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Background: Cardiovascular disease is the leading cause of morbidity and mortality in children with chronic kidney disease (CKD). We aim to estimate the prevalence of cardiac abnormalities in children up to age 16 years with CKD and their association with various risk factors.Methods: This cross-sectional observational study was conducted on 107 CKD children. We assessed the systolic and diastolic function using 2D echocardiographic evaluation and M-mode measurements of the left ventricle (LV) indexed for BSA and z-scores were calculated. Results were compared with age, sex, stage of CKD, anaemia, estimated glomerular filtration rate (eGFR) and various laboratory parameters.Results: LV diastolic dysfunction was seen in 88%, followed by increased LV dimensions in 33.6%, LV systolic dysfunction in 16%, right ventricle systolic dysfunction in 11.2% while increased pulmonary artery (PA) systolic pressure was seen in 9.3% of cases. LV dimensions correlated directly with parathormone levels and inversely with eGFR, serum calcium and haemoglobin levels. Left ventricular hypertrophy correlated directly with parathormone while inversely with eGFR, serum calcium and haemoglobin. Ejection fraction directly correlated to eGFR and serum calcium while inversely related to parathormone. Left PA pressure directly correlated with age and inversely with eGFR. Right ventricular systolic function assessed by tricuspid annular plane systolic excursion correlated inversely with haemoglobin.Conclusion: LV diastolic dysfunction and increased LV dimensions were the most common cardiac abnormality in children with CKD. LV dimensions correlated directly with parathormone levels and inversely with eGFR, serum calcium and haemoglobin. Diastolic dysfunction positively correlated with serum creatinine and parathormone levels. [ABSTRACT FROM AUTHOR]

Context: Dietary antioxidants are important in protecting against human diseases. Oxidative stress, a non- traditional risk factors of cardio-vascular disease is far more prevalent in chronic kidney disease (CKD) patients than in normal subjects. Evidence Acquisitions: Directory of Open Access Journals (DOAJ), Google Scholar, Pubmed (NLM), LISTA (EBSCO) and Web of Science have been searched. Results: Oxidative stress could be a consequence of an increase in reactive oxygen species as well as a decrease in antioxidant defenses. Among the important factors that can be involved in triggering oxidative stress is insufficient dietary intake of antioxidants. Malnourished CKD patients are reported to have more oxidative stress than well nourished ones. Conclusions: Moving beyond the importance of assessment of dietary protein and energy in pre dialysis CKD patients to the assessment of dietary antioxidants is of utmost importance to help combat enhanced oxidative stress levels in such patients. [ABSTRACT FROM AUTHOR]

ABSTRACT: Use of active forms of vitamin D is advocated in patients with chronic kidney disease (CKD) for treatment of mineral bone disease because of the presumption that native forms of vitamin D would not undergo significant activation to calcitriol, the most active biological form of vitamin D. We present secondary analysis looking at bone turnover in subjects who completed the randomized, double blind, placebo‐controlled trial investigating the effect of cholecalciferol supplementation on vascular function in nondiabetic CKD stage G3­G4 and vitamin D ≤20 ng/mL (Clinical Trials Registry of India: CTRI/2013/05/003648). Patients were randomized (1:1) to receive either two directly observed oral doses of 300,000 IU of cholecalciferol or matching placebo at baseline and 8 weeks. Of the 120 subjects enrolled, 58 in the cholecalciferol group and 59 in the placebo group completed the study. At 16 weeks, the serum 25(OH)D and 1,25(OH)2D levels increased in the cholecalciferol group but not in the placebo group (between‐group difference in mean change: 23.40 ng/mL; 95% CI, 19.76 to 27.06; p < 0.001, and 14.98 pg/mL; 95% CI, 4.48 to 27.18; p = 0.007, respectively). Intact parathyroid hormone (iPTH) decreased in the cholecalciferol group (between‐group difference in mean change –100.73 pg/mL (95% CI, –150.50 to –50.95; p < 0.001). Serum total and bone‐specific alkaline phosphatase (SAP, BAP) and serum C‐terminal cross‐linked collagen type I telopeptides (CTX‐1) were significantly reduced in cholecalciferol group (between group difference for change in mean: –20.25 U/L; 95% CI, –35.14 to –5.38 U/L; p = 0.008 for SAP; –12.54 U/L; 95% CI, –22.09 to –2.98 U/L; p = 0.013 for BAP; and –0.21 ng/mL; 95% CI, –0.38 to –0.05 ng/mL; p = 0.05 for CTX‐1). Correlation analysis showed significant correlation of Δ25(OH)D with ΔiPTH (r = –0.409, p < 0.0001), Δ1,25(OH)2D (r = 0.305, p = 0.001), ΔSAP (r = –0.301, p = 0.002), ΔBAP (r = –0.264, p = 0.004), and ΔCTX‐1 (r = –0.210, p = 0.0230). Cholecalciferol supplementation corrects vitamin D deficiency and is effective in lowering serum intact parathyroid hormone and bone turnover markers in early stages of CKD. © 2017 American Society for Bone and Mineral Research. [ABSTRACT FROM AUTHOR]

