Cause-Specific Deaths in Non–Dialysis-Dependent CKD

CKD is associated with higher risk of death, but details regarding differences in cause-specific death in CKD are unclear. We examined the leading causes of death among a non–dialysis-dependent CKD population using an electronic medical record-based CKD registry in a large healthcare system and the Ohio Department of Health mortality files. We included 33,478 white and 5042 black patients with CKD who resided in Ohio between January 2005 and September 2009 and had two measurements of eGFR<60 ml/min per 1.73 m² obtained 90 days apart. Causes of death (before ESRD) were classified into cardiovascular, malignancy, and non-cardiovascular/non-malignancy diseases and non–disease-related causes. During a median follow-up of 2.3 years, 6661 of 38,520 patients (17%) with CKD died. Cardiovascular diseases (34.7%) and malignant neoplasms (31.8%) were the leading causes of death, with malignancy-related deaths more common among those with earlier stages of kidney disease. After adjusting for covariates, each 5 ml/min per 1.73 m² decline in eGFR was associated with higher risk of death due to cardiovascular disease (hazard ratio [HR], 1.10; 95% confidence interval [95% CI], 1.08 to 1.12) and non-cardiovascular/non-malignancy diseases (HR, 1.12; 95% CI, 1.09 to 1.14) but not to malignancy. In the adjusted models, blacks had overall-mortality hazard ratios similar to those of whites but higher hazard ratios for cardiovascular deaths. Further studies to confirm these findings and explain the mechanisms for differences are warranted. In addition to lowering cardiovascular burden in CKD, efforts to target known risk factors for cancer at the population level are needed.     

Subclinical Atherosclerosis Measures for Cardiovascular Prediction in CKD

Whether inclusion of the coronary artery calcium score improves cardiovascular risk prediction in individuals with CKD, a population with unique calcium-phosphate homeostasis, is unknown. Among 6553 participants ages 45–84 years without prior cardiovascular disease in the Multi-Ethnic Study of Atherosclerosis, coronary artery calcium score was assessed for cardiovascular risk prediction beyond the Framingham predictors in those with (n=1284) and without CKD and contrasted with carotid intima-media thickness and ankle-brachial index (two other measures of subclinical atherosclerosis). During a median follow-up of 8.4 years, 650 cardiovascular events (coronary heart disease, stroke, heart failure, and peripheral artery disease) occurred (236 events in subjects with CKD). In Cox proportional hazards models adjusted for Framingham predictors, each subclinical measure was independently associated with cardiovascular outcomes, with larger adjusted hazard ratios (HRs; per 1 SD) for coronary artery calcium score than carotid intima-media thickness or ankle-brachial index in subjects without and with CKD (HR, 1.69; 95% confidence interval [95% CI], 1.45 to 1.97 versus HR, 1.12; 95% CI, 1.00 to 1.25 and HR, 1.20; 95% CI, 1.08 to 1.32, respectively). Compared with inclusion of carotid intima-media thickness or ankle-brachial index, inclusion of the coronary artery calcium score led to greater increases in C statistic for predicting cardiovascular disease and net reclassification improvement. Coronary artery calcium score performed best for the prediction of coronary heart disease and heart failure, regardless of CKD status. In conclusion, each measure improved cardiovascular risk prediction in subjects with CKD, with the greatest improvement observed with coronary artery calcium score.     

Uric acid has a J‐shaped association with cardiovascular and all‐cause mortality in kidney transplant recipients

The association between serum uric acid and kidney graft and recipient survival is uncertain. During 2000–2011, we measured serum uric acid at week 10 after transplantation. Of 2748 transplanted patients, 2200 (80.1%) attended this visit. After a median follow‐up of 7.4 yr, 378 patients had died, 143 from a cardiovascular cause, and 185 patients lost their graft. The third quintile of uric acid levels (357–405 μM) had the lowest mortality risk and was used as reference group. In Cox proportional hazard models adjusting for graft and patient characteristics, the fifth quintile of uric acid levels (>474 μM) was independently associated with cardiovascular mortality (hazard ratio [HR] = 2.87 [1.55–5.32], p = 0.001) and all‐cause mortality (HR = 1.57 [1.09–2.25], p = 0.02). Also, the lowest quintile of uric acid levels (<309 μM) showed a trend toward increased risk of cardiovascular mortality (HR = 1.79 [0.90–3.58], p = 0.10) and all‐cause mortality (HR = 1.31 [0.89–1.93], p = 0.18). The increased risk at low uric acid levels was confined to diabetic recipients. Uric acid was not associated with death‐censored graft loss. In conclusion, uric acid has a J‐shaped association with cardiovascular and all‐cause mortality in kidney transplant recipients.     

