Plasma Vitamin C and Cancer Mortality in Kidney Transplant Recipients

There is a changing trend in mortality causes in kidney transplant recipients (KTR), with a decline in deaths due to cardiovascular causes along with a relative increase in cancer mortality rates. Vitamin C, a well-known antioxidant with anti-inflammatory and immune system enhancement properties, could offer protection against cancer. We aimed to investigate the association of plasma vitamin C with long-term cancer mortality in a cohort of stable outpatient KTR without history of malignancies other than cured skin cancer. Primary and secondary endpoints were cancer and cardiovascular mortality, respectively. We included 598 KTR (mean age 51 ± 12 years old, 55% male). Mean (SD) plasma vitamin C was 44 ± 20 μmol/L. At a median follow-up of 7.0 (IQR, 6.2–7.5) years, 131 patients died, of which 24% deaths were due to cancer. In Cox proportional hazards regression analyses, vitamin C was inversely associated with cancer mortality (HR 0.50; 95%CI 0.34–0.74; p < 0.001), independent of potential confounders, including age, smoking status and immunosuppressive therapy. In secondary analyses, vitamin C was not associated with cardiovascular mortality (HR 1.16; 95%CI 0.83–1.62; p = 0.40). In conclusion, plasma vitamin C is inversely associated with cancer mortality risk in KTR. These findings underscore that relatively low circulating plasma vitamin C may be a meaningful as yet overlooked modifiable risk factor of cancer mortality in KTR.

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Physical activity and risk of cardiovascular events and all-cause mortality among kidney transplant recipients

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfaa038 ◽

2020 ◽

Vol 35 (8) ◽

pp. 1436-1443

Author(s):

Augustine W Kang ◽

Andrew G Bostom ◽

Hongseok Kim ◽

Charles B Eaton ◽

Reginald Gohh ◽

...

Keyword(s):

Physical Activity ◽

Kidney Transplant ◽

Proportional Hazards ◽

Controlled Trial ◽

Cox Proportional Hazards ◽

Transplant Recipients ◽

Kidney Transplant Recipients ◽

Cvd Risk ◽

All Cause Mortality ◽

Cvd Mortality

Abstract Background Insufficient physical activity (PA) may increase the risk of all-cause mortality and cardiovascular disease (CVD) morbidity and mortality among kidney transplant recipients (KTRs), but limited research is available. We examine the relationship between PA and the development of CVD events, CVD death and all-cause mortality among KTRs. Methods A total of 3050 KTRs enrolled in an international homocysteine-lowering randomized controlled trial were examined (38% female; mean age 51.8 ± 9.4 years; 75% white; 20% with prevalent CVD). PA was measured at baseline using a modified Yale Physical Activity Survey, divided into tertiles (T1, T2 and T3) from lowest to highest PA. Kaplan–Meier survival curves were used to graph the risk of events; Cox proportional hazards regression models examined the association of baseline PA levels with CVD events (e.g. stroke, myocardial infarction), CVD mortality and all-cause mortality over time. Results Participants were followed up to 2500 days (mean 3.7 ± 1.6 years). The cohort experienced 426 CVD events and 357 deaths. Fully adjusted models revealed that, compared to the lowest tertile of PA, the highest tertile experienced a significantly lower risk of CVD events {hazard ratio [HR] 0.76 [95% confidence interval (CI) 0.59–0.98]}, CVD mortality [HR 0.58 (95% CI 0.35–0.96)] and all-cause mortality [HR 0.76 (95% CI 0.59–0.98)]. Results were similar in unadjusted models. Conclusions PA was associated with a reduced risk of CVD events and all-cause mortality among KTRs. These observed associations in a large, international sample, even when controlling for traditional CVD risk factors, indicate the potential importance of PA in reducing CVD and death among KTRs.

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Renin-Angiotensin System Blockers and the Risk of COVID-19-Related Mortality in Patients with Kidney Failure

Clinical Journal of the American Society of Nephrology ◽

10.2215/cjn.18961220 ◽

2021 ◽

pp. CJN.18961220

Author(s):

Maria Jose Soler ◽

Marlies Noordzij ◽

Daniel Abramowicz ◽

Gabriel de Arriba ◽

Carlo Basile ◽

...

