Folic Acid For Vascular Outcome Reduction In Transplantation Research Articles

Racial Differences in Medication Utilization for Secondary Prevention of Cardiovascular Disease in Kidney Transplant Recipients: A Post Hoc Analysis of the FAVORIT Trial Cohort

Rationale & ObjectiveBlack kidney transplant recipients have higher prevalences of cardiovascular disease (CVD) risk factors and less intensive risk factor control than White kidney transplant recipients. Our objective was to evaluate racial disparities in receipt of statins and aspirin for secondary CVD prevention among kidney transplant recipients in the Folic Acid for Vascular Outcome Reduction in Transplantation (FAVORIT) trial.Study DesignCohort study.Setting & ParticipantsFAVORIT participants of White, Black, and Other races from the United States and Canada with a history of CVD at study entry or who experienced a nonfatal CVD event during follow-up.PredictorRace.OutcomeReceipt of statins and aspirin for secondary CVD prevention.Analytical ApproachWe used parametric (Weibull), proportional-hazards, interval-censored survival models to evaluate the independent association of race with receipt of statins and aspirin for secondary CVD prevention.ResultsOf the 4,110 kidney transplant recipients enrolled in FAVORIT trial, 978 met the inclusion criteria (78% White, 17% Black, and 6% Other race). Compared with the White race, Black and Other races were associated with lower hazards of receiving statins (Black race: adjusted HR, 0.76 [95% CI, 0.60-0.97]; Other race: adjusted HR, 0.87 [95% CI, 0.60-1.27]) and aspirin (Black race: adjusted HR, 0.85 [95% CI, 0.67-1.08]; Other race: adjusted HR, 0.63 [95% CI, 0.43-0.94]).LimitationsLack of granular information on potential indications or contraindications for aspirin or statin use for secondary CVD prevention.ConclusionsPost hoc findings from the FAVORIT trial demonstrated that Black race was associated with a lower likelihood of receiving statins and Other race was associated with a lower likelihood of receiving aspirin for secondary CVD prevention. This represents a potential target to improve CVD care in non-White kidney transplant recipients.

Lower Extremity Vascular Intervention Is Associated With Increased Mortality Following Kidney Transplantation

Approximately 25% of patients with end-stage renal disease (ESRD) have concomitant peripheral artery disease (PAD). Although kidney transplantation increases overall survival and quality of life in patients with ESRD, these patients remain at high risk for post-transplant sequelae related to PAD, including lower extremity revascularization procedures and amputations. The objective of this study was to determine the incidence of, and risk factors for, lower extremity vascular intervention (LEVI) following kidney transplantation using the Folic Acid for Vascular Outcome Reduction in Transplantation (FAVORIT) dataset.

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

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. Among 4110 enrolled participants, 98 were excluded for missing baseline remnant cholesterol levels and covariates. Nonfasting remnant cholesterol levels were calculated based on the lipid profiles in 3812 FAVORIT trial participants at randomization. A Wilcoxon-type test for trend was used to compare baseline characteristics across remnant cholesterol quartiles. Cox proportional hazards regression was used to evaluate the association of baseline remnant cholesterol levels with time to primary and secondary study outcomes. During a median follow-up of 4.0 years we documented 548 CVD incident events, 343 transplant failures and 452 all-cause deaths. When comparing the highest quartile (quartile 4) to quartile 1, proportional hazard modeling revealed a significant increase in CVD risk {hazard ratio [HR] 1.32 [95% confidence interval (CI) 1.04-1.67]} and all-cause mortality risk [HR 1.34 (95% CI 1.01-1.69)]. A nonsignificant increase in transplant failure was seen as well [HR 1.20 (95% CI 0.87-1.64)]. Remnant cholesterol is associated with CVD and all-cause mortality in long-term KTRs. A randomized controlled clinical trial in KTRs that assesses the potential impact of remnant cholesterol-lowering therapy on these outcomes may be warranted.

