Adjustment For Renal Function Research Articles

Novel measure of electrical dyssynchrony predicts response in cardiac resynchronization therapy: Results from the SMART-AV Trial

Cardiac resynchronization therapy (CRT) reduces mortality and morbidity in selected heart failure patients. However, not all patients respond to CRT. We hypothesized that a novel measure of electrical dyssynchrony, sum absolute QRST integral (SAI QRST), predicts CRT response independent of QRS duration and morphology. We retrospectively analyzed baseline 12-lead electrocardiograms of SmartDelay Determined AV Optimization: A comparison to other AV delay methods used in cardiac resynchronization therapy (SMART-AV) trial study participants (N = 234; mean age 67 years; 163 (70%) men; 140 (60%) ischemic cardiomyopathy; mean left ventricular ejection fraction 25%; mean QRS duration 152 ms; 179 (77%) had left bundle branch block). Baseline pre-implant electrocardiograms were digitized, transformed into orthogonal XYZ, and analyzed automatically by customized MATLAB software. SAI QRST was measured as an averaged arithmetic sum of absolute areas under the QRST curve. Patients were followed prospectively 6 months after CRT-defibrillator implantation. Patients with a decrease in left ventricular end-systolic volume ≥15 mL after 6 months of CRT were considered responders. The logistic regression model was adjusted for age, sex, bundle branch block morphology, left ventricular ejection fraction, cardiomyopathy type, and QRS duration. Patients with the high mean SAI QRST (third tertile) had 2.5 times greater odds of response than those with the low mean SAI QRST (first tertile: odds ratio [OR] 2.5; 95% confidence interval [CI] 1.3-5.0; P = .010) and 1.9 times greater than the lower 2 tertiles combined (OR 1.9; 95% CI 1.1-3.5; P = .03). Adjustment for renal function (OR 2.33; 95% CI 1.32-4.11; P = .003) and left ventricular lead position in right anterior oblique and left anterior oblique views (OR 1.7; 95% CI 0.9-3.2; P = .087) did not attenuate association of SAI QRST with outcome. High SAI QRST independently predicts CRT response in the SMART-AV study.

Associations of Soluble CD14 and Endotoxin with Mortality, Cardiovascular Disease, and Progression of Kidney Disease among Patients with CKD.

CD14 plays a key role in the innate immunity as pattern-recognition receptor of endotoxin. Higher levels of soluble CD14 (sCD14) are associated with overall mortality in hemodialysis patients. The influence of kidney function on plasma sCD14 levels and its relationship with adverse outcomes in patients with CKD not yet on dialysis is unknown. This study examines the associations between plasma levels of sCD14 and endotoxin with adverse outcomes in patients with CKD. We measured plasma levels of sCD14 and endotoxin in 495 Leuven Mild-to-Moderate CKD Study participants. Mild-to-moderate CKD was defined as presence of kidney damage or eGFR<60 ml/min per 1.73 m(2) for ≥3 months, with exclusion of patients on RRT. Study participants were enrolled between November 2005 and September 2006. Plasma sCD14 was negatively associated with eGFR (ρ=-0.34, P<0.001). During a median follow-up of 54 (interquartile range, 23-58) months, 53 patients died. Plasma sCD14 was predictive of mortality, even after adjustment for renal function, Framingham risk factors, markers of mineral bone metabolism, and nutritional and inflammatory parameters (hazard ratio [HR] per SD higher of 1.90; 95% confidence interval [95% CI],1.32 to 2.74; P<0.001). After adjustment for the same risk factors, plasma sCD14 was also a predictor of cardiovascular disease (HR, 1.30; 95% CI, 1.00 to 1.69; P=0.05). Although plasma sCD14 was associated with progression of CKD, defined as reaching ESRD or doubling of serum creatinine in models adjusted for CKD-specific risk factors (HR, 1.24; 95% CI, 1.01 to 1.52; P=0.04), significance was lost when adjusted for proteinuria (HR, 1.19; 95% CI, 0.96 to 1.48; P=0.11). There was neither correlation between plasma endotoxin and sCD14 (ρ=-0.06, P=0.20) nor was endotoxin independently associated with adverse outcome during follow-up. Plasma sCD14 is elevated in patients with decreased kidney function and associated with mortality and cardiovascular disease in patients with CKD not yet on dialysis.