Prognostic efficacy of combined index of cardiac biomarkers for cardiovascular and all-cause mortality on hemodialysis patients

Objective To evaluate cardiac biomarkers as biological risk factors for cardiovascular and all-cause motality in HD patients. In addition, a multimarker approach including inflammatory index was performed to improve the cardiovascular and all-cause risk assessment of these patients. Methods The author measured Troponin-T (TnT), N-terminal pro brain natriuretic peptide (NT-proBNP) and high-sensitivity C-reactive protein (HsCRP), collected the clinical data at baseline(January 2012) in 229 HD patients in three hemodialysis centers in Haidian District of Beijing, recorded time and cause of death in the next 1000 days. Kaplan-Meier was used to calculate survival rate and impact factors of prognosis. Cox proportional hazard model was used to estimate significance of TnT, NT-proBNP and HsCRP and adjusted hazard ratios (HRs) of death. Results During the follow-up, 37 patients died, mainly from cardiac cause (54.05%, 20/37). Univariate analysis found old age, diabetes, cardiovascular disease, low serum albumin, CRP≥3 mg/L, TnT≥0.1 mg/L, NT-proBNP≥4381 ng/L were associated with prognosis. Elevated cTnT, NT-proBNP or HsCRP were all associated with increased cardiovascular and all-cause motality. Moreover, the combination of all parameters (NT-proBNP≥4381 ng/L and TnT≥0.1 mg/L and HsCRP≥3 mg/L) were dramatically associated with increased cardiovascular cause mortality (HR=25.25, P＜0.01) and all-cause mortality (HR=27.33, P＜0.01). The association were significant even after full adjustment for cardiovascular (HR=14.33, P＜0.01) and all-cause mortality (HR=11.54, P＜0.01) respectively. Conclusions A combined index of cardiovascular risk factors could provide supplementary risk stratification in HD patients for cardiovascular mortality and all-cause mortality, strongly supporting the annual routine determination of these biomarkers.     

Risk of cardiovascular thrombotic events after surgical castration versus gonadotropin-releasing hormone agonists in Chinese men with prostate cancer

We investigated the cardiovascular thrombotic risk after surgical castration (SC) versus gonadotropin-releasing hormone agonists (GnRHa) in Chinese men with prostate cancer. All Chinese prostate cancer patients who were treated with SC or GnRHa from year 2000 to 2009 were reviewed and compared. The primary outcome was any new-onset of cardiovascular thrombotic events after SC or GnRHa, which was defined as any event of acute myocardial infarction or ischemic stroke. The risk of new-onset cardiovascular thrombotic event was compared between the SC group and the GnRHa group using Kaplan–Meier method. Multivariate Cox regression analysis was performed to adjust for other potential confounding factors. A total of 684 Chinese patients was included in our study, including 387 patients in the SC group and 297 patients in the GnRHa group. The mean age in the SC group (75.3 ± 7.5 years) was significantly higher than the GnRHa group (71.8 ± 8.3 years) (P < 0.001). There was increased risk of new cardiovascular thrombotic events in the SC group when compared to the GnRHa group upon Kaplan–Meier analysis (P = 0.014). Upon multivariate Cox regression analysis, age (hazard ratio [HR] 1.072, 95% confidence interval [CI] 1.04–1.11, P< 0.001), hyperlipidemia (HR 2.455, 95% CI 1.53–3.93, P< 0.001), and SC (HR 1.648, 95% CI 1.05–2.59, P = 0.031) were significant risk factors of cardiovascular thrombotic events. In conclusion, SC was associated with increased risk of cardiovascular thrombotic events when compared to GnRHa. This is an important aspect to consider while deciding on the method of androgen deprivation therapy, especially in elderly men with known history of hyperlipidemia.     

