Impact of pretransplant recipient body mass index on post heart transplant mortality: A systematic review and meta‐analysis

The ISHLT's 2016 Guidelines on the selection of heart transplant (HT) candidates recommends weight loss prior to listing for persons with body mass (BMI) index greater than 35 kg/m². We conducted a systematic review to assess the impact of BMI on all‐cause mortality. We searched to identify eligible observational studies that followed HT recipients. We used the GRADE system to quantify absolute effects and quality of evidence, and meta‐analyzed survival curves to assess post‐transplant mortality across BMI categories. We found a significantly increased risk of mortality in patients with BMI > 30 kg/m² across all age categories, independently of transplant era and study source (BMI 30‐34.9: HR 1.10, 95% CI 1.04‐1.17; BMI ≥ 35: HR 1.24, 95% CI 1.12‐1.38). We also found an increased risk of death in underweight (BMI < 18.5 kg/m²) candidates over 39 years of age (Age 40‐65: HR 1.24, 95% CI 1.02‐1.53; Age > 65: HR 1.70, 95% 1.13‐2.57). We found obesity and underweight BMI to be associated with mortality post‐HT. The similar and overlapping increased risk of mortality in patients with BMI 30‐34.9 and BMI ≥ 35 does not support the recently updated ISHLT guidelines. Future evidence in the form of randomized controlled trials is required to assess effectiveness of interventions targeting obesity‐related comorbidities and weight management.     

Development and outcomes of de novo donor‐specific antibodies in low,moderate, and high immunological risk kidney transplant recipients

De novo donor‐specific antibodies (dnDSA) play an important role in antibody‐mediated rejection (ABMR) and graft failure, yet their development in kidney transplant recipients (KTx) of higher immunological risk has not been characterized. We prospectively determined the incidence of dnDSA at 3 and 12 months posttransplant and assessed their associations with outcomes in recipients stratified by low, moderate, and high immunological risk. Adult KTx were screened for DSA pretransplant, months 3 and 12 posttransplant, and when clinically indicated. Outcomes included incidence of dnDSA, death‐censored graft survival (DCGS), and ABMR. Of 371 recipients, 154 (42%) were transplanted across a pretransplant DSA that became undetectable by 12 months posttransplant in 78% of cases. dnDSA were detected in 16% (95% confidence interval [CI]: 12‐20%) by 3 months and 23% (95% CI: 18‐29%) by 12 months posttransplant. Incidence at 12 months was higher in the moderate (30%) and high‐risk groups (29%) compared to the low‐risk group (16%). dnDSA were associated with an increased risk of ABMR (hazard ratio [HR] 2.2; 95% CI: 1.1‐4.4; P = .04) but were not an independent risk factor for DCGS. In conclusion, dnDSA were more frequent in transplant recipients of higher immune risk and associated with an increased risk of ABMR.     

Underweight and obesity increase the risk of mortality after lung transplantation: a systematic review and meta‐analysis

Many studies have found an association between abnormal body mass index (BMI) and poor outcomes among lung transplant recipients. We performed a systematic review and meta‐analysis to identify outcomes associated with an abnormal pretransplant BMI after lung transplantation (LTx). The MEDLINE and EMBASE databases were searched from inception to May 2015 with focus on original observational studies with post‐transplant survival data in candidates with abnormal BMI (underweight, overweight, or obese). We performed meta‐analyses examining survival and primary graft dysfunction after LTx. We identified 866 citations; 13 observational cohort studies involving 40 742 participants met our inclusion criteria for systematic review. Seven of the 13 were included in the meta‐analysis. There was a significant risk of mortality after LTx in candidates with underweight and obesity (underweight versus normal, relative risk [RR] 1.36, 95% confidence interval [CI] 1.11–1.66, I² = 0%; obesity vs. normal, RR 1.90, 95% CI 1.45–2.56, I² = 0%; overweight vs. normal, RR 1.36, 95% CI 1.11–1.66, I² = 0). There was also a significant risk of primary graft dysfunction in obese (RR 1.92, 95% CI 1.39–2.65, I² = 0%) and overweight (RR 1.72, 95% CI, 1.32–2.24, I² = 0%) candidates. Lung transplant candidates who are underweight or obese have a higher risk of post‐transplant mortality than recipients with a normal BMI.     

