Identifying Factors Associated with Long-Term Graft Survival Following Heart Transplantation Using Statistics and Machine Learning Methods

2021 ◽  
Author(s):  
◽  
Ahmed Alnajar

Background Social determinants of health (SDH) such as poverty, unequal access to health care, and lack of education have recently been found to contribute to health inequities. In the field of heart transplantation, it is known that patients of color have a higher early mortality risk than white patients, even after taking differences in comorbidities into account. However, the role of SDH in predicting disease patterns and transplant outcomes has not been determined. The purpose of this study was to assess long-term heart transplantation success based on patients' SDH. Methods A retrospective analysis of 34,584 adult heart transplant recipients from 2004 to 2021 was performed using the Organ Procurement and Transplantation Network database. Established and modern SDH indices—including the Agency for Healthcare Research and Quality Index, the Area Deprivation Index, the Social Vulnerability Index , the Social Deprivation Index, and the Crime Risk Index—were evaluated. A survival analysis using the Kaplan-Meier method assessed the indices' association with overall graft survival or failure. A temporal decomposition model was used to identify overlapping phases of graft survival. Multivariable clustered Cox regression, LASSO and random forest models were used to determine the association of these indices with post-transplantation risk of graft failure. Results On average, patients falling into the lower quartile across different SDH indices had a 20% increased risk of graft failure. After accounting for recipient and donor biological factors and comorbidities, recipients' indices remained statistically significant. Individual sociodemographic variables were highly predictive of graft failure across different hazard intervals. Recipients' SDH indices were most predictive throughout the constant and late post-transplantation phases. On the other hand, donor SDH indices were less significant across all intervals. Conclusion To improve survival outcomes, a collaborative effort to counsel and support disadvantaged transplant recipients should be considered.

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Vatsa Dave ◽  
Kevan R. Polkinghorne ◽  
Khai Gene Leong ◽  
John Kanellis ◽  
William R. Mulley

Abstract The evidence supporting an initial mycophenolate mofetil (MMF) dose of 2 g daily in tacrolimus-treated renal transplant recipients is limited. In a non-contemporaneous single-centre cohort study we compared the incidence of leukopaenia, rejection and graft dysfunction in patients initiated on MMF 1.5 g and 2 g daily. Baseline characteristics and tacrolimus trough levels were similar by MMF group. MMF doses became equivalent between groups by 12-months post-transplant, driven by dose reductions in the 2 g group. Leukopaenia occurred in 42.4% of patients by 12-months post-transplant. MMF 2 g was associated with a 1.80-fold increased risk of leukopaenia compared to 1.5 g. Rejection occurred in 44.8% of patients by 12-months post-transplantation. MMF 2 g was associated with half the risk of rejection relative to MMF 1.5 g. Over the first 7-years post-transplantation there was no difference in renal function between groups. Additionally, the development of leukopaenia or rejection did not result in reduced renal function at 7-years post-transplant. Leukopaenia was not associated with an increased incidence of serious infections or rejection. This study demonstrates the initial MMF dose has implications for the incidence of leukopaenia and rejection. Since neither dose produced superior long-term graft function, clinical equipoise remains regarding the optimal initial mycophenolate dose in tacrolimus-treated renal transplant recipients.


Author(s):  
Seung Hwan Song ◽  
Hoon Young Choi ◽  
Ha Yan Kim ◽  
Chung Mo Nam ◽  
Hyeon Joo Jeong ◽  
...  

Abstract Background Bisphosphonates are administered to post-transplantation patients with mineral and bone disorders; however, the association between bisphosphonate therapy and long-term renal graft survival remains unclear. Methods This nested case-control study investigated the effects of bisphosphonates on long-term graft outcomes after kidney transplantation. We enrolled 3,836 kidney transplant recipients treated from April 1979 to June 2016 and matched patients with graft failure to those without (controls). Annual post-transplant bone mineral density assessments were performed, and recipients with osteopenia or osteoporosis received bisphosphonate therapy. The associations between bisphosphonate use, and long-term graft outcomes and graft survival were analyzed using conditional logistic regression and landmark analyses, respectively. Results A landmark analysis demonstrated that the death-censored graft survival was significantly higher in bisphosphonate users than in non-users in the entire cohort (log-rank test, P < .001). In the nested case-control matched cohort, bisphosphonate users had a significantly reduced risk of graft failure than did non-users (odds ratio, 0.38; 95% confidence interval, 0.30–0.48). Bisphosphonate use, increased cumulative duration of bisphosphonate use over one year, and increased cumulative bisphosphonate dose above the first quartile were associated with a reduced risk of graft failure, after adjustments. Conclusions Bisphosphonates may improve long-term graft survival in kidney transplant recipients.