Unearthing uric acid: an ancient factor with recently found significance in renal and cardiovascular disease

Uric acid is strongly associated with cardiovascular and renal disease, but is usually not considered to have a causal role. However, recent experimental, epidemiological, and clinical studies provocatively suggest that uric acid may contribute to the development of hypertension, metabolic syndrome, and kidney disease in some patients. Clinical studies are urgently needed to examine this important possibility.     

Serum Uric Acid as a Predictor for Development of Diabetic Nephropathy in Type 1 Diabetes: An Inception Cohort Study

OBJECTIVE

Experimental and clinical studies have suggested that uric acid may contribute to the development of hypertension and kidney disease. Whether uric acid has a causal role in the development of diabetic nephropathy is not known. The objective of the present study is to evaluate uric acid as a predictor of persistent micro- and macroalbuminuria.

RESEARCH DESIGN AND METHODS

This prospective observational follow-up study consisted of an inception cohort of 277 patients followed from onset of type 1 diabetes. Of these, 270 patients had blood samples taken at baseline. In seven cases, uric acid could not be determined; therefore, 263 patients (156 men) were available for analysis. Uric acid was measured 3 years after onset of diabetes and before any patient developed microalbuminuria.

RESULTS

During a median follow-up of 18.1 years (range 1.0–21.8), 23 of 263 patients developed persistent macroalbuminuria (urinary albumin excretion rate >300 mg/24 h in at least two of three consecutive samples). In patients with uric acid levels in the highest quartile (>249 μmol/l), the cumulative incidence of persistent macroalbumnuria was 22.3% (95% CI 10.3–34.3) compared with 9.5% (3.8–15.2) in patients with uric acid in the three lower quartiles (log-rank test, P = 0.006). In a Cox proportional hazards model with sex and age as fixed covariates, uric acid was associated with subsequent development of persistent macroalbuminuria (hazard ratio 2.37 [95% CI 1.04–5.37] per 100 μmol/l increase in uric acid level; P = 0.04). Adjustment for confounders did not change the estimate significantly.

CONCLUSIONS

Uric acid level soon after onset of type 1 diabetes is independently associated with risk for later development of diabetic nephropathy.Diabetes is the leading cause of end-stage renal disease (ESRD) in the Western world, and the number of patients diagnosed each year with ESRD due to diabetes is rising (1). The complex pathogenesis for the development of diabetic nephropathy is not fully understood (2). One factor that has been associated with cardiovascular and renal disease is serum uric acid. Recently, experimental and clinical studies have suggested that uric acid may contribute to the development of hypertension, the metabolic syndrome, and kidney disease (3). The role of uric acid in the development of diabetic nephropathy is not understood. The objective of the present study is therefore to evaluate uric acid as a predictor of persistent micro- and macroalbuminuria in an inception cohort of type 1 diabetic patients followed from onset of diabetes.     

Serum Levels of Uric Acid and Diabetes Mellitus Influence Survival after Surgery for Primary Hyperparathyroidism: A Prospective Cohort Study

Background Primary hyperparathyroidism (pHPT) is associated with an increased mortality attributable to cardiovascular disease (CVD), suggested to be alleviated by surgery. The exact mechanism of the beneficial influence of parathyroidectomy on survival is unknown. Furthermore, studies suggest that there is no increased mortality compared to the mortality rate in the general population during recent years. This study therefore investigated relative survival (RS), as well overall mortality associated with the clinical and biochemical variables in patients undergoing operation for sporadic pHPT. Furthermore, the influence of surgery on biochemical variables associated with pHPT was analyzed. Methods A group of 323 patients with sporadic pHPT operated between September 1989 and July 2003 were followed from surgery over a 10-year period. The median and mean follow-up time was 69 and 70 months, respectively (range: 1–120 months). Relative survival (RS) was calculated, and the impact of clinical and biochemical variables on overall death were evaluated. Results Postoperatively, serum levels of triglycerides and uric acid decreased. Glucose levels and glomerular filtration rate remained unchanged. A decreased RS was evident during the latter part of the 10 year follow-up period. In the multivariate Cox-analysis, diabetes mellitus (hazard ratio [HR] = 2.8, 95%; confidence interval [CI] 1.2–6.7), and the combination of an increased level of serum uric acid and cardiovascular disease (CVD) (HR = 8.6, 95%; CI 1.5–49.7) was associated with a higher mortality. The increased risk of death was evident for patients with persistently increased levels of uric acid postoperatively (HR = 4.8, 95%; CI = 1.4–16.01) Conclusions Patients undergoing operation for pHPT had a decreased RS during a 10-year follow-up compared to the general population. This decrease in RS is associated with diabetes mellitus and increased levels of uric acid pre-and postoperatively.     

