Diagnosis and Management of Mineral Metabolism in CKD

BACKGROUND  

Chronic kidney disease (CKD) affects over 26 million Americans and is frequently complicated early in its course by disordered mineral metabolism and metabolic bone disease. Since CKD-related bone loss is often indistinguishable from osteoporosis by standard bone densitometry, many CKD patients may be inappropriately treated with bisphosphonates rather than CKD-specific therapies.     

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 (P_trend<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.     

Effects of Dietary Sodium and Calcium on Blood Pressure Reactivity in the shr and WKY

Salt-sensitive spontaneously hypertensive rats (SHR) and their normotensive control strain, Wistar-Kyoto rats (WKY) were fed four diets varying in sodium chloride and calcium content in order to assess the effects of diet on learned blood pressure responses. The animals were exposed to a classical conditioning paradigm in which one tone was always followed by a brief electric shock and a second tone was never followed by shock. Sodium chloride loading raised baseline blood pressure in both strains, while supplemental calcium attenuated blood pressure. Sodium chloride potentiated blood pressure orienting responses to initial presentations of the tones among calcium deficient, but not calcium replete SHR. Increased sodium chloride intake also potentiated the learned pressor responses to the tone paired with shock in the SHR, but not the WKY. Calcium intake had no apparent effect on the learned blood pressure responses to the two tones.     

纤维素饮食及其代谢产物与结直肠癌的化学预防

以合成或天然物质抑制癌前病变的发展是结直肠癌化学预防的重要环节。纤维素来源于植物成分．多项流行病学调查和临床试验结果证实高纤维素饮食可降低结直肠癌的发生率。纤维素的剂量、使用时机、时间长短及其种类均可影响癌变过程。纤维素饮食预防结直肠癌的机制包括纤维素在结肠中经厌氧菌发酵产生丁酸盐等短链脂肪酸（SCFA），通过抑制组蛋白脱乙酰基酶（HDAC）而提高抑癌基因p21^WAF1相关染色体活性，从而阻滞细胞周期。本文就纤维素饮食及其代谢产物与结直肠癌化学预防的相关研究结果作一简要分析。     

Optimal Dietary Calcium Intake in Primary Hyperparathyroidism

PURPOSE: The purpose of this study was to investigate whether dietary calcium intake in primary hyperparathyroidism is associated with differences in bone mineral density and biochemical parameters, and to determine whether these observations are related to 1,25-dihydroxyvitamin D.PATIENTS AND METHODS: Dietary calcium intake was determined from diet records in 71 unselected patients enrolled in an ongoing longitudinal study on the natural history of primary hyperparathyroidism. Subjects were placed into one of three dietary calcium groups based on their mean dietary calcium intake: very low (<300 mg/day; mean = 199 ± 14), low (300 to 800 mg/day; mean = 529 ± 21), and US RDA (>800 mg/day; mean = 1023 ± 73). Biochemical indices were indicative of patients with modern day primary hyperparathyroidism, showing mild hypercalcemia (2.79 ± 0.02 mmol/L), low normal serum phosphorus (0.90 ± 0.03 mmol/L), elevated parathyroid hormone levels by mid-molecule (764 ± 69 pg/mL) and immunoradiometric (118 ± 8 pg/mL) assays, and high normal 1,25-dihydroxyvitamin D (60 ± 3 pg/mL) and urinary calcium excretion (6.3 ± 0.4 mmol/day). Bone mineral density was measured by dual energy x-ray absorptiometry at the lumbar spine, right femoral neck and distal third of the nondominant radius for each subject.RESULTS: Over the entire range, there was no significant effect of dietary calcium on serum parathyroid hormone levels, calcium, phosphorus, 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, urinary calcium excretion, or bone mineral density of the lumbar spine, femoral neck or distal one-third radius. Serum 1,25-dihydroxyvitamin D was elevated in 37 patients (52%). Despite similarly low dietary calcium intake among patients with normal and elevated levels of 1,25-dihydroxyvitamin D (477 ± 50 mg/day vs. 533 ± 40 mg/day), patients with elevated levels of 1,25-dihydroxyvitamin D had higher parathyroid hormone levels by immunoradiometric assay (136 ± 11 pg/mL vs. 97 ± 10 pg/mL; P <.05), and urinary calcium (7.4 ± 0.05 mmol/day vs. 5.1 ± 0.05 mmol/day; P <.05 or 0.82 ± 0.04 mmol/mmol creatinine vs. 0.56 ± 0.04 mmol/mmol creatinine; P <.01).CONCLUSIONS: The data suggest that patients with normal levels of 1,25-dihydroxyvitamin D can liberalize their calcium intake without adverse consequences. However those with elevated levels of 1,25-dihydroxyvitamin D are advised to be more restrictive in order to prevent hypercalciuria.     

