The Role of Angiopoietins in Cardiovascular Outcomes of Kidney Transplant Recipients: An Ancillary Study from the FAVORIT.

Introduction: Kidney transplant recipients (KTRs) have increased risk of cardiovascular disease (CVD) mortality. We investigated vascular biomarkers, angiopoietin-1, and angiopoietin-2 (angpt-1, -2), in CVD development in KTRs.

Methods: This ancillary study from the FAVORIT evaluates the associations of baseline plasma angpt-1, -2 levels in CVD development (primary outcome) and graft failure (GF) and death (secondary outcomes) in 2000 deceased donor KTRs.

Oral Nicotinamide for Actinic Keratosis Prevention in Kidney Transplant Recipients: A Pilot Double-Blind, Randomized, Placebo-Controlled Trial.

Background: Oral nicotinamide (NAM) has shown promise in preventing actinic keratoses (AKs) in trials based outside of the United States. We assessed the efficacy of oral NAM supplementation in kidney transplant recipients with a history of keratinocyte carcinoma.

Material And Methods: Patients enrolled in a 2-week run-in phase, during which NAM 1000 mg was taken twice daily.

DNAm-based signatures of accelerated aging and mortality in blood are associated with low renal function.

Background: The difference between an individual's chronological and DNA methylation predicted age (DNAmAge), termed DNAmAge acceleration (DNAmAA), can capture life-long environmental exposures and age-related physiological changes reflected in methylation status. Several studies have linked DNAmAA to morbidity and mortality, yet its relationship with kidney function has not been assessed. We evaluated the associations between seven DNAm aging and lifespan predictors (as well as GrimAge components) and five kidney traits (estimated glomerular filtration rate [eGFR], urine albumin-to-creatinine ratio [uACR], serum urate, microalbuminuria and chronic kidney disease [CKD]) in up to 9688 European, African American and Hispanic/Latino individuals from seven population-based studies.

Remnant cholesterol is prospectively associated with cardiovascular disease events and all-cause mortality in kidney transplant recipients: the FAVORIT study.

Background: The cholesterol content of circulating triglyceride-rich lipoproteins is characterized as remnant cholesterol, although little is known about its role in the development of cardiovascular disease (CVD) outcomes, all-cause mortality or transplant failure in kidney transplant recipients (KTRs). Our primary aim was to investigate the prospective association of remnant cholesterol and the risk of CVD events in renal transplant recipients with secondary aims evaluating remnant cholesterol and renal graft failure and all-cause mortality among participants in the Folic Acid for Vascular Outcome Reduction in Transplantation (FAVORIT) trial.

Methods: Among 4110 enrolled participants, 98 were excluded for missing baseline remnant cholesterol levels and covariates.

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

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.

Blood Pressure, Chronic Kidney Disease Progression, and Kidney Allograft Failure in Kidney Transplant Recipients: A Secondary Analysis of the FAVORIT Trial.

Background: In chronic kidney disease, intensive systolic blood pressure (SBP) control reduces mortality at a cost of greater acute kidney injury risk. Kidney transplantation involves implantation of denervated kidneys and immunosuppressive medications that increase acute kidney injury risk. The optimal blood pressure (BP) target in kidney transplant recipients (KTRs) is uncertain.

Physical Activity and Cardiovascular Risk among Kidney Transplant Patients.

Purpose: Research examining the relationship between physical activity (PA) and cardiovascular disease (CVD) risk factors among kidney transplant recipients (KTR) is limited. Accordingly, we sought to 1) describe the levels of PA in KTR and 2) analyze the associations between PA levels and CVD risk factors in KTR.

Methods: Baseline data from KTR participants in a large multiethnic, multicenter trial (the Folic Acid for Vascular Outcome Reduction in Transplantation) were examined.

Albuminuria and Allograft Failure, Cardiovascular Disease Events, and All-Cause Death in Stable Kidney Transplant Recipients: A Cohort Analysis of the FAVORIT Trial.

Rationale & Objective: Cardiovascular disease (CVD) is common and overall graft survival is suboptimal among kidney transplant recipients. Although albuminuria is a known risk factor for adverse outcomes among persons with native chronic kidney disease, the relationship of albuminuria with cardiovascular and kidney outcomes in transplant recipients is uncertain.

Study Design: Post hoc longitudinal cohort analysis of the Folic Acid for Vascular Outcomes Reduction in Transplantation (FAVORIT) Trial.

Serum Calcification Propensity and Fetuin-A: Biomarkers of Cardiovascular Disease in Kidney Transplant Recipients.

Background: "T50," shortened transformation time from primary to secondary calciprotein particles may reflect deranged mineral metabolism predisposing to vascular calcification and cardiovascular disease (CVD). The glycoprotein fetuin-A is a major T50 determinant.

