Visfatin serum concentration is associated with cardiac allograft vasculopathy in heart transplant recipients

Cardiac allograft vasculopathy (CAV) still is one of the most important limiting factors of long‐term survival following heart transplant (HT). This study aimed to investigate the association between proinflammatory adipokine‐visfatin and the incidence of CAV in HT recipients. After HT, 182 patients who had a follow‐up visit at the Transplantation Clinic between 2016 and 2017 were analyzed. The median age was 60.5 years, and 76.4% were men. The incidence of CAV was 54.9%. According to the multivariable proportional hazard regression analysis, visfatin level (1.795 [1.539‐2.094]; P < .001) was significantly associated with CAV, and statin use was protective against CAV (0.504 [0.32‐0.793]; P = .003). The area under the receiver operating characteristic curve indicated an excellent discriminatory power of visfatin (0.9548 [0.9281‐0.9816]) for CAV detection. The cutoff value of 5.42 ng/mL for visfatin yielded a sensitivity of 89% and specificity of 91%. This is the first study to demonstrate that visfatin serum concentrations are independently associated with the incidence of CAV in HT recipients. Visfatin allows for simple and cheap detection of CAV given its excellent discriminatory ability and high sensitivity and specificity. In addition, we have found an independent association between the statin use and a lower risk of CAV.     

Noninvasive detection of graft injury after heart transplant using donor‐derived cell‐free DNA: A prospective multicenter study

Standardized donor‐derived cell‐free DNA (dd‐cfDNA) testing has been introduced into clinical use to monitor kidney transplant recipients for rejection. This report describes the performance of this dd‐cfDNA assay to detect allograft rejection in samples from heart transplant (HT) recipients undergoing surveillance monitoring across the United States. Venous blood was longitudinally sampled from 740 HT recipients from 26 centers and in a single‐center cohort of 33 patients at high risk for antibody‐mediated rejection (AMR). Plasma dd‐cfDNA was quantified by using targeted amplification and sequencing of a single nucleotide polymorphism panel. The dd‐cfDNA levels were correlated to paired events of biopsy‐based diagnosis of rejection. The median dd‐cfDNA was 0.07% in reference HT recipients (2164 samples) and 0.17% in samples classified as acute rejection (35 samples; P = .005). At a 0.2% threshold, dd‐cfDNA had a 44% sensitivity to detect rejection and a 97% negative predictive value. In the cohort at risk for AMR (11 samples), dd‐cfDNA levels were elevated 3‐fold in AMR compared with patients without AMR (99 samples, P = .004). The standardized dd‐cfDNA test identified acute rejection in samples from a broad population of HT recipients. The reported test performance characteristics will guide the next stage of clinical utility studies of the dd‐cfDNA assay.     

A prospective multicenter pilot study of HIV-positive deceased donor to HIV-positive recipient kidney transplantation: HOPE in action

HIV-positive donor to HIV-positive recipient (HIV D+/R+) transplantation is permitted in the United States under the HIV Organ Policy Equity Act. To explore safety and the risk attributable to an HIV+ donor, we performed a prospective multicenter pilot study comparing HIV D+/R+ vs HIV-negative donor to HIV+ recipient (HIV D−/R+) kidney transplantation (KT). From 3/2016 to 7/2019 at 14 centers, there were 75 HIV+ KTs: 25 D+ and 50 D− (22 recipients from D− with false positive HIV tests). Median follow-up was 1.7 years. There were no deaths nor differences in 1-year graft survival (91% D+ vs 92% D−, P = .9), 1-year mean estimated glomerular filtration rate (63 mL/min D+ vs 57 mL/min D−, P = .31), HIV breakthrough (4% D+ vs 6% D−, P > .99), infectious hospitalizations (28% vs 26%, P = .85), or opportunistic infections (16% vs 12%, P = .72). One-year rejection was higher for D+ recipients (50% vs 29%, HR: 1.83, 95% CI 0.84-3.95, P = .13) but did not reach statistical significance; rejection was lower with lymphocyte-depleting induction (21% vs 44%, HR: 0.33, 95% CI 0.21-0.87, P = .03). In this multicenter pilot study directly comparing HIV D+/R+ with HIV D−/R+ KT, overall transplant and HIV outcomes were excellent; a trend toward higher rejection with D+ raises concerns that merit further investigation.     