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

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. Prior observational studies from the Folic Acid for Vascular Outcome Reduction in Transplantation (FAVORIT) trial demonstrate associations of lower SBP levels and reduced mortality risk, but the relationship of BP with kidney allograft function remains unknown. Thus, in FAVORIT, we investigated the relationship of SBP and diastolic blood pressure (DBP) with risk of kidney allograft failure and estimated glomerular filtration rate (eGFR) slope among stable KTRs. Cox proportional hazards and multivariable linear regression models adjusted for demographics, transplant characteristics, comorbidities, baseline eGFR, and urine albumin-to-creatinine ratio were used to determine associations of SBP and DBP with time to a composite kidney outcome of ≥50% eGFR decline or dialysis dependence, and with annualized eGFR change, respectively. Multivariable restricted cubic spline plots were developed to evaluate the functional form of the relationships. Among 3,598 KTRs, mean age was 52 ± 9 years, SBP was 136 ± 20 mm Hg, DBP was 79 ± 12 mm Hg, and eGFR was 49 ± 18 ml/minute/1.73 m2. There were 369 events of ≥50% eGFR decline or dialysis dependence during a mean follow-up of 4.0 ± 1.5 years. There was no association of either SBP (compared with SBP 120 to <130 mm Hg, hazard ratio (HR) for the SBP < 110 was 1.01 (95% confidence interval (CI) 0.60 to 1.70) and 130 to <140 was 0.89 (0.64 to 1.24)) or DBP (compared with DBP 70 to <80 mm Hg, HR for the DBP 60 to <70 was 1.00 (95% CI 0.74 to 1.34) and 80 to <90 was 0.90 (0.68 to 1.18)) with the kidney failure outcome or annualized eGFR slope, and, when examined using restricted cubic splines, there was no evidence of "J"- or "U"-shaped relationships. In a large sample of stable KTRs, we found no evidence of thresholds at which lower BPs were related to higher risk of allograft failure or eGFR decline. In light of prior findings of mortality benefit at low SBP, these observational findings suggest lower BP may be beneficial in KTRs. This important question requires confirmation in future randomized trials in 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. We conducted a case cohort analysis using a randomly selected subset of patients (random subcohort, n = 433), and all individuals who developed kidney allograft failure (cases, n = 226) during follow-up. Serum uromodulin was determined in this total of n = 613 FAVORIT trial participants at randomization. Death-censored kidney allograft failure was the study outcome. Results: The 226 kidney allograft failures occurred during a median surveillance of 3.2 years. Unadjusted, weighted Cox proportional hazards modeling revealed that lower serum uromodulin, tertile 1 vs. tertile 3, was associated with a threefold greater risk for kidney allograft failure (hazards ratio [HR], 95% CI 3.20 [2.05–5.01]). This association was attenuated but persisted at twofold greater risk for allograft failure, after adjustment for age, sex, smoking, allograft type and vintage, prevalent diabetes mellitus and cardiovascular disease (CVD), total/high-density lipoprotein cholesterol ratio, systolic blood pressure, estimated glomerular filtration rate, and natural log urinary albumin/creatinine: HR 2.00, 95% CI (1.06–3.77). Conclusions: Lower serum uromodulin, a possible indicator of less well-preserved renal tubular function, remained associated with greater risk for kidney allograft failure, after adjustment for major, established clinical kidney allograft failure and CVD risk factors, in a large, multiethnic cohort of long-term, stable KTRs.

Abstract P282: Cross-sectional Relationship Between Physical Activity and Cardiovascular Risk Factors in Kidney Transplant Patients: A Baseline Examination of the Folic Acid for Vascular Outcome Reduction in Transplantation (FAVORIT) Trial

