Vitamin D insufficiency and effect of cholecalciferol in children with chronic kidney disease

Vitamin D insufficiency is common in patients with chronic kidney disease (CKD) and may contribute to mineral bone disease. In a prospective interventional study, we estimated the prevalence of vitamin D insufficiency (serum 25-hydroxyvitamin D3 [25OHD] < 30 ng/ml), and examined the effect of high-dose (600,000 IU) cholecalciferol supplementation after 6 weeks on serum 25OHD and parathyroid hormone (PTH) levels in children with CKD stages 2–4. Forty-two children (86% boys) with a mean age of 7.7 ± 3.8 (range 2-–5) years were studied. Thirty-seven children (82.1%) had vitamin D insufficiency; 18 (42.8%) had 25OHD < 16 ng/ml. The median 25OHD increased significantly from 16.7 (95% CI 11.3, 19.8) to 46.2 (34.5, 44.6) ng/ml in patients with vitamin D insufficiency (P <0.001). The median PTH decreased significantly from 51.3 (95% CI 46.7, 71.5) to 37.1 (29.0, 54.6) pg/ml (P = 0.003). Nineteen patients (47.5%) had >30% reduction in the PTH after supplementation. Serum calcium, phosphorus, and estimated GFR did not change significantly. We conclude that vitamin D insufficiency is highly prevalent in children with CKD stages 2–4. High-dose cholecalciferol is safe and effective in correcting vitamin D insufficiency and results in a significant reduction in PTH levels in vitamin D-insufficient children.     

Vitamin D supplementation improves endothelial dysfunction in patients with non-dialysis chronic kidney disease

Purpose

Hypovitaminosis D is common in chronic kidney disease (CKD) and is associated with endothelial dysfunction and cardiovascular events. This study aimed to investigate the effects of vitamin D supplementation on endothelial dysfunction in non-dialysis CKD patients.

Materials and methods

Seventy-one non-dialysis CKD patients with low vitamin D (serum 25(OH)D < 30 ng/mL) were recruited. Patients received oral cholecalciferol 50,000 units once a week for 12 weeks. Changes in endothelial function by brachial artery flow-mediated dilation (FMD), soluble vascular cell adhesion molecule-1 (sVCAM-1), and sE-selectin were studied.

Results

There was a significant increase in serum levels of 25(OH)D after cholecalciferol supplementation (33.7 ± 12.1 vs. 13.2 ± 5.4 ng/mL, P < 0.001). Multivariable regression analysis showed that higher proteinuria (β = ? 0.548, P < 0.001) and lower levels of 25(OH)D (β = 0.360, P < 0.001) at baseline were related to lower 25(OH)D level after supplementation. FMD increased significantly from 4.4 ± 1.3 to 5.1 ± 1.5% (P < 0.001), and soluble endothelial biomarkers decreased: sVCAM-1 from 926.9 ± 158.0 to 867.0 ± 129.0 ng/mL (P < 0.001), and sE-selectin 69.7 ± 15.8 to 63.3 ± 14.7 ng/mL (P < 0.001).

Conclusions

Vitamin D supplementation can improve endothelial dysfunction in pre-dialysis CKD patients.

     

Randomized controlled trial of supported discharge in patients with exacerbations of chronic obstructive pulmonary disease

BACKGROUND: A randomised trial was performed on patients presenting to hospital with an exacerbation of chronic obstructive pulmonary disease (COPD) to compare outcomes in those managed at home with support with those admitted to hospital in the standard manner. METHODS: Over an 18 month period all patients presenting to the Royal Infirmary of Edinburgh on weekdays (n=718) with a diagnosis of an exacerbation of COPD were assessed for inclusion in the trial. Patients with impaired level of consciousness, acute confusion, acute changes on radiography, or an arterial pH of <7.35 or with other serious medical or social reasons for admission were excluded. Patients randomised to home support were discharged with an appropriate treatment package (antibiotics, corticosteroids, nebulised bronchodilators and, if necessary, home oxygen). They were visited by a nurse the following day and thereafter at intervals of 2-3 days until recovery when they were discharged from follow up. Parallel observations were made on patients allocated to normal hospital admission up to the point of discharge. Patients in both groups were assessed at home eight weeks after the initial assessment. RESULTS: Among weekday patients 353 (50%) were considered obligatory admissions, 140 (19%) were admitted because of co-morbidity, 17 (2%) because of poor social circumstances, and 24 (3%) did not consent to the trial. The remaining 184 (26%) were randomised (2:1) either to home support or to a standard hospital admission. The median time to discharge was 7 days for the home support group and 5 days for the admitted group (p<0.01); 25% of the home support group and 34% of the admitted group were readmitted before the final assessment at eight weeks (p>0.05). There were no significant differences between the groups in attendances by GPs and carers or in health status measured eight weeks after the initial assessment. Satisfaction with the service was good. The mean total health service cost per patient was estimated as 877 pounds sterling for the home support group and 1753 pounds sterling for the admitted group. CONCLUSIONS: This study shows that home supported discharge is a well tolerated, safe, and economic alternative to hospital admission for a proportion of patients referred to hospital for admission for an exacerbation of COPD.     