Pediatric heart transplantation at adult‐specialty centers in the United States: A multicenter registry analysis

Recent Organ Procurement and Transplantation Network bylaw revisions mandate that US transplant programs have an “approved pediatric component” in order to perform heart transplantation (HT) in patients <18 years old. The impact of this change on adolescents, a group known to be at high risk for graft loss and nonadherence, is unknown. We studied all US primary pediatric (age <18 years) HT from 2000 to 2015 to compare graft survival between centers organized mainly for adult versus pediatric care. Centers were designated as pediatric‐ or adult‐specialty care according to the ratio of pediatric:adult HT performed and minimum age of HT (pediatric‐specialty defined as ratio>0.7; adult‐specialty ratio<0.05 and minimum age >8 years). In propensity score‐matched cohorts, we observed no difference in graft loss by center type (median survival: adult 12.4 years vs pediatric 9.2 years, P = .174). Compared to the matched pediatric cohort, adult‐specialty center recipients lived closer to their transplant center (31 vs 45 miles, P = .012), and trended toward fewer out‐of‐state transplants (15 vs 25%, P = .082). Our data suggest that select adolescents can achieve similar midterm graft survival at centers organized primarily for adult HT care. Regardless of post‐HT setting, the development of care models that demonstrably improve adherence may be of greatest benefit to improving survival of this high‐risk population.     

An Update on Heart Transplantation in Human Immunodeficiency Virus–Infected Patients

Cardiovascular diseases have become a significant cause of morbidity in patients with human immunodeficiency virus (HIV) infection. Heart transplantation (HT) is a well‐established treatment of end‐stage heart failure (ESHF) and is performed in selected HIV‐infected patients in developed countries. Few data are available on the prognosis of HIV‐infected patients undergoing HT in the era of combined antiretroviral therapy (cART) because current evidence is limited to small retrospective cohorts, case series, and case reports. Many HT centers consider HIV infection to be a contraindication for HT; however, in the era of cART, HT recipients with HIV infection seem to achieve satisfactory outcomes without developing HIV‐related events. Consequently, selected HIV‐infected patients with ESHF who are taking effective cART should be considered candidates for HT. The present review provides epidemiological data on ESHF in HIV‐infected patients from all published experience on HT in HIV‐infected patients since the beginning of the epidemic. The practical management of these patients is discussed, with emphasis on the challenging issues that must be addressed in the pretransplant (including HIV criteria) and posttransplant periods. Finally, proposals are made for future management and research priorities.     

Circulating delta‐like Notch ligand 1 is correlated with cardiac allograft vasculopathy and suppressed in heart transplant recipients on everolimus‐based immunosuppression

Cardiac allograft vasculopathy (CAV) causes heart failure after heart transplantation (HTx), but its pathogenesis is incompletely understood. Notch signaling, possibly modulated by everolimus (EVR), is essential for processes involved in CAV. We hypothesized that circulating Notch ligands would be dysregulated after HTx. We studied circulating delta‐like Notch ligand 1 (DLL1) and periostin (POSTN) and CAV in de novo HTx recipients (n = 70) randomized to standard or EVR‐based, calcineurin inhibitor‐free immunosuppression and in maintenance HTx recipients (n = 41). Compared to healthy controls, plasma DLL1 and POSTN were elevated in de novo (P < .01; P < .001) and maintenance HTx recipients (P < .001; P < .01). Use of EVR was associated with a treatment effect for DLL1. For de novo HTx recipients, a change in DLL1 correlated with a change in CAV at 1 (P = .021) and 3 years (P = .005). In vitro, activation of T cells increased DLL1 secretion, attenuated by EVR. In vitro data suggest that also endothelial cells and vascular smooth muscle cells (VSMCs) could contribute to circulating DLL1. Immunostaining of myocardial specimens showed colocalization of DLL1 with T cells, endothelial cells, and VSMCs. Our findings suggest a role of DLL1 in CAV progression, and that the beneficial effect of EVR on CAV could reflect a suppressive effect on DLL1. Trial registration numbers— SCHEDULE trial: ClinicalTrials.gov NCT01266148; NOCTET trial: ClinicalTrials.gov NCT00377962.     