Associations of 25(OH) and 1,25(OH)2 vitamin D with long-term outcomes in stable renal transplant recipients.

Vitamin D deficiency is common in renal transplant recipients (RTR). The long-term implications of vitamin D deficiency in RTR remain unclear. We investigated whether 25(OH) or 1,25(OH)2 vitamin D levels are associated with mortality, renal function decline, and graft failure in stable RTR. Observational study with longitudinal design. Followup was 7.0, interquartile range (IQR) 6.2-7.5 years. Single-center outpatient clinic. 435 stable RTR (51% men, mean age 52 ± 12 years) were included at a median [IQR] of 6 [3-12] years after kidney transplantation. All-cause mortality, annual change of estimated glomerular filtration rate (eGFR), and graft failure. Mean 25-hydroxyvitamin D [25(OH)D] and 1,25-dihydroxyvitamin D [1,25(OH)2D] were 21.6 ± 9.1 ng/ml and 45.2 ± 19.0 pg/ml, respectively. During followup, 99 patients (22.8%) died and 44 patients (10.1%) developed graft failure. In univariable analysis, both 25(OH)D and 1,25(OH)2D were significantly associated with mortality (hazard ratio [HR], 0.64; 95% confidence interval (CI), 0.51-0.81; P < .001 and HR 0.69 [95% CI, 0.55-0.87], P = .002 per SD increase, respectively). The inverse association of 25(OH)D with mortality remained significant after adjustment for potential confounders (HR 0.68 [95% CI, 0.52-0.89], P = .004 per SD increase). The associations of 1,25(OH)2D with mortality and graft failure lost significance after adjustment for renal function. Severe vitamin D deficiency (25[OH]D <12 ng/ml) was independently associated with stronger annual eGFR decline. Low 25(OH)D is independently associated with an increased risk of all-cause mortality and 25(OH)D <12 ng/ml with a rapid eGFR decline in stable RTR. The association of low 1,25(OH)2D with mortality or graft failure depends on renal function. These results should encourage randomised controlled trials evaluating the effect of vitamin D supplementation after kidney transplantation.

FGF23 is associated with disease severity and prognosis in chronic heart failure.

Elevated levels of fibroblast growth factor 23 (FGF23) are associated with incident heart failure in individuals with or without chronic kidney disease. We aimed to investigate the association between serum FGF23 concentrations and disease severity and long-term outcome in patients with stable heart failure. Serum levels of C-term FGF23 (Ct-FGF23) concentrations, inorganic phosphate (Pi ), parathormone (PTH) and 25-hydroxyvitamin D (25(OH)D) were measured in 208 patients with nonischaemic heart failure (age 48±15years; 70% male; NYHA Class I 27·8%, NYHA Class II 43·4%, NYHA Class III/IV 28·8%; LV-EF 34±15%; eGFR ≥60mL/min/1·73m(2) in 86%). Median Ct-FGF23 levels were 18·2RU/mL (7·5-40·8RU/mL). A dose-response relationship was found between median Ct-FGF23 levels and increasing NYHA class (I: 11·9RU/mL, II: 15·8RU/mL, III/IV: 38·8RU/mL; P<0·001). Ct-FGF23 correlated with NTproBNP (r=0·307, P<0·001), central venous pressure, mean pulmonary arterial pressure, pulmonary capillary wedge pressure and inversely correlated with cardiac output after adjustment for renal function (eGFR) and Pi . LnCt-FGF23 was related with the combined endpoint of death or heart transplantation (hazard ratio 1·452 [1·029-2·048]; P=0·034) independent of Pi , PTH, 25(OH)D, age and sex. The phosphatonin FGF23 is strongly associated with disease severity and long-term outcome in patients with nonischaemic heart failure and preserved renal function. Further studies are needed to evaluate the pathophysiologic role of FGF23 and its potential as a biomarker in heart failure.

Association between circulating FGF23, α-Klotho, and left ventricular diastolic dysfunction among patients with preserved ejection fraction.