Keyword(s):

Kidney Transplant ◽

Mortality Risk ◽

Kidney Failure ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

Transplant Recipients ◽

Angiotensin Ii Receptor ◽

Kidney Transplant Recipients ◽

Dialysis Patients ◽

Converting Enzyme Inhibitors

Background: There is concern about potential deleterious effects of angiotensin-converting enzyme inhibitors (ACEi) and angiotensin II receptor blockers (ARB) in patients with COVID-19. Patients with kidney failure, who often use ACEi/ARB, are at higher risk of more severe COVID-19. However, there are no data available on the association of ACEi/ARB use with COVID-19 severity in this population. Methods: Data were retrieved from the ERACODA database of kidney transplant and dialysis patients affected by COVID-19, between February 1 and October 1 2020, and had information on 28-day mortality. Cox proportional-hazards regression was used to calculate hazard ratios (HRs) for the relation between ACEi/ARB use and 28-day mortality risk. Additionally, we studied the association of ACEi/ARB discontinuation with 28-day mortality. Results: We evaluated 1,511 patients, 459 kidney transplant recipients and 1,052 dialysis patients. At COVID-19 diagnosis, 189 (41%) of the transplant and 288 (27%) of the dialysis patients were on ACEi/ARB. In transplant, 88 (19%) and in dialysis patients 244 (23%) died within 28 days of initial presentation. In transplant and dialysis patients, there was no association between ACEi/ARB use and 28-day mortality in both crude and adjusted models (adjusted HR=1.12, 95%CI: 0.69-1.83 in transplant; 1.04, 95%CI: 0.73-1.47 in dialysis patients). Among transplant recipients, ACEi/ARB discontinuation was associated with higher mortality risk after adjustment for demographics and comorbidities, but the association was no longer statistically significant after adjustment for COVID-19 severity (adjusted HR=1.36, 95%CI: 0.40-4.58). Among dialysis patients, ACEi/ARB discontinuation was not associated with mortality in any model. Similar results were obtained across subgroups when ACEi and ARB were studied separately and when other outcomes for COVID-19 severity were studied e.g., hospital admission, intensive care unit admission or need for ventilator support. Conclusions: Amongst kidney transplant and dialysis patients with COVID-19, there was no significant association of ACEi/ARB use or ACEi/ARB discontinuation with mortality.

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Plasma Vitamin C and Risk of Late Graft Failure in Kidney Transplant Recipients: Results of the TransplantLines Biobank and Cohort Study

Antioxidants ◽

10.3390/antiox10050631 ◽

2021 ◽

Vol 10 (5) ◽

pp. 631

Author(s):

Camilo G. Sotomayor ◽

Nicolas I. Bustos ◽

Manuela Yepes-Calderon ◽

Diego Arauna ◽

Martin H. de Borst ◽

...

Keyword(s):

Cohort Study ◽

Vitamin C ◽

Kidney Transplant ◽

Graft Failure ◽

Cox Regression ◽

Plasma Vitamin ◽

Kidney Graft ◽

Transplant Recipients ◽

Kidney Transplant Recipients ◽

Risk Of Death

Recent studies have shown that depletion of vitamin C is frequent in outpatient kidney transplant recipients (KTR) and that vitamin C is inversely associated with risk of death. Whether plasma vitamin C is associated with death-censored kidney graft failure remains unknown. We investigated KTR who participated in the TransplantLines Insulin Resistance and Inflammation Biobank and Cohort Study. The primary outcome was graft failure (restart of dialysis or re-transplantation). Overall and stratified (pinteraction < 0.1) multivariable-adjusted Cox regression analyses are presented here. Among 598 KTR (age 51 ± 12 years-old; 55% males), baseline median (IQR) plasma vitamin C was 44.0 (31.0–55.3) µmol/L. Through a median follow-up of 9.5 (IQR, 6.3‒10.2) years, 75 KTR developed graft failure (34, 26, and 15 events over increasing tertiles of vitamin C, log-rank p < 0.001). Plasma vitamin C was inversely associated with risk of graft failure (HR per 1–SD increment, 0.69; 95% CI 0.54–0.89; p = 0.004), particularly among KTR with triglycerides ≥1.9 mmol/L (HR 0.46; 95% CI 0.30–0.70; p < 0.001; pinteraction = 0.01) and among KTR with HDL cholesterol ≥0.91 mmol/L (HR 0.56; 95% CI 0.38–0.84; p = 0.01; pinteraction = 0.04). These findings remained materially unchanged in multivariable-adjusted analyses (donor, recipient, and transplant characteristics, including estimated glomerular filtration rate and proteinuria), were consistent in categorical analyses according to tertiles of plasma vitamin C, and robust after exclusion of outliers. Plasma vitamin C in outpatient KTR is inversely associated with risk of late graft failure. Whether plasma vitamin C‒targeted therapeutic strategies represent novel opportunities to ease important burden of graft failure necessitates further studies.