Increased Mortality and Graft Loss With Kidney Retransplantation Among Human Immunodeficiency Virus (HIV)–Infected Recipients

Excellent outcomes have been demonstrated in primary human immunodeficiency virus (HIV)–positive (HIV+) kidney transplant recipients, but a subset will lose their graft and seek retransplantation (re‐KT). To date, no study has examined outcomes among HIV+ re‐KT recipients. We studied risk for death and graft loss among 4149 (22 HIV+ vs. 4127 HIV‐negative [HIV?]) adult re‐KT recipients reported to the Scientific Registry of Transplant Recipients (SRTR) (2004–2013). Compared to HIV? re‐KT recipients, HIV+ re‐KT recipients were more commonly African American (63.6% vs. 26.7%, p < 0.001), infected with hepatitis C (31.8% vs. 5.0%, p < 0.001) and had longer median time on dialysis (4.8 years vs. 2.1 years, p = 0.02). There were no significant differences in length of time between the primary and re‐KT events by HIV status (1.5 years vs. 1.4 years, p = 0.52). HIV+ re‐KT recipients experienced a 3.11‐fold increased risk of death (adjusted hazard ratio [aHR]: 3.11, 95% confidence interval [CI]: 1.82–5.34, p < 0.001) and a 1.96‐fold increased risk of graft loss (aHR: 1.96, 95% CI: 1.14–3.36, p = 0.01) compared to HIV? re‐KT recipients. Re‐KT among HIV+ recipients was associated with increased risk for mortality and graft loss. Future research is needed to determine if a survival benefit is achieved with re‐KT in this vulnerable population.     

The effect of antiplatelet therapy on survival and cardiac allograft vasculopathy following heart transplantation: A systematic review and meta‐analysis

Cardiac allograft vasculopathy (CAV) is mediated by endothelial inflammation, platelet activation and thrombosis. Antiplatelet therapy may prevent the development of CAV. This systematic review and meta‐analysis summarizes and appraises the evidence on the effect of antiplatelet therapy after heart transplantation (HT). CENTRAL(Ovid), MEDLINE(Ovid), Embase(Ovid) were searched from inception until April 30, 2020. Outcomes included CAV, all‐cause mortality, and CAV‐related mortality. Data were pooled using random‐effects models. Seven observational studies including 2023 patients, mean age 52 years, 22% female, 47% with ischemic cardiomyopathy followed over a mean 7.1 years proved eligible. All studies compared acetylsalicylic acid (ASA) to no treatment and were at serious risk of bias. Data from 1911 patients in 6 studies were pooled in the meta‐analyses. The evidence is very uncertain about the effect of ASA on all‐cause or CAV‐related mortality. ASA may reduce the development of CAV (RR 0.75, 95% CI: 0.44–1.29) based on very low certainty evidence. Two studies that conducted propensity‐weighted analyses showed further reduction in CAV with ASA (HR 0.31, 95% CI: 0.13–0.74). In conclusion, there is limited evidence that ASA may reduce the development of CAV. Definitive resolution of the impact of antiplatelet therapy on CAV and mortality will require randomized clinical trials.     

Center‐Level Experience and Kidney Transplant Outcomes in HIV‐Infected Recipients

Excellent outcomes among HIV+ kidney transplant (KT) recipients have been reported by the NIH consortium, but it is unclear if experience with HIV+ KT is required to achieve these outcomes. We studied associations between experience measures and outcomes in 499 HIV+ recipients (SRTR data 2004–2011). Experience measures examined included: (1) center‐level participation in the NIH consortium; (2) KT experiential learning curve; and (3) transplant era (2004–2007 vs. 2008–2011). There was no difference in outcomes among centers early in their experience (first 5 HIV+ KT) compared to centers having performed > 6 HIV+ KT (GS adjusted hazard ratio [aHR]: 1.05, 95% CI: 0.68–1.61, p = 0.82; PS aHR: 0.93; 95% CI: 0.56–1.53, p = 0.76), and participation in the NIH‐study was not associated with any better outcomes (GS aHR: 1.08, 95% CI: 0.71–1.65, p = 0.71; PS aHR: 1.13; 95% CI: 0.68–1.89, p = 0.63). Transplant era was strongly associated with outcomes; HIV+ KTs performed in 2008–2011 had 38% lower risk of graft loss (aHR: 0.62; 95% CI: 0.42–0.92, p = 0.02) and 41% lower risk of death (aHR: 0.59; 95% CI: 0.39–0.90, p = 0.01) than that in 2004–2007. Outcomes after HIV+ KT have improved over time, but center‐level experience or consortium participation is not necessary to achieve excellent outcomes, supporting continued expansion of HIV+ KT in the US.     