Besides regulating calcium-phosphate metabolism, fibroblast growth factor-23 (FGF23) and Klotho have been proposed to have other roles in heart and vasculature. For example, FGF23 has been associated with cardiac hypertrophy and reduced left ventricular ejection fraction among patients with chronic kidney disease and cardiovascular disorders. The purpose of the study was to investigate whether serum FGF23 and α-Klotho concentrations are associated with cardiac diastolic dysfunction and related parameters among cardiac patients with preserved left ventricular ejection fraction. The current study enrolled 269 patients (69 women, 200 men) who were admitted to our cardiology department between October 2012 and January 2014 and had a left ventricular ejection fraction of >50%. Cardiac diastolic function was assessed by blood flow and tissue Doppler velocities, plasma B-type natriuretic peptide (BNP) concentration, and cardiac hypertrophy. After adjusting for sex, and age, logistic regression analysis showed that log(α-Klotho), but not log(FGF23), was significantly associated with diastolic dysfunction. After further adjustment for renal function, blood hemoglobin, and serum albumin levels, the negative association between log(α-Klotho) and diastolic dysfunction retained statistical significance with an odds ratio of 0.50 (95% confidence interval 0.31-0.81, P = 0.005, per 1 standard deviation). Among patients with preserved LVEF, serum α-Klotho concentrations were negatively associated with diastolic dysfunction. Whether modulation of serum levels α-Klotho will ameliorate cardiac diastolic function among patients with this disorder awaits further investigation.

Validation of insulin sensitivity surrogate indices and prediction of clinical outcomes in individuals with and without impaired renal function

As chronic kidney disease (CKD) progresses with abnormalities in glucose and insulin metabolism, commonly used insulin sensitivity indices (ISIs) may not be applicable in individuals with CKD. Here we sought to validate surrogate ISIs against the glucose disposal rate by the gold-standard hyperinsulinemic euglycemic glucose clamp (HEGC) technique in 1074 elderly men of similar age (70 years) of whom 495 had and 579 did not have CKD (estimated glomerular filtration rate (eGFR) under 60 ml/min per 1.73 m(2) (median eGFR of 46 ml/min per 1.73 m(2))). All ISIs provided satisfactory (weighted κ over 0.6) estimates of the glucose disposal rate in patients with CKD. ISIs derived from oral glucose tolerance tests (OGTTs) agreed better with HEGC than those from fasting samples (higher predictive accuracy). Regardless of CKD strata, all ISIs allowed satisfactory clinical discrimination between the presence and absence of insulin resistance (glucose disposal rate under 4 mg/kg/min). We also assessed the ability of both HEGC and ISIs to predict all-cause and cardiovascular mortality during a 10-year follow-up. Neither HEGC nor ISIs independently predicted mortality. Adjustment for renal function did not materially change these associations. Thus, ISIs can be applied in individuals with moderately impaired renal function for diagnostic purposes. For research matters, OGTT-derived ISIs may be preferred. Our data do not support the hypothesis of kidney function mediating insulin sensitivity (IS)-associated outcomes nor a role for IS as a predictor of mortality.

The impact of frailty on pharmacokinetics in older people: using gentamicin population pharmacokinetic modeling to investigate changes in renal drug clearance by glomerular filtration

Frailty, a multifactorial biological syndrome characterized by a cumulative dysregulation of physiological processes, is associated with changes in pharmacokinetics and pharmacodynamics. The aim of this study was to quantify the effect of frailty on glomerular filtration of drugs, using the probe drug gentamicin. Gentamicin concentrations and clinical data including the Reported Edmonton Frail Scale score were pooled from two prospective observational inpatient studies, one on prophylactic gentamicin for urologic surgery and one on therapeutic gentamicin for the empiric treatment of sepsis. Population pharmacokinetic modeling was performed using non-linear mixed effects modeling (NONMEM program) to determine the impact of frailty on gentamicin clearance. A one-compartment linear pharmacokinetic model best described the data and the addition of frailty to the model reduced the random variability in gentamicin clearance by 12 % after adjustment for renal function (estimated creatinine clearance using lean body weight) and lean body weight. Frail patients had an approximately 12 % lower (bootstrapping results: 14 % median) gentamicin clearance than non-frail patients (calculated as a fractional effect of frailty). Frailty may independently predict reduced clearance of gentamicin in older patients. Frailty could be considered in the development of dosing guidelines for drugs that undergo significant excretion through glomerular filtration.