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FC 028COVID-19 RELATED MORTALITY IN KIDNEY TRANSPLANT AND DIALYSIS PATIENTS: A COMPARATIVE, PROSPECTIVE REGISTRY BASED STUDY

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfab145.004 ◽

2021 ◽

Vol 36 (Supplement_1) ◽

Author(s):

Alexandre Candellier ◽

Eric Jean Goffin ◽

Priya Vart ◽

Marlies Noordzij ◽

Miha Arnol ◽

...

Keyword(s):

Kidney Transplantation ◽

Replacement Therapy ◽

Kidney Transplant ◽

Hemodialysis Patients ◽

Cox Proportional Hazards ◽

Elderly Subjects ◽

Transplant Recipients ◽

Kidney Transplant Recipients ◽

Kidney Replacement Therapy ◽

Adjusted Model

Abstract Background and Aims Studies examining kidney failure patients with COVID-19 reported higher mortality in hemodialysis patients than in kidney transplant recipients. However, hemodialysis patients are often older and have more comorbidities. This study investigated the association of type of kidney replacement therapy with COVID-19 severity adjusting for differences in characteristics. Method Data were retrieved from the European Renal Association COVID-19 Database (ERACODA), which includes kidney replacement therapy patients diagnosed with COVID-19 from all over Europe. We included all kidney transplant recipients and hemodialysis patients who presented between February 1st and December 1st 2020 and had complete information reason for COVID-19 screening and vital status at day 28. The diagnosis of COVID-19 was made based on a PCR of a nasal or pharyngeal swab specimens and/or COVID-19 compatible findings on a lung CT scan. The association of kidney transplantation or hemodialysis with 28-day mortality was examined using Cox proportional-hazards regression models adjusted for age, sex, frailty and comorbidities. Additionally, this association was investigated in the subsets of patients that were screened because of symptoms or have had routine screening. Results A total of 1,670 patients (496 functional kidney transplant recipients and 1,174 hemodialysis patients) were examined. 16.9% of kidney transplant recipients and 23.9% of hemodialysis patients died within 28 days of presentation. In an unadjusted model, the risk of 28-day mortality was 33% lower in kidney transplant recipients compared with hemodialysis patients (hazard ratio (HR): 0.67, 95% CI: 0.52, 0.85). However, in an age, sex and frailty adjusted model, the risk of 28-day mortality was 29% higher in kidney transplant recipients (HR=1.29, 95% CI: 1.00, 1.68), whereas in a fully adjusted model the risk was even 43% higher (HR=1.43, 95% CI: 1.06, 1.93). This association in patients who were screened because of symptoms (n=1,145) was similar (fully adjusted model HR=1.46, 95% CI: 1.05, 2.04). Results were similar when other endpoints were studied (e.g. risk for hospitalization, ICU admission or mortality beyond 28 days) as well as across subgroups. Only age was found to interact significantly, suggesting that the increased mortality risk associated with kidney transplantation was especially present in elderly subjects. Conclusion In this study, kidney transplant recipients had a greater risk of a more severe course of COVID-19 compared with hemodialysis patients when adjusted for age, sex and comorbidities.