Higher rates of rejection in HIV‐infected kidney transplant recipients on ritonavir‐boosted protease inhibitors: 3‐year follow‐up study

Rejection rates in HIV‐infected kidney transplant (KTx) recipients are higher than HIV‐negative recipients. Immunosuppression and highly active antiretroviral therapy (HAART) protocols vary with potentially significant drug‐drug interactions, likely influencing outcomes. This is an IRB‐approved, single‐center, retrospective study of adult HIV‐infected KTx patients between 5/2009 and 12/2014 with 3‐year follow‐up, excluding antibody‐depleting induction. A total of 42 patients were included; median age was 52 years, 81% male, 50% African American, 29% Hispanic, 17% Caucasian. The most common renal failure etiology was hypertensive nephrosclerosis (50%) with 5.8 median years of pre‐transplant dialysis. All patients received IL‐2 receptor antagonist, were maintained on tacrolimus (76%) or cyclosporine (17%), and 40% received ritonavir‐boosted PI‐based HAART (rtv+) regimen. Patient and graft survival at 3 years were 93% and 90%. At 1‐, 2‐, and 3‐year time points, median serum creatinine was 1.49, 1.35, and 1.67; treated biopsy‐proven rejection was 38%, 38%, and 40.5%; and 92% of episodes were acute rejection. At these time points, rejection rates were significantly higher with boosted PI HAART regimens compared to other HAART regimens, 59% vs 24% (P = 0.029), 59% vs 24% (P = 0.029), and 68% vs 24% (P = 0.01). Despite higher rejection rates, HIV‐infected KTx recipients have reasonable outcomes. Given significantly higher rejection rates using rtv+ regimens, alternative HAART regimens should be considered prior to transplantation.     

Coronary Microvascular Dysfunction Correlates With the New Onset of Cardiac Allograft Vasculopathy in Heart Transplant Patients With Normal Coronary Angiography

Coronary microvascular dysfunction is emerging as a strong predictor of outcome in heart transplantation (HT). We assessed the validity of microvascular dysfunction, defined by means of a reduced coronary flow reserve (CFR), as a factor associated with new onset epicardial cardiac allograft vasculopathy (CAV) or death. We studied 105 patients at 4 ± 1 years post‐HT with a normal coronary angiography (CA). New onset CAV was assessed by CA. CFR was assessed in the left anterior descending (LAD) coronary artery by transthoracic Doppler echocardiography and calculated as the ratio of hyperaemic to basal blood flow velocity. A CFR ≤ 2.5 was considered abnormal. Epicardial CAV onset or death was assessed during a follow‐up of 10 years. New onset CAV was diagnosed in 30 patients (28.6%) (Group A), and the CA was normal in the remaining 75 patients (71.4%) (Group B). Group A had reduced CFR compared with group B (2.4 ± 0.6 vs. 3.2 ± 0.7, p < 0.0001). A CFR ≤ 2.5 was independently associated with a higher probability of new onset CAV (p < 0.0001) and a higher probability of death, regardless of CAV onset (p < 0.01). Microvascular dysfunction is independently associated with the onset of epicardial CAV, and associated with a higher risk of death, regardless of CAV onset.     

Challenges and Clinical Decision‐Making in HIV‐to‐HIV Transplantation: Insights From the HIV Literature

Life expectancy among HIV‐infected (HIV+) individuals has improved dramatically with effective antiretroviral therapy. Consequently, chronic diseases such as end‐stage liver and kidney disease are growing causes of morbidity and mortality. HIV+ individuals can have excellent outcomes after solid organ transplantation, and the need for transplantation in this population is increasing. However, there is a significant organ shortage, and HIV+ individuals experience higher mortality rates on transplant waitlists. In South Africa, the use of organs from HIV+ deceased donors (HIVDD) has been successful, but until recently federal law prohibited this practice in the United States. With the recognition that organs from HIVDD could fill a critical need, the HIV Organ Policy Equity (HOPE) Act was passed in November 2013, reversing the federal ban on the use of HIV+ donors for HIV+ recipients. In translating this policy into practice, the biologic risks of using HIV+ donors need to be carefully considered. In this mini‐review, we explore relevant aspects of HIV virology, antiretroviral treatment, drug resistance, opportunistic infections and HIV‐related organ dysfunction that are critical to a transplant team considering HIV‐to‐HIV transplantation.     

