The Associations between Peripheral Artery Disease and Physical Outcome Measures in Men and Women with Chronic Kidney Disease.

BACKGROUND: Peripheral artery disease (PAD) is highly prevalent and associated with significant morbidity and mortality, but sex-based differences are incompletely understood. We sought to define the associations between PAD and physical outcome measures and to determine if these associations differed by sex in the Chronic Renal Insufficiency Cohort. METHODS: Among 3,543 participants, we assessed the cross-sectional relationship between PAD severity defined by ankle-brachial index; and (1) physical activity (metabolic equivalent [MET]-hr/wk), (2) walking pace (slow versus medium and/or fast), and (3) physical function (12-item Short Form Health Survey [SF-12]) at baseline. RESULTS: In a multivariable linear regression model, PAD severity was not associated with physical activity defined by total MET-hr per wk in men or women (P = 0.432). However, PAD severity was significantly associated with walking activity (P = 0.037), although this relationship did not differ by sex (P = 0.130). Similarly, PAD severity was significantly associated with walking pace (P < 0.001), although this relationship did not differ by sex (P = 0.086). In contrast, there was an independent association between PAD severity and SF-12 (P = 0.018), with a significant interaction by sex (P < 0.001). CONCLUSIONS: These data suggest that tools used to evaluate the functional consequences of PAD should focus on walking activity and walking pace, as well as physical function, where sex-specific associations should be accounted for.

Genetic African Ancestry and Markers of Mineral Metabolism in CKD.

BACKGROUND AND OBJECTIVES: Disorders of mineral metabolism are more common in African Americans with CKD than in European Americans with CKD. Previous studies have focused on the differences in mineral metabolism by self-reported race, making it difficult to delineate the importance of environmental compared with biologic factors. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: In a cross-sectional analysis of 3013 participants of the Chronic Renal Insufficiency Cohort study with complete data, we compared markers of mineral metabolism (phosphorus, calcium, alkaline phosphatase, parathyroid hormone, fibroblast growth factor 23, and urine calcium and phosphorus excretion) in European Americans versus African Americans and separately, across quartiles of genetic African ancestry in African Americans (n=1490). RESULTS: Compared with European Americans, African Americans had higher blood concentrations of phosphorus, alkaline phosphatase, fibroblast growth factor 23, and parathyroid hormone, lower 24-hour urinary excretion of calcium and phosphorus, and lower urinary fractional excretion of calcium and phosphorus at baseline (P<0.001 for all). Among African Americans, a higher percentage of African ancestry was associated with lower 24-hour urinary excretion of phosphorus (Ptrend<0.01) in unadjusted analyses. In linear regression models adjusted for socio-demographic characteristics, kidney function, serum phosphorus, and dietary phosphorus intake, higher percentage of African ancestry was significantly associated with lower 24-hour urinary phosphorus excretion (each 10% higher African ancestry was associated with 39.6 mg lower 24-hour urinary phosphorus, P<0.001) and fractional excretion of phosphorus (each 10% higher African ancestry was associated with an absolute 1.1% lower fractional excretion of phosphorus, P=0.01). CONCLUSIONS: A higher percentage of African ancestry was independently associated with lower 24-hour urinary phosphorus excretion and lower fractional excretion of phosphorus among African Americans with CKD. These findings suggest that genetic variability might contribute to racial differences in urinary phosphorus excretion in CKD.

Sex Differences in the Incidence of Peripheral Artery Disease in the Chronic Renal Insufficiency Cohort.

BACKGROUND: To define how the incidence of peripheral artery disease (PAD) in chronic kidney disease differs according to sex and age. METHODS AND RESULTS: The Chronic Renal Insufficiency Cohort (CRIC) is a multicenter, prospective cohort study of chronic kidney disease participants. Fine and Gray methods were used to determine the cumulative incidence of PAD, defined by an ankle brachial index <0.90 or a confirmed PAD event, with death as a competing event. Adjusted subdistribution hazard ratios from the Fine and Gray model determined the risk of PAD according to sex. A priori, we hypothesized that the relationship between sex and cumulative incidence of PAD differed according to age. The mean age of the 3174 participants in this study was 56.6 years and consisted of 55% males. During a median follow-up of 5.9 years, 17.8% developed PAD, 13.0% were lost to follow-up and 11.1% died. Females had a 1.53-fold greater adjusted PAD risk compared with males (95% confidence interval, 1.27-1.84; P<0.001). These sex-related differences in PAD risk also differed by age (P=0.013). Women, compared with men were at a markedly increased risk for PAD at younger ages; however, at ages >70 years, the risk was similar across both the sexes. Older men had a substantially greater PAD risk compared with younger men. In women, PAD risk did not vary with age. CONCLUSIONS: Females with chronic kidney disease have a higher PAD risk compared with males at younger ages. There is an important need to improve our understanding of the biological and clinical basis for these differences.

Healthy lifestyle and risk of kidney disease progression, atherosclerotic events, and death in CKD: findings from the Chronic Renal Insufficiency Cohort (CRIC) Study.

BACKGROUND: In general populations, healthy lifestyle is associated with fewer adverse outcomes. We estimated the degree to which adherence to a healthy lifestyle decreases the risk of renal and cardiovascular events among adults with chronic kidney disease (CKD). STUDY DESIGN: Prospective cohort. SETTING & PARTICIPANTS: 3,006 adults enrolled in the Chronic Renal Insufficiency Cohort (CRIC) Study. PREDICTORS: 4 lifestyle factors (regular physical activity, body mass index [BMI] of 20-<25kg/m(2), nonsmoking, and "healthy diet"), individually and in combination. OUTCOMES: CKD progression (50% decrease in estimated glomerular filtration rate or end-stage renal disease), atherosclerotic events (myocardial infarction, stroke, or peripheral arterial disease), and all-cause mortality. MEASUREMENTS: Multivariable-adjusted Cox proportional hazards. RESULTS: During a median follow-up of 4 years, we observed 726 CKD progression events, 355 atherosclerotic events, and 437 deaths. BMI≥25kg/m(2) and nonsmoking were associated with reduced risk of CKD progression (HRs of 0.75 [95% CI, 0.58-0.97] and 0.61 [95% CI, 0.45-0.82] for BMIs of 25 to <30 and ≥30kg/m(2), respectively, versus 20 to <25kg/m(2); HR for nonsmoking of 0.68 [95% CI, 0.55-0.84] compared to the current smoker reference group) and reduced risk of atherosclerotic events (HRs of 0.67 [95% CI, 0.46-0.96] for BMI of 25-<30 vs 20-<25kg/m(2) and 0.55 [95% CI, 0.40-0.75] vs current smoker). Factors associated with reduced all-cause mortality were regular physical activity (HR, 0.64 [95% CI, 0.52-0.79] vs inactive), BMI≥30kg/m(2) (HR, 0.64 [95% CI, 0.43-0.96] vs 20-<25kg/m(2)), and nonsmoking (HR, 0.45 [95% CI, 0.34-0.60] vs current smoker). BMI<20kg/m(2) was associated with increased all-cause mortality risk (HR, 2.11 [95% CI, 1.13-3.93] vs 20-<25kg/m(2)). Adherence to all 4 lifestyle factors was associated with a 68% lower risk of all-cause mortality compared to adherence to no lifestyle factors (HR, 0.32; 95% CI, 0.11-0.89). LIMITATIONS: Lifestyle factors were measured only once. CONCLUSIONS: Regular physical activity, nonsmoking, and BMI≥25kg/m(2) were associated with lower risk of adverse outcomes in this cohort of individuals with CKD.