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Circulating Advanced Glycation Endproducts and Long-Term Risk of Cardiovascular Mortality in Kidney Transplant Recipients

Clinical Journal of the American Society of Nephrology ◽

10.2215/cjn.00540119 ◽

2019 ◽

Vol 14 (10) ◽

pp. 1512-1520

Author(s):

Camilo G. Sotomayor ◽

António W. Gomes-Neto ◽

Marco van Londen ◽

Rijk O. B. Gans ◽

Ilja M. Nolte ◽

...

Keyword(s):

Confidence Interval ◽

Kidney Transplant ◽

Cardiovascular Mortality ◽

Advanced Glycation Endproducts ◽

Hazard Ratio ◽

Transplant Recipients ◽

Kidney Transplant Recipients ◽

Advanced Glycation ◽

Mediation Analyses ◽

Glycation Endproducts

Background and objectivesIn kidney transplant recipients, elevated circulating advanced glycation endproducts (AGEs) are the result of increased formation and decreased kidney clearance. AGEs trigger several intracellular mechanisms that ultimately yield excess cardiovascular disease. We hypothesized that, in stable kidney transplant recipients, circulating AGEs are associated with long-term risk of cardiovascular mortality, and that such a relationship is mediated by inflammatory, oxidative stress, and endothelial dysfunction biomarkers.Design, setting, participants, & measurementsProspective cohort study of stable kidney transplant recipients recruited between 2001 and 2003 in a university setting. We performed multivariable-adjusted Cox regression analyses to assess the association of AGEs (i.e., Nε-[Carboxymethyl]lysine (CML) and Nε-[Carboxyethyl]lysine (CEL), measured by tandem mass spectrometry) with cardiovascular mortality. Mediation analyses were performed according to Preacher and Hayes’s procedure.ResultsWe included 555 kidney transplant recipients (age 51±12 years, 56% men). During a median follow-up of 6.9 years, 122 kidney transplant recipients died (52% deaths were due to cardiovascular causes). CML and CEL concentrations were directly associated with cardiovascular mortality (respectively, hazard ratio, 1.55; 95% confidence interval, 1.24 to 1.95; P<0.001; and hazard ratio, 1.53; 95% confidence interval 1.18 to 1.98; P=0.002), independent of age, diabetes, smoking status, body mass index, eGFR and proteinuria. Further adjustments, including cardiovascular history, did not materially change these findings. In mediation analyses, free thiol groups and soluble vascular cell adhesion molecule-1 consistently explained approximately 35% of the association of CML and CEL with cardiovascular mortality.ConclusionsIn stable kidney transplant recipients, circulating levels of AGEs are independently associated with long-term risk of cardiovascular mortality.PodcastThis article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2019_09_17_CJN00540119.mp3

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Infection and Malignancy Outweigh Cardiovascular Mortality in Kidney Transplant Recipients: Post Hoc Analysis of the FAVORIT Trial

The American Journal of Medicine ◽

10.1016/j.amjmed.2017.08.038 ◽

2018 ◽

Vol 131 (2) ◽

pp. 165-172 ◽

Cited By ~ 15

Author(s):

Larry A. Weinrauch ◽

John A. D'Elia ◽

Matthew R. Weir ◽

Suphamai Bunnapradist ◽

Peter V. Finn ◽

...

Keyword(s):

Kidney Transplant ◽

Cardiovascular Mortality ◽

Transplant Recipients ◽

Kidney Transplant Recipients ◽

Post Hoc Analysis ◽

Post Hoc

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Coffee consumption and mortality in three Eastern European countries: results from the HAPIEE (Health, Alcohol and Psychosocial factors In Eastern Europe) study

Public Health Nutrition ◽

10.1017/s1368980016001749 ◽

2016 ◽

Vol 20 (1) ◽

pp. 82-91 ◽

Cited By ~ 14

Author(s):

Giuseppe Grosso ◽

Urszula Stepaniak ◽

Agnieszka Micek ◽

Denes Stefler ◽

Martin Bobak ◽

...