Introduction: Data characterizing the potential relationship between physical activity and cardiovascular disease (CVD) risk factors in kidney transplant recipients (KTRs) are limited in the published literature. Accordingly, we sought to: (1) describe the levels of physical activity (PA) in KTRs; and (2) analyze the associations between PA levels and CVD risk factors in KTRs. We report the largest cross-sectional study of PA levels and CVD risk factors in KTRs to date. Methods: Baseline data from the large multiethnic, multicenter trial (FAVORIT) were examined with n = 4034 participants (37% female; mean age 51.9 ± 9.4 years; 75% White; 97% with stage 2T-4T Chronic Kidney Disease; 20% with prevalent CVD). PA was categorized in tertiles (low, moderate, high) derived from a modified PA summary score from the Yale Physical Activity Survey (YPAS). CVD risk factors were examined across levels of PA by ANOVA, Kruskal-Wallis rank test and hierarchical multiple regression modeling. Results: Collectively, participants were less active (mean YPAS 39.9 ± 20.6) compared to similar-aged rheumatoid arthritis (48 ± 21) and osteoarthritis (51 ± 20) samples from other studies. Participants in the “high” PA tertile reported more vigorous PA and walking, compared to participants in moderate and low tertiles (both p &lt; .001). No differences were observed for daily household, occupational or sedentary activities (i.e., standing, sitting, moving about) across PA tertiles. More participants in the “low” PA tertile were overweight/obese and had a history of prevalent diabetes and/or CVD, compared with more active participants (all p &lt; .001). Hierarchical multiple regression revealed that lower age ( p = .002), having a cadaveric donor source ( p = .006), shorter transplant vintage ( p = .025), lower pulse pressure ( p &lt; .001) and no history of diabetes ( p &lt; .001) were significantly associated with higher PA scores. Conclusion: KTR participants appear to be less active than samples of other chronically ill participants. In our data, lower levels of PA were positively associated with the presence of most CVD risk factors in the KTR population. Furthermore, higher PA levels were associated with younger age and variables associated with more positive KTR outcomes. Future longitudinal analyses of this unique KTR cohort will examine whether higher PA levels are associated with reduced risk for the development of hard, centrally-adjudicated CVD outcomes.

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

ObjectiveNow that long-term survival after successful renal transplantation is no longer limited by excessive cardiovascular risk, the primary care physician should consider that infection and malignancy are leading noncardiovascular causes of death even in the recipient with diabetes. MethodsWe accessed the National Institutes of Health–sponsored Folic Acid for Vascular Outcome Reduction in Transplantation (FAVORIT) study population (4010 renal transplant recipients with elevated homocysteine levels) studied to determine whether folate and B12 supplementation would reduce cardiovascular end points. This trial had a null result. Patients were classified as being nondiabetic or having type 1 or type 2 diabetes. ResultsWe report an excess (cardiovascular and noncardiovascular) 6-year mortality risk associated with the presence of diabetes mellitus. Two thirds of fatal events in our renal transplant recipients were centrally adjudicated as noncardiovascular. The incidence of noncardiovascular death was 70% higher in the diabetic patient cohort than in the nondiabetic cohort. ConclusionsThese results demonstrate that infection (but not malignancy) risks are far higher in diabetic than nondiabetic immunosuppressed individuals (although noncardiovascular death rate in nondiabetic individuals also exceeded cardiovascular deaths) and may play a larger role in the excess mortality populations than previously thought. Given that follow-up in this study was 4 to 10 years after allograft surgery, there was a lesser degree of acute rejection requiring high-dose immunosuppression than in the initial postallograft years. This unique perspective allows transplant recipients to return to primary physicians when taking low doses of immunosuppressive agents and provides focus for follow-up care.

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

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. Cohort study. The Folic Acid for Vascular Outcome Reduction in Transplantation (FAVORIT) Trial, a large, multicenter, multiethnic, controlled clinical trial that provided definitive evidence that high-dose vitamin B-based lowering of plasma homocysteine levels did not reduce CVD events, transplant failure, or total mortality in stable KTRs. Serum phosphorus levels were determined in 3,138 FAVORIT trial participants at randomization. During a median follow-up of 4.0 years, the cohort had 436 CVD events, 238 transplant failures, and 348 deaths. Proportional hazards modeling revealed that each 1-mg/dL higher serum phosphorus level was not associated with a significant increase in CVD risk (HR, 1.06; 95% CI, 0.92-1.22), but increased transplant failure (HR, 1.36; 95% CI, 1.15-1.62) and total mortality risk associations (HR, 1.21; 95% CI, 1.04-1.40) when adjusted for treatment allocation, traditional CVD risk factors, kidney measures, type of kidney transplant, transplant vintage, and use of calcineurin inhibitors, steroids, or lipid-lowering drugs. These associations were strengthened in models without kidney measures: CVD (HR, 1.14; 95% CI, 1.00-1.31), transplant failure (HR, 1.72; 95% CI, 1.46-2.01), and mortality (HR, 1.34; 95% CI, 1.15-1.54). We lacked data for concentrations of parathyroid hormone, fibroblast growth factor 23, or vitamin D metabolites. Serum phosphorus level is marginally associated with CVD and more strongly associated with transplant failure and total mortality in long-term KTRs. A randomized controlled clinical trial in KTRs that assesses the potential impact of phosphorus-lowering therapy on these hard outcomes may be warranted.