INTERMACS Profiling Identifies Risk of Death or VAD among Medically-Managed Advanced Heart Failure Patients

Purpose INTERMACS profiles provide important prognostic information for patients with advanced heart failure (HF) receiving mechanical support. The role for INTERMACS profiling of advanced HF patients undergoing an initial strategy of medical management is not yet known. Methods and Materials The MedaMACS Screening Pilot enrolled 167 pts with chronic NYHA Class III-IV HF, EF≤30%, and ≥1 HF hospitalization in the prior year. Pts were excluded if listed for transplant or on inotropes. Comprehensive data were collected from usual care, with INTERMACS profiles assigned at enrollment using standard definitions. Subjects were followed for 12mos, or until death, VAD or transplant. Event rates were calculated by the Kaplan-Meier method and risk of death or VAD was analyzed using Cox modeling. Results Mean age was 57yrs, EF 17%, 47% had an ischemic etiology, and 57% had HF >5yrs. At enrollment 23% of subjects were INTERMACS profile 4, 32% profile 5, and 45% profile 6/7. Cumulative follow-up was 117 patient-yrs. Patients in lower INTERMACS profiles had been hospitalized more often in the prior 6 mos, were less often on a beta-blocker, and had higher Seattle HF model scores. Lower INTERMACS profile was associated with increased risk of death or VAD by 12 months. [ figure 1 ] Successively lower INTERMACS profile remained strongly associated with failure of medical therapy (HR 1.61, 95%CI 1.12-2.39) after adjustment for renal function, right ventricular function, and Seattle HF score quartile. Conclusions INTERMACS profiles are a useful short-hand for risk stratification in advanced HF. Lower profiles identify patients who may benefit from current mechanical support devices under existing indications.

Living donor age and kidney transplant outcomes: an assessment of risk across the age continuum

Detailed data on living donor age, and its interplay with recipient age, in predicting allograft and recipient outcomes are wanting. We used the Scientific Registry of Transplant Recipients (2000-2009, n=49589) to assess the effect of living donor age on delayed graft function (DGF), total graft failure, death-censored graft failure, death with graft function, and graft failure with death as a competing risk using logistic and Cox proportional hazards models. Potential nonlinear associations were modeled using fractional polynomial functions. There was a significant 1.87-fold increase in the adjusted odds of DGF in the oldest versus youngest age groups. The 10-year adjusted hazard ratios (HR) for total graft failure, death-censored graft failure, and death with graft function increased in a nonlinear fashion across the range of living donor age studied. Graft failure was most accentuated in the youngest recipient age groups in competing risk models. Adjustment for renal function at 6- and 12-months post-transplant markedly attenuated the association between living donor age and graft/patient outcomes. Our findings confirm the important influence of living donor age on transplant outcomes and provide detailed estimates of risk across the living donor age continuum.

Low-Level Lead Exposure and the Prevalence of Gout

Blood lead levels (BLLs) less than 1.21 µmol/L (<25 µg/dL) among adults are considered acceptable by current national standards. Lead toxicity can lead to gouty arthritis (gout), but whether the low lead exposure in the contemporary general population confers risk for gout is not known. To determine whether BLLs within the range currently considered acceptable are associated with gout. Population-based cross-sectional study. The National Health and Nutrition Examination Survey for 2005 through 2008. 6153 civilians aged 40 years or older with an estimated glomerular filtration rate greater than 10 mL/min per 1.73 m2. Outcome variables were self-reported physician diagnosis of gout and serum urate level. Blood lead level was the principal exposure variable. Additional data collected were anthropometric measures, blood pressure, dietary purine intake, medication use, medical history, and serum creatinine concentration. The prevalence of gout was 6.05% (95% CI, 4.49% to 7.62%) among patients in the highest BLL quartile (mean, 0.19 µmol/L [3.95 µg/dL]) compared with 1.76% (CI, 1.10% to 2.42%) among those in the lowest quartile (mean, 0.04 µmol/L [0.89 µg/dL]). Each doubling of BLL was associated with an unadjusted odds ratio of 1.74 (CI, 1.47 to 2.05) for gout and 1.25 (CI, 1.12 to 1.40) for hyperuricemia. After adjustment for renal function, diabetes, diuretic use, hypertension, race, body mass index, income, and education level, the highest BLL quartile was associated with a 3.6-fold higher risk for gout and a 1.9-fold higher risk for hyperuricemia compared with the lowest quartile. Blood lead level does not necessarily reflect the total body lead burden. Blood lead levels in the range currently considered acceptable are associated with increased prevalence of gout and hyperuricemia.