The impact of wait list body mass index changes on the outcome after liver transplantation

Obesity is associated with poor health outcomes in the general population, but the evidence surrounding the effect of body mass index (BMI) on postliver transplantation survival is contradictory. The aim of this study was to assess the impact of wait list BMI and BMI changes on the outcomes after liver transplantation. Using the Scientific Registry of Transplant Recipients, we compared survival among different BMI categories and examined the impact of wait list BMI changes on post‐transplantation mortality for patients undergoing liver transplantation. Cox proportional hazards multivariate regression was carried out to adjust for confounding factors. Among 38 194 recipients, underweight patients had a poorer survival compared with normal weight (HR = 1.3, 95% CI: 1.13–1.49). Conversely, overweight and mildly obese men experienced better survival rates compared with their lean counterparts (HR = 0.9, 95% CI: 0.84–0.96, and HR = 0.86, 95% CI: 0.79–0.93 respectively). Female patients gaining weight over 18.5 kg/m² while on the wait list showed improving outcomes (HR = 0.46, (95% CI: 0.28–0.76)) compared with those remaining underweight. This study supports the harmful impact of underweight on postliver transplant survival, and highlights the need for a specific monitoring and management of candidates with BMIs close to 18.5 kg/m². Obesity does not constitute an absolute contraindication to liver transplantation.     

Longitudinal profile of circulating T follicular helper lymphocytes parallels anti‐HLA sensitization in renal transplant recipients

Antibody‐mediated rejection is responsible for 30%‐50% of renal graft failures. Differentiation of B cells into antibody‐producing plasmablasts depends on the collaboration of follicular helper T cells (Tfh). We analyzed circulating Tfh (cTfh) in kidney recipients and studied cTfh relationship with anti‐HLA antibody production and graft outcome. cTfh were longitudinally analyzed in a prospective cohort of patients (n = 206), pre‐ and posttransplantation. Clinical data, HLA sensitization, and cTfh function were recorded. Both pretransplant and 6‐month posttransplant cTfh were able to derive IgG‐producing plasmablasts. Pretransplant cTfh was decreased in patients, especially in those who received dialysis. However, these cells were increased in patients with previous allograft or transfusions and in HLA‐sensitized recipients. After transplantation cTfh expanded, significantly more in patients who developed de novo anti‐HLA antibodies than in patients who remained unsensitized. Augmented pretransplant cTfh positively correlated with higher intensity of pretransplant anti‐HLA class I and with de novo anti‐HLA class I and anti‐HLA class II antibodies. Consistently, pretransplantation cTfh were higher in patients who experienced acute rejection (HR = 1.14 [1.04‐1.25]). Thus, we show a role for Tfh in anti‐HLA sensitization and rejection. Multicenter studies with additional patient cohorts are needed to validate these results. Immunosuppressive drugs targeting Tfh could be useful to improve outcomes.     

Association of diagnosed obstructive sleep apnea with kidney transplant outcomes

Obstructive sleep apnea (OSA) is common but underdiagnosed among patients with kidney disease. This study examines whether the diagnosis of OSA in kidney transplant recipients (KTR) affected death, death‐censored graft failure (DCGF), and acute rejection (AR). We analyzed the records of KTR who underwent transplant between 2000 and 2015. A total of 4014 kidney transplants were performed during the study period. Of these, 415 (10.3%) had a diagnosis of pretransplant OSA. Pretransplant OSA was associated with a higher risk of death in unadjusted analyses. After adjustment for potential confounders, pretransplant OSA was not associated with risk of death (HR = 1.04, 95% CI: 0.80‐1.36). Similarly, pretransplant OSA was associated with a slightly higher incidence of DCGF or AR but neither associations were significant (HR: 1.23, 95% CI: 0.85‐1.47 for DCGF; HR 1.10, 95% CI: 0.90‐1.36 for AR). A total of 117 (3.3%) were diagnosed with de novo OSA after transplant. Similar to the pretransplant OSA, unadjusted HR for death was significantly higher in the de novo OSA group (HR: 1.48, 95% CI: 1.19‐1.84); however, after adjustment, de novo OSA was not significantly associated with risk of death (HR: 1.15, 95% CI: 0.92‐1.45). Similarly, DCGF and AR rates were not significantly associated with de novo OSA (HR: 1.10, 95% CI: 0.84‐1.44 for DCGF; HR 1.10, 95% CI: 0.90‐1.33 for AR). Our work did not detect significant associations between OSA and risk of death, graft failure, and rejection but the estimates might be underestimated due to underdiagnosis of OSA.     