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 (eGFRcys ), B2M (eGFRB2M ), and creatinine (eGFRcr ) 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 51.6 years, median transplant vintage 4 years, 38% women, 23.6% nonwhite race) with enrichment for cardiovascular events (N = 306; 54 within the subcohort), mortality (N = 208; 68 within the subcohort), and kidney failure (N = 208; 52 within the subcohort). Mean eGFRcr , eGFRcys , and eGFRB2M were 46.0, 43.8, and 48.8 mL/min/1.73m2 , respectively. After multivariable adjustment, hazard ratios for eGFRcys and eGFRB2M <30 versus 60+ were 2.02 (95% confidence interval [CI] 1.09-3.76; p = 0.03) and 2.56 (1.35-4.88; p = 0.004) for cardiovascular events; 3.92 (2.11-7.31) and 4.09 (2.21-7.54; both p < 0.001) for mortality; and 9.49 (4.28-21.00) and 15.53 (6.99-34.51; both p < 0.001) for kidney failure. Associations persisted with additional adjustment for baseline eGFRcr . We conclude that cystatin C and B2M are strongly associated with cardiovascular events, mortality, and kidney failure in stable kidney transplant recipients.

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

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. Case-cohort study. The FAVORIT (Folic Acid for Vascular Outcome Reduction in Transplantation) Trial was a randomized double-blind trial testing vitamin therapy to lower homocysteine levels in stable kidney transplant recipients. We selected a subset of participants at random (n=491) and all individuals with allograft failure during follow-up (cases; n=257). Using spot urine specimens from the baseline visit, we measured 4 urinary proteins known to correlate with tubulointerstitial fibrosis on biopsy (urine α1-microglobulin [A1M], monocyte chemoattractant protein 1 [MCP-1], and procollagen type III and type I amino-terminal amino pro-peptide). Death-censored allograft failure. In models adjusted for demographics, chronic kidney disease risk factors, eGFR, and ACR, higher concentrations of urine A1M (HR per doubling, 1.73; 95% CI, 1.43-2.08) and MCP-1 (HR per doubling, 1.60; 95% CI, 1.32-1.93) were strongly associated with allograft failure. When additionally adjusted for concentrations of other urine fibrosis and several urine injury markers, urine A1M (HR per doubling, 1.76; 95% CI, 1.27-2.44]) and MCP-1 levels (HR per doubling, 1.49; 95% CI, 1.17-1.89) remained associated with allograft failure. Urine procollagen type III and type I levels were not associated with allograft failure. We lack kidney biopsy data, BK titers, and HLA antibody status. Urine measurement of tubulointerstitial fibrosis may provide a noninvasive method to identify kidney transplant recipients at higher risk for future allograft failure, above and beyond eGFR and urine ACR.

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.