Dietary Calcium Intake and Blood Pressure in Normotensive Subjects

ABSTRACT. Epidemiological and prospective studies in man and animals have indicated an inverse relationship between calcium intake and cardiovascular mortality and blood pressure (BP). We have therefore studied the effect of dietary calcium on blood pressure in two groups of women. In a cross-sectional study 103 early postmenopausal women were stratified into three groups according to daily calcium intake calculated from a questionnaire. Both diastolic and systolic blood pressures were identical in the three groups. We thereafter conducted a prospective placebo-controlled trial on the effect of calcium supplementation. Twenty-eight healthy women were randomized to placebo treatment (n=14) or calcium supplementation 2000 mg daily (n=14) for one year. In both groups BP remained at initial levels throughout the study and was identical in the two groups at measurements every three months. We thus conclude that calcium supplementation has no effect on BP in normotensive subjects on a high calcium diet.     

Variability of Blood Pressure in Ambulatory Hypertensive Patients: Effects of Verapamil on Twice and Thrice Daily Dose Regimens

ABSTRACT The antihypertensive effects of verapamil over 24 hours were assessed on twice and thrice daily dose regimens on 12 patients (25–65 years of age; mean age 50) with essential hypertension (WHO stages I–II) in a randomised, double-blind, cross-over trial. After a dose titration period starting with either verapamil 80 mg tid or 120 mg bid the patients kept their maintenance dose (240, 360 or 480 mg daily) for 4 weeks before crossing over to the other administration schedule. Repeated ambulatory blood pressure (BP) curves were recorded in 10 patients with a non-invasive portable device (Pressurometer III, Del Mar Avionics). The BP reductions (causal BP values) obtained by 2- and 3-dose regimens were of similar magnitude (from 170±19/105±8 on placebo to 140±17/87±7 and to 146±14/88±8 by 2- and 3-dose respectively). Analyses of BP curves revealed close similarity in profiles on the two dose regimens, although DBP was significantly (p<0.05) lower by 3-dose as compared to 2-dose regimen during the period 0.00–2.59 a.m. Long-term (circadian rhythm) and short-term variability did not differ between the regimens. Despite the slight difference in DBP curves after midnight, the overall impression is that verapamil given both twice and thrice daily provides adequate BP control throughout 24 hours.     

心得安改善短效钙拮抗剂心痛定心率变异性的研究

探讨β受体阻滞剂心得安是否可以改善短效钙拮抗剂心痛定的心率变异性(HRV)。将101例观察对象随机分为对照组(只使用心痛定,n=49)和试验组(使用心痛定和心得安,n=52),分别在服药前及服药后7～10天做24h动态心电图检测,分析HRV指标:正常RR间期的标准差(SDNN)、每5min平均RR间期的标准差(SDANN)、相邻RR之差的均方根(RMSSD)、相邻RR之差>50ms占总窦性心搏的百分数(PNN50)、低频(LF)、高频(HF)、低频和高频比值(LF/HF)。结果:对照组在治疗后心率(HR)加快,SDNN、SDANN显著降低(分别为105.2±31.8msvs126.9±32.0ms、98.9±20.1msvs107.9±19.8ms,P均<0.05),LF、LF/HF升高(分别229.3±77.1Hzvs196.1±64.8Hz、5.4±1.9vs3.8±1.8,P均<0.05),HRV降低;而试验组在治疗后心率无明显改变,SDNN、SDANN、LF、HF升高(分别为140.1±29.8msvs129.1±31.9ms、127.8±21.1msvs108.2±20.1ms、209.8±70.1Hzvs197.3±65.1Hz、148.5±48.8Hzvs123.5±41.0Hz,P均<0.05),LF/HF降低(P<0.05),治疗组HRV升高。结论:心得安能改善短效钙拮抗剂心痛定的HRV。     

Bone Mineral Density and Serum Biochemical Predictors of Bone Loss in Patients with CKD on Dialysis

Background

and objectives Use of bone mineral density (BMD) by dual-energy x-ray absorptiometry (DXA) is controversial for diagnosing bone loss in CKD patients on dialysis. The alternative quantitative computed tomography (QCT) is expensive and requires high radiation exposure. This study compared the two techniques and evaluated serum biochemical parameters for prediction of bone loss.

