The use of non-transplant biologics in solid organ transplant recipients: A practical review for the frontline clinician.

Biologics have become the forefront of medicine for management of autoimmune conditions, leading to improved quality of life. Many autoimmune conditions occur in solid organ transplant (SOT) recipients and persist following transplant. However, the use of biologics in this patient population is not well studied, and questions arise related to risk of infection and adjustments to induction and maintenance immunosuppression. Guidelines have been published highlighting management strategies of biologics around the time of elective surgical procedures, but this is not always feasible in urgent situations, especially with deceased donor transplantation. The aim of this review is to summarize the current literature regarding the use of these agents in solid organ transplant recipients, and specifically address induction and maintenance immunosuppression, as well as the need for alternative infective prevention strategies to create a practical reference for the frontline clinician, when faced with this complex clinical scenario.

Management of Transplant Renal Artery Pseudoaneurysm and Literature Review.

Renal transplantation is the ultimate treatment for end-stage renal disease patients. However, vascular complications can impact renal allograft outcomes. Extrarenal pseudoaneurysms (EPSA) are a rare complication occurring in 1% of transplant recipients. We report a case series of extrarenal pseudoaneurysm after kidney transplant with different clinical presentations and management strategies. Given the rarity of EPSA, literature describing this complication is limited to single case reports or small retrospective case series. We also provide an up-to-date review of 76 articles on mycotic, bacterial, and idiopathic EPSAs. Allograft removal is considered standard treatment, but new endovascular alternatives may allow allograft salvage. EPSA should be managed with a multidisciplinary approach. Surveillance with renal ultrasound is recommended in patients considered high risk.

Immune Thrombocytopenia in a Kidney Transplant Recipient Treated with Romiplostim.

We present a case of immune thrombocytopenia following a living donor kidney transplant. Thrombocytopenia started two days after transplant and continued up to seven weeks after transplant, despite an extensive workup, treatment with steroids, intravenous immune globulin, and alterations in immunosuppression and other medications. In the absence of platelet transfusions, the patient's platelet count remained < 20,000/mm3. Platelet count responded to romiplistim (Nplate®, Amgen Inc.) within two weeks and has remained stable for twelve months after initiation of this agent. The patient's graft function has also been stable. This experience suggests romiplostim is safe and effective for persistent immune thrombocytopenia in kidney transplant recipients.

Anticoagulant-induced hemorrhagic cholecystitis with hemobilia after deceased donor kidney transplant and literature review.

INTRODUCTION AND IMPORTANCE: Hemobilia and hemorrhagic cholecystitis are uncommon causes of right upper quadrant abdominal pain. The development of intra-gallbladder and biliary bleeding has been primarily associated with abdominal trauma, malignancy, liver transplant, and iatrogenic injury to the biliary tree and vasculature. Spontaneous anticoagulant induced hemorrhagic cholecystitis and hemobilia are incredibly rare events and have only been documented by a handful of case reports. CASE PRESENTATION: A 55-year-old male who had recently undergone a deceased-donor kidney transplant was transferred to our academic institution for evaluation of subjective fever, right upper quadrant abdominal and back pain. The patient demonstrated localized tenderness in the right abdomen and was found to have hemorrhagic cholecystitis on imaging. He subsequently underwent urgent cholecystectomy and recovered without any subsequent complications. CLINICAL DISCUSSION: Hemorrhagic cholecystitis and hemobilia are a rare cause of right-sided or generalized abdominal pain. Diagnosis is made primarily by pathognomonic findings on CT and US imaging. Prompt diagnosis is essential in preventing mortality and/or significant morbidity. The standard treatment consists of urgent/emergent cholecystectomy. CONCLUSION: A rare sequelae of anticoagulant use, intra-biliary bleeding must be considered as a differential diagnosis in anticoagulated patients presenting with right upper quadrant abdominal pain.

A call for transplant stewardship: The need for expanded evidence-based evaluation of induction and biologic-based cost-saving strategies in kidney transplantation and beyond.

