Impact of antiretroviral regimen on renal transplant outcomes in HIV-infected recipients.

BACKGROUND: Protease inhibitors (PI) pose a challenge post-transplant due to significant drug interactions with calcineurin inhibitors, prompting many clinicians to convert patients to non-interacting regimens prior to transplant. The purpose of this study was to examine the impact of PI-based regimens on graft outcomes in HIV-infected renal transplant recipients. METHODS: In this retrospective cohort study, 50 HIV-infected renal allograft recipients (27 receiving a PI regimen, 23 receiving a non-PI regimen) transplanted between 2003-2015 were analyzed. RESULTS: Cumulative rejection rates at 12 and 36 months were 41% and 54% in the PI group vs 52% and 86% in the non-PI group. At last follow-up, the overall risk of acute rejection in the PI group was 46% lower compared with the non-PI cohort (P = 0.12). Patients who received a PI-based regimen had significantly reduced graft failure rates (P = 0.027). There was no difference between groups in the degree of interstitial fibrosis/tubular atrophy, arteriolar hyalinosis, arterial sclerosis, or glomerular sclerosis on available biopsies, despite longer follow-up time in the PI group. CONCLUSIONS: Our study suggests that PI-based antiretroviral therapy regimens are associated with improved graft survival and that patients can achieve adequate outcomes on a PI-based regimen when necessary. Due to study limitations, further studies are needed to determine the optimal immunosuppression/antiretroviral therapy regimen post-transplant.

Safety events in kidney transplant recipients: results from the folic Acid for vascular outcome reduction in transplant trial.

BACKGROUND: Kidney transplant recipients are at increased risk for adverse safety events related to their reduced renal function and many medications. METHODS: We determined the incidence of adverse safety events based on previously defined Agency for Healthcare and Research Quality (AHRQ) International Classification of Diseases-9 (ICD-9) code-derived patient safety indicators (PSI) in the Folic Acid for Vascular Outcome Reduction in Transplant trial participants who had a hospitalization stratified by tertiles of estimated glomerular filtration rate (GFR). We also examined the frequency of Micromedex defined two precautionary drug-drug interactions, and two medications whose use may be contraindicated because of reduced GFR from the Folic Acid for Vascular Outcome Reduction in Transplant trial medication thesaurus at baseline, and annually among 4,110 participants. Logistic regression was used to examine the relationship between patient safety events and baseline demographic and clinical variables at a participant level. Event rates were estimated at participant and visit levels. RESULTS: Of the 2,514 patients with a hospitalization, 978 (38.9%) experienced an AHRQ PSI. Factors which were associated with more common AHRQ PSI included: U.S. location, history of cardiovascular disease or diabetes, and lower tertile of estimated GFR. At a participant level, 2,524 of the 4,110 participants (61.4%) were taking calcineurin inhibitor and statin, 378 (9.2%) were taking azathioprine and an angiotensin-converting enzyme inhibitor, 171 (12.9%) were taking a sulfonylurea), 45 (3.4%) were taking metformin despite a baseline GFR below 40 mL per min per 1.73 m. CONCLUSION: We conclude that patient safety events are not uncommon in kidney transplant recipients. Careful monitoring is necessary to prevent adverse outcomes.

A comprehensive review of everolimus clinical reports: a new mammalian target of rapamycin inhibitor.

As new immunosuppressive agents are introduced to the market, clinicians are faced with the daunting task of sifting through the published literature to decide the value that the agent will add to their own practice. We often must extrapolate information provided through study in other solid-organ transplantation populations than our specific area of interest as we interpret the results and outcomes. With these challenges in mind, this compilation of published work for the newest mammalian target of rapamycin inhibitor everolimus (Certican; Novartis Pharmaceuticals, Hanover, NJ) (Zortress; Novartis Pharmaceuticals, Basel, Switzerland) is intended to provide a concise but thorough presentation of available literature so that the reader who may be unfamiliar with the agent can make their own judgment. Both Ovid and PubMed search engines were queried with a particular focus on high-impact articles noted in the Web of Science or Citation Index. Work described solely in abstract or case report form was excluded, as well as meta-analyses or those that were editorial or commentary in nature. Included were publications presented using the English language that described adult human subjects who received a heart, lung, kidney, or liver allograft. The goal of this strategy was to allow for the inclusion of pertinent literature in an unbiased fashion. Tables are provided that outline trial specific information, leaving a discussion of major outcomes to the text of the review.