Background: Accurate estimation of glomerular filtration rate (GFR) is important for diagnosis and risk stratification in chronic kidney disease and for selection of living donors. Ethnic differences have required correction factors in the originally developed creatinine-based GFR estimation equations for populations around the world. Existing equations have not been validated in the vegetarian Indian population. We examined the performance of creatinine and cystatin-based GFR estimating equations in Indians.Methods: GFR was measured by urinary clearance of inulin. Serum creatinine was measured using IDMS-traceable Jaffe's and enzymatic assays, and cystatin C by colloidal gold immunoassay. Dietary protein intake was calculated by measuring urinary nitrogen appearance. Bias, precision and accuracy were calculated for the eGFR equations.Results: A total of 130 participants (63 healthy kidney donors and 67 with CKD) were studied. About 50% were vegetarians, and the remainder ate meat 3.8 times every month. The average creatinine excretion were 14.7 mg/kg/day (95% CI: 13.5 to 15.9 mg/kg/day) and 12.4 mg/kg/day (95% CI: 11.2 to 13.6 mg/kg/day) in males and females, respectively. The average daily protein intake was 46.1 g/day (95% CI: 43.2 to 48.8 g/day). The mean mGFR in the study population was 51.66 ± 31.68 ml/min/1.73m2. All creatinine-based eGFR equations overestimated GFR (p < 0.01 for each creatinine based eGFR equation). However, eGFR by CKD-EPICys was not significantly different from mGFR (p = 0.38). The CKD-EPICys exhibited lowest bias [mean bias: -3.53 ± 14.70 ml/min/1.73m2 (95% CI: -0.608 to -0.98)] and highest accuracy (P30: 74.6%). The GFR in the healthy population was 79.44 ± 20.19 (range: 41.90-134.50) ml/min/1.73m2.Conclusion: Existing creatinine-based GFR estimating equations overestimate GFR in Indians. An appropriately powered study is needed to develop either a correction factor or a new equation for accurate assessment of kidney function in the Indian population. [ABSTRACT FROM AUTHOR]

Context: Dietary antioxidants are important in protecting against human diseases. Oxidative stress, a non- traditional risk factors of cardio-vascular disease is far more prevalent in chronic kidney disease (CKD) patients than in normal subjects. Evidence Acquisitions: Directory of Open Access Journals (DOAJ), Google Scholar, Pubmed (NLM), LISTA (EBSCO) and Web of Science have been searched. Results: Oxidative stress could be a consequence of an increase in reactive oxygen species as well as a decrease in antioxidant defenses. Among the important factors that can be involved in triggering oxidative stress is insufficient dietary intake of antioxidants. Malnourished CKD patients are reported to have more oxidative stress than well nourished ones. Conclusions: Moving beyond the importance of assessment of dietary protein and energy in pre dialysis CKD patients to the assessment of dietary antioxidants is of utmost importance to help combat enhanced oxidative stress levels in such patients. [ABSTRACT FROM AUTHOR]

Aim: Vitamin D is being increasingly recognized as an important player in disease. Hypovitaminosis D is widespread in chronic kidney disease (CKD) populations around the world. The vitamin D status of Indian CKD patients is not known. Methods: Levels of 25(OH) vitamin D and parathyroid hormone (PTH) were measured in adult north Indian male patients with newly diagnosed stage IV–V CKD and matched control subjects drawn from the same population. A total of 100 (34 stage IV and 66 stage V) patients with CKD and 72 controls were studied. Results: Only 4% control and 1% of CKD subjects had normal (>30 ng/mL) vitamin D levels. Approximately 68% of control and 77% of the CKD population had vitamin D deficiency (<15 ng/ml) whereas the remaining 38% control and 22% CKD patients had insufficient (15–30 ng/mL) vitamin D levels. Levels were lower in CKD subjects compared to their family members, and the CKD patients were significantly more likely to have severe vitamin D deficiency (<5 ng/mL). A strong negative correlation was noted between vitamin D and PTH. No significant correlation was found between vitamin D levels and body mass index, bodyfat percentage, serum albumin or calcium levels. Conclusion: Vitamin D deficiency is highly prevalent in north Indians, and this is more pronounced in CKD subjects. There is a significant inverse correlation between the vitamin D and PTH levels. The clinical significance of this deficiency and the potential benefits to be derived from vitamin D supplementation in this population merits further studies. [ABSTRACT FROM AUTHOR]