Development of an antibody specific to major histocompatibility antigens detectable by flow cytometry after lung transplant is associated with bronchiolitis obliterans syndrome

BACKGROUND: Chronic allograft rejection manifested as bronchiolitis obliterans syndrome (BOS) is the leading cause of late death after lung transplantation. Although increasing evidence suggests an association between anti-human leukocyte antigens (HLA) antibodies and chronic rejection of kidney or heart allografts, the clinical significance of anti-HLA antibodies in lung recipients is less clear, especially in previously unsensitized recipients. The use of flow cytometry based panel reactive antibody (flow-PRA) provides a highly sensitive means to identify the development of de novo anti-HLA antibodies in lung recipients. METHODS: Flow-PRA testing was used to analyze the pre- and posttransplant sera in stable BOS free lung recipients who survived at least 6 months. Patients without prior sensitization as defined by a negative pretransplant flow-PRA were analyzed posttransplant for the presence of anti-HLA antibodies by flow-PRA. A proportional hazards model was used to determine the impact of anti-HLA antibody on BOS risk. RESULTS: Sera from 90 recipients at Duke University with negative pretransplant flow-PRA were tested by flow-PRA at various time points after transplant. Sera from 11% (10/90) of recipients were found to contain anti-HLA antibodies detectable by flow-PRA. Nine patients (90%) developed anti-HLA antibodies specific for donor antigens, and one patient developed anti-HLA class II antibodies, not specific to donor antigens. Among the nine patients with donor antigen specific antibodies, flow-PRA specificity analysis demonstrated eight were specific for class II antigens and one for class I antigens. In a multivariate model that controls for other BOS risk factors, a positive posttransplant flow-PRA was significantly associated with BOS grades 1,2, or 3 (hazard ratios [HR] 3.19; 95% confidence interval [CI]: 1.41-7.12, P=0.005) and BOS grade 2 or 3 (HR 4.08; 95% CI: 1.66-10.04, P=0.002). Four patients with de novo anti-HLA antibodies died during follow-up; all four had BOS. Among BOS patients, the presence of anti-HLA antibodies was associated with a significantly worse survival (P =0.05, log-rank test). CONCLUSIONS: Although uncommon, previously unsensitized lung transplant recipients can develop anti-HLA antibodies to donor class II antigens. The development of de novo anti-HLA antibodies significantly increases the risk for BOS, independent of other posttransplant events. Furthermore, de novo anti-HLA antibodies identify BOS patients with significantly worse survival. Additional studies are needed to determine if class II-directed anti-HLA antibodies contribute mechanistically to the chronic rejection process in lung recipients.     

Is pre‐transplant sensitization against angiotensin II type 1 receptor still a risk factor of graft and patient outcome in kidney transplantation in the anti‐HLA Luminex era? A retrospective study

We aimed to assess the correlation of anti‐angiotensin II type 1 receptor antibodies (anti‐AT1R‐Abs) before transplantation on a multicentric cohort of kidney transplant recipients (2008–2012), under tacrolimus and mycophenolate mofetil (MMF), screened by Luminex technology for anti‐HLA immunization. Anti‐AT1R antibody levels were measured by ELISA in pretransplantation sera of 940 kidney recipients from three French centers of the DIVAT cohort. Multivariable Cox models estimated the association between pretransplant anti‐angiotensin II type 1 receptor antibodies and time to acute rejection episodes (ARE) or time to graft failure. Within our cohort, 387 patients (41.2%) had pretransplant AT1R‐Abs higher than 10 U/ml and only 8% (72/970) greater than 17 U/ml. The cumulative probability of clinically relevant (cr)‐ARE was 22.5% at 1 year post‐transplantation [95% CI (19.9–25.4%)]. The cumulative probability of graft failure and patient death were 10.6% [95% CI (8.4–13.3%)] and 5.7% [95% CI (4.0–8.1%)] at 3 years post‐transplantation, respectively. Multivariate Cox models indicated that pretransplant anti‐AT1R antibody levels higher than 10 U/ml were not significantly independently associated with higher risks of acute rejection episodes [HR = 1.04, 95% CI (0.80–1.35)] nor with risk of graft failure [HR = 0.86, 95% CI (0.56–1.33)]. Our study did not confirm an association between pretransplant anti‐AT1R antibody levels and kidney transplant outcomes.     