Rising expenditures threaten healthcare sustainability. While transplant programs are typically considered profitable, transplant medications are expensive and frequently targeted for cost savings. This review aims to summarize available literature supporting cost-containment strategies used in solid organ transplant. Despite widespread use of these tactics, we found the available evidence to be fairly low quality. Strategies mainly focus on induction, particularly rabbit antithymocyte globulin (rATG), given its significant cost and the lack of consensus surrounding dosing. While there is higher-quality evidence for high single-dose rATG, and dose-rounding protocols to reduce waste are likely low risk, more aggressive strategies, such as dosing rATG by CD3+ target-attainment or on ideal-body-weight, have less robust support and did not always attain similar efficacy outcomes. Extrapolation of induction dosing strategies to rejection treatment is not supported by any currently available literature. Cost-saving strategies for supportive therapies, such as IVIG and rituximab also have minimal literature support. Deferral of high-cost agents to the outpatient arena is associated with minimal risk and increases reimbursement, although may increase complexity and cost-burden for patients and infusion centers. The available evidence highlights the need for evaluation of unique patient-specific clinical scenarios and optimization of therapies, rather than simple blanket application of cost-saving initiatives in the transplant population.

Effects of Sofosbuvir-Based Hepatitis C Treatment Regimens on Calcineurin Inhibitor Dosing in Liver and Kidney Transplant Recipients.

OBJECTIVES: Available data have suggested that directacting antivirals for hepatitis C virus may decrease calcineurin inhibitor concentrations. In this study, our aim was to determine the effects of hepatitis C directacting antivirals on calcineurin inhibitor doses and trough levels. MATERIALS AND METHODS: This retrospective, singlecenter study included 52 abdominal transplant recipients treated with sofosbuvir-based regimens between 2014 and 2017. The primary outcome was percent change in calcineurin inhibitor troughs and total daily doses between the week before treatment with direct-acting antivirals, days 21 to 35 oftreatment, and days 21 to 35 aftertreatment. Secondary outcomes included sustained virologic response and biopsyproven acute rejection rates. RESULTS: The median percent difference in calcineurin inhibitor troughs from pretreatment to during treatment was -20.5% (interquartile range, -36.2% to 13.1%) and from pretreatment to posttreatment was -13.5% (interquartile range, -33.7% to 10.7%). Corresponding percent changes in calcineurin inhibitor doses were 0% (interquartile range, 0%-0%) and 0% (interquartile range, -10.5% to 33.3%), respectively. Patients on tacrolimus experienced statistically significant changes in troughs but not doses. During treatment, 65% of patients required no dose change, 23% underwent a dose increase, and 12% had a dose decrease. The sustained virologic response rate was 98%, and the biopsy-proven acute rejection rate was 0%. CONCLUSIONS: Hepatitis C direct-acting antiviraltherapy may decrease calcineurin inhibitor levels, but this was not associated with clinically different dosing requirements or rejection rates.

Alternatives to immediate release tacrolimus in solid organ transplant recipients: When the gold standard is in short supply.

Given the current climate of drug shortages in the United States, this review summarizes available comparative literature on the use of alternative immunosuppressive agents in adult solid organ transplant recipients including kidney, pancreas, liver, lung, and heart, when immediate-release tacrolimus (IR-TAC) is not available. Alternative options explored include extended-release tacrolimus (ER-TAC) formulations, cyclosporine, belatacept, mammalian target of rapamycin inhibitors, and novel uses of induction therapy for maintenance immunosuppression. Of available alternatives, only ER-TAC formulations are of non-inferior efficacy compared to IR-TAC when used de novo or after conversion in stable kidney transplant recipients (KTRs). All other alternatives were associated with higher rates of biopsy-proven rejection, but improved tolerance from classic adverse effects of IR-TAC including nephrotoxicity and development of diabetes. While most alternative therapies are approved in KTRs, access via third-party payors is an obstacle in non-KTRs. In the setting of IR-TAC shortage, alternate therapeutic options may be plausible depending on the organ population and individual patient situation to ensure appropriate, effective immunosuppression for each patient.

Delayed vs initial cytomegalovirus prophylaxis after kidney transplantation.