2020 ◽  
Vol 9 (2) ◽  
pp. 440 ◽  
Author(s):  
Edmund J. Gore ◽  
António W. Gomes-Neto ◽  
Lei Wang ◽  
Stephan J. L. Bakker ◽  
Hubert G. M. Niesters ◽  
...  

Following transplantation, patients must take immunosuppressive medication for life. Torquetenovirus (TTV) is thought to be marker for immunosuppression, and TTV–DNA levels after organ transplantation have been investigated, showing high TTV levels, associated with increased risk of infections, and low TTV levels associated with increased risk of rejection. However, this has been investigated in studies with relatively short follow-up periods. We hypothesized that TTV levels can be used to assess long term outcomes after renal transplantation. Serum samples of 666 renal transplant recipients were tested for TTV DNA. Samples were taken at least one year after renal transplantation, when TTV levels are thought to be relatively stable. Patient data was reviewed for graft failure, all-cause mortality and death due to infectious causes. Our data indicates that high TTV levels, sampled more than one year post-transplantation, are associated with all-cause mortality with a hazard ratio (HR) of 1.12 (95% CI, 1.02–1.23) per log10 increase in TTV viral load, (p = 0.02). Additionally, high TTV levels were also associated with death due to infectious causes (HR 1.20 (95% CI 1.01–1.43), p = 0.04). TTV levels decrease in the years following renal transplantation, but remain elevated longer than previously thought. This study shows that TTV level may aid in predicting long-term outcomes, all-cause mortality and death due to an infectious cause in renal transplant patients sampled over one year post-transplantation.


2021 ◽  
Vol 28 (1) ◽  
pp. 661-670
Author(s):  
Lawrence Kasherman ◽  
Jeffrey Doi ◽  
Katherine Karakasis ◽  
Jeffrey Schiff ◽  
Abhijat Kitchlu ◽  
...  

Solid organ transplant recipients on long-term immunosuppressive medication are at increased risk of developing malignancy, and treatment of advanced cancers with angiogenesis inhibitors in this context has not been widely studied. We present a case of recurrent high-grade serous ovarian carcinoma treated with paclitaxel and bevacizumab in the context of prior renal transplantation where the patient responded well to treatment with controlled toxicities, discussing the potential for increased rates of adverse events and drug interactions in this select population.


Antioxidants ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1102
Author(s):  
Angelica Rodriguez-Niño ◽  
Diego O. Pastene ◽  
Adrian Post ◽  
M. Yusof Said ◽  
Antonio W. Gomes-Neto ◽  
...  

Carnosine affords protection against oxidative and carbonyl stress, yet high concentrations of the carnosinase-1 enzyme may limit this. We recently reported that high urinary carnosinase-1 is associated with kidney function decline and albuminuria in patients with chronic kidney disease. We prospectively investigated whether urinary carnosinase-1 is associated with a high risk for development of late graft failure in kidney transplant recipients (KTRs). Carnosine and carnosinase-1 were measured in 24 h urine in a longitudinal cohort of 703 stable KTRs and 257 healthy controls. Cox regression was used to analyze the prospective data. Urinary carnosine excretions were significantly decreased in KTRs (26.5 [IQR 21.4–33.3] µmol/24 h versus 34.8 [IQR 25.6–46.8] µmol/24 h; p < 0.001). In KTRs, high urinary carnosinase-1 concentrations were associated with increased risk of undetectable urinary carnosine (OR 1.24, 95%CI [1.06–1.45]; p = 0.007). During median follow-up for 5.3 [4.5–6.0] years, 84 (12%) KTRs developed graft failure. In Cox regression analyses, high urinary carnosinase-1 excretions were associated with increased risk of graft failure (HR 1.73, 95%CI [1.44–2.08]; p < 0.001) independent of potential confounders. Since urinary carnosine is depleted and urinary carnosinase-1 imparts a higher risk for graft failure in KTRs, future studies determining the potential of carnosine supplementation in these patients are warranted.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Juhan Lee ◽  
Eun Jin Kim ◽  
Jae Geun Lee ◽  
Beom Seok Kim ◽  
Kyu Ha Huh ◽  
...  