Uric acid, microalbuminuria and cardiovascular events in high-risk patients

BACKGROUND: Elevated levels of serum uric acid and albuminuria are associated with cardiovascular disease, but the relationships have not consistently been demonstrated to be independent of hypertension, other risk factors, or each other. The purpose of this study was to evaluate people at high risk for cardiovascular disease for the influence of uric acid and microalbuminuria on cardiovascular events. METHODS: Consecutive consenting patients undergoing elective angiography (n = 316) had coronary artery disease, risk factors, renal function and diuretic use assessed at baseline. Cardiovascular mortality and major clinical events (myocardial infarction, stroke, amputation, and kidney failure) were ascertained over 5 years. RESULTS: Cardiovascular events occurred in 10% of the patients. Significant correlates (p < 0.05) of cardiovascular events with baseline measures included uric acid > or =5.2 mg/dl, total cholesterol > or =200 mg/dl, severe angiographic coronary artery disease, loop diuretic therapy, and diagnosis of hypertension. A stepwise Cox modeling procedure identified uric acid (p = 0.040), the interaction of hypertension and uric acid (p = 0.029), the interaction of total cholesterol and severe coronary artery disease (p = 0.001) and loop diuretic therapy (p = 0.009) as significant independent predictors of events. Although microalbuminuria was not retained in the final multivariate model, it was associated with poorer cardiovascular disease outcomes. The mean event-free survival for albumin-to-creatinine >30 mg/g was 51 months and for albumin-to-creatinine <30 mg/g the mean was 57 months (p = 0.021). CONCLUSIONS: Uric acid > or =5.2 mg/dl independently imparted a 3.5-fold increased risk (OR 3.5, 95% CI 1.0-11.9) for cardiovascular death and major clinical events over a 5-year period. Uric acid may be a contributing factor to the progression of atherosclerosis and its complications.     

Increased risk of modality failure with higher serum uric acid level in continuous ambulatory peritoneal dialysis patients: a prospective cohort study

BackgroundPeritoneal dialysis (PD) is one of the most important kidney replacement therapies for patients with end‐stage kidney disease (ESKD). PD technique failure can lead to an escalated cost and increased infectious and cardiovascular risk, up and including to death. The accumulation of uric acid (UA) was associated with adverse outcomes in ESKD patients. However, the relationship between serum UA and technique failure is little explored.MethodsHere, a total of 266 continuous ambulatory peritoneal dialysis (CAPD) patients (age, 41.8 ± 12.6 years; 125 males) were enrolled and followed up for 31.7 months. Serum UA levels were examined at baseline and each visit. Subjects were divided into three groups according to their baseline serum UA concentrations. Multivariable Cox regression models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) of PD technique failure.ResultsThe level of serum UA increased gradually as time prolonged. During the follow-up period, 77 (28.9%) patients occurred PD technique failure, of which 56 (21.1%) transferred to hemodialysis (HD) and 21 (7.9%) died. Compared to the lowest UA tertile, after adjusting for potential confounders, HRs of technique failure in tertile 2 and tertile 3 were 1.82 (95% CI: 0.95–3.49) and 2.03 (95% CI: 1.05–3.92), respectively, and p for trend was 0.043. Adjusted HRs of all-cause technique failure, transferring to HD and mortality with each 1 mg/dL increase in serum UA were 1.20 (95% CI: 1.03–1.40, p = 0.019), 1.22 (95% CI: 1.01–1.48, p = 0.039), and 1.25 (95% CI: 0.94–1.67, p = 0.128), respectively.ConclusionHigher serum UA level predicted higher risk of technique failure in CAPD patients.     