It is recommended to start cytomegalovirus (CMV) prophylaxis within 10 days of solid organ transplant, if indicated. Our center underwent a cost-savings initiative to delay CMV prophylaxis initiation from postoperative day zero to postoperative day 7 or upon discharge, hypothesizing this would not affect clinical outcomes but could impact costs. The purpose of this retrospective study was to determine the effects of early vs delayed (<72 vs >72 hours after transplant) CMV prophylaxis in kidney and kidney/pancreas transplant recipients transplanted between June 2014 and January 2017. The primary endpoint was incidence of CMV infection within 1 year. Secondary endpoints included CMV disease, CMV testing, and valganciclovir cost during index hospitalization. A total of 173 patients (114 early, 59 delayed) were included. CMV infection occurred in 61% vs 54% in the early vs delayed group (P = .5). Excluding low-level DNAemia (QNAT < 200 IU/mL), infection occurred in 30% vs 22% in the early vs late group (P = .4). The median days to starting prophylaxis were 0 and 6 in the early and delayed group (P < .05), which led to a median cost savings of $497.00 per patient during index hospitalization (P < .05). Delaying prophylaxis initiation did not impact CMV outcomes in this cohort and decreased costs.

Effects of clotrimazole troches on tacrolimus dosing in heart transplant recipients.

BACKGROUND: Tacrolimus is a cornerstone of immunosuppression after transplantation but is highly susceptible to changes from interacting variables and has a narrow therapeutic index. Clotrimazole troches are commonly used as a non-systemic antifungal to prevent oral candidiasis. Studies suggest that clotrimazole troches, though minimally absorbed systemically, may affect tacrolimus concentrations by inhibition of metabolic enzyme activity in the intestines. However, the magnitude of the impact of clotrimazole on tacrolimus dosing requirements to maintain goal levels is not well described. METHODS: To assess this, tacrolimus dose adjustments and trough concentrations were retrospectively examined in 95 heart transplant recipients before and after the discontinuation of clotrimazole. RESULTS: The median percent tacrolimus dose change was an increase of 66.7% (IQR 28.6%, 100%) after clotrimazole discontinuation, and the median trough concentration percent change from baseline to the first trough after clotrimazole discontinuation (in the absence of a dose change) was -42.5% (IQR -52.3%, -30.9%). Five cases of allograft rejection were observed. CONCLUSION: In conclusion, clotrimazole troches exert a meaningful interaction with tacrolimus that requires close monitoring and dose adjustment. The data from this single-center study provide novel information that could guide providers on the degree of tacrolimus dose adjustment needed when discontinuing clotrimazole prophylaxis after heart transplantation.

Review of Infectious Disease Prophylaxis in Solid Organ Transplantation.

As immunosuppressive therapy has evolved over the years, rejection rates in solid organ transplant have declined, but infections remain a significant cause of morbidity and mortality in this population. Prophylaxis against bacterial, viral, and fungal infections is often used to prevent infection from common pathogens during high-risk periods. As an integral part of the multidisciplinary medical team, it is important that nurses caring for transplant recipients be familiar with methods to detect and prevent infectious diseases in this population. This article presents a review of risk factors for and prevalence of common infectious pathogens, as well as important considerations regarding prophylactic medications in solid organ transplant recipients.

Use of a Cholestyramine Washout in a Patient With Septic Shock on Leflunomide Therapy: A Case Report and Review of the Literature.

Patients presenting with infections while receiving disease-modifying antirheumatic agents (DMARD) may be predisposed to a higher degree illness due to immunosuppression. This can be particularly problematic in patients who are receiving DMARDs with prolonged pharmacokinetic profiles. Leflunomide is a DMARD that has a prolonged half-life due to enterohepatic recirculation. We report a case of a patient with severe septic shock secondary to a prosthetic joint infection in which therapeutic levels of leflunomide were discovered, despite the patient ceasing therapy several weeks prior to admission. An orogastric cholestyramine washout was given to the patient to expedite the removal of the drug. Serum levels rapidly declined over the next several days, corresponding with resolution of her sepsis. A review of the literature relevant to the incidence of DMARD-related infections was conducted as well as discussion regarding the role of leflunomide drug monitoring and cholestyramine-facilitated removal of the drug in episodes of acute infectious syndromes.