The risk of cytomegalovirus infection after treatment of acute rejection in renal transplant recipients

The risk of cytomegalovirus infection (CMV) after rejection treatment is poorly understood. To investigate this, we conducted a case/control (1:2) analysis of adult renal transplant recipients between January 1, 2005 and December 31, 2015, via incidence density sampling and survival analysis. Our objective was to evaluate the association of prior acute rejection with subsequent CMV, including epidemiology and outcomes. There were 2481 eligible renal transplants within the study period and 251 distinct CMV infections. Despite the use of antiviral prophylaxis rejection was a significant risk factor for CMV on unadjusted (HR 1.73 [1.34, 2.24] P < 0.05) and adjusted analysis (HR 1.46 [1.06, 2.04] P < 0.05). When matching cases to controls patients with CMV had significantly more rejection prior to CMV diagnosis (26.7% vs 14.2%, P < 0.01). CMV was associated with a twofold increased risk of prior rejection on unadjusted (OR 1.94, 95%CI: 1.28‐2.96, P < 0.01) and adjusted analysis (OR 2.16, 95% CI: 1.31‐3.58, P < 0.01). Patients with rejection preceding CMV had significantly increased graft loss (HR 2.89, 95% CI: 1.65‐5.09, P < 0.01) and mortality (HR 1.82, 95% CI: 1.12‐4.24, P = 0.03) as compared to those CMV cases without rejection. In conclusion, rejection is a risk factor for CMV infection that appears to persist for 1 year. Preceding rejection events increased risk of graft loss and mortality in CMV patients. Given this, prolonged surveillance monitoring for CMV after rejection may be warranted. Studies are needed investigating optimal monitoring strategies.     

Posttransplant muscle mass measured by urinary creatinine excretion rate predicts long‐term outcomes after liver transplantation

Long‐term survival in orthotopic liver transplant (OLT) recipients remains impaired because of many contributing factors, including a low pretransplant muscle mass (or sarcopenia). However, influence of posttransplant muscle mass on survival is currently unknown. We hypothesized that posttransplant urinary creatinine excretion rate (CER), an established noninvasive marker of total body muscle mass, is associated with long‐term survival after OLT. In a single‐center cohort study of 382 adult OLT recipients, mean ± standard deviation CER at 1 year posttransplantation was 13.3 ± 3.7 mmol/24 h in men and 9.4 ± 2.6 mmol/24 h in women. During median follow‐up for 9.8 y (interquartile range 6.4‐15.0 y), 104 (27.2%) OLT recipients died and 44 (11.5%) developed graft failure. In Cox regression analyses, as continuous variable, low CER was associated with increased risk for mortality (HR = 0.43, 95% CI: 0.26‐0.71, P = .001) and graft failure (HR = 0.42, 95% CI: 0.20‐0.90, P = .03), independent of age, sex, and body surface area. Similarly, OLT recipients in the lowest tertile had an increased risk for mortality (HR = 2.69; 95% CI: 1.47‐4.91, P = .001) and graft failure (HR = 2.77, 95% CI: 1.04‐7.39, P = .04), compared to OLT recipients in the highest tertile. We conclude that 1 year posttransplant low total body muscle mass is associated with long‐term risk of mortality and graft failure in OLT recipients.     

Pretransplant Numbers of CD16+ Monocytes as a Novel Biomarker to Predict Acute Rejection After Kidney Transplantation: A Pilot Study

