolimus (Eve) has shown good efficacy and safety profiles in clinical trials in combination with low doses of cyclosporine but there is limited experience in other modes, especially with calcineurin inhibitor elimination. We developed a retrospective study to analyze its clinical use after approval in Europe in 2005. Herein we have presented the results of a series of 272 patients followed for the first 6 months after Eve introduction. In 93.8% of cases Eve was introduced after the first month posttransplantation (conversion use), and 6 months after introduction, the CNI had been eliminated in 75% of cases. The main indication for Eve introduction was the diagnosis of a malignant neoplasm (42%), whereas the combined indication of prevention and/or treatment of toxicity, especially nephrotoxicity, accounted for 46.3% of cases. Initial doses were low (1.37 mg/d), but were progressively increased up to 2 mg/d at 6 months. Renal function remained unchanged during the follow-up period, whereas proteinuria moderately increased. Only 5 cases (2%) of acute rejection episodes were observed with excellent patient and graft survivals at 6 months after conversion. Further analysis of this extensive series of patients with a longer follow-up is needed.

Safety and efficacy of tacrolimus rescue therapy in 55 kidney transplant patients treated with cyclosporine.

To evaluate the efficacy and safety of conversion from cyclosporine to tacrolimus, we analyzed 55 kidney transplant patients who were converted due to cosmetic reasons in 42 patients, acute rejection in 2 patients, and other causes in 11 patients. At the doses and levels used, the development of diabetes mellitus was minimized. Disappearance of cosmetic side-effects and improvement of cardiovascular risk factors, together with conservation of renal function, encourage us to use tacrolimus as an efficacious and safe immunosuppressive therapy.

Análisis estadístico de la incidencia de cánceres "de novo" en pacientes trasplantados renales: una nueva metodología de estudio / Statistic analysis of cancer "de novo" incidence in renal transplant patients: a new study

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Case Reports. Infection due to Scedosporium apiospermum in renal transplant recipients: a report of two cases and literature review of central nervous system and cutaneous infections by Pseudallescheria boydii/Sc. apiospermum.

Two cases of infections due to Scedosporium apiospermum in renal transplant recipients, one localized in the central nervous system, the other in the skin, are presented, and a literature review of 21 cases of central nervous system and cutaneous infections due to Pseudallescheria boydii/Sc. apiospermum is given.

Presentación de cánceres en receptores trasplantados con órgano sólido / No disponible

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Valoración del tratamiento sustitutivo integrado en pacientes en insuficiencia renal terminal: selección versus elección / Assessment of integrated replacement therapy in patients with terminal renal insufficiency: selection vs election

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