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The Effect of Extended Release Niacin on Markers of Mineral Metabolism in CKD.

ABSTRACT: BACKGROUND AND OBJECTIVES:Niacin downregulates intestinal sodium-dependent phosphate transporter 2b expression and reduces intestinal phosphate transport. Short-term studies have suggested that niacin lowers serum phosphate concentrations in patients with CKD and ESRD. However, the long-term effects of niacin on serum phosphate and other mineral markers are unknown. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS:The Atherothrombosis Intervention in Metabolic Syndrome with Low HDL/High Triglycerides: Impact on Global Health Trial was a randomized, double-blind, placebo-controlled trial testing extended release niacin in persons with prevalent cardiovascular disease. We examined the effect of randomized treatment with niacin (1500 or 2000 mg) or placebo on temporal changes in markers of mineral metabolism in 352 participants with eGFR<60 ml/min per 1.73 m2 over 3 years. Changes in each marker were compared over time between the niacin and placebo arms using linear mixed effects models. RESULTS:Randomization to niacin led to 0.08 mg/dl lower plasma phosphate concentrations per year of treatment compared with placebo (P<0.01) and 0.25 mg/dl lower mean phosphate 3 years after baseline (3.32 versus 3.57 mg/dl; P=0.03). In contrast, randomization to niacin was not associated with statistically significant changes in plasma intact fibroblast growth factor 23, parathyroid hormone, calcium, or vitamin D metabolites over 3 years. CONCLUSIONS:The use of niacin over 3 years lowered serum phosphorous concentrations but did not affect other markers of mineral metabolism in participants with CKD.

SUBMITTER: Malhotra R

PROVIDER: S-EPMC5753310 | biostudies-other | 2018 Jan

REPOSITORIES: biostudies-other

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The Effect of Extended Release Niacin on Markers of Mineral Metabolism in CKD.

Malhotra Rakesh R Katz Ronit R Hoofnagle Andrew A Bostom Andrew A Rifkin Dena E DE Mcbride Ruth R Probstfield Jeffrey J Block Geoffrey G Ix Joachim H JH

Clinical journal of the American Society of Nephrology : CJASN 20171205 1

<h4>Background and objectives</h4>Niacin downregulates intestinal sodium-dependent phosphate transporter 2b expression and reduces intestinal phosphate transport. Short-term studies have suggested that niacin lowers serum phosphate concentrations in patients with CKD and ESRD. However, the long-term effects of niacin on serum phosphate and other mineral markers are unknown.<h4>Design, setting, participants, & measurements</h4>The Atherothrombosis Intervention in Metabolic Syndrome with Low HDL/H ...[more]

PMID: 29208626

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Project description:Background and objectivesDisorders 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, & measurementsIn 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).ResultsCompared 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).ConclusionsA 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.

Project description:Background and objectivesIn children with CKD, information is limited regarding the prevalence and determinants of fibroblast growth factor 23 excess and 1,25-dihyroxyvitamin D deficiency across the spectrum of predialysis CKD. This study characterized circulating concentrations of fibroblast growth factor 23 and 1,25-dihyroxyvitamin D, and investigated their interrelationships and associations with GFR and secondary hyperparathyroidism in children with CKD who were enrolled in the Chronic Kidney Disease in Children observational cohort study.Design, setting, participants, & measurementsPlasma fibroblast growth factor 23 concentrations and determinants of mineral metabolism were measured in 464 children ages 1-16 years with predialysis CKD. GFR was measured by plasma disappearance of iohexol in 70% of participants and estimated by the Chronic Kidney Disease in Children estimating equation using serum creatinine and cystatin C concentrations in the remainder of the participants. Participants were grouped according to CKD stage and by 10-ml/min categories of GFR.ResultsMedian GFR for the cohort was 45 ml/min per 1.73 m(2) (interquartile range=33-57; range=15-109). Plasma fibroblast growth factor 23 concentration was above the normal range in 67% of participants (with higher levels observed among participants with lower GFR) before higher levels of serum parathyroid hormone and phosphorus were observed. Plasma fibroblast growth factor 23 levels were 34% higher in participants with glomerular disease than in participants with nonglomerular disease, despite similar GFR. Serum phosphorus levels, adjusted for age, were significantly lower at GFR of 60-69 ml/min per 1.73 m(2) than higher GFR, but thereafter they became higher in parallel with fibroblast growth factor 23 as GFR declined. Serum 1,25-dihyroxyvitamin D concentrations were lower in those participants with low GFR values, high fibroblast growth factor 23 levels, 25-hydroxyvitamin D deficiency, and proteinuria. Secondary hyperparathyroidism was present in 55% of participants with GFR<50 ml/min per 1.73 m(2).ConclusionIn children with predialysis CKD, high plasma fibroblast growth factor 23 is the earliest detectable abnormality in mineral metabolism, and levels are highest in glomerular diseases.