Delayed autologous stem cell transplantation following cardiac transplantation experience in patients with cardiac amyloidosis

This study sought to retrospectively investigate the outcomes of patients with light‐chain amyloidosis (AL) with advanced cardiac involvement who were treated with a strategy of heart transplantation (HT) followed by delayed autologous stem cell transplantation (ASCT) at 1‐year posttransplant. Patients with AL amyloidosis with substantial cardiac involvement have traditionally had very poor survival (eg, several months). A few select centers have reported their outcomes for HT followed by a strategy of early ASCT (ie, 6 months) for CA. The outcomes of patients undergoing a delayed strategy have not been reported. All patients with AL amyloidosis at a single institution undergoing evaluation for HT from 2004‐2018 were included. Retrospective analyses were performed. Sixteen patients underwent HT (including two combined heart‐kidney transplant) for AL amyloidosis. ASCT was performed in a total of nine patients to date at a median 13.5 months (12.8‐32.9 months) post‐HT. Survival was 87.5% at 1 year and 76.6% at 5 years, comparable to institutional outcomes for nonamyloid HT recipients. In addition to these 16 patients, two patients underwent combined heart‐lung transplantation. A strategy of delayed ASCT 1‐year post‐HT for patients with AL amyloidosis is feasible, safe, and associated with comparable outcomes to those undergoing an earlier ASCT strategy.     

Expanding clarity or confusion? Volatility of the 5‐tier ratings assessing quality of transplant centers in the United States

Outcomes of patients receiving solid organ transplants in the United States are systematically aggregated into bi‐annual Program‐Specific Reports (PSRs) detailing risk‐adjusted survival by transplant center. Recently, the Scientific Registry of Transplant Recipients (SRTR) issued 5‐tier ratings evaluating centers based on risk‐adjusted 1‐year graft survival. Our primary aim was to examine the reliability of 5‐tier ratings over time. Using 10 consecutive PSRs for adult kidney transplant centers from June 2012 to December 2016 (n = 208), we applied 5‐tier ratings to center outcomes and evaluated ratings over time. From the baseline period (June 2012), 47% of centers had at least a 1‐unit tier change within 6 months, 66% by 1 year, and 94% by 3 years. Similarly, 46% of centers had at least a 2‐unit tier change by 3 years. In comparison, 15% of centers had a change in the traditional 3‐tier rating at 3 years. The 5‐tier ratings at 4 years had minimal association with baseline rating (Kappa 0.07, 95% confidence interval [CI] ‐0.002 to 0.158). Centers had a median of 3 different 5‐tier ratings over the period (q1 = 2, q3 = 4). Findings were consistent for center volume, transplant rate, and baseline 5‐tier rating. Cumulatively, results suggest that 5‐tier ratings are highly volatile, limiting their utility for informing potential stakeholders, particularly transplant candidates given expected waiting times between wait listing and transplantation.     

Comprehensive Bio‐Imaging Using Myocardial Perfusion Reserve Index During Cardiac Magnetic Resonance Imaging and High‐Sensitive Troponin T for the Prediction of Outcomes in Heart Transplant Recipients