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. Post hoc cohort analysis of FAVORIT, a randomized trial examining the effect of homocysteine-lowering vitamins on CVD in kidney transplant recipients. Prevalent adult kidney transplant recipients with hyperhomocysteinemia and stable kidney function from the United States, Canada, and Brazil participating in FAVORIT, with no known history of CVD. Aspirin use, with aspirin users matched to nonusers using a propensity score. Incident CVD events, kidney failure, all-cause mortality, a composite of CVD events or mortality, and a composite of kidney failure or mortality. Cox proportional hazards models with a robust variance to account for the correlation in outcomes within matched pairs were sequentially adjusted for demographic, clinical, and laboratory characteristics to assess the association between aspirin use and events. 981 aspirin users were matched to 981 nonusers. During a 4-year mean follow up, there were 225 CVD events, 200 deaths, 126 kidney failure events, 301 composite kidney failure or mortality events, and 324 composite CVD or mortality events. Adjusted models showed no significant difference associated with aspirin use in risk for CVD events, all-cause mortality, kidney failure, composite of kidney failure or mortality, or composite ofprimary CVD events or mortality (HRs of 1.20 [95% CI, 0.92-1.58], 0.92 [95% CI, 0.69-1.23], 1.19 [95% CI,0.81-1.74], 1.03 [0.82-1.31], and 1.11 [95% CI, 0.88-1.38], respectively). We did not examine dose or continued use of aspirin after randomization. CVD history is dependent on participant report at baseline. Aspirin use was non-randomly assigned. Aspirin use is not associated with reduced risk for incident CVD, all-cause mortality, or kidney failure in stable kidney transplant recipients with no history of CVD.

Abstract MP28: Filtration Markers, Cardiovascular Disease and All-cause Mortality in Kidney Transplant Recipients: The FAVORIT Trial

Background: Cardiovascular disease (CVD) is common in kidney transplant recipients (KTRs). The level of kidney function (glomerular filtration rate [GFR]) estimated from serum creatinine has been shown to be independently associated with CVD outcomes in a wide range of populations, including KTRs. In other populations, CVD outcomes are more strongly associated with the alternative filtration markers serum cystatin C and beta-2-microglobulin (B2M) than creatinine, but this has not been evaluated in KTRs. Methods: We performed a case-cohort study of participants of the Folic Acid for Vascular Outcome Reduction in Transplantation (FAVORIT) Trial, a randomized, double blind clinical trial of homocysteine lowering with B vitamins in KTRs. Study participants were enrolled from 2002-07 from centers in the US, Canada &amp; Brazil; we studied a 15% random subcohort of eligible baseline participants (N=508; mean age 52 years, 38% women) and all additional eligible adjudicated CVD (CVD death, myocardial infarction, resuscitated sudden death, stroke, N=211) and all-cause mortality (N=314) events that occurred through June 2009. Filtration markers measured at baseline were expressed as estimated GFR using established CKD-EPI equations (eGFRcr, eGFRcys &amp; eGFRB2M). Associations of eGFRcr, eGFRcys &amp; eGFRB2M with CVD and mortality were evaluated with weighted Cox proportional hazard regression to account for the case-cohort design. Results: In multivariable adjusted models eGFRcr was not significantly associated with CVD or all-cause mortality. In contrast, both lower eGFRcys and eGFRB2M were associated with increased risk of CVD and all-cause mortality (Figure). Findings were similar when eGFR was treated as a continuous variable. Conclusion: Similar to non-transplant cohorts, cystatin C and B2M have stronger risk associations for CVD and all-cause mortality compared to creatinine in KTRs. These findings likely reflect differences in their non-GFR determinants; future work is needed to evaluate non-GFR determinants in KTRs.

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

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

Urine Injury Biomarkers and Risk of Adverse Outcomes in Recipients of Prevalent Kidney Transplants: The Folic Acid for Vascular Outcome Reduction in Transplantation Trial.

Recipients of kidney transplants (KTR) are at increased risk for cardiovascular events, graft failure, and death. It is unknown whether urine kidney injury biomarkers are associated with poor outcomes among KTRs. We conducted a post hoc analysis of the Folic Acid for Vascular Outcome Reduction in Transplantation (FAVORIT) Trial using a case-cohort study design, selecting participants with adjudicated cardiovascular events, graft failure, or death. Urine neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), IL-18, and liver-type fatty acid binding protein (L-FABP) were measured in spot urine samples and standardized to urine creatinine concentration. We adjusted for demographics, cardiovascular risk factors, eGFR, and urine albumin-to-creatinine ratio. Patients had 291 cardiovascular events, 257 graft failure events, and 359 deaths. Each log increase in urine NGAL/creatinine independently associated with a 24% greater risk of cardiovascular events (adjusted hazard ratio [aHR], 1.24; 95% confidence interval [95% CI], 1.06 to 1.45), a 40% greater risk of graft failure (aHR, 1.40; 95% CI, 1.16 to 1.68), and a 44% greater risk of death (aHR, 1.44; 95% CI, 1.26 to 1.65). Urine KIM-1/creatinine and IL-18/creatinine independently associated with greater risk of death (aHR, 1.29; 95% CI, 1.03 to 1.61 and aHR, 1.25; 95% CI, 1.04 to 1.49 per log increase, respectively) but not with risk of cardiovascular events or graft failure. Urine L-FABP did not associate with any study outcomes. In conclusion, among prevalent KTRs, higher urine NGAL, KIM-1, and IL-18 levels independently and differentially associated with greater risk of adverse outcomes.

