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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., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Vitamin D deficiency associates with mortality in patients with CKD, and vitamin D supplementation might mitigate cardiovascular disease risk in CKD. In this randomized, double-blind, placebo-controlled trial, we investigated the effect of cholecalciferol supplementation on vascular function in 120 patients of either sex, aged 18-70 years, with nondiabetic CKD stage 3-4 and vitamin D deficiency (serum 25-hydroxyvitamin D ≤20 ng/ml). We randomized patients using a 1:1 ratio to receive either two directly observed oral doses of cholecalciferol (300,000 IU) or matching placebo at baseline and 8 weeks. The primary outcome was change in endothelium-dependent brachial artery flow-mediated dilation at 16 weeks. Secondary outcome measures included changes in pulse wave velocity and circulating biomarkers. Cholecalciferol supplementation significantly increased endothelium-dependent brachial artery flow-mediated dilation at 16 weeks, whereas placebo did not (between-group difference in mean change: 5.49%; 95% confidence interval, 4.34% to 6.64%; P <0.001). Intervention also led to significant favorable changes in pulse wave velocity and circulating IL-6 levels. Thus, in nondiabetic patients with stage 3-4 CKD and vitamin D deficiency, vitamin D supplementation may improve vascular function. This study is registered with the Clinical Trials Registry of India (no.: CTRI/2013/05/003648)., (Copyright © 2017 by the American Society of Nephrology.)

There is evidence to suggest that M‐type phospholipase A2 (PLA2R) antibodies activate the mannose‐binding lectin (MBL) cascade, resulting in glomerular damage and proteinuria in patients with primary membranous nephropathy (PMN). Furthermore, there are few reports indicating that aberrant MBL activation is associated with endothelial dysfunction and accelerated atherosclerosis. While PMN is a common cause of adult nephrotic syndrome, and patients are at increased risk of cardiovascular disease (CVD), there is a lack of research that explores the factors that contribute to this condition. This study aims to determine the MBL levels in PMN and their relation to the clinical activity and endothelial dysfunction in PMN. The MBL levels of 22 biopsy‐confirmed PMN patients were assessed at baseline and after 6 months of immunosuppressive therapy. In order to evaluate endothelial dysfunction in PMN patients, flow‐mediated vasodilation (FMD) was measured at baseline and after treatment. A total of 22 healthy controls were included in this study to measure MBL levels and FMD. A significant difference was observed between MBL levels in PMN patients and healthy controls (p <.01). MBL levels decreased significantly after immunosuppressive therapy (p =.04). The baseline MBL levels and FMD levels exhibited a strong correlation (Spearman correlation coefficient [ρ] = 0.51: p =.01). In conclusion, the study signals the activation of the MBL cascade and its association with endothelial dysfunction in PMN patients. [ABSTRACT FROM AUTHOR]

Background/Aims: The CD4+ T cell subset lacking surface CD28 plays a role in atherosclerotic cardiovascular disease. The association between CD4+CD28null T cells and early atherosclerotic changes in chronic kidney disease (CKD) has never been investigated. We evaluated the frequency of circulating CD4+CD28null cells in 128 CKD and 62 control subjects. Methods: Phenotype (CD4 and CD28) and cytotoxic potential (perforin and granzyme B expression) were studied by flow cytometry. Systemic inflammation (hsCRP, IL-6 and TNF-α) was analyzed by ELISA. Common carotid artery intima-media thickness (CCA-IMT) was measured with an ultrasound system. The effect of TNF-α and IL-6 on these cells was evaluated in vitro. Results: The frequency of CD4+CD28null cells was significantly increased in CKD patients (10.14 ± 0.8 vs. 3.53 ± 0.36, p < 0.0001). The expression of perforin and granzyme B on CD4+CD28null cells was found to be significantly higher compared to CD4+CD28+ cells (p < 0.0001). A larger proportion of CD4+CD28null cells obtained from CKD subjects showed the expression of perforin and granzyme B compared to those from healthy controls. CKD patients showed increased CCA-IMT (p < 0.0001). CD4+CD28null cells were positively correlated with the IMT (r = 0.505, p < 0.0001). CKD subjects showed increased levels of hsCRP, IL-6 and TNF-α. Only the TNF-α level showed a correlation with CD4+CD28null cells (r = 0.45, p < 0.0001). In vitro treatment with TNF-α but not IL-6 resulted in further downregulation of CD28 on the CD4+ T cell surface. Conclusions: CKD subjects exhibit an increase in the circulating cytotoxic CD4+CD28null T lymphocyte population. CD4+CD28null cell expansion correlated with preclinical atherosclerotic changes. TNF-α shows a specific relationship and might have a role in the expansion of this subset in CKD. Copyright © 2012 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

ABSTRACT: Aim: Cardiovascular disease (CVD) is the leading cause of death among chronic kidney disease (CKD) patients. The role of vitamin D remains controversial in this process. We evaluated the relationship between 25-hydroxyvitamin D, abnormal T helper cells (CD4+CD28null cells), systemic inflammation and atherosclerosis in CKD patients. Methods: A total of 101 stage 4-5 non-dialysis CKD patients and 40 healthy controls were studied. Common carotid artery intima media thickness (CCA-IMT) was measured with an ultrasound system. 25(OH) vitamin D and highly sensitive C-reactive protein (hsCRP) were measured in serum by enzyme linked immunosorbent assay. The frequency of circulating CD4+CD28null cells was evaluated by flowcytometry. Results: CKD subjects exhibited higher CCA-IMT (0.71 ± 0.01 vs 0.56 ± 0.01 mm, P < 0.0001), hsCRP (90.7 ± 5.8 vs 50.1 ± 8.6 µg/mL, P < 0.0001), CD4+CD28null cell frequency (9.1 ± 0.9 vs 3.6 ± 0.5%, P < 0.0001) and lower 25(OH) vitamin D levels (17.9 ± 1.9 vs 26.9 ± 3.5 ng/mL, P < 0.0001). In CKD subjects, serum 25 (OH) vitamin D level showed a strong inverse correlation with CCA-IMT ( r = −0.729, P < 0.0001) and correlated with CD4+CD28null cell frequency ( r = −0.249, P = 0.01) and hsCRP ( r = −0.2, P = 0.047). We also noted correlation of IMT with patient age ( r = 0.291, P = 0.004) and CD4+CD28null cells ( r = 0.34, P = 0.001). On multiple regression analysis, 25(OH) vitamin D level, diabetic status and CD4+CD28null cell frequency exhibited independent association with IMT in CKD subjects. Conclusions: Vitamin D deficiency, inflammatory activation and higher frequency of CD4+CD28null T lymphocyte population correlate with preclinical atherosclerotic changes in CKD population. These findings suggest possible linkage between vitamin D metabolism and T cell modulation - abnormalities that may contribute to development of atherosclerosis in CKD. [ABSTRACT FROM AUTHOