Angela Q. Maldonado

Impact of IgM and IgG3 anti-HLA alloantibodies in primary renal allograft recipients.

Background With standard IgG donor-specific anti-HLA antibody (DSA) testing, it is unclear which immunoglobulin-G (IgG) DSA positive patients will fail. We looked further into the immune response by studying immunoglobulin-M (IgM) and IgG subclass 3 (IgG3) DSA to determine if these identify the IgG DSA patients at highest risk for allograft loss. Methods In 189 consecutively transplanted primary renal allograft recipients, sera were collected sequentially pre- and posttransplant. Of the 189, 179 patients had sera available to retrospectively test for anti-HLA IgG, IgM, and IgG3 antibodies via LABScreen single-antigen bead assay and were included in the study. All patients had a negative crossmatch. Per patient, all DSA (IgM, IgG3, and IgG) refers to the same serologic specificity. Results Overall, 100 (56%) patients developed an alloimmune response (IgM or IgG DSA positive, or both). Ninety-five patients developed IgM DSA and 47 patients developed IgG DSA. IgM DSA was detected in 42 of 47 patients with IgG DSA. IgM DSA alone did not increase the allograft loss risk, whereas IgG DSA did (P=0.002). Once IgG DSA appeared, IgM DSA persisted in 33 patients and an isotype switch to IgG3 positive DSA occurred in 25 patients. Patients with IgM persistent IgG3 positive DSA (n=19) were more likely to have allograft failure than those without (P=0.02). Conclusion This study shows the evolution of the humoral immune response from IgM to IgG DSA posttransplant. We found that development of IgM persistent IgG3 positive DSA identifies the most dangerous IgG DSA subpopulation.

Onset and progression of de novo donor‐specific anti‐human leukocyte antigen antibodies after BK polyomavirus and preemptive immunosuppression reduction

BK polyomavirus (BKPyV) viremia/nephropathy and reduction in immunosuppression following viremia may increase the risk of alloimmune activation and allograft rejection. This study investigates the impact of BKPyV viremia on de novo donor anti‐human leukocyte antigen (HLA)‐specific antibodies (dnDSA).

Billing for outpatient transplant pharmacy services.

PURPOSE The economic impact of out-patient pharmacy services in a transplant program was evaluated. METHODS Full-time kidney transplant pharmacy services were implemented at Providence Sacred Heart Medical Center (PSHMC) in the fall of 2008, with two pharmacists combining hours to provide one full-time-equivalent position. At PSHMC, posttransplantation patients are seen three times per week. The number of patient visits with pharmacists for 2010 was compared with the total number of patient visits. The face-to-face time spent with the patient was translated to a level of billing that was associated with a set reimbursement schedule. For each patient encounter in which a pharmacist was involved, the incremental difference between the nursing and pharmacy levels of billing was examined, as were the levels most often billed by pharmacists. The difference in billing levels between pharmacists and nurses for the same patient encounter was also evaluated. RESULTS Overall, pharmacist visits accounted for 208 (22%) of the 994 out-patient kidney transplant visits in 2010, with pharmacists billing at a higher level of acuity compared with nursing for the same patient encounter 48% of the time. This translated to an approximate increase of

Assessing pharmacologic and nonpharmacologic risks in candidates for kidney transplantation.

100 per patient visit. For the one-year study period, pharmacists utilizing facility- fee billing increased out-patient reimbursement by approximately

Building a business plan to support a transplantation pharmacy practice model

10,000. CONCLUSION By utilizing outpatient facility-fee billing for pharmacy services, the transplant program at PSHMC increased reimbursement in the outpatient setting.

Effects of plasmapheresis on mycophenolic acid concentrations.