Proton pump inhibitor usage is associated with higher all-cause mortality and CV events in peritoneal dialysis patients

ObjectivesA long period of inappropriate proton pump inhibitors (PPI) treatment has been proved to be associated with adverse prognosis in general population and hemodialysis patients. This study was conducted to clarify the impact of PPI usage on mortality and adverse cardiovascular (CV) events in peritoneal dialysis (PD) patients.Methods and designThis is a retrospective study. A total of 905 patients were enrolled from two PD centers, including 211 patients on PPI treatment and 618 patients not on PPIs. Kaplan–Meier curves were used to identify the incidence of adverse outcomes. Multivariate Cox regression models and inverse probability of treatment weighting (IPTW) were applied to analyze hazard ratios (HRs) for adverse outcomes.ResultsDuring follow-up, 162 deaths and 102 CV events were recorded. Kaplan–Meier curve demonstrated all-cause mortality (log-rank test p = .018) and CV events (log-rank test p = .024) were significantly higher in PPI usage group. Multivariate Cox regression models and IPTW showed that PPI usage was an indicator for all-cause mortality (HR = 1.35, 95%CI = 1.09–1.67, p = .006) and CV events (HR = 1.78, 95%CI = 1.35–2.32, p < .001).ConclusionsPPI usage is associated with higher all-cause mortality and CV events in PD patients. Clinicians are supposed to be more careful when using PPI and need to master the indications more rigorously in patients receiving PD treatment.     

Genetic markers associated with long‐term cardiovascular outcome in kidney transplant recipients

There is a clear genetic contribution to the risk of cardiovascular diseases, and a composite genetic risk score (GRS) based on 27 single nucleotide polymorphisms (SNPs) was reported to predict risk of cardiovascular events in the general population. We aimed to evaluate this risk score in renal transplant recipients, a population with heightened cardiovascular risk, with a yet unknown genetic contribution. A total of 1640 participants from the ALERT trial (Assessment of Lescol in Renal Transplantation), a study comparing fluvastatin with placebo in stable renal transplant recipients, were genotyped for all SNPs making up the GRS. Risk alleles were weighted by the log of odds ratios reported in genome wide association studies and summed. Associations between GRS and time from study inclusion to first major cardiovascular event (MACE) were analyzed by Cox regression. In analyses adjusted for cardiovascular risk factors, GRS was significantly associated with MACE (hazard ratio [HR] 1.81, P = .006) when comparing genetic high‐risk patients (quartile 4) with genetic low‐risk participants (quartile 1). A 27‐SNP GRS, which predicted cardiovascular events in the nontransplant population, appears to have predictive value also in kidney allograft recipients. Refining the score to better fit the transplant population seems feasible.     

Immune Sensitization and Mortality in Wait-Listed Kidney Transplant Candidates

Cardiovascular mortality is the leading cause of death in ESRD. Whereas innate and adaptive immunity have established roles in cardiovascular disease, the role of humoral immunity is unknown. We conducted a retrospective cohort study in first-time adult kidney transplant candidates (N=161,308) using data from the Scientific Registry of Transplant Recipients and the Centers for Medicare and Medicaid Services to evaluate whether anti–human leukocyte antigen antibodies, measured as panel reactive antibodies (PRAs), are related to mortality in ESRD. Relationships between time-varying PRAs and all-cause or cardiovascular mortality were assessed using Cox proportional hazards models. The analysis was repeated in subcohorts of candidates at lower risk for significant comorbidities, activated on the waiting list after 2007, or unsensitized at activation. Competing risks analyses were also conducted. Fully adjusted models showed increased hazard ratios (HRs [95% confidence intervals]) for all-cause mortality (HR, 1.02 [95% CI, 0.99 to 1.06]; HR, 1.11 [95% CI,1.07 to 1.16]; and HR,1.21 [95% CI,1.15 to 1.27]) and cardiovascular mortality (HR, 1.05 [95% CI,1.00 to 1.10]; HR,1.11 [95% CI,1.05 to 1.18]; and HR,1.21 [95% CI,1.12 to 1.31]) in PRA 1%–19%, PRA 20%–79%, and PRA 80%–100% categories compared with PRA 0%, respectively. Associations between PRA and the study outcomes were accentuated in competing risks models and in lower-risk patients and persisted in other subcohorts. Our findings suggest that PRA is an independent predictor of mortality in wait-listed kidney transplant candidates. The mechanisms by which PRA confers an incremental mortality risk in sensitized patients, and the role of transplantation in modifying this risk, warrant further study.     