Acute rejection is one of the major immunological determinants of kidney graft function and survival. Early biomarkers to predict rejection are lacking. Emerging evidence reveals a crucial role for the monocyte/macrophage lineage cells in the pathogenesis of rejection. We hypothesized that higher pretransplant numbers of proinflammatory CD16+ monocytes can predict rejection. The study cohort consisted of 104 kidney transplant recipients (58 with no rejection and 46 with biopsy‐proven rejection) and 33 healthy persons. Posttransplant median follow‐up time was 14.7 mo (interquartile range 0.3–34 mo). Pretransplantation blood samples were analyzed by flow cytometry for monocyte immunophenotypes. Groups were compared by Cox regression models for the occurrence of acute rejection. We documented a significantly increased absolute number of pretransplant CD16+ monocytes in patients who developed biopsy‐proven rejection after transplantation compared with those with no rejection (hazard ratio [HR] 1.60, 95% CI 1.28–2.00, p < 0.001) and healthy persons (HR 1.47, 95% CI 1.18–1.82, p < 0.001). In parallel, significantly fewer absolute numbers of CD16? monocytes were observed at pretransplant time points in rejectors versus nonrejectors (HR 0.74, 95% CI 0.58–0.94, p < 0,014). A higher pretransplant number of CD16+ monocytes is significantly associated with a higher risk of acute rejection after kidney transplantation.     

Comparison of Outcomes in Patients Undergoing Renal Transplantation With Impaired vs Normal Left Ventricular Ejection Fraction

BackgroundRenal transplantation improves long-term outcomes in patients with end-stage renal disease (ESRD); however, patients with impaired left ventricular ejection fraction (LVEF) are less likely to be selected for renal transplantation. We sought to evaluate the effect of renal transplantation in this population.MethodsWe retrospectively evaluated 181 patients who underwent renal transplantation between 2011 and 2016. For patients with pretransplant LVEF <50% (cohort 1) and ≥50% (cohort 2), we evaluated the effect of renal transplantation on LVEF, graft failure, and mortality.ResultsCohort 1 comprised 24 patients (mean age, 47 years; pretransplant LVEF 38%). Cohort 2 comprised 157 patients (mean age, 53 years; pretransplant LVEF 64%). Forty-six percent of cohort 1 experienced significant improvement in LVEF posttransplant, with mean LVEF improvement from 38% to 66%. There was no significant association between pretransplant LVEF and graft failure (hazard ratio [HR] = 2.7; 95% confidence interval [CI], 0.6-11.4; P = .1) or mortality (HR = 1.02; 95% CI, 0.3-3.6; P = .9). Coronary artery disease predicted mortality (HR = 3.12; 95% CI, 1.2-8.4; P = .02). Older age trended toward higher mortality (HR = 1.04; 95% CI, 1.0-1.1; P = .05). Younger age predicted graft failure (HR = 0.96; 95% CI, 0.8-0.9; P = .02).ConclusionsIn patients with ESRD undergoing renal transplantation, there was no significant association between pretransplant LVEF and mortality or graft failure, suggesting that patients with ESRD with impaired LVEF can experience positive posttransplant outcomes.     

Induction immunosuppression agents as risk factors for incident cardiovascular events and mortality after kidney transplantation

Low T cell counts and acute rejection are associated with increased cardiovascular events (CVEs); T cell–depleting agents decrease both. Thus, we aimed to characterize the risk of CVEs by using an induction agent used in kidney transplant recipients. We conducted a secondary data analysis of patients who received a kidney transplant and used Medicare as their primary insurance from 1999 to 2010. Outcomes of interest were incident CVE, all‐cause mortality, CVE‐related mortality, and a composite outcome of mortality and CVE. Of 47 258 recipients, 29.3% received IL‐2 receptor antagonist (IL‐2RA), 33.3% received anti‐thymocyte globulin (ATG), 7.3% received alemtuzumab, and 30.0% received no induction. Compared with IL‐2RA, there was no difference in the risk of CVE in the ATG (adjusted hazard ratio [aHR] 0.98, 95% confidence interval [CI] 0.92‐1.05) and alemtuzumab group (aHR 1.01, 95% CI 0.89‐1.16), but slightly higher in the no induction group (aHR 1.06, 95% CI 1.00‐1.14). Acute rejection did not modify this association in the latter group but did increase CVE by 46% in the alemtuzumab group. There was no difference in the hazard of all‐cause or CVE‐related mortality. Only in the ATG group, a 7% lower hazard of the composite outcome of mortality and CVE was noted. Induction agents are not associated with incident CVE, although prospective trials are needed to determine a personalized approach to prevention.     

