Conversion from tacrolimus to belatacept improves renal function in kidney transplant patients with chronic vascular lesions in allograft biops

BACKGROUND: Conversion from tacrolimus to belatacept has been shown to be beneficial for an increasing number of kidney transplant (KT) patients. Predicting factors for favorable outcomes are still unknown. We aimed to investigate whether histological vascular lesions at the time of conversion might correlate with greater improvement in renal function post-conversion. METHODS: The study was conducted on a retrospective cohort of 34 KT patients converted from tacrolimus to belatacept. All patients underwent an allograft biopsy prior to conversion. We analyzed the evolution of the estimated glomerular filtration rate (eGFR) at 3 and 12 months after conversion. RESULTS: Median time to conversion was 6 (2-37.2) months post-transplant. About 52.9% of patients had moderate-to-severe chronic vascular lesions (cv2-3). We observed an increase in eGFR in the whole cohort from 35.4 to 41 mL/min/1.73 m2 at 3 months (P = 0.032) and 43.7 at 12 months (P = 0.013). Nine patients experienced acute rejection post-conversion, with one graft loss observed beyond the first year after conversion. Patients with cv2-3 had significant improvement in eGFR at 12 months (+8.6 mL/min/1.73 m2; 31.6 to 40.2 mL/min/1.73 m2; P = 0.047) compared with those without these lesions (+6.8 mL/min/1.73 m2; 40.9 to 47.7 mL/min/1.73 m2; P = 0.148). CONCLUSIONS: Conversion from tacrolimus to belatacept has a beneficial effect in terms of renal function in KT patients. This benefit might be more significant in patients with cv in the biopsy

Conversion from tacrolimus to belatacept improves renal function in kidney transplant patients with chronic vascular lesions in allograft biops

BACKGROUND: Conversion from tacrolimus to belatacept has been shown to be beneficial for an increasing number of kidney transplant (KT) patients. Predicting factors for favorable outcomes are still unknown. We aimed to investigate whether histological vascular lesions at the time of conversion might correlate with greater improvement in renal function post-conversion. METHODS: The study was conducted on a retrospective cohort of 34 KT patients converted from tacrolimus to belatacept. All patients underwent an allograft biopsy prior to conversion. We analyzed the evolution of the estimated glomerular filtration rate (eGFR) at 3 and 12 months after conversion. RESULTS: Median time to conversion was 6 (2-37.2) months post-transplant. About 52.9% of patients had moderate-to-severe chronic vascular lesions (cv2-3). We observed an increase in eGFR in the whole cohort from 35.4 to 41 mL/min/1.73 m2 at 3 months (P = 0.032) and 43.7 at 12 months (P = 0.013). Nine patients experienced acute rejection post-conversion, with one graft loss observed beyond the first year after conversion. Patients with cv2-3 had significant improvement in eGFR at 12 months (+8.6 mL/min/1.73 m2; 31.6 to 40.2 mL/min/1.73 m2; P = 0.047) compared with those without these lesions (+6.8 mL/min/1.73 m2; 40.9 to 47.7 mL/min/1.73 m2; P = 0.148). CONCLUSIONS: Conversion from tacrolimus to belatacept has a beneficial effect in terms of renal function in KT patients. This benefit might be more significant in patients with cv in the biopsy

Efficacy and Safety of Direct Acting Antivirals in Kidney Transplant Recipients with Chronic Hepatitis C Virus Infection

The prevalence of Hepatitis C Virus (HCV) infection is significantly higher in patients with end-stage renal disease compared to the general population and poses important clinical challenges in patients who undergo kidney transplantation. Historically, interferon-based treatment options have been limited by low rates of efficacy and significant side effects, including risk of precipitating rejection. Limited data exist on the use of all-oral, interferon-free direct-acting antiviral (DAA) therapies in kidney transplant recipients. In this study, we performed a retrospective chart review with prospective clinical follow-up of post-kidney transplant patients treated with DAA therapies at three major hospitals in Boston, MA. A total of 24 kidney recipients with HCV infection received all-oral DAA therapy post-transplant. Patients were predominantly male (79%) with a median age of 60 years (range 34–70 years), median creatinine of 1.2 mg/dL (0.66–1.76), and 42% had advanced fibrosis or cirrhosis. The majority had HCV genotype 1a infection (58%). All patients received full-dose sofosbuvir; it was paired with simeprevir (9 patients without and 3 patients with ribavirin), ledipasvir (7 patients without and 1 patient with ribavirin) or ribavirin alone (4 patients). The overall sustained virologic response (SVR12) was 91% (21 out of 23 patients). One patient achieved SVR4 but demised prior to SVR12 check point due to treatment unrelated cause. Two treatment failures were successfully retreated with alternative DAA regimens and achieved SVR. Both initials failures occurred in patients with advanced fibrosis or cirrhosis, with genotype 1a infection, and prior HCV treatment failure. Adverse events were reported in 11 patients (46%) and were managed clinically without discontinuation of therapy. Calcineurin inhibitor trough levels did not significantly change during therapy. In this multi-center series of patients, all-oral DAA therapy appears to be safe and effective in post-kidney transplant patients with chronic HCV infection

Sustained Virologic Response.

<p>Overall sustained virologic response, stratified by stage of fibrosis. The graph indicates the number of patient who achieved undetectable HCV viral load at 12 weeks post-treatment. Of note, one patient had a negative HCV viral load measured at week 4 post-treatment and was counted towards achieving SVR.</p

Hepatitis C Direct-Acting Antiviral.

<p>FDA approved direct-acting antiviral treatment for hepatitis C. HCV RNA is translated into a long polyprotein which consists of three structural proteins and seven non-structural (NS) proteins. The NS3/4A protease cleaves the downstream NS proteins into individual subunits. The major DAA classes consist of NS3/4A protease inhibitors, NS5A replication complex inhibitors and NS5B polymerase inhibitors.</p

Study Population.

<p>HCV DAA regimen stratification of the study population. A flow chart of the study population, stratifying by the type/combination of DAA regimens patients received. Abbreviations SOF: sofosbuvir; SMV: simeprevir; LDV: ledipasvir; RBV: ribavirin</p

Tacrolimus Trough Levels.

<p>Tacrolimus trough levels while on antiviral treatment. The chart demonstrates the trough level of tacrolimus on the sixteen patients receiving this agent, individually, at different treatment time points.</p

Adverse Events Reported While on Treatment.

<p>Adverse Events Reported While on Treatment.</p