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 4.1 years (25th to 75th percentiles, 1.7-7.4); mean systolic BP was 136±20 mmHg and mean diastolic BP was 79±12 mmHg. There were 497 CVD events and 406 deaths. After adjustment for demographic and transplant characteristics and CVD risk factors, each 20-mmHg increase in baseline systolic BP associated with a 32% increase in subsequent CVD risk (hazard ratio [HR], 1.32; 95% confidence interval [95% CI], 1.19 to 1.46) and a 13% increase in mortality risk (HR, 1.13; 95% CI, 1.01 to 1.27). Similarly, after adjustment, at diastolic BP levels<70 mmHg, each 10-mmHg decrease in diastolic BP level associated with a 31% increase in CVD risk (HR, 1.31; 95% CI, 1.06 to 1.62) and a 31% increase in mortality risk (HR, 1.31; 95% CI, 1.03 to 1.66). However, at diastolic BP levels>70 mmHg, there was no significant relationship between diastolic BP and outcomes. Higher systolic BP strongly and independently associated with increased risk of CVD and all-cause mortality, without evidence of a J shape, whereas only lower levels of diastolic BP associated with increased risk of CVD and death in this trial.

Kidney Function and Risk of Cardiovascular Disease and Mortality in Kidney Transplant Recipients: The FAVORIT Trial

In kidney transplant recipients, cardiovascular disease (CVD) is the leading cause of death. The relationship of kidney function with CVD outcomes in transplant recipients remains uncertain. We performed a post hoc analysis of the Folic Acid for Vascular Outcome Reduction in Transplantation (FAVORIT) Trial to assess risk factors for CVD and mortality in kidney transplant recipients. Following adjustment for demographic, clinical and transplant characteristics, and traditional CVD risk factors, proportional hazards models were used to explore the association of estimated GFR with incident CVD and all-cause mortality. In 4016 participants, mean age was 52 years and 20% had prior CVD. Mean eGFR was 49 ± 18 mL/min/1.73 m(2) . In 3676 participants with complete data, there were 527 CVD events over a median of 3.8 years. Following adjustment, each 5 mL/min/1.73 m(2) higher eGFR at levels below 45 mL/min/1.73 m(2) was associated with a 15% lower risk of both CVD [HR = 0.85 (0.80, 0.90)] and death [HR = 0.85 (0.79, 0.90)], while there was no association between eGFR and outcomes at levels above 45 mL/min/1.73 m(2) . In conclusion, in stable kidney transplant recipients, lower eGFR is independently associated with adverse events, suggesting that reduced kidney function itself rather than preexisting comorbidity may lead to CVD.

Cognitive Dysfunction and Depression in Adult Kidney Transplant Recipients: Baseline Findings from the FAVORIT Ancillary Cognitive Trial (FACT)