Renal Dysfunction Is a Stronger Determinant of Systemic Neutrophil Gelatinase–Associated Lipocalin Levels Than Myocardial Dysfunction in Systolic Heart Failure

Background Neutrophil gelatinase–associated lipocalin (NGAL) is released by renal tubular cells in response to inflammation and injury. Recent studies have demonstrated that NGAL is up-regulated in cardiomyocytes within the failing myocardium. However, the overall relationship between systemic NGAL levels and myocardial structure and performance has not been established. Methods and Results We measured systemic NGAL levels in 130 subjects with chronic systolic heart failure (HF) and comprehensive echocardiographic evaluation, as well as 69 subjects with acute decompensated systolic HF and hemodynamic evaluation. In the chronic HF cohort, higher plasma NGAL levels were modestly associated with increasing age ( r = 0.18; P = .035), higher New York Heart Association functional class (rank sums: P = .022) and impaired renal function (eGFR: r = −0.53; P < .0001; cystatin C: r = 0.60; P < .0001). Plasma NGAL levels were modestly associated with indices of diastolic dysfunction (mitral E/Ea: r = 0.27; P = .002; LAVi: r = 0.25; P = .011; tricuspid E/Ea: r = 0.20; P = .029), but not after adjustment for renal function ( P > .10 for all). In Cox proportional hazards analysis, plasma NGAL predicted cardiac death or transplantation after adjustment for age, gender, left ventricular ejection fraction, and mitral E/Ea (hazard ratio 1.68, 95% confidence interval 1.08–2.57; P = .022), but not after adjustment for renal function ( P = .83). In the acute HF cohort, we did not observe any relationship between NGAL and hemodynamic indices, but NGAL strongly correlated with renal function. Conclusions Systemic NGAL levels are largely determined by underlying impairment of renal rather than myocardial function. Our findings did not support any prognostic significance or relationship between systemic NGAL levels and indices of cardiac structure and function after adjustment for underlying renal function.

The International Scoring System (ISS) for Multiple Myeloma Remains a Robust Prognostic Tool Independently of Patients' Renal Function

AbstractAbstract 3036The ISS introduced by Greipp et al (J Clin Oncol 2005) represents today the most widely used staging system for patients with multiple myeloma (MM) because it is based on two readily available variables: serum albumin and beta2-microglobulin. Serum beta2-microglobulin not only reflects myeloma tumor load but it is also increased in patients with renal dysfunction. Thus, there have been concerns that ISS-3 stage may include MM patients with renal impairment in whom elevated beta2-microglobulin does not reflect tumor burden but rather the degree of renal dysfunction. To address this issue, we assessed the impact of patients' renal function on the prognostic performance of ISS. Our analysis included data from 1516 patients with symptomatic MM that had been entered into the database of the Greek Myeloma Study Group. Renal function was assessed by the estimated GFR (eGFR), which was calculated using the modified MDRD formula (eGFR in mL/min/1.73 m2 = 186 × (Serum Creatinine)−1.154 × (Age)−0.203 × (0.742 if female) × (1.212 if African-American) and the degree of renal dysfunction was staged according to the National Kidney Foundation-Kidney Disease Outcomes Quality Initiative (KDOQI) classification of chronic kidney disease (CKD) as follows: stage 1 eGFR ≥90 ml/min; stage 2 eGFR of 60–89 ml/min; stage 3 eGFR of 30–59 ml/min; stage 4 eGFR of 15–29 ml/min and stage 5 eGFR <15 ml/min or under dialysis. At the time of treatment initiation, 788 patients had stage 1 or 2 CKD and 728 patients had stage 3–5 CKD. According to ISS, 29% patients had ISS-1, 38% patients had ISS-2 and 33% ISS-3. Renal impairment was significantly more common in ISS-3 patients: 76% of ISS-3 patients had stage 3–5 CKD compared to 42% and 27% for ISS-2 and ISS-1, respectively (p<0.001). Similarly, the incidence of stage 4 or 5 CKD was higher in ISS-3 (23% and 20%, respectively) than in patients with ISS-2 (6% and 1.5%, respectively) or ISS-1 (4% and 1%, p<0.001). In the univariate analysis, which included all patients, stage 3–5 CKD was associated with inferior survival (31 months vs. 51 months for those with stage 1 or 2 CKD, p<0.001). However, CKD stages had not an independent prognostic value in the multivariate analysis. Subsequently, we analyzed the prognostic significance of renal function in each ISS group separately. ISS-1 patients with stage 1 or 2 CKD had a median survival of 76 months vs. 56 months for patients with stage 3–5 CKD (p=0.053). In ISS-2, the respective median survival was 49 months and 29 months for stage 1–2 CKD vs. stage 3–5 CKD (p=0.02). In contrast, in patients with ISS-3 the median survival was similar (30 vs. 24 months, p=0.292) for patients with stage 1–2 CKD and stage 3–5 CKD. Multivariate analysis performed in each ISS subgroup revealed that renal function (either as a dichotomous or as a continuous variable) was not an independent prognostic factor in any of ISS stages: HR=1.031, p=0.873 for ISS-1; HR=0.996, p=0.123 for ISS-2 and HR=1.09, p=0.6 for ISS-3. We conclude that ISS is a simple, yet powerful prognostic staging system. The robustness of ISS remains unaffected by the degree of renal function. In patients with ISS-3, which includes many patients with renal dysfunction, elevated beta2-microglobulin reflects tumor burden, despite its increase due to renal impairment. Our data in a large population of myeloma patients indicate that adjustment for renal function will not improve the prognostic performance across all ISS stages. Disclosures:No relevant conflicts of interest to declare.