Vitamin D supplementation for the improvement of vascular function in patients with chronic kidney disease: a meta-analysis of randomized controlled trials

International Urology and Nephrology - The efficacy of vitamin D on vascular function remains controversial in chronic kidney disease (CKD) patients. The aim of the present work was to perform a...     

Zinc levels after iron supplementation in patients with chronic kidney disease.

OBJECTIVE: The goal of this study was to evaluate the effects of iron supplementation on zinc distribution in nondialyzed chronic kidney disease (CKD) patients. DESIGN: Prospective nonrandomized observational study. SETTING: Outpatients of the Nephrology Division at Federal University of S?o Paulo. PATIENTS: Zinc and iron status of 38 nondialyzed patients (63% male; creatinine clearance, 34.5+/-13.3 mL/min/1.73 m2) was evaluated before and after 3 intramuscular injections of 100 mg iron each. MAIN OUTCOME MEASURES: The following parameters were analyzed: erythrocytes and plasma zinc, zinc protoporphyrin (ZPP), plasma ferritin, transferrin saturation (TFS), and total iron. The patients' diets were analyzed by the Association of Official Analytical Chemists method for macronutrients, and neutron activation analysis was used for iron and zinc concentration determinations. RESULTS: Ferritin and TFS increased from 86.3+/-67.5 ng/mL to 105.4+/-63.7 ng/mL and from 19.5+/-7.4% to 23.2+/-6.7% (P <.05), respectively, after iron supplementation. Absolute iron deficiency (ferritin <100 microg/L and TFS <20%) was present in 41% of the patients and decreased to 15.7% after iron treatment. In comparison with baseline values (76.4+/-16.7 microg/dL), there were no significant changes in plasma zinc levels, but after supplementation the number of patients with low plasma zinc levels decreased from 46.1% to 23.7% (P =.08). At baseline, erythrocyte zinc was 49.0+/-7.6 microg Zn/gHb, and 76.3% of the patients had high erythrocyte zinc concentration. After iron treatment, erythrocyte zinc decreased to 45.5+/-7.3 microg Zn/gHb (P =.001). No significant change was observed in ZPP concentration. The analysis of the diet showed energy and protein intakes of 26.2+/-7.1 kcal/kg/day and 0.89+/-0.2 g/kg/day, respectively, and a low intake of both iron and zinc. CONCLUSIONS: This study suggests that iron deficiency may contribute to the inadequate distribution of zinc in patients with CKD and that iron supplementation may decrease the abnormal elevated erythrocyte zinc levels of these patients.     

A randomized controlled trial of oral versus intravenous iron in chronic kidney disease

BACKGROUND: It is unknown whether intravenous iron or oral iron repletion alone can correct anemia associated with chronic kidney disease (CKD). We conducted a randomized multicenter controlled trial in adult anemic, iron-deficient non-dialysis CKD (ND-CKD) patients (>or=stage 3) not receiving erythropoiesis-stimulating agents (ESAs). METHODS: The participants were randomized to receive either a sodium ferric gluconate complex (intravenous iron) 250 mg i.v. weekly x 4 or ferrous sulfate (oral iron) 325 mg t.i.d. x 42 days. Hemoglobin (Hgb), ferritin and transferrin saturation (TSAT) were measured serially, and the Kidney Disease Quality of Life (KDQoL) questionnaire was administered on days 1 and 43. The primary outcome variable was change from baseline (CFB) to endpoint in Hgb values. RESULTS: Seventy-five patients were analyzed (intravenous iron n = 36, oral iron n = 39). CFB in Hgb was similar in the two groups (intravenous iron 0.4 g/dl vs. oral iron 0.2 g/dl, p = n.s.). However, the increase in Hgb was only significant with intravenous iron (p < 0.01). In comparison to oral iron, intravenous iron achieved greater improvements in ferritin (232.0 +/- 160.8 vs. 55.9 +/- 236.2 ng/ml, p < 0.001) and TSAT (8.3 +/- 7.5 vs. 2.9 +/- 8.8%, p = 0.007). Intravenous iron caused greater improvements in KDQoL scores than oral iron (p < 0.05). The most common side effect reported with intravenous iron was hypotension, while constipation was more common with oral iron. CONCLUSIONS: Oral and intravenous iron similarly increase Hgb in anemic iron-depleted ND-CKD patients not receiving ESAs. Although in comparison to oral iron, intravenous iron may result in a more rapid repletion of iron stores and greater improvement in quality of life, it exposes the patients to a greater risk of adverse effects and increases inconvenience and cost.     