Revisiting mortality predictability of serum albumin in the dialysis population: time dependency, longitudinal changes and population-attributable fraction.

BACKGROUND: Hypoalbuminaemia is a marker of malnutrition-inflammation complex syndrome (MICS) and a strong predictor of cardiovascular (CV) death in maintenance haemodialysis (MHD) patients. However, serum albumin may change over time. Hence, its time-varying associations with outcome may be different. METHODS: Associations between 3-month averaged serum albumin levels, measured in a single laboratory using bromocresol green, and CV mortality were studied longitudinally in a 2-year cohort of 58,058 MHD patients. Mortality predictability of fixed baseline and trimonthly-varying serum albumin concentrations were compared. RESULTS: Hazard ratios (HRs) of CV death strictly increased across decrements of baseline serum albumin, whereas the HR for time-varying serum albumin decrements below 3.8 g/dl did not differ. A drop in serum albumin in the first 6 months was associated with increasing all-cause and CV death risks in the subsequent 18 months, while a rise in serum albumin was a predictor of better survival independent of baseline serum albumin. The multivariate adjusted population-attributable fraction of death due to baseline serum albumin <3.8 g/dl was 19%. CONCLUSIONS: Time-varying hypoalbuminaemia predicts all-cause and CV death differently from fixed measures of serum albumin in MHD patients. An increase in serum albumin over time is associated with better survival independent of baseline serum albumin or other MICS surrogates. If this association is causal, an intervention that could increase serum albumin >3.8 g/dl might reduce the number of MHD deaths in the USA by approximately 10,000 annually. Nutritional interventions examining benefits of increasing serum albumin in MHD patients are urgently needed.     

Uric acid and incident kidney disease in the community

Uric acid may mediate aspects of the relationship between hypertension and kidney disease via renal vasoconstriction and systemic hypertension. To investigate the relationship between uric acid and subsequent reduced kidney function, limited-access data of 13,338 participants with intact kidney function in two community-based cohorts, the Atherosclerosis Risks in Communities and the Cardiovascular Health Study, were pooled. Mean baseline serum uric acid was 5.9 +/- 1.5 mg/dl, mean baseline serum creatinine was 0.9 +/- 0.2 mg/dl, and mean baseline estimated GFR was 90.4 +/- 19.4 ml/min/1.73 m(2). During 8.5 +/- 0.9 yr of follow-up, 712 (5.6%) had incident kidney disease defined by GFR decrease (>or=15 ml/min/1.73 m(2) with final GFR <60 ml/min/1.73 m(2)), while 302 (2.3%) individuals had incident kidney disease defined by creatinine increase (>or=0.4 mg/dl with final serum creatinine >1.4 mg/dl in men and 1.2 mg/dl in women). In GFR- and creatinine-based logistic regression models, baseline uric acid level was associated with increased risk for incident kidney disease (odds ratio 1.07 [95% confidence interval 1.01 to 1.14] and 1.11 [95% confidence interval 1.02 to 1.21] per 1-mg/dl increase in uric acid, respectively), after adjustment for age, gender, race, diabetes, systolic BP, hypertension, cardiovascular disease, left ventricular hypertrophy, smoking, alcohol use, education, lipids, albumin, hematocrit, baseline kidney function and cohort; therefore, elevated serum uric acid level is a modest, independent risk factor for incident kidney disease in the general population.     