The role of intravenous iron in contributing to oxidative stress and endothelial dysfunction in chronic kidney disease (CKD) is debatable. The present study assessed differences in fasting plasma malondialdehyde (pMDA) levels 30 minutes before and after intravenous infusion of low molecular weight iron dextran (ID) (n = 19), iron-sucrose (IS) (n = 20), and sodium ferrigluconate complex (SFGC) (n = 20) in stage 3 and 4 CKD patients. Post-infusion pMDA levels were significantly raised with respect to baseline (p < 0.001). pMDA was significantly higher in the SFGC group vs. IS (3.02 ± 0.84 μmol/L vs. 2.82 ± 0.44 μmol/L, p = 0.034) or SFGC vs. ID (3.02 ± 0.84 μmol/L vs. 2.92 ± 0.20 μmol/L, p = 0.048). There was no difference between IS vs. ID (2.82 ± 0.44 μmol/L vs. 2.92 ± 0.20 μmol/L, p = 0.21). To conclude, all forms of parenteral iron, especially SFGC, significantly raise pMDA levels in the immediate post-transfusion period. [ABSTRACT FROM AUTHOR]

Vitamin D deficiency is common and associated with mortality in chronic kidney disease (CKD) patients. Cardiovascular disease (CVD) is the commonest cause of mortality in CKD patients. In a randomized, double blind, placebo controlled trial, we have recently reported favorable effects of vitamin D supplementation on vascular & endothelial function and inflammatory biomarkers in vitamin D deficient patients with non-diabetic stage 3–4 CKD (J Am Soc Nephrol 28: 3100–3108, 2017). Subjects in the placebo group who had still not received vitamin D after completion of the trial received two oral doses 300,000 IU of oral cholecalciferol at 8 weeks interval followed by flow mediated dilatation (FMD), pulse wave velocity (PWV), circulating endothelial and inflammatory markers (E-Selectin, vWF, hsCRP and IL-6), 125 (OH) 2 D, iPTH and iFGF-23 assessment at 16 weeks. 31 subjects completed this phase of the study. Last values recorded in the preceding clinical trial were taken as baseline values. Serum 25(OH)D and 1,25(OH) 2 D increased and FMD significantly improved after cholecalciferol supplementation [mean change in FMD%: 5.8% (95% CI: 4.0–7.5%, p < 0.001]. Endothelium independent nitroglycerine mediated dilatation, PWV, iPTH, iFGF-23 and IL-6 also showed favorable changes. The data further cement the findings of beneficial effects of correction of vitamin D deficiency on vascular function. [ABSTRACT FROM AUTHOR]

Vitamin D deficiency, cardiovascular disease and abnormal bone mineral metabolism are common in chronic kidney disease (CKD). Abnormal bone mineral metabolism has been linked to vascular calcification in CKD. Sclerostin has emerged as an important messenger in cross talk between bone-vascular axis. We analyzed sclerostin in subjects who participated in the randomized, double blind, placebo controlled trial investigating the effect of cholecalciferol supplementation on vascular function in non­diabetic CKD stage G3-4 and vitamin D ≤ 20 ng/ml [CTRI/2013/05/003648]. Patients were randomized (1:1) to receive either two directly observed oral doses of 300,000 IU of cholecalciferol or matching placebo at baseline and 8 weeks. Of the 120 subjects enrolled, 58 in the cholecalciferol group and 59 in the placebo group completed the study. At baseline, serum levels of sclerostin were similar in both groups (cholecalciferol - median;190pg/ml, IQR;140–260 pg/ml and placebo - median;180 pg/ml, IQR; 140–240 pg/ml, p = 0.67). 16 weeks after cholecalciferol supplementation, there was no change in level of sclerostin (mean change;1.10 pg/ml, 95%CI; −27.34 to 29.34 pg/ml, p = 0.25). However, a significant decrease in sclerostin level was noted in the placebo group (mean change; −31.94 pg/ml, 95%CI; −54.76 to −9.13 pg/ml, p = 0.002). Change (Δ) in sclerostin level at 16 weeks correlated negatively with Δ eGFR (r = −0.20, p = 0.03) and positively with Δuric acid (r = 0.37, p < 0.001) but not with Δ25(OH) D (r = 0.06, p = 0.54), Δ iPTH (r = − 0.03, p = 0.78) ΔFGF23 (r = − 0.08, p = 0.38) and Δ125 (OH) 2 D (r = − 0.04, p = 0.65). In conclusion, high dose cholecalciferol supplementation did not change sclerostin levels in non-diabetic stage 3–4 CKD subjects. [ABSTRACT FROM AUTHOR]