Project description:Rationale & objectiveThe pathogenesis of disordered mineral metabolism in chronic kidney disease (CKD) is largely informed by cross-sectional studies of humans and longitudinal animal studies. We sought to characterize the longitudinal evolution of disordered mineral metabolism during the course of CKD.Study designRetrospective analysis nested in a cohort study.Setting & participantsParticipants in the Chronic Renal Insufficiency Cohort (CRIC) Study who had up to 5 serial annual measurements of estimated glomerular filtration rate, fibroblast growth factor 23 (FGF-23), parathyroid hormone (PTH), serum phosphate, and serum calcium and who subsequently reached end-stage kidney disease (ESKD) during follow-up (n = 847).ExposureYears before ESKD.OutcomesSerial FGF-23, PTH, serum phosphate, and serum calcium levels.Analytical approachTo assess longitudinal dynamics of disordered mineral metabolism in human CKD, we used "ESKD-anchored longitudinal analyses" to express time as years before ESKD, enabling assessments of mineral metabolites spanning 8 years of CKD progression before ESKD.ResultsMean FGF-23 levels increased markedly as time before ESKD decreased, while PTH and phosphate levels increased modestly and calcium levels declined minimally. Compared with other mineral metabolites, FGF-23 levels demonstrated the highest rate of change (velocity: first derivative of the function of concentration over time) and magnitude of acceleration (second derivative). These changes became evident approximately 5 years before ESKD and persisted without deceleration through ESKD onset. Rates of changes in PTH and phosphate levels increased modestly and without marked acceleration around the same time, with modest deceleration immediately before ESKD, when use of active vitamin D and phosphate binders increased.LimitationsIndividuals who entered the CRIC Study at early stages of CKD and who did not progress to ESKD were not studied.ConclusionsAmong patients with progressive CKD, FGF-23 levels begin to increase 5 years before ESKD and continue to rapidly accelerate until transition to ESKD.

Project description:Niacin is an antidyslipidemic agent that may cause blood sugar elevation in patients with diabetes, but its effects on glucose and insulin values in nondiabetic statin-treated subjects with cardiovascular disease and at high risk for diabetes are less well known.This was a prespecified, intent-to-treat analysis of the Atherothrombosis Intervention in Metabolic syndrome with low high-density lipoprotein/high triglycerides: Impact on Global Health outcomes trial which randomized 3,414 participants at 92 centers in the US and Canada to extended-release niacin (ERN) plus simvastatin/ezetimibe (ERN) or simvastatin/ezetimibe plus placebo (Placebo). Baseline and annual fasting glucose and insulin values were measured. Those experiencing an adverse event indicative of diabetes or starting medications for diabetes were considered to have confirmed diabetes. In addition, nondiabetic subjects with 2 annual follow-up glucose measurements were categorized into normal, impaired fasting glucose or newly diagnosed diabetes (presumed or confirmed) states.Compared with placebo, ERN increased annual fasting glucose from baseline to 1 year in both those with normal (7.9 ± 15.8 vs 4.3 ± 10.3 mg/dL; P < .001) and impaired fasting glucose (4.1 ± 18.7 vs 1.4 ± 14.9; P < .02) and increased insulin levels. Both effects waned over the next 2 years. There were less consistent effects in those with baseline diabetes. There was an increased risk of progressing from normal to presumed or confirmed impaired fasting glucose (ERN 197/336) cases (58.6%) vs placebo 135/325 cases (41.5%; P < .001) over time, but no difference in diabetes development in the 2 treatment groups except in those with normal fasting glucose at baseline.The addition of ERN to simvastatin/ezetimibe had marginal effects on glycemia in those with diabetes at baseline, and there was a trend toward increased development of new-onset diabetes. In addition, ERN increased the risk of developing impaired fasting glucose, which may have deleterious consequences over time and warrants further study.

Dataset Information

The Effect of Extended Release Niacin on Markers of Mineral Metabolism in CKD.

Publications

The Effect of Extended Release Niacin on Markers of Mineral Metabolism in CKD.

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