Keyword(s):

Cancer Mortality ◽

Alcohol Intake ◽

Proportional Hazards ◽

Smoking Status ◽

Coffee Consumption ◽

Cox Proportional Hazards ◽

Similar Amount ◽

Cox Proportional Hazards Models ◽

Eastern European Countries ◽

Moderate Alcohol Intake

AbstractObjectiveTo test the association between coffee consumption and risk of all-cause, CVD and cancer death in a European cohort.DesignProspective cohort study. Cox proportional hazards models with adjustment for potential confounders to estimate multivariable hazard ratios (HR) and 95 % CI were used.SettingCzech Republic, Russia and Poland.SubjectsA total of 28561 individuals followed for 6·1 years.ResultsA total of 2121 deaths (43·1 % CVD and 35·7 % cancer mortality) occurred during the follow-up. Consumption of 3–4 cups coffee/d was associated with lower mortality risk in men (HR=0·83; 95 % CI 0·71, 0·99) and women (HR=0·63; 95 % CI 0·47, 0·84), while further intake showed non-significant reduced risk estimates (HR=0·71; 95 % CI 0·49, 1·04 and HR=0·51; 95 % CI 0·24, 1·10 in men and women, respectively). Decreased risk of CVD mortality was also found in men (HR=0·71; 95 % CI 0·54, 0·93) for consumption of 3–4 cups coffee/d. Stratified analysis revealed that consumption of a similar amount of coffee was associated with decreased risk of all-cause (HR=0·61; 95 % CI 0·43, 0·87) and cancer mortality (HR=0·59; 95 % CI 0·35, 0·99) in non-smoking women and decreased risk of all-cause mortality for >4 cups coffee/d in men with no/moderate alcohol intake.ConclusionsCoffee consumption was associated with decreased risk of mortality. The protective effect was even stronger when stratification by smoking status and alcohol intake was performed.

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CANCER MORTALITY IN KIDNEY TRANSPLANT RECIPIENTS

Transplantation Journal ◽

10.1097/01.tp.0000331940.27688.ee ◽

2008 ◽

Vol 86 (Supplement) ◽

pp. 296

Author(s):

B Kiberd ◽

C Rose ◽

J Gill

Keyword(s):

Kidney Transplant ◽

Cancer Mortality ◽

Transplant Recipients ◽

Kidney Transplant Recipients

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Trends in the Causes of Death among Kidney Transplant Recipients in the United States (1996–2014)

American Journal of Nephrology ◽

10.1159/000495081 ◽

2018 ◽

Vol 48 (6) ◽

pp. 472-481 ◽

Cited By ~ 27

Author(s):

Ahmed A. Awan ◽

Jingbo Niu ◽

Jenny S. Pan ◽

Kevin F. Erickson ◽

Sreedhar Mandayam ◽

...

Keyword(s):

United States ◽

Kidney Transplant ◽

Cardiovascular Mortality ◽

Causes Of Death ◽

Graft Loss ◽

Graft Function ◽

The United States ◽

Mortality Data ◽

Transplant Recipients ◽

Kidney Transplant Recipients

Background: Death with graft function remains an important cause of graft loss among kidney transplant recipients (KTRs). Little is known about the trend of specific causes of death in KTRs in recent years. Methods: We analyzed United States Renal Data System data (1996–2014) to determine 1- and 10-year all-cause and cause-specific mortality in adult KTRs who died with a functioning allograft. We also studied 1- and 10-year trends in the various causes of mortality. Results: Of 210,327 KTRs who received their first kidney transplant from 1996 to 2014, 3.2% died within 1 year after transplant. Cardiovascular deaths constituted the majority (24.7%), followed by infectious (15.2%) and malignant (2.9%) causes; 40.1% of deaths had no reported cause. Using 1996 as the referent year, all-cause as well as cardiovascular mortality declined, whereas mortality due to malignancy did not. For analyses of 10-year mortality, we studied 94,384 patients who received a first kidney transplant from 1996 to 2005. Of those, 22.1% died over 10 years and the causative patterns of their causes of death were similar to those associated with 1-year mortality. Conclusions: Despite the downtrend in mortality over the last 2 decades, a significant percentage of KTRs die in 10-years with a functioning graft, and cardiovascular mortality remains the leading cause of death. These data also highlight the need for diligent collection of mortality data in KTRs.

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