The role of capecitabine in the management of breast cancer in elderly patients

Abstract Breast cancer is frequently diagnosed in older women, yet treatment standards are based largely on clinical trials conducted in younger women. Survival outcomes for breast cancer in older women are suboptimal, partly because of underuse of appropriate therapy. Capecitabine is an oral fluoropyrimidine with a favorable side effect profile that is an attractive therapeutic option for older breast cancer patients. However, dose adjustments for renal function and careful monitoring of adherence, potential drug interactions, and toxicity are particularly important in this population. The article reviews the safety and efficacy data from studies with capecitabine monotherapy or capecitabine in combination with other therapies for breast cancer, with a particular focus on elderly patients.

Improvement of the cardiac marker N-terminal-pro brain natriuretic peptide through adjustment for renal function: a stratified multicenter trial

N-terminal-pro brain natriuretic peptide (NT-proBNP) is a useful cardiac marker that is also influenced by renal dysfunction. It was our objective to assess the relationship between NT-proBNP concentrations in plasma and worsening renal function, and to attempt adjustment of NT-proBNP for renal dysfunction in a prospective, stratified multi-center study. We stratified 203 male patients according to their cardiac status and the estimated glomerular filtration rate (eGFR). Cardiac disease was assessed by medical history, physical examination and standardized echocardiography. Patients were stratified according to the following: absence of cardiac history and abnormalities (control, CTRL, n=66), cardiac history without left ventricular hypertrophy (LVH) or left ventricular systolic dysfunction (LVD) (history, n=30), LVH without systolic dysfunction (LVH, n=68), and LVD [ejection fraction (EF) <40%, LVD, n=39]. Renal disease was stratified according to the eGFR: 15-30 mL/min (n=52), 31-75 mL/min (n=99), and >75 mL/min (n=52). NT-proBNP was correlated with eGFR in the entire study population and for all levels of cardiac disease (all p<0.01). Regression analysis allowed adjustment of NT-proBNP for eGFR in a continuous manner, and this adjustment significantly improved the predictive value (receiver operating characteristic curve for symptomatic LVD from 0.80 to 0.86, p<0.01; sensitivity from 74% to 83% and specificity from 68% to 79%). NT-proBNP correlates inversely and significantly with eGFR throughout all levels of cardiac strata. We propose for the first time a continuous adjustment algorithm which markedly improves the predictive values of NT-proBNP in male patients with impaired renal function.

Elevated Homocysteine Is a Predictor of All-Cause Mortality in a Prospective Cohort of Renal Transplant Recipients

Background: In patients with chronic kidney disease, an elevated homocysteine concentration is associated with an increased incidence of cardiovascular events. Aim: The aim of this study was to investigate the relationship between homocysteine concentration and all-cause mortality during prospective follow-up of a renal transplant cohort. Methods: A total of 378 renal transplant recipients were recruited between June 2000 and December 2002. Homocysteine was measured at baseline and mortality data was collected at a median of 2,441 days after enrolment. Results: In univariate analysis, homocysteine was a significant predictor of mortality (p < 0.001). In multivariate analysis, homocysteine remained a significant independent predictor of mortality following adjustment for traditional cardiovascular risk factors (p = 0.01), vitamin B₁₂ and folate (p < 0.001) and estimated glomerular filtration rate (p = 0.03). Conclusions: In the renal transplant recipients enrolled in this study, homocysteine concentration was a significant predictor of mortality in univariate survival analysis and in multivariate survival analysis following adjustment for traditional cardiovascular risk factors and following adjustment for renal function. Assessing the effect of lowering homocysteine concentration on the survival of patients with a renal transplant is therefore worthy of further study.