We sought to determine the ability of quantitative myocardial perfusion reserve index (MPRI) by cardiac magnetic resonance (CMR) and high‐sensitive troponin T (hsTnT) for the prediction of cardiac allograft vasculopathy (CAV) and cardiac outcomes in heart transplant (HT) recipients. In 108 consecutive HT recipients (organ age 4.1 ± 4.7 years, 25 [23%] with diabetes mellitus) who underwent cardiac catheterization, CAV grade by International Society for Heart & Lung Transplantation (ISHLT) criteria, MPRI, late gadolinium enhancement (LGE) and hsTnT values were obtained. Outcome data including cardiac death and urgent revascularization (“hard cardiac events”) and revascularization procedures were prospectively collected. During a follow‐up duration of 4.2 ± 1.4 years, seven patients experienced hard cardiac events and 11 patients underwent elective revascularization procedures. By multivariable analysis, hsTnT and MPRI both independently predicted cardiac events, surpassing the value of LGE and CAV by ISHLT criteria. Furthermore, hsTnT and MPRI provided complementary value. Thus, patients with high hsTnT and low MPRI showed the highest rates of cardiac events (annual event rate = 14.5%), while those with low hsTnT and high MPRI exhibited excellent outcomes (annual event rate = 0%). In conclusion, comprehensive “bio‐imaging” using hsTnT, as a marker of myocardial microinjury, and CMR, as a marker of microvascular integrity and myocardial damage by LGE, may aid personalized risk‐stratification in HT recipients.     

Outcomes of Patients Undergoing Combined Heart–Kidney Transplantation With or Without Prior Ventricular Assist Device

BackgroundBoth combined heart–kidney transplantation and ventricular assist devices (VADs) pose significant challenges, including sensitization, immunosuppressive treatment, and infrastructure demands. Despite these challenges, we hypothesized that the recipients of combined heart–kidney transplants with and without VADs would have equivalent survival. We aimed to compare the survival of heart–kidney transplant recipients with and without prior VAD placement.MethodsWe retrospectively analyzed all patients enrolled in the United Network for Organ Sharing database who underwent heart–kidney transplants. We created a matched cohort of patients undergoing heart–kidney transplantation with or without prior VAD using 1:1 nearest propensity-score matching with preoperative variables.ResultsIn the propensity-matched cohort, 399 patients underwent heart–kidney transplantation with prior VAD, and 399 underwent heart–kidney transplantation without prior VAD. The estimated survival of heart-–kidney recipients with prior VAD was 84.8% at one year, 81.2% at 3 years, and 75.3% at 5 years. The estimated survival of heart–kidney recipients without prior VAD was 86.8.7% at one year, 84.0% at 3 years, and 78.8% at 5 years. There was no statistically significant difference in the survival of heart–kidney transplant recipients with or without prior VAD at one year (P = .42; Figure 2), 3 years (P = .34), or 5 years (P = .30).ConclusionDespite the increased challenge of heart–kidney transplantation in recipients with prior VAD, we demonstrated that these patients have similar survival to those who underwent heart–kidney transplantation without previous VAD placement.     

The evolving risk of sudden cardiac death after heart transplant. An analysis of the ISHLT Thoracic Transplant Registry

Sudden cardiac death (SCD) is responsible for ~10% of post‐heart transplant deaths. We conducted a retrospective analysis of the ISHLT registry evaluating the risk of post‐transplant SCD. Adult heart transplant recipients (2004‐2014) surviving the first year were included. We used multivariable multistate competing risk survival analysis to evaluate the impact of history of treated rejection and cardiac allograft vasculopathy (CAV) on SCD risk. We used a probabilistic analytical model and Monte Carlo simulation to estimate the impact of CAV severity and graft dysfunction on SCD. We included 25 242 recipients. During a median follow‐up of 4.7 (2.3‐7.0) years, 582 patients died suddenly. Treated rejection (HR 1.76, 95% CI 1.36‐2.31) and CAV (HR 3.32, 95% CI 2.73‐4.03) were important risk factors for SCD. The estimated SCD risk in patients with severe CAV without and with graft dysfunction was 3.2% (95% CI 2.0‐4.6) and 5.4% (95% CI 3.8‐7.0), respectively, at 2 years from the CAV diagnosis, and 4.9% (95% CI 3.4‐6.5) and 8.0% (95% CI 6.1‐10.0), respectively, in those who also had treated rejection. These results provide evidence that recipients with severe CAV and graft dysfunction or treated rejection are at clinically significant increased SCD risk. The benefit of ICD post‐transplant remains uncertain.     