Low Vitamin D and High Fibroblast Growth Factor 23 Serum Levels Associate with Infectious and Cardiac Deaths in the HEMO Study

Longitudinal studies testing the relationship between repeated measures of vitamin D or fibroblast growth factor 23 (FGF23) and infectious and cardiac hospitalizations and death in hemodialysis patients have not been reported. We examined the association between yearly 25-hydroxyvitamin D (25(OH)D), 1,25-dihydroxyvitamin D (1,25(OH)₂D), and FGF23 serum levels and various clinical outcomes using time-dependent Cox regression models with repeated yearly measures and fixed-covariate Cox models with only baseline values after controlling for important clinical covariates in the HEMO study. During a median follow-up of 3 years, 582 of the 1340 participants died, and 499 and 514 participants had a hospitalization or death attributed to infectious and cardiac causes, respectively. Patients in the highest 25(OH)D quartile had the lowest risk of infectious events (hazard ratio [HR] 0.66 versus the lowest quartile; 95% confidence interval [95% CI], 0.49–0.89), cardiac events (HR, 0.71; 95% CI, 0.53–0.96), and all-cause mortality (HR, 0.46; 95% CI, 0.34–0.62) in time-dependent analyses. No significant associations of 1,25(OH)₂D with clinical outcomes were observed in time-dependent or fixed-covariate Cox models. In contrast, the highest FGF23 quartile was associated with a higher risk of infectious events (HR, 1.57 versus the lowest quartile; 95% CI, 1.13–2.18), cardiac events (HR, 1.49; 95% CI, 1.06–2.08), and all-cause mortality (HR, 1.50; 95% CI, 1.07–2.12) in fixed-covariate Cox models. The addition of inflammation markers into the statistical models did not attenuate these associations. Thus, disordered mineral metabolism may affect outcomes in chronic hemodialysis patients.     

Association of Height with Elevated Mortality Risk in ESRD: Variation by Race and Gender

The association of adult height with mortality has been extensively investigated in the general population, but little is known about this relationship among dialysis patients. We explored the relationship between height and mortality in a retrospective cohort study of 1,171,842 adults who began dialysis in the United States from 1995 to 2008 and were followed until December 31, 2010. We evaluated height-mortality associations in sex-specific quintiles of increasing height (Q1–Q5) using multivariable Cox regression models adjusted for demographics, comorbid conditions, lifestyle and disability indicators, socioeconomic status, and body weight. For men, compared with the referent quintile (Q1 <167 cm), successive height quintiles had significantly increased hazard ratios (HRs [95% confidence interval]) for mortality: 1.04 (1.02–1.06), 1.08 (1.06–1.10), 1.12 (1.11–1.14), and 1.18 (1.16–1.20) for Q2–Q5, respectively. For women (referent Q1 <155 cm), HRs for mortality were 1.00 (0.99–1.02), 1.05 (1.03–1.06), 1.05 (1.03–1.07), and 1.08 (1.06–1.10) for Q2–Q5, respectively. However, stratification by race showed the pattern of association differed significantly by race (P<0.001 for interaction). For black men, unlike other race groups, height only associated with mortality in Q5, with an HR of 1.06 (1.02–1.09). For black women, HRs for mortality were 0.94 (0.91–0.97), 0.98 (0.95–1.02), 0.96 (0.93–0.99), and 0.99 (0.96–1.02) for Q2–Q5, respectively. These results indicate tallness is associated with higher mortality risks for adults starting dialysis, but this association did not extend to black patients.     

Serum nitric oxide metabolites and hard clinical endpoints: a population-based prospective study

Objective. Limited data are available regarding prognostic value of nitric oxide metabolites (NOx) for clinical hard end points. In this study, we defined optimum cut-off values of serum NOx for predicting all-cause and cardiovascular disease (CVD) mortality events and prospectively investigated their hazards in the presence of traditional risk factors. Design. Serum NOx concentrations were measured at baseline (2006–2008) and 3520 adult men and women were followed during 7.7 years for all-cause and cardiovascular disease (CVD) mortality. To determine the optimal cut-off points of serum NOx, the receiver operator characteristic (ROC) curve analysis was used. Multivariate Cox proportional hazard models were used to estimate the hazard ratios (HRs) with 95% confidence intervals (95% CIs) of all-cause and CVD mortality below and above the defined optimal cut-off points of serum NOx. Results. Mean age of participants was 44.5?±?16.0 years at baseline and 40.2% were male. Median (inter-quartile range) of serum NOx levels was 25.0 µmol/L (19.0–37.0), at baseline. The optimal cut-off points of serum NOx levels for predicting CVD and all-cause mortality were 30.5 and 32.5 µmol/L, respectively. In the presence of age, sex, body mass index, smoking, type 2 diabetes, hypertension, and history of CVD, a significant increased risk of CVD mortality (HR?=?1.98, 95% CI?=?1.10–3.58) and all-cause mortality (HR?=?1.52, 95% CI?=?1.05–2.21) was observed for serum NOx values higher than their cut-offs. Conclusion. Serum NOx level may be predictor of CVD mortality and death, in general populations.     