Immunosuppressive agents as risk factors for BK virus nephropathy: an overview and update.

IMPORTANCE OF THE FIELD: BK virus has emerged as an important cause of graft dysfunction and failure in renal transplant recipients. Risk factors for BK virus nephropathy (BKN) are not well established, but evidence suggests that it is the result of a complex interplay between multiple donor- and recipient-related factors. AREAS COVERED IN THIS REVIEW: The purpose of this article is to review the current understanding on the effect of various immunosuppressive agents on BK viral replication and the results of different reported immunosuppression reduction protocols. WHAT THE READER WILL GAIN: The intensity of overall immunosuppression has been accepted as a major risk factor for the development of BKN. We review the data regarding the contribution of different anti-rejection agents to the risk of BK virus-induced graft injury. TAKE HOME MESSAGE: Although reduction in immunosuppression on detection of BK viral replication appears to be the most successful means in preserving allograft function, data are emerging that support the stronger association of the disease with tacrolimus, in contrast to mycophenolate compounds. Therefore, initial dose reduction for tacrolimus may be more beneficial than this anti-metabolite preemptively or after diagnosis of BKN.

Drug interactions in transplant patients: what everyone should know.

PURPOSE OF REVIEW: Adverse events due to drug-drug interactions remain a challenge in the postsurgical care of transplant recipients. A combination of potent and selective immunosuppressive drugs, which have a narrow therapeutic index, with medications for the treatment of comorbidities such as dyslipidemia, infection, psychiatric conditions, and hypertension, can lead to life-threatening drug-drug interactions. RECENT FINDINGS: There are a number of important drug-drug interactions which are important for physicians to consider. It is critical to understand the pharmacodynamics and pharmacokinetics of drug-drug interactions, their potential impact on patient care, and the management strategies. SUMMARY: Close therapeutic drug monitoring and evaluation of drug-specific side effects continue to be an important key to minimize adverse events due to drug-drug interactions.

Maintenance immunosuppressive agents as risk factors for BK virus nephropathy: a case-control study.

BACKGROUND: The specific role of different immunosuppressive agents as risk factors for BK virus nephropathy (BKN) has not been well studied. METHODS: In this case-control study, we examined the association of tacrolimus (TAC), mycophenolate mofetil (MMF), and prednisone with BKN in renal allograft recipients transplanted between 1997 and 2004 at our center who underwent biopsies for allograft dysfunction. Drug levels or doses were recorded during the 3 months before the index biopsy. Random effects logistic modeling was used for data analysis. RESULTS: There were 33 cases with BKN, biopsied at 16.4+/-2.8 months and 66 matched controls with biopsies at 21.5+/-2.1 months posttransplant (P=0.16). After adjusting for sex, race, retransplant status, diabetes, donor source, and induction agent, TAC blood level was associated with increased risk of BKN (odds ratio [OR] 1.3, 95% confidence interval [CI] 1.02-1.7, P=0.03), whereas MMF dose was not (OR 1.0, 95% CI 0.99-1.0, P=0.2). Moreover, prednisone dose was also found to be a significant risk factor for BKN (OR 1.22, 95% CI 1.04-1.4, P=0.02). CONCLUSIONS: The results of this study show that BKN is associated with TAC level and prednisone dose and not with MMF dose. This suggests that reducing TAC and prednisone dose and maintaining MMF may be a more appropriate initial approach for the treatment of BKN. Further studies are needed to compare the efficacy and safety of this approach with the currently recommended one.