Clinical outcomes in kidney transplant recipients receiving long-term therapy with inhibitors of the mammalian target of rapamycin

Inhibitors of the mammalian target of rapamycin (mTOR), sirolimus and everolimus, reduce the incidence of acute rejection following kidney transplantation, but their impact on clinical outcomes beyond 2 years after transplantation is unknown. We examined risks of mortality and allograft loss in a prospective observational study of 993 prevalent kidney transplant recipients who enrolled a median of 72 months after transplantation. During a median follow-up of 37 months, 87 patients died and 102 suffered allograft loss. In the overall population, use of mTOR inhibitors at enrollment was not associated with altered risk of allograft loss, and their association with increased mortality was of borderline significance. However, history of malignancy was the strongest predictor of both mortality and therapy with an mTOR inhibitor. Among patients without a history of malignancy, use of mTOR inhibitors was associated with significantly increased risk of mortality in propensity score-adjusted (hazard ratio [HR] 2.6; 95% CI, 1.2, 5.5; p = 0.01), multivariable-adjusted (HR 3.2; 95% CI, 1.5, 6.5; p = 0.002) and one-to-one propensity score-matched analyses (HR 5.6; 95% CI 1.2, 25.7; p = 0.03). Additional studies are needed to examine the long-term safety of mTOR inhibitors in kidney transplantation, especially among recipients without a history of malignancy.     

Recipient body mass index and age interact to impact survival after heart transplantation

Although recipient body mass index (BMI) and age are known risk factors for mortality after heart transplantation, how they interact to influence survival is unknown. Our study utilized the UNOS registry from 1997 to 2012 to define the interaction between BMI and age and its impact on survival after heart transplantation. Recipients were stratified by BMI: underweight (<18.5), normal weight (18.5–24.99), overweight (25–29.99), and either moderate (30–34.99), severe (35–39.99), or very severe (≥40) obesity. Recipients were secondarily stratified based on age: 18–40 (younger recipients), 40–65 (reference group), and ≥65 (advanced age recipients). Among younger recipients, being underweight was associated with improved adjusted survival (HR 0.902; p = 0.010) while higher mortality was seen in younger overweight recipients (HR 1.260; p = 0.005). However, no differences in adjusted survival were appreciated in underweight and overweight advanced age recipients. Obesity (BMI ≥ 30) was associated with increased adjusted mortality in normal age recipients (HR 1.152; p = 0.021) and even more so with young (HR 1.576; p < 0.001) and advanced age recipients (HR 1.292; p = 0.001). These results demonstrate that BMI and age interact to impact survival as age modifies BMI–mortality curves, particularly with younger and advanced age recipients.     

Impact of Obesity on Postoperative and Long-term Outcomes in a General Surgery Population: A Retrospective Cohort Study

Background

The obesity paradox has been demonstrated postoperatively in several surgical populations, but only a few studies have reported long-term survival. This study evaluates the presence of the obesity paradox in a general surgery population, reporting both postoperative and long-term survival.

Methods

This retrospective study included 10,427 patients scheduled for elective, noncardiac surgery. Patients were classified as underweight (body mass index (BMI) < 18.5 kg/m²); normal weight (BMI 18.5–24.9 kg/m²); overweight (BMI 25.0–29.9 kg/m²); obesity class I (BMI 30.0–34.9 kg/m²); obesity class II (BMI 35.0–39.9 kg/m²); and obesity class III (BMI ≥ 40.0 kg/m²). Study endpoints were 30-day postoperative and long-term mortality, including cause-specific mortality. Multivariable analyses were used to evaluate mortality risks for each BMI category.

Results

Within 30 days after surgery, 353 (3.4 %) patients died. Overweight was the only category associated with postoperative mortality, showing improved survival [odds ratio 0.7; 95 % confidence interval (CI) 0.6–0.9]. During the long-term follow-up 4,884 (47 %) patients died. Underweight patients had the highest mortality risk [hazard ratio (HR) 1.4; 95 % CI 1.2–1.6), particularly due to high cancer-related deaths. In contrast, overweight and obese patients demonstrated improved survival (overweight: HR 0.8, 95 % CI 0.8–0.9; obesity class I: HR 0.7, 95 % CI 0.7–0.8; obesity class II: HR 0.7, 95 % CI 0.6–0.9; obesity class III: HR 0.7, 95 % CI 0.5–1.0), mainly because of a strongly reduced risk of cancer-related death.