Association of low glomerular filtration rate and albuminuria with peripheral arterial disease: The National Health and Nutrition Examination Survey, 1999–2004

Microalbuminuria may be an early sign of intra-renal vascular dysfunction and a marker of vascular risk in the general population as well as in high-risk individuals. However, the association between albuminuria and PAD has been demonstrated only in few small studies. The aim of current study is to evaluate the relative impact of albuminuria and glomerular filtration rate on the risk of peripheral artery disease (PAD) in a nationally representative sample population.Data (ankle brachial index [ABI], urine albumin, fasting glucose, and glomerular filtration rate [GFR] estimated using the Modification of Diet in Renal Disease [MDRD] Study equation) were collected on 7068 adults from the National Health and Nutrition Examination Survey (NHANES 1999–2004). PAD was defined as ABI <0.9 or >1.4. There was a trend towards an association between the presence of abnormal renal function (GFR<60mL/min/1.73m2) and PAD in the non-diabetic patients (OR of 1.43, 95% CI: 0.98–2.09; P=0.07) where as the presence of abnormal renal function was strongly associated PAD in the diabetic patients (OR of 2.3, 95% CI: 1.34–3.95; P=0.046). On the contrary, albuminuria was independently associated with PAD in the non-diabetic (OR, 1.87; 95% CI, 1.38–2.52; P=0.0003) but not in the diabetic patients (OR: 1.08, 95% CI: 0.68–1.73, P=0.7411).We concluded that albuminuria, independent of renal function, is strongly associated with PAD in non-diabetic subjects. As diabetes develops and HbA1c level increases, the predictive value of albuminuria gradually diminishes after adjustment for renal function.

N-terminal Pro-Brain Natriuretic Peptide Levels Predict Left Ventricular Systolic Function in Patients with Chronic Kidney Disease

N-terminal pro-brain natriuretic peptide (NT-proBNP) can be a useful marker for left ventricular (LV) dysfunction in patients without kidney disease. This study was conducted to clarify the relationship between NT-proBNP and LV systolic function in patients with decreased renal function. We studied 256 chronic kidney disease (CKD) patients, patients on dialysis were excluded. The median glomerular filtration rate was 24 (13-36) mL/min/1.73 m2 and the median NT-proBNP was 4,849 (1,310-19,009) pg/mL. The prevalence of LV systolic dysfunction increased from the lower to the upper NT-proBNP quartiles (I, 17%; II, 34%; III, 61%; and IV, 72%; p<0.001 for trend). The NT-proBNP quartile was an independent predictor of LV systolic dysfunction after adjustment for renal function, compared with quartile I: II, odds ratio (OR) 3.99 (95% confidence interval [CI],1.34-11.93); III, OR 11.28 (95% CI, 3.74-33.95); and IV, OR 36.97 (95% CI, 11.47-119.1). Area under the curve and optimum cut points for NT-proBNP to detect LV systolic dysfunction were 0.781 and 2,165 pg/mL in CKD stage 3, 0.812 and 4,740 pg/mL in CKD stage 4, and 0.745 and 15,892 pg/mL in CKD stage 5. The NT-proBNP level was a predictor of LV systolic dysfunction in CKD patients. Optimum cut points should be stratified according to renal function.