Hyperhomocysteinemia and B-vitamin deficiency may be treatable risk factors for cognitive impairment and decline. Hyperhomocysteinemia, cognitive impairment, and depression are all common in individuals with kidney disease, including kidney transplant recipients. Accordingly, we assessed the prevalence of cognitive impairment and depressive symptoms in transplant recipients and their association with kidney function, plasma total homocysteine, and B-vitamin concentrations. Cross-sectional analysis of baseline data from the Folic Acid for Vascular Outcome Reduction In Transplantation (FAVORIT) Ancillary Cognitive Trial (FACT), which included 183 participants in FAVORIT who underwent detailed neuropsychological assessment before the study intervention. The mean age was 54.0 ± 9.5 years (range: 7 to 386 months). Men comprised 55.2% of the cohort, and the mean time between the current transplant and cognitive testing was 7.0 ± 5.8 years. Twenty-four percent of participants reported neurological or psychiatric complaints, and 30% exhibited symptoms of mild to severe depression. Testing revealed evidence of significant and selective deficits in this population: 33% performed more than 1 standard deviation (SD) below normed means on a memory test, 58% fell lower than 1 SD below the norms on a test of attention and mental processing speed, and 33% to 42% fell lower than 1 SD below the norms on several tests of executive function. Lower estimated glomerular filtration rate and lower folate were associated with poorer performance on tests of memory and executive function. These observations confirm previous reports of mood and cognitive impairments in adult kidney transplant recipients. Further research is needed to determine the benefit of B-vitamin supplementation and other interventions in this patient population.

Relationship Between Baseline Physical Activity, Self-reported Coronary Heart Disease (CHD) and CHD Risk Factors In Renal Transplant Recipients: Findings From The Folic Acid For Vascular Outcome Reduction In Transplantation (FAVORIT) Trial

PURPOSE: To evaluate the relationships between level of physical activity and cardiometabolic health in kidney transplant recipients. METHODS:Baseline data were analyzed in 4,110 stable kidney transplant recipients (1,528 women and 2,582 men) enrolled in the FAVORIT Trial. Physical activity was measured using the Yale Physical Activity Survey (YPAS) summary (SS), walking (WALK) and sitting (SIT) scores. Self-reported CHD and CHD risk factors were assessed. Trends in cardiometabolic health were examined across tertiles of YPAS-SS. RESULTS:Subjects were 51.9 ± 9.4 years old and 77% were White. A kidney transplant was received 5.5 ± 5 years ago, 91% had stage II or III chronic kidney disease, and 20% had prevalent CHD. YPAS-SS was 39.9 (± 20.6), WALK was 11.8 ± 12 and SIT was 2.3 ± 1. Total cholesterol, LDL-C, HDL-C, and triglycerides respectively were 184.5 ± 43.9 mg/dl, 89.5 ± 44.6 mg/dl, 46.2 ± 13.9 mg/dl and 199.8 ± 182.5 mg/dl. Smoking pack-years were 18.0 ± 21.2, systolic blood pressure (BP) was 136 ± 19.7 mmHg, and diastolic BP was 78.5 ± 12.2 mmHg. Distribution of risk factors across tertiles of YPAS-SS were examined; corresponding 2-sided p-values from Kruskal-Wallis rank test are reported. 34% of overweight/obese patients were in the 1st tertile (lower activity) vs. 24% of non-overweight patients (p=0.001); 38% of diabetic patients were in the 1st tertile vs. 27% of non-diabetic patients (p<0.0001); and 41% of patients with prevalent CHD were in the 1st tertile vs 28% of those without prevalent CHD (p=0.0003). Associations with smoking status and hypertension were in the opposite direction (i.e., 28% of current and 29% of former smokers are in the 1st tertile vs. 33% of never smokers (p=0.047); 34% of normotensive patients were in the 1st tertile vs. 27% of hypertensive subjects, p=0.029). CONCLUSIONS:Significant associations between levels of physical activity and several cardiometabolic risk factors and prevalent CHD were not always in the expected direction. These results demonstrate the complexity of relationships between the YPAS-SS and traditional CHD risk factors in persons with CKD.

52 Prevalence of CVD Risk Factors and their Treatment in Chronic, Stable Kidney Transplant Recipients in the Folic Acid for Vascular Outcome Reduction in Transplantation (FAVORIT) Trial

52 Prevalence of CVD Risk Factors and their Treatment in Chronic, Stable Kidney Transplant Recipients in the Folic Acid for Vascular Outcome Reduction in Transplantation (FAVORIT) Trial

Baseline Characteristics of Participants in the Folic Acid for Vascular Outcome Reduction in Transplantation (FAVORIT) Trial

Baseline Characteristics of Participants in the Folic Acid for Vascular Outcome Reduction in Transplantation (FAVORIT) Trial