Conclusions

In this surgical population the obesity paradox was validated at the long term, mainly because of decreased cancer-related deaths among obese patients.     

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.     

Neutropenia in kidney and liver transplant recipients: Risk factors and outcomes

No studies have directly compared the key characteristics and outcomes of kidney (KTx) and liver transplantation (LTx) recipients with neutropenia. In this single‐center, retrospective, cohort study, we enrolled all adult patients who received a KTx or LTx between 2000 and 2011. Neutropenia was defined as 2 consecutive absolute neutrophil count (ANC) values <1500/mm³ in patients without preexisting neutropenia. The first neutropenia episode occurring during the first year post‐transplantation was analyzed. A total of 663 patients with KTx and 354 patients with LTx met the inclusion criteria. Incidence of neutropenia was 20% in KTx and 38% in LTx, respectively. High‐risk CMV status and valganciclovir (VGCV) use were significant predictors of neutropenia for KTx recipients, but only VGCV use vs nonuse in LTx recipients. Neutropenia was associated with worse survival in KTx recipients (adjusted HR 1.95, 95% CI 1.18‐3.22, P<.01), but not in LTx recipients (adjusted HR 0.75, 95% CI 0.52‐1.10, P=.15). Sixteen acute rejection episodes were associated with preceding neutropenia in KTx recipients (HR 1.77, 95% CI 1.16‐2.68, P=.007) and 24 acute rejection episodes in LTx recipients (HR 1.41, 95% CI 0.97‐2.04, P=.07). Incidence of infection was similar in patients with and without neutropenia among KTx and LTx recipients.     

Impact of pretransplant donor‐specific antibodies on kidney allograft recipients with negative flow cytometry cross‐matches

The Luminex test can detect low levels of donor‐specific antibody (DSA) that cannot be detected by flow‐cytometric cross‐matching (FCXM) in kidney transplantation (KT). This study evaluated the impact of DSA on clinical outcomes in KT recipients negative on FCXM. Of 575 consecutive patients who underwent living donor KT between January 2013 and July 2016, 494 (85.9%) were DSA‐negative and 81 (14.1%) were DSA‐positive. Although rates of acute cellular rejection (ACR) at 1 year were similar in the 2 groups (P = .54), the incidence of antibody‐mediated rejection (ABMR) was significantly higher in the DSA‐positive group (P < .01). There was no statistically significant association between rejection‐free graft survival (RFGS) rates and pretransplant class I DSA. However, evaluation of pretransplant class II DSA showed that RFGS rates were significantly lower in patients with mean fluorescence intensity (MFI) >3000 than in patients with DSA‐negative (P < .01). On multivariate analyses, class II DSA MFI ≥5000 was a significant risk factor for acute rejection (hazard ratio, 7.48; P < .01). These findings suggested that pretransplant DSA alone did not affect graft survival in KT recipients without desensitization. However, class II DSA MFI >5000 was an independent predictor of acute rejection in DSA‐positive patients.     

Outcomes of Steroid‐Avoidance Protocols in Pediatric Kidney Transplant Recipients

Advances in immunosuppression have facilitated increased use of steroid‐avoidance protocols in pediatric kidney transplantation. To evaluate such steroid avoidance, a retrospective cohort analysis of pediatric kidney transplant recipients between 2002 and 2009 in the United Network for Organ Sharing database was performed. Outcomes (acute rejection and graft loss) in steroid‐based and steroid‐avoidance protocols were assessed in 4627 children who received tacrolimus and mycophenolate immunosuppression and did not have multiorgan transplants. Compared to steroid‐based protocols, steroid avoidance was associated with decreased risk of acute rejection at 6 months posttransplant (8.3% vs. 10.9%, p = 0.02) and improved 5‐year graft survival (84% vs. 78%, p < 0.001). However, patients not receiving steroids experienced less delayed graft function (p = 0.01) and pretransplant dialysis, were less likely to be African‐American and more frequently received a first transplant from a living donor (all p < 0.001). In multivariate analysis, steroid avoidance trended toward decreased acute rejection at 6 months, but this no longer reached statistical significance, and there was no association of steroid avoidance with graft loss. We conclude that, in clinical practice, steroid avoidance appears safe with regard to graft rejection and loss in pediatric kidney transplant recipients at lower immunologic risk.