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Kidney function, bone-mineral metabolism markers, and future risk of peripheral artery disease.

ABSTRACT: BACKGROUND AND AIMS:Reduced kidney function is a risk factor for lower-extremity peripheral artery disease (PAD). However, the associations of novel filtration markers with PAD are yet to be quantified. Moreover, little is known on whether bone-mineral metabolism (BMM) markers are related to incident PAD beyond kidney function. METHODS:Using data from 12,472 participants at baseline (1990-1992) of the Atherosclerosis Risk in Communities (ARIC) study, we comprehensively quantified the associations of kidney related markers with incident PAD (defined as hospitalizations with diagnosis of lower-extremity atherosclerosis, revascularization, or amputation). Kidney related markers of interest included estimated glomerular filtration rate (eGFR) (based on creatinine, cystatin C, and both), cystatin C, beta-2 microglobulin (B2M), and BMM markers (serum fibroblast growth factor 23, parathyroid hormone, calcium, and phosphorus). RESULTS:During a median follow-up of 21 years, 471 participants developed incident PAD. Low eGFR was significantly associated with future PAD risk, with slightly stronger relationship when cystatin C was used (adjusted hazard ratio [HR] 6.3-8.3 for eGFR <30 and 2.4-3.5 for eGFR 30-59 vs. eGFR ?90 mL/min/1.73 m2). Among all filtration markers, B2M had the strongest association with incident PAD (HR for top vs. bottom quartile 2.60 [95% CI: 1.91-3.54] for B2M vs. 1.20 [0.91-1.58] for creatinine-based eGFR). Among BMM markers, only phosphorus remained significant for PAD risk beyond potential confounders, including kidney function (HR 1.47 [1.11-1.94] in top quartile). CONCLUSIONS:Kidney dysfunction was independently associated with future PAD risk, particularly when assessed with cystatin C and B2M. Among the BMM markers tested, phosphorus was most robustly associated with incident PAD beyond kidney function. Our results suggest the potential usefulness of novel filtration markers for PAD risk assessment and the possible role of phosphorus in the pathophysiology of PAD.

SUBMITTER: Yang C

PROVIDER: S-EPMC5705382 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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Kidney function, bone-mineral metabolism markers, and future risk of peripheral artery disease.

Yang Chao C Kwak Lucia L Ballew Shoshana H SH Garimella Pranav S PS Jaar Bernard G BG Folsom Aaron R AR Heiss Gerardo G Selvin Elizabeth E Lutsey Pamela L PL Coresh Josef J Matsushita Kunihiro K

Atherosclerosis 20170922

<h4>Background and aims</h4>Reduced kidney function is a risk factor for lower-extremity peripheral artery disease (PAD). However, the associations of novel filtration markers with PAD are yet to be quantified. Moreover, little is known on whether bone-mineral metabolism (BMM) markers are related to incident PAD beyond kidney function.<h4>Methods</h4>Using data from 12,472 participants at baseline (1990-1992) of the Atherosclerosis Risk in Communities (ARIC) study, we comprehensively quantified ...[more]

PMID: 28992939

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Project description:ObjectiveWe have previously shown that peripheral artery disease (PAD) is associated with marked impairment of endothelial function (EF). Given that poor EF is associated with functional status of PAD patients as well as with increased morbidity and mortality in patients undergoing vascular procedures, determination of factors associated with poor EF in a PAD cohort is important. We hypothesized that decreased kidney function is associated with impaired EF in patients with PAD.MethodsThis was a cross-sectional study of PAD patients presenting to a vascular surgery outpatient clinic at the San Francisco Veterans Affairs Medical Center including patients enrolled in the OMEGA-PAD I trial (NCT01310270) and the OMEGA-PAD Cohort. Brachial artery flow-mediated vasodilation was performed to assess EF. Kidney function was characterized by estimated glomerular filtration rate with the abbreviated Modification of Diet in Renal Disease formula. Linear regression was performed to assess the relationship between EF and kidney function in claudicants.ResultsNinety-seven patients with intermittent claudication participated in this study. Mean age was 69 ± 8 years, 97% were male, and 79% were white. Comorbidities included hypertension (91%), dyslipidemia (87%), coronary artery disease (42%), and diabetes mellitus (38%). Mean ankle-brachial index was 0.73 ± 0.14 and mean flow-mediated vasodilation was 7.0% ± 3.8%, indicating impaired EF. Linear regression showed an association between kidney function and EF (by 10 mL/min/1.73 m(2); β, 0.12; confidence interval, 0.05-0.20; P = .001). After multivariable regression adjusting for age, race, log tumor necrosis factor α, hypertension, dyslipidemia, and diabetes, estimated glomerular filtration rate remained significantly associated with EF (P = .033).ConclusionsIn patients with PAD, decreased kidney function is associated with endothelial dysfunction. Further longitudinal studies are needed to better understand the impact of kidney function on PAD progression and the role of endothelial dysfunction in this process.