Randomised controlled trial of inhaled corticosteroids in patients with chronic obstructive pulmonary disease

BACKGROUND—Inhaled corticosteroids are known to bebeneficial for patients with asthma, but their role in treatingpatients with stable chronic obstructive pulmonary disease (COPD)remains controversial. A study was undertaken to determine whetherinhaled corticosteroids are of functional benefit in patients who didnot show improvement with a trial of oral corticosteroids.
METHODS—In phase I patients with stable COPD weregiven a two week course of oral placebo followed by two weeks ofprednisone 40 mg per day in a single blind manner to distinguishbetween responders and non-responders to oral corticosteroids. In phaseII a double blind, randomised, parallel group trial of inhaledbudesonide 1600 µg per day versus placebo was carried out in 79 non-responders to oral corticosteroids. The primary outcome measure wasforced expiratory volume in one second (FEV₁), andsecondary outcome measures were exercise capacity, dyspnoea withexertion, quality of life, peak expiration flow rate, and respiratory symptoms.
RESULTS—Randomisation allocated 39 subjects toinhaled corticosteroids and 40 to placebo. There was no difference inthe change in FEV₁ from baseline between the treatment andplacebo groups; mean difference -12 ml (95% CI -88 to 63) at threemonths and -4 ml (95% CI -95 to 87) at six months. The proportionof patients with a 15% or greater improvement was no higher amongthose receiving inhaled corticosteroids than in the placebo group atany of the follow up visits. Changes in secondary outcomes were also no different.
CONCLUSIONS—Inhaledcorticosteroids,even at high doses, were of no physiological or functional benefit inthese patients with advanced COPD.

     

Vitamin D status and mortality risk in patients with chronic kidney disease

Several studies have shown that mineral metabolism disorders play a major role in determining a higher mortality rate for end-stage renal disease patients. Vitamin D deficiency is associated with cardiovascular events in hemodialysis patients. Recently, an association between vitamin D insufficiency and cardiovascular or renal events has been found, in patients with chronic renal failure who have not started renal replacement therapy yet. To further investigate this issue, we evaluated the relationship between blood levels of 25-hydroxyvitamin D (25-OH D; > or ≤30 ng/mL) and mortality or dialysis dependence in 104 incident consecutive patients with chronic kidney disease stages 3-5, over a period of 17 months, with a follow-up of 2 years in a cross-sectional analysis. The correlation between different levels of vitamin D and the risk of events has been estimated by using a probit model. Explanatory variables employed concerned age, sex, blood pressure, BMI, and number of co-morbid factors. The average 25-OH D concentration was of 30.13 ng/mL. During follow-up (>16 months), each patient experienced an average of 1.28 events. Vitamin D has been shown to reduce the probability of cardiovascular or renal events. Vitamin D intake for more than 12 months can reduce the probability of such events by 11.42%. Each co-morbid factor, instead, raises the probability of events by 29%. Lower probabilities of experiencing an adverse cardiovascular event might depend on higher levels of vitamin D. The influence of 25-OH D on survival in chronic kidney disease patients may be related to unrecognized factors that need to be further explored.     

Cardiovascular disease in patients with chronic kidney disease

Cardiovascular disease (CVD) is the major cause of morbidity and mortality in patients with renal failure. Patients with chronic kidney disease have significant CVD, and carry a high cardiovascular burden by the time they commence renal replacement therapy (RRT). The severity of CVD that has been observed in dialysis patients lead to a growing body of research examining the pathogenesis and progression of CVD during the progression of chronic kidney disease (CKD) to end-stage renal disease (ESRD) (ie, predialysis phase). Multiple factors are involved in the development of CVD in CKD. More importantly, critical and key factors seem to develop early in the course of CKD, and result in preventable worsening of CVD in this patient population. Anemia is common in patients with CKD, and has been shown to have an independent role in the genesis of left ventricular hypertrophy (LVH) and subsequent CVD. Unfortunately, it is underdiagnosed and undertreated in patients with CKD. Early intervention, and better correction of anemia, seems to gain a great momentum in the prevention and management of CVD in CKD. Hypertension is another risk factor that has been targeted by the National Kidney Foundation Task Force on CVD in chronic kidney disease. This article reviews the different factors involved in the pathogenesis of CVD in CKD and the evidence supporting early and aggressive intervention.     