Amino-Terminal Pro–B-Type Natriuretic Peptide Testing in Renal Disease

Concentrations of amino-terminal pro-B-type natriuretic peptides (NT-proBNP) are typically higher in patients with chronic kidney disease (CKD) than in those without CKD. These elevated levels of NT-proBNP in patients with CKD do not simply reflect the reduced clearance of the peptide; rather, they largely reflect a true-positive finding, identifying the presence of heart disease in these patients, while similarly indicating prognosis as well. Although modestly stronger inverse correlations exist between renal function and NT-proBNP compared with B-type natriuretic peptide (BNP), the dependence of both peptides on renal clearance is similar. Across the range of CKD, correlations between BNP and NT-proBNP remain strong, and the prognostic impact of NT-proBNP in patients with CKD is preserved. When evaluating the patient with acute dyspnea and CKD, both BNP and NT-proBNP are affected similarly, with higher decision limits necessary compared with patients with preserved renal function. Importantly, when using NT-proBNP to evaluate a patient with dyspnea and impaired renal function, the recommended cut points of 450, 900, and 1,800 ng/L for those aged <50, 50-75, and >75 years, respectively, do not require further adjustment for renal function. Thus, NT-proBNP testing remains useful for the diagnostic and prognostic evaluation of patients with CKD.

Resistin, acute coronary syndrome and prognosis results from the Athero Gene study

Objective Resistin, an adipocyte and macrophage derived cytokine, causes insulin resistance and glucose intolerance. We investigated the impact of resistin as a diagnostic marker in patients with acute coronary syndrome and its prognostic value for future cardiovascular events. Methods Resistin levels were determined in 1153 patients with stable angina (SAP), 380 patients with unstable angina, 278 patients with non-ST-elevation myocardial infarction (NSTEMI) and 111 patients with ST-elevation myocardial infarction (STEMI). All patients have been followed up for a median follow-up of 2.6 years. During follow-up, 70 patients died from cardiovascular causes. Results Compared to SAP, resistin levels (5.1 ng/mL in SAP) were elevated in patients with angina at rest (5.89 ng/mL, P = 0.001), in patients with NSTEMI (6.00 ng/mL, P < 0.001), and in patients with STEMI (5.98 ng/mL, P < 0.001). Resistin levels rose at 3–6 h after chest pain onset (5.46 ng/mL), persisted elevated among those individuals presenting between 6 and 12 h after chest pain onset (5.57 ng/mL) and peaked in individuals presenting more than 12 h after chest pain onset (5.74 ng/mL). An increase of one standard deviation of resistin levels was associated with a 1.22-fold (95% CI 1.04–1.43; P = 0.02) risk for future fatal cardiovascular events in a model adjusted for risk factors and clinical and therapeutic variables. When adjustment for renal function was applied, this association lost its statistical significance. Conclusions Resistin levels are elevated in patients presenting with unstable angina, NSTEMI and STEMI and might play a role as a diagnostic marker. In addition, systemic resistin level is moderately associated with future cardiovascular death in patients with documented coronary artery disease.

High serum pentosidine concentrations are associated with increased arterial stiffness and thickness in patients with type 2 diabetes

Accumulation of advanced glycation end products in vessel walls may increase arterial stiffness and/or thickness, contributing to a high incidence of cardiovascular disease (CVD) in patients with diabetes. We investigated whether serum concentrations of pentosidine, a well-defined advanced glycation end product, are associated with arterial stiffness or thickness in patients with type 2 diabetes. Pentosidine was measured in sera from 98 patients with type 2 diabetes and 61 age-matched control subjects by a competitive enzyme-linked immunosorbent assay. Arterial stiffness was evaluated by heart-brachial and brachial-ankle pulse wave velocities (PWVs) measured using an automatic device. Arterial thickness was determined ultrasonographically as carotid intima-media wall thickness (IMT). Serum concentrations of pentosidine were significantly higher in patients with diabetes than in control subjects (64.4 ± 21.0 vs 22.8 ± 7.0 μg/L; P < .0001). In patients with diabetes, serum pentosidine correlated positively with heart-brachial PWV ( r = 0.304; P < .01) but not with brachial-ankle PWV. Serum pentosidine also correlated positively with carotid IMT in patients with diabetes ( r = 0.300; P < .01). Serum pentosidine concentrations were significantly higher in patients with diabetes with CVD than in those without (72.3 ± 23.7 vs 62.3 ± 19.8 μg/L; P = .0453). By multivariate analysis, only age (partial coefficient = 0.308; P < .05) and serum creatinine (partial coefficient = 0.328; P < .01) retained significant influence on serum pentosidine. After adjustment for renal function, carotid IMT still correlated positively with serum pentosidine (partial coefficient = 0.2736; P = .021). In conclusion, serum pentosidine was positively associated with both arterial stiffness and thickness and CVD in patients with type 2 diabetes.