Methods: The Folic Acid For Vascular Outcome Prevention In Transplantation (FAVORIT) cohort is a completed, large, multiethnic controlled clinical trial cohort of chronic, stable kidney transplant recipients (KTRs).

Serum Uromodulin: A Biomarker of Long-Term Kidney Allograft Failure.

Background: Uromodulin is a kidney-derived glycoprotein and putative tubular function index. Lower serum uromodulin was recently associated with increased risk for kidney allograft failure in a preliminary, longitudinal single-center -European study involving 91 kidney transplant recipients (KTRs).

Methods: The Folic Acid for Vascular Outcome Reduction in Transplantation (FAVORIT) trial is a completed, large, multiethnic controlled clinical trial cohort, which studied chronic, stable KTRs.

Physical Activity in Kidney Transplant Recipients: A Review.

Physical activity has known health benefits and is associated with reduced cardiovascular risk in the general population. Relatively few data are available for physical activity in kidney transplant recipients. Compared to the general population, physical activity levels are lower overall in kidney recipients, although somewhat higher compared to the dialysis population.

The Effect of Extended Release Niacin on Markers of Mineral Metabolism in CKD.

Background And Objectives: Niacin downregulates intestinal sodium-dependent phosphate transporter 2b expression and reduces intestinal phosphate transport. Short-term studies have suggested that niacin lowers serum phosphate concentrations in patients with CKD and ESRD. However, the long-term effects of niacin on serum phosphate and other mineral markers are unknown.

Hypothesis: Potential Utility of Serum and Urine Uromodulin Measurement in Kidney Transplant Recipients?

Seventy years after its discovery, studies of the myriad properties, and potential disease associations of uromodulin are now burgeoning. Although normative ranges for serum/plasma uromodulin concentrations were established over 30 years ago, their external validation occurred only in very recent, larger studies. As tubular function indices, serum and urinary uromodulin may be more sensitive indicators of kidney graft dysfunction undetected by glomerular filtration markers, or proteinuria.

Impact of Hyperuricemia on Long-term Outcomes of Kidney Transplantation: Analysis of the FAVORIT Study.

Background: Elevated uric acid concentration is associated with higher rates of cardiovascular (CV) morbidity and mortality in the general population. It is not known whether hyperuricemia increases the risk for CV death or transplant failure in kidney transplant recipients.

Study Design: Post hoc cohort analysis of the FAVORIT Study, a randomized controlled trial that examined the effect of homocysteine-lowering vitamins on CV disease in kidney transplantation.

Serum Phosphorus and Risk of Cardiovascular Disease, All-Cause Mortality, or Graft Failure in Kidney Transplant Recipients: An Ancillary Study of the FAVORIT Trial Cohort.

Background: Mild hyperphosphatemia is a putative risk factor for cardiovascular disease [CVD], loss of kidney function, and mortality. Very limited data are available from sizable multicenter kidney transplant recipient (KTR) cohorts assessing the potential relationships between serum phosphorus levels and the development of CVD outcomes, transplant failure, or all-cause mortality.

Study Design: Cohort study.

Urinary Markers of Fibrosis and Risk of Cardiovascular Events and Death in Kidney Transplant Recipients: The FAVORIT Trial.

Cardiovascular risk remains high in kidney transplant recipients (KTRs) despite improved kidney function after transplant. Urinary markers of kidney fibrosis and injury may help to reveal mechanisms of this risk. In a case-cohort study among stable KTRs who participated in the FAVORIT trial, we measured four urinary proteins known to correlate with kidney tubulointerstitial fibrosis on biopsy (urine alpha 1 microglobulin [α1m], monocyte chemoattractant protein-1 [MCP-1], procollagen type I [PINP] and type III [PIIINP] N-terminal amino peptide) and evaluated associations with cardiovascular disease (CVD) events (n = 300) and death (n = 371).

Filtration Markers, Cardiovascular Disease, Mortality, and Kidney Outcomes in Stable Kidney Transplant Recipients: The FAVORIT Trial.

Cystatin C and beta-2-microglobulin (B2M) are filtration markers associated with adverse outcomes in nontransplant populations, sometimes with stronger associations than for creatinine. We evaluated associations of estimated glomerular filtration rate from cystatin C (eGFR ), B2M (eGFR ), and creatinine (eGFR ) with cardiovascular outcomes, mortality, and kidney failure in stable kidney transplant recipients using a case-cohort study nested within the Folic Acid for Vascular Outcome Reduction in Transplantation (FAVORIT) Trial. A random subcohort was selected (N = 508; mean age 51.

More than skin deep? Potential nicotinamide treatment applications in chronic kidney transplant recipients.