PURPOSE Pharmacotherapy concerns and other factors with a bearing on patient selection for kidney transplantation are discussed. SUMMARY The process of selecting appropriate candidates for kidney transplantation involves multidisciplinary assessment to evaluate a patients mental, social, physical, financial, and medical readiness for successful surgery and good posttransplantation outcomes. Transplantation pharmacists can play important roles in the recognition and stratification of pharmacologic and nonpharmacologic risks in prospective kidney transplant recipients and the identification of issues that require a mitigation strategy. Key pharmacotherapy-related issues and considerations during the risk assessment process include (1) anticoagulation concerns, (2) cytochrome P-450 isoenzyme-mediated drug interactions, (3) mental health-related medication use, (4) chronic pain-related medication use, (5) medication allergies, (6) use of hormonal contraception and replacement therapy, (7) prior or current use of immunosuppressants, (8) issues with drug absorption, (9) alcohol use, (10) tobacco use, (11) active use of illicit substances, and (12) use of herbal supplements. Important areas of nonpharmacologic risk include vaccine delivery, infection prophylaxis and treatment, and socially related factors such as nonadherent behavior, communication barriers, and financial, insurance, or transportation challenges that can compromise posttransplantation outcomes. CONCLUSION Consensus opinions of practitioners in transplantation pharmacy regarding the pharmacologic and nonpharmacologic factors that should be considered in assessing candidates for kidney transplantation are presented.

Prevalence of CYP3A5 Genomic Variances and Their Impact on Tacrolimus Dosing Requirements among Kidney Transplant Recipients in Eastern North Carolina

Pharmacists have been part of the multidisciplinary transplantation care team for more than four decades. The first article detailing the pharmacist’s role on the transplantation team was published in this journal in 1976.[1][1] Since the 1970s, a pharmacist’s presence within the transplantation

Nonadherence to therapy after adult solid organ transplantation: A focus on risks and mitigation strategies

Although plasmapheresis (PP) is a widely used intervention in immunologic disease states, there is an absence of literature on its effects on the pharmacokinetics of mycophenolic acid (MPA) (1). Supplemental dosing is often necessary for highly protein-bound drugs with low volumes of distribution (V

Transplant recipients are vulnerable to coverage denial under Medicare Part D

To assess the prevalence of CYP3A5 genomic variances and their impact on tacrolimus (TAC) dosing requirements among kidney transplant recipients in eastern North Carolina, we conducted a single‐center retrospective cohort study at a large tertiary care medical center. A total of 162 adults who received a kidney transplant between March 1, 2013, and February 28, 2015, and received oral TAC as part of their maintenance immunosuppression were enrolled. Of these patients, 85 patients expressed a genotype with a CYP3A5*1 variant (CYP3A5*1 group), and 77 patients expressed genotypes with other CYP3A5 variants (nonexpressor group). All patients were followed for 1 year posttransplantation. The primary end point was the TAC total daily dose (TDD) required to achieve the first therapeutic trough level based on the presence or absence of the CYP3A5*1 variant. The prevalence of different CYP3A5 variants across race/ethnicities in the study cohort was determined by CYP3A5 genotyping for each patient. The CYP3A5*1 and nonexpressor groups did not differ significantly with respect to sex, mean age, or mean weight. The CYP3A5*1 group was largely African American (93%, p≤0.0005) compared with other race/ethnicities. Among the CYP3A5*1 expressors compared with nonexpressors, the mean TAC TDD in milligrams at the first therapeutic TAC level was significantly higher (12 vs 8 mg/day, p≤0.001). Similarly, the mean TAC TDD in milligrams/kilogram was 50% greater among CYP3A5*1 expressors (0.15 vs 0.1 mg/kg/day, p≤0.0005). The predominant genotypic variants were CYP3A5*3/*3 (33%), CYP3A5*1/*3 (20%), and CYP3A5*1/*1 (19%). This study illustrates the prevalence of the CYP3A5*1 variant among African‐American kidney transplant recipients and the effect of this gene expression on the TAC TDD. Patients with the CYP3A5*1 variant require higher TAC doses, on average, to achieve desirable drug levels. In addition, this study provides transplant clinicians with insight and support to dose TAC more aggressively in African‐American kidney transplant recipients who may be at higher risk for both toxicities as well as poor clinical outcomes related to inadequate immunosuppression.

Racial Differences in Incident De Novo Donor-Specific Anti-HLA Antibody among Primary Renal Allograft Recipients

Nonadherence to therapy remains a principal challenge in optimizing long-term graft survival in solid organ transplant recipients. The consequential outcomes of rejection, graft loss, and survival due to nonadherence are reported primarily from studies of renal transplant recipients; outcomes data