Retransplant and Medical Therapy for Cardiac Allograft Vasculopathy: International Society for Heart and Lung Transplantation Registry Analysis

Cardiac retransplantation for heart transplant recipients with advanced cardiac allograft vasculopathy (CAV) remains controversial. The International Society for Heart and Lung Transplantation Registry was used to examine survival in adult heart recipients with CAV who were retransplanted (ReTx) or managed medically (MM). Recipients transplanted between 1995 and 2010 who developed CAV and were either retransplanted within 2 years of CAV diagnosis (ReTx) or alive at ≥2 years after CAV diagnosis, managed medically (MM), without retransplant, constituted the study groups. Donor, recipient, transplant characteristics and long‐term survival were compared. The population included 65 patients in ReTx and 4530 in MM. During a median follow‐up of 4 years, there were 24 deaths in ReTx, and 1466 in MM. Survival was comparable at 9 years (55% in ReTx and 51% in MM; p = 0.88). Subgroup comparison suggested survival benefit for retransplant versus MM in patients who developed systolic graft dysfunction. Adjusted predictors for 2‐year mortality were diagnosis of CAV in the early era and longer time since CAV diagnosis following primary transplant. Retransplant was not an independent predictor in the model. Challenges associated with retransplantation as well as improved CAV treatment options support the current consensus recommendation limiting retransplant to highly selected patients with CAV.     

Early steroid withdrawal in HIV-infected kidney transplant recipients: Utilization and outcomes

Kidney transplant (KT) outcomes for HIV-infected (HIV+) persons are excellent, yet acute rejection (AR) is common and optimal immunosuppressive regimens remain unclear. Early steroid withdrawal (ESW) is associated with AR in other populations, but its utilization and impact are unknown in HIV+ KT. Using SRTR, we identified 1225 HIV+ KT recipients between January 1, 2000, and December 31, 2017, without AR, graft failure, or mortality during KT admission, and compared those with ESW with those with steroid continuation (SC). We quantified associations between ESW and AR using multivariable logistic regression and interval-censored survival analysis, as well as with graft failure and mortality using Cox regression, adjusting for donor, recipient, and immunologic factors. ESW utilization was 20.4%, with more zero HLA mismatch (8% vs 4%), living donors (26% vs 20%), and lymphodepleting induction (64% vs 46%) compared to the SC group. ESW utilization varied widely across 129 centers, with less use at high- versus moderate-volume centers (6% vs 21%, P < .001). AR was more common with ESW by 1 year (18.4% vs 12.3%; aOR: _1.081.61_2.41, P = .04) and over the study period (aHR: _1.021.39_1.90, P = .03), without difference in death-censored graft failure (aHR _0.600.91_1.36, P = .33) or mortality (aHR: _0.751.15_1.77, P = .45). To reduce AR after HIV+ KT, tailoring of ESW utilization is reasonable.     

Impact of Protease Inhibitor–Based Anti‐Retroviral Therapy on Outcomes for HIV+ Kidney Transplant Recipients

Excellent outcomes have been demonstrated among select HIV‐positive kidney transplant (KT) recipients with well‐controlled infection, but to date, no national study has explored outcomes among HIV+ KT recipients by antiretroviral therapy (ART) regimen. Intercontinental Marketing Services (IMS) pharmacy fills (1/1/01–10/1/12) were linked with Scientific Registry of Transplant Recipients (SRTR) data. A total of 332 recipients with pre‐ and posttransplantation fills were characterized by ART at the time of transplantation as protease inhibitor (PI) or non–PI‐based ART (88 PI vs. 244 non‐PI). Cox proportional hazards models were adjusted for recipient and donor characteristics. Comparing recipients by ART regimen, there were no significant differences in age, race, or HCV status. Recipients on PI‐based regimens were significantly more likely to have an Estimated Post Transplant Survival (EPTS) score of >20% (70.9% vs. 56.3%, p = 0.02) than those on non‐PI regimens. On adjusted analyses, PI‐based regimens were associated with a 1.8‐fold increased risk of allograft loss (adjusted hazard ratio [aHR] 1.84, 95% confidence interval [CI] 1.22–2.77, p = 0.003), with the greatest risk observed in the first posttransplantation year (aHR 4.48, 95% CI 1.75–11.48, p = 0.002), and a 1.9‐fold increased risk of death as compared to non‐PI regimens (aHR 1.91, 95% CI 1.02–3.59, p = 0.05). These results suggest that whenever possible, recipients should be converted to a non‐PI regimen prior to kidney transplantation.