Non-melanoma cutaneous carcinomas, or skin cancers, predominantly squamous cell carcinomas (SCCs), are the most common malignancies occurring in kidney transplant recipients (KTRs). Squamous cell carcinoma risk is dramatically elevated in KTRs, occurring at rates of up 45-250 times those reported in general populations. New non-melanoma skin cancers in KTRs with a prior non-melanoma skin cancer also develop at 3-times the rate reported in non-KTRs with the same clinical history.

Urine Fibrosis Markers and Risk of Allograft Failure in Kidney Transplant Recipients: A Case-Cohort Ancillary Study of the FAVORIT Trial.

Background: Kidney tubulointerstitial fibrosis marks risk for allograft failure in kidney transplant recipients, but is poorly captured by estimated glomerular filtration rate (eGFR) or urine albumin-creatinine ratio (ACR). Whether urinary markers of tubulointerstitial fibrosis can noninvasively identify risk for allograft failure above and beyond eGFR and ACR is unknown.

Study Design: Case-cohort study.

Aspirin Use and Incident Cardiovascular Disease, Kidney Failure, and Death in Stable Kidney Transplant Recipients: A Post Hoc Analysis of the Folic Acid for Vascular Outcome Reduction in Transplantation (FAVORIT) Trial.

Background: Cardiovascular disease (CVD) is the leading cause of death in kidney transplant recipients. Whether aspirin may reduce the risk for CVD, death, and kidney failure outcomes is uncertain.

Study Design: Post hoc cohort analysis of FAVORIT, a randomized trial examining the effect of homocysteine-lowering vitamins on CVD in kidney transplant recipients.

B-Type Natriuretic Peptide and Cardiac Troponin I Are Associated With Adverse Outcomes in Stable Kidney Transplant Recipients.

Background: Approximately 200 000 kidney transplant recipients are living in the United States; they are at increased risk for cardiovascular and other adverse outcomes. Biomarkers predicting these outcomes are needed. Using specimens collected during the Folic Acid for Vascular Outcome Reduction in Transplantation trial, we determined whether plasma levels of B-type natriuretic peptide (BNP) and cardiac troponin I are associated with adverse outcomes in stable kidney transplant recipients.

Adiposity patterns and the risk for ESRD in postmenopausal women.

Background And Objectives: Body mass index and waist circumference associate with adverse health outcomes, including CKD. Studies of the association of body mass index and ESRD have been inconsistent; these adiposity measures have not been previously assessed together for ESRD risk or among postmenopausal women.

Design, Settings, Participants, & Measurements: This was prospective cohort study of 20,117 postmenopausal women enrolled in the multiethnic cohort of the Women's Health Initiative.

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

Background: Kidney transplant recipients are at increased risk for adverse safety events related to their reduced renal function and many medications.

Methods: We determined the incidence of adverse safety events based on previously defined Agency for Healthcare and Research Quality (AHRQ) International Classification of Diseases-9 (ICD-9) code-derived patient safety indicators (PSI) in the Folic Acid for Vascular Outcome Reduction in Transplant trial participants who had a hospitalization stratified by tertiles of estimated glomerular filtration rate (GFR). We also examined the frequency of Micromedex defined two precautionary drug-drug interactions, and two medications whose use may be contraindicated because of reduced GFR from the Folic Acid for Vascular Outcome Reduction in Transplant trial medication thesaurus at baseline, and annually among 4,110 participants.

Effect of niacin on FGF23 concentration in chronic kidney disease.

Background: Elevated serum phosphorus and FGF23 are independent cardiovascular risk factors in patients with chronic kidney disease. In a randomized controlled trial of patients with dyslipidemia assigned to either extended release niacin (ERN) alone, ERN combined with the selective prostaglandin D2 receptor subtype 1 inhibitor laropiprant (ERN-L) or placebo, niacin lowered serum phosphorus; however, it is not known if it lowers FGF23 concentrations.

Methods: This is an ancillary study to a multicenter, randomized, double-blind, placebo-controlled trial among patients with dyslipidemia and an estimated glomerular filtration rate (eGFR) of 30-74 ml/min/1.

BP, cardiovascular disease, and death in the Folic Acid for Vascular Outcome Reduction in Transplantation trial.

The optimal BP level in kidney transplant recipients remains uncertain. This post hoc analysis of the Folic Acid for Vascular Outcome Reduction in Transplantation (FAVORIT) trial cohort assessed associations of BP with a pooled cardiovascular disease (CVD) outcome and with all-cause mortality. In 3474 prevalent kidney transplant patients, mean age was 52±9 years, 63% were men, 76% were white, 20% had a history of CVD, 40% had a history of diabetes mellitus, and the median time since transplant was 4.