Design, setting, participants, & measurements

This prospective study enrolled patients from dialysis centers throughout Kentucky. BMD of the spine and hip was measured at baseline and after 1 year by DXA and QCT. Customary and novel serum biochemical parameters were obtained at the same times, including calcium, phosphorus, whole and intact parathyroid hormone, bone-specific alkaline phosphatase, procollagen type 1 N-terminal propeptide, tartrate-resistant acid phosphatase-5b, Dickkopf-1, fibroblast growth factor, and sclerostin. Rates of detection of osteoporosis by DXA and QCT were compared. Correlations were calculated between baseline biochemical parameters and BMD at baseline and changes over 1 year. Multivariable regression was performed to adjust for age, sex, body mass index, and race.

Results

Eighty-one patients completed the study (mean age=52.6±12.3 years, 56% men, 53% African American, and median dialysis vintage=41 months). At baseline, QCT and DXA of the spine identified similar rates of osteoporosis (13.6% and 13.6%), but at the hip, DXA identified more osteoporosis (22.2% versus 13.6%). At any site and by either method, 33.3% of the patients were osteoporotic. Baseline BMD correlated with sclerostin, intact parathyroid hormone, bone-specific alkaline phosphatase, tartrate-resistant acid phosphatase-5b, and fibroblast growth factor. At 1 year, hip QCT identified a higher number of patients experiencing bone loss (51.3%) than DXA (38.5%). After multivariable adjustment, baseline sclerostin and tartrate-resistant acid phosphatase-5b predicted bone loss measured by QCT of the hip; procollagen type 1 N-terminal propeptide predicted cortical spine bone gain by QCT.

Conclusions

QCT identified prospectively more bone loss at the hip than DXA. The baseline serum biochemical parameters sclerostin and tartrate-resistant acid phosphatase-5b were noninvasive independent predictors of bone loss in CKD patients on dialysis.     

Effects of Leaching Behavior of Calcium Ions on Compression and Durability of Cement-Based Materials with Mineral Admixtures

Leaching of calcium ions increases the porosity of cement-based materials, consequently resulting in a negative effect on durability since it provides an entry for aggressive harmful ions, causing reinforcing steel corrosion. This study investigates the effects of leaching behavior of calcium ions on the compression and durability of cement-based materials. Since the parameters influencing the leaching behavior of cement-based materials are unclear and diverse, this paper focuses on the influence of added mineral admixtures (fly ash, slag and silica fume) on the leaching behavior of calcium ions regarding compression and durability of cemented-based materials. Ammonium nitrate solution was used to accelerate the leaching process in this study. Scanning electron microscopy, X-ray diffraction analysis, and thermogravimetric analysis were employed to analyze and compare the cement-based material compositions prior to and after calcium ion leaching. The experimental results show that the mineral admixtures reduce calcium hydroxide quantity and refine pore structure through pozzolanic reaction, thus enhancing the compressive strength and durability of cement-based materials.     

Daily Exercise Reduces Measures of Heart Rate and Blood Pressure Variability in Hypertensive Rats

This study was designed to test the hypothesis that daily spontaneous running (DSR) reduces measures of heart rate and blood pressure variability in spontaneously hypertensive rats (SHR). After 8 weeks of DSR or sedentary control, rats were chronically instrumented with arterial catheters. Daily exercise reduced most measures of heart rate (HR) and blood pressure variability. Specifically DSR decreased heart rate, Low Frequency Power (LF: 0.19–0.61?Hz), and Low Frequency/High Frequency (HF: 1.2–2.5?Hz) ratio of HR. Furthermore, Total Power (TP), LF power, and LF/HF ratio of systolic blood pressure were reduced by daily spontaneous running. Finally, TP, LF and HF powers and LF/HF ratios of diastolic blood pressure were reduced by daily spontaneous running. These data demonstrate that daily exercise reduces sympathetic activity and possibly increases cardiac reserve in hypertensive animals.