AbstractSerum bilirubin, a potent endogenous antioxidant, has been associated with decreased risks of cardiovascular disease, diabetes, and kidney disease. However, the effects of serum bilirubin on kidney transplant outcomes remain undetermined. We analyzed 1628 patients who underwent kidney transplantations between 2003 and 2017. Patients were grouped into sex-specific quartiles according to mean serum bilirubin levels, 3–12 months post-transplantation. Median bilirubin levels were 0.66 mg/dL in males and 0.60 mg/dL in females. The intra-individual variability of serum bilirubin levels was low (9%). Serum bilirubin levels were inversely associated with graft loss, death-censored graft failure, and all-cause mortality, independent of renal function, donor status, and transplant characteristics. Multivariable analysis revealed that the lowest serum bilirubin quartile was associated with increased risk of graft loss (HR 2.64, 95% CI 1.67–4.18, P < 0.001), death-censored graft failure (HR 2.97, 95% CI 1.63–5.42, P < 0.001), and all-cause mortality (HR 2.07, 95% CI 1.01–4.22, P = 0.046). Patients with lower serum bilirubin were also at greater risk of rejection and exhibited consistently lower glomerular filtration rates than those with higher serum bilirubin. Serum bilirubin levels were significantly associated with transplantation outcomes, suggesting that bilirubin could represent a therapeutic target for improving long-term transplant outcomes.


2014 ◽  
Vol 97 (9) ◽  
pp. 925-933 ◽  
Author(s):  
Jeffrey J. Gaynor ◽  
Gaetano Ciancio ◽  
Giselle Guerra ◽  
Junichiro Sageshima ◽  
Lois Hanson ◽  
...  

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S636-S636
Author(s):  
Kyla L Naylor ◽  
Alexandra Ouédraogo ◽  
Sarah E Bota ◽  
Shahid Husain ◽  
J Michael Paterson ◽  
...  

Abstract Background Invasive fungal infection (IFI) in solid-organ transplant (SOT) recipients is associated with significant morbidity and mortality. The long-term probability of post-transplant IFI is poorly understood. Methods We conducted a population-based cohort study using linked administrative healthcare databases from Ontario, Canada to determine the incidence rate, 1-, 5- and 10-year cumulative probability of IFI-related hospitalization, and 1-year post-IFI all-cause mortality in SOT recipients from 2002 to 2016. We also examined post-IFI death-censored graft failure in renal transplant patients. Results We included 9326 SOT recipients (median follow-up 5.35 years). Overall, the incidence of IFI was 8.3 per 1000 person-years (95% confidence interval [CI]: 7.5–9.1). The 1-year cumulative probability of IFI was 7.4% (95% CI: 5.8–9.3%), 5.4% (95% CI: 3.6–8.1%), 1.8% (95% CI: 1.3–2.5%), 1.2% (95% CI: 0.5–3.2%), and 1.1% (95% CI: 0.9–1.4%) for lung, heart, liver, kidney-pancreas, and kidney-only transplant recipients, respectively. Lung transplant recipients had both the highest incidence rate and the highest 10-year probability of IFI: 43.0 per 1,000 person-years (95% CI: 36.8–50.0) and 26.4% (95% CI: 22.4–30.9%), respectively. Lung transplantation was also associated with the highest 1-year cumulative probability of post-IFI all-cause mortality (40.2%,95% CI: 33.1–48.3%). Among kidney transplant recipients, the 1-year probability of death-censored graft failure after IFI was 9.8% (95% CI: 6.0–15.8%). Conclusion The 1-year cumulative probability of IFI varies widely among SOT recipients. Lung transplantation was associated with the highest incidence of IFI with considerable 1-year all-cause mortality. The findings of this study considerably improved our understanding of the long-term probability of post-transplant IFI. Disclosures All authors: No reported disclosures.


Author(s):  
Hilda E. Fernandez ◽  
Bethany J. Foster

Pediatric kidney transplant recipients are distinguished from adult recipients by the need for many decades of graft function, the potential effect of CKD on neurodevelopment, and the changing immune environment of a developing human. The entire life of an individual who receives a transplant as a child is colored by their status as a transplant recipient. Not only must these young recipients negotiate all of the usual challenges of emerging adulthood (transition from school to work, romantic relationships, achieving independence from parents), but they must learn to manage a life-threatening medical condition independently. Regardless of the age at transplantation, graft failure rates are higher during adolescence and young adulthood than at any other age. All pediatric transplant recipients must pass through this high-risk period. Factors contributing to the high graft failure rates in this period include poor adherence to treatment, potentially exacerbated by the transfer of care from pediatric- to adult-oriented care providers, and perhaps an increased potency of the immune response. We describe the characteristics of pediatric kidney transplant recipients, particularly those factors that may influence their care throughout their lives. We also discuss the risks associated with the transition from pediatric- to adult-oriented care and provide some suggestions to optimize transition to adult-oriented transplant care and long-term outcomes.


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