Impact of schizophrenia and related disorders on mortality from breast cancer: A population-based cohort study in Denmark, 1995–2011

ObjectivesTo investigate overall and breast cancer-specific mortality in early-stage breast cancer patients with and without schizophrenia or related disorders.MethodsWe used Danish national registers to identify all women with no prior history of cancer or organic mental disorders, who were diagnosed with early-stage breast cancer 1995–2011. Logistic regression models were used to calculate the odds ratios (ORs) for not being allocated to guideline treatment. Cox regression models were used to compute hazard ratios (HRs) for overall and breast cancer-specific deaths among women allocated or not allocated to guideline treatment.ResultsWe identified 56,152 women with early-stage breast cancer diagnosed in 1995–2011, of whom 499 women also had been diagnosed with schizophrenia or related disorders. The likelihood of women with schizophrenia or related disorders for not being allocated to guideline treatment was increased (adjusted OR, 1.50; 95% confidence interval (CI), 1.15–1.94). The adjusted HR for all-cause mortality was 1.55; 95% CI, 1.32–1.82 and 1.12 (95% CI, 0.98–1.50) for breast cancer-specific mortality; women allocated to guideline treatment had an adjusted HR for breast cancer-specific death of 1.42 (95% CI, 1.11–1.82). The adjusted HR for death due to unnatural causes was 3.67 (95% CI, 1.80–7.35).ConclusionThe survival of women with schizophrenia or related disorders after breast cancer is significantly worse than that of women without these disorders. These patients are less likely to be allocated to guideline treatment, and, among those who are, mortality from both breast cancer and other causes is increased.     

Uric acid and nocturnal nondipping in hypertensive patients with normal renal function

BACKGROUND: The effect of uric acid on nocturnal dipping in hypertensive patients is unknown. We analyzed the specific relationship between uric acid and nocturnal dipping status in newly diagnosed essential hypertensive patients with normal renal function. METHODS: Two hundred fifteen patients with newly diagnosed essential hypertension underwent 24-hour ambulatory blood pressure monitoring, biochemistry analysis and 24-hour urine testing. RESULTS: Patients were classified as either dippers (157 patients) or nondippers (58 patients). Uric acid levels were higher in nondippers than in dippers (345.0 +/- 65.4 mmol/L vs. 270.6 +/- 59.5 mmol/L, p<0.0001) and positively correlated with the following blood pressure (BP) values: average nighttime ambulatory systolic BP (r=0.325, p<0.0001), average nighttime ambulatory diastolic BP (r=0.203, p=0.003), nighttime mean arterial BP (r=0.285, p<0.0001) and mean 24-hour arterial BP (r=0.197, p=0.004). Uric acid was also positively correlated with nighttime heart rate (r=0.293, p=0.001). Univariate logistic regression analysis showed that a high serum uric acid level (odds ratio [OR] = 3.566; 95% confidence interval [95% CI], 2.397-5.303; p<0.0001) and smoking (OR=2.294; 95% CI, 1.155-4.498; p=0.018) increased the risk of nocturnal nondipping. The results of multivariate analysis showed that serum uric acid levels (OR=3.453; 95% CI, 1.466-8.134; p=0.005) together with fasting blood glucose (OR=1.148; 95% CI, 1.028-1.281; p=0.014) were associated with the nondipping pattern. CONCLUSIONS: This study is the first to demonstrate that increased serum uric acid levels are associated with nondipping blood pressure patterns in patients with essential hypertension.