Enderby, Cher Y.

AbstractTacrolimus is utilized as maintenance immunosuppression in solid organ transplant (SOT). Current literature has reported conflicting conversion ratios when transitioning between oral and sublingual tacrolimus, and the exact conversion ratio has not been fully established in SOT. The purpose of this study was to determine the conversion ratios between oral and sublingual tacrolimus needed to achieve equivalent whole blood concentrations in heart, kidney, liver, and lung transplant recipients. A retrospective, single‐center analysis was conducted at Mayo Clinic in Florida. One hundred and eighteen hospitalized SOT recipients who received oral and sublingual tacrolimus during the same inpatient admission from June 1, 2012, through June 1, 2017, were reviewed. The median conversion ratio of sublingual to oral tacrolimus was 1.34 (IQR: 1.03‐1.93) in all SOT, 1.25 (IQR: 1.08‐1.64) in heart transplant, 1.23 (IQR: 1.1‐2.06) in kidney transplant, 1.64 (IQR: 1.27‐2.29) in liver transplant, and 1.34 (IQR: 0.94‐1.93) in lung transplant. A slightly higher dose of oral tacrolimus is needed in the majority of solid organ recipients in our population when converting between sublingual to oral tacrolimus administration.

Background: Treprostinil is a prostacyclin analogue that directly vasodilates pulmonary and systemic arterial vascular beds. The United States Food and Drug Administration approved inhaled treprostinil in July 2009 for the treatment of group 1 pulmonary arterial hypertension. Inhaled treprostinil avoids issues with continuous infusion prostanoids. This study describes a single institutional experience with inhaled treprostinil. Methods: This was a retrospective review of group 1 pulmonary arterial hypertension patients receiving inhaled treprostinil from July 2009 through September 2015. Patient demographics, vital signs, prognostic indicators, pulmonary arterial hypertension assessments, treprostinil dosing, pulmonary arterial hypertension medications, and physician assessment were collected. Prognostic indicators and the physician assessment were used to assess treatment response. A modified Registry to Evaluate Early and Long-term Pulmonary Arterial Hypertension Disease Management (REVEAL) risk score was calculated prior to and after initiation of inhaled treprostinil. Results: The mean time on inhaled treprostinil for the 16 patients was 21 ± 17 months. A total of 31% discontinued treatment. The New York Heart Association Functional Class, right ventricular size, and right ventricular function improved after inhaled treprostinil. Directional improvement in B-type natriuretic peptide, 6-minute walk distance, right arterial pressure and mean pulmonary artery pressure were also observed. The mean modified REVEAL risk score (RRS) was 7 ± 3 at baseline. The RRS decreased in 7 of the 11 patients that improved and remained stable in 2 patients. Conclusion: The majority of patients in this consecutive series receiving inhaled treprostinil tolerated treatment. Most patients remained on therapy for over 12 months. Clinical assessments of disease severity all changed directionally toward improvement and the overall risk assessment was improved or stable in 56% by the RRS.

Pulmonary arterial hypertension is a chronic, progressive disease of the pulmonary vasculature resulting in poor outcomes if left untreated. The management of group 1 pulmonary arterial hypertension has included the use of prostanoids, phosphodiesterase-5 inhibitors, and endothelin receptor antagonists targeting the prostacyclin, endothelin-1, and nitric oxide pathways. Three new medications have been approved by the US Food and Drug Administration over the past couple of years. Macitentan is the newest endothelin receptor antagonist, riociguat is a soluble guanylate cyclase stimulator, and treprostinil diolamine is the first oral prostanoid. This review will focus on the key trials leading to their approval, special considerations for each medication, and their potential place in therapy. The use of combination therapy as initial therapy in pulmonary arterial hypertension will also be discussed.

AbstractAlemtuzumab and rabbit antithymocyte globulin (rATG) are commonly used for induction therapy in renal transplantation. This retrospective, single‐center, cohort study evaluated cumulative incidence of one‐yr biopsy‐proven acute rejection (BPAR) among 200 consecutive primary non‐sensitized kidney transplant recipients who received either alemtuzumab (n = 100) or rATG (n = 100) induction followed by rapid steroid taper, tacrolimus, and mycophenolate mofetil. Protocol biopsies, plasma and urine BK virus PCR, serum creatinine and iothalamate glomerular filtration rate (iGFR), were obtained at 1, 4, and 12 months from transplantation. The one‐yr BPAR rates were similar between the alemtuzumab and rATG groups; however, rejection Banff IA and higher was more common in the alemtuzumab arm (18% vs. 5%, p = 0.047). After adjusting for confounding variables, alemtuzumab was still associated with Banff IA and higher rejection (adjusted OR: 3.7, CI: 1.2–10.5, p = 0.02). Despite similar rates of BK viremia, more patients in the alemtuzumab arm developed BK nephropathy (16% vs. 3%, p = 0.046). One‐year iGFR (53.4 ± 20.2 vs. 71.9 ± 27.2 mL/min/1.73 m2, p = 0.002) and three‐yr graft survival (89.5% vs. 95%, p = 0.05) were lower in the alemtuzumab group. In low immunological risk kidney transplant recipients on steroid‐free immunosuppression, alemtuzumab was associated with more severe rejection and BK nephropathy compared to rATG.

AbstractBackgroundConcomitant administration of the triazole antifungals, voriconazole or itraconazole, with tacrolimus can result in significant drug interaction in the transplant recipient. Limited published information exists regarding tacrolimus dosing when transitioning from voriconazole to itraconazole. The objective of this study was to evaluate the extent of the drug interaction with antifungal prophylaxis using voriconazole followed by a change to itraconazole in lung transplant recipients receiving tacrolimus.MethodsThis prospective study included lung transplant recipients receiving antifungal prophylaxis with voriconazole followed by a switch to itraconazole. Patients were followed from the time of transplant until two months after converting to itraconazole. All patients received standard immunosuppression with tacrolimus, mycophenolate mofetil, and a corticosteroid. Tacrolimus dose normalized concentrations using concentration/dose ratio were compared while receiving voriconazole versus itraconazole.ResultsTwenty lung transplant recipients were included in the final analysis. No difference was found with the tacrolimus dose normalized concentrations on voriconazole 254 ± 28 (ng/mL)/(mg/kg) compared with itraconazole 234 ± 34 (ng/mL)/(mg/kg), p = 0.65.ConclusionTacrolimus dosage adjustments were not necessary when converting from voriconazole to itraconazole. Validation in a larger population is needed to confirm these findings.