Project description:Background and objectivesMineral and bone disorders (MBDs) are common in long-term dialysis patients and are risk factors for unfavorable outcomes. The associations between pretransplant levels of MBD surrogates and outcomes after kidney transplantation are not clear.Design, setting, participants, & measurementsData from the Scientific Registry of Transplant Recipients up to June 2007 were linked to the 5-year (July 2001-June 2006) cohort of a large dialysis organization in the United States. All dialysis patients who received a kidney transplant during this period were identified and divided into groups according to increments of pretransplant MBD markers. Unadjusted and multivariate adjusted predictors of transplant outcomes were examined.ResultsThe 11,776 patients were aged 47 ± 14 years and 39% were women. Compared with recipients with pretransplant time-averaged serum alkaline phosphatase of 80-120 U/L, recipients with pretransplant serum alkaline phosphatase of 120-160 and ≥160 U/L had 49% and 64% higher graft failure censored all-cause mortality in multivariable adjusted models. There was no significant association between time-averaged serum alkaline phosphatase categories and risk of death censored graft failure, delayed graft function (DGF), or acute rejection (AR). Compared with recipients with pretransplant time-averaged serum parathyroid hormone (PTH) levels of 150-300 pg/ml, there was no significant association with graft censored death among recipients with pretransplant serum PTH ≥800 pg/ml. In addition, the risk of graft failure, DGF, and AR did not show any association with time-averaged serum intact PTH level. There was no significant association between time-averaged serum calcium categories and risk of graft failure censored death, DGF, and AR.ConclusionsIn this cohort, hemodialysis patients with pretransplant serum alkaline phosphatase >120 U/L have unfavorable post-transplant mortality, whereas there was no association between serum PTH and serum calcium levels and post-transplant outcomes.

Project description:Kidney function decreases with age; however, the long-term influence on bone density (BMD) in older women already at risk of osteoporosis is unknown. We followed kidney function and bone loss for 10 years. Declining kidney function was adversely associated with bone loss and mineral homeostasis in old women, though it attenuated with advanced aging.IntroductionExisting studies do not fully address the relationship between kidney function and bone metabolism with advanced aging in Caucasian women. This study describes the association between kidney function, BMD, bone loss and bone metabolism in older women and provides a review of the available literature for context.MethodsWe studied participants from the OPRA cohort with follow-up after 5 and 10 years. Using plasma cystatin C (cysC), estimated glomerular function rate (eGFR) was evaluated at age 75 (n = 981), 80 (n = 685) and 85 (n = 365). Women were stratified into "normal" function (CKD stages 1-2), "intermediate" (stage 3a) and "poor" (stages 3b-5), and outcome measures-BMD, bone loss and markers of mineral homeostasis-were compared.ResultsFemoral neck (FN) BMD positively associated with kidney function at 75 years old ([Formula: see text] = 0.001, p = 0.028) and 80 years old ([Formula: see text] = 0.001, p = 0.001), although with small effect size. Prevalence of osteoporosis (FN T-score ? - 2.5) did not differ with kidney function. Measured at age 75, women with poor kidney function had higher annual percentage bone loss over 5 years compared to those with normal function (2.3%, 95% CI 1.8-2.8 versus 1.3%, 95% CI 1.1-1.5, p = 0.007), although not when measured from age 80 or 85. Additionally, markers of mineral homeostasis (PTH, phosphate, vitamin D, calcium), CRP and osteocalcin differed by kidney function.ConclusionsIn old women, kidney function is associated with BMD, bone loss and altered mineral homeostasis; probably, a relationship attenuated in the very elderly.

Project description:BackgroundChronic kidney disease-mineral and bone disorder (CKD-MBD) in dogs is associated with hypovitaminosis D, increased parathyroid hormone (PTH), and increased fibroblast growth factor-23 (FGF-23) concentrations. Best practice for vitamin D metabolite supplementation in CKD-MBD remains unknown.ObjectiveTo provide an extended-release calcifediol supplement to dogs with CKD and to measure its effects on variables indicative of CKD-MBD.AnimalsTen dogs with International Renal Interest Society stages 2 and 3 CKD.MethodsIn a prospective study, dogs received a calcifediol supplement for 84 days. Serum 25-hydroxyvitamin D (25[OH]D), 1,25-dihydroxyvitamin D (1,25[OH]2 D), 24,25-dihydroxyvitamin D (24,25[OH]2 D), creatinine, calcium, phosphorus, PTH, plasma FGF-23 concentrations, and urine profiles were measured monthly during supplementation. Urine calcium to creatinine (UCa/Cr) ratios and fractional excretion of calcium, phosphorus, and sodium were determined.ResultsAll serum vitamin D metabolite concentrations increased significantly by day 84 (P < .001): [25(OH)D (median 249.9 ng/mL; range, 149.7-469.9 ng/mL) compared to baseline (median 50.2 ng/mL; range, 31.3-66.0 ng/mL); 1,25(OH)2 D (median 66.1 pg/mL; range, 56.9-88.1 pg/mL) compared to baseline (median 37.3 pg/mL; range, 29.3-56.7 pg/mL); 24,25(OH)2 D (median 81.4 ng/mL; range, 22.1-151.7 ng/mL) compared to baseline (median 15.4 ng/mL; range, 6.9-40.6 ng/mL)]. There were no significant differences in calcium, phosphorus, PTH concentrations, UCa/Cr or fractional excretion of calcium. No dog developed ionized hypercalcemia. Plasma FGF-23 concentrations increased by day 84 (median 1219 pg/mL; range, 229-8824 pg/mL) compared to baseline (median 798 pg/mL; range, 103-4.145 pg/mL) (P < .01).Conclusions and clinical importanceCalcifediol supplementation for 84 days was well-tolerated in dogs with IRIS stages 2 and 3 CKD. It remains to be determined how long-term supplementation would affect CKD progression and QOL.

Dataset Information

Kidney function, bone-mineral metabolism markers, and future risk of peripheral artery disease.

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Kidney function, bone-mineral metabolism markers, and future risk of peripheral artery disease.

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