Cystatin C相关方程在计算慢性肾脏病肾小球滤过率的对照研究

目的 评价血清半胱氨酸蛋白酶抑制剂C（Cystatin C,CysC）相关方程在不同病因引起慢性肾脏病（CKD）患者的肾小球滤过率（GFR）计算中的临床应用价值。方法选择CKD患者255例,运用MDRD方程（mGFR）、MDRD简化方程（rnGFR）、Hoek方程（hGFR）、2006年中华医学会肾脏病学分会推荐的方程（c-cGFR1,c-cGFR2）计算GFR,与^99m-二乙撑三胺五乙酸（^99m TcDT-PA）肾动态显像测得的。肾小球滤过率（sGFR）进行比较。结果在分期比较中,各方程估算的GFR和sGFR相关性一般,CysC相关方程能更敏感反应GFR;在不同病因分组中,各方程估算的GFR和sGFR均明显相关,特别是c-cGFR2。结论在CysC相关方程中,以2006中华公式2计算的c-cG-FR2与sGFR相关性及一致性最好,并且在糖尿病肾脏病组中,各方程相关系数优于其他组别,有必要进一步大规模临床研究证明其应用价值。     

The effect of cholecalciferol supplementation on allograft function in incident kidney transplant recipients: A randomized controlled study

It is unknown whether cholecalciferol supplementation improves allograft outcomes in kidney transplant recipients (KTRs). We conducted a single-center randomized, double-blind, placebo-controlled trial of daily 4000 IU cholecalciferol supplementation in KTRs at 1-month posttransplant. The primary endpoint was the change in eGFR from baseline to 12-month posttransplant. Secondary endpoints included severity of interstitial fibrosis and tubular atrophy (IFTA) at 12-month posttransplant and changes in urinary biomarkers. Of 193 randomized patients, 180 participants completed the study. Changes in eGFR were 1.2 mL/min/1.73 m² (95% CI; −0.7 to 3.1) in the cholecalciferol group and 1.8 mL/min/1.73 m² (95% CI, −0.02 to 3.7) in the placebo group, with no significant between-group difference (−0.7 mL/min/1.73 m² [95% CI; −3.3 to 2.0], p = 0.63). Subgroup analyses showed detrimental effects of cholecalciferol in patients with eGFR <45 mL/min/1.73 m² (P_interaction <0.05, between-group difference; −4.3 mL/min/1.73 m² [95% CI; −7.3 to −1.3]). The degree of IFTA, changes in urine albumin-to-creatinine ratio, or adverse events including hypercalcemia and infections requiring hospitalization did not differ between groups. In conclusion, cholecalciferol supplementation did not affect eGFR change compared to placebo among incident KTRs. These findings do not support cholecalciferol supplementation for improving allograft function in incident KTRs. Clinical trial registry: This study was registered in the University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR) as UMIN000020597 (please refer to the links below). UMIN-CTR: https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000023776     

慢性肾脏病患者维生素D不足与缺乏

目的 了解慢性肾脏病(CKD)患者维生素D不足与缺乏的患病率,为合理的维生素D治疗提供依据。 方法 对358例住院CKD患者的临床资料进行回顾性分析。用酶标法测定血清25（OH）D3水平,并常规检测血红蛋白（Hb）、Scr、BUN、CO2CP、白蛋白(Alb)、血清钙、磷、全段甲状旁腺激素（iPTH）等。分析25（OH）D3水平与临床指标的关系。 结果 358例患者的25（OH）D3平均水平为（18.58±11.7） µg/L,显著低于正常值（P < 0.01）;CKD1~5期患者25（OH）D3水平分别为（25.84±9.71）、（20.76±6.99）、（20.40±17.02）、（19.49±11.29）和（14.16±7.98） µg/L。维生素D缺乏患病率为39.66%;在CKD1~5期中分别为5.00%、17.50%、37.21%、42.37%和57.14%,患病率随CKD分期逐级增加。维生素D不足患病率为44.97%,在CKD1~5期中分别为72.50%、47.50%、45.35%、33.90%和40.60%。维生素D缺乏及不足患病率为84.63%,在CKD1~5期中分别为77.50%、65.00%、82.56%、76.27%和97.74%,CKD各期间差异无统计学意义。单因素相关分析显示,25（OH）D3与Hb（r = 0.163）、Alb（r = 0.291）、Scr（r = -0.236）、eGFR（r = 0.156）和iPTH（r = -0.178）相关（P < 0.01）。多元线性回归分析显示,25（OH）D3与Alb呈正相关,而和iPTH、Scr呈负相关。CRP、钙磷乘积等与25（OH）D3无相关。按K/DOQI指南,根据25（OH）D3和iPTH水平,CKD3~5期患者符合维生素D治疗指征的比例分别为87.20%、83.05%和26.31%;而仅根据iPTH水平,符合治疗指征的比例仅为16.28%、35.59%和26.31%。 结论 CKD患者维生素D缺乏和不足患病率高。Alb、Scr和iPTH是CKD患者维生素D水平的重要影响因子。应在CKD人群中开展维生素D水平检测,并早期、合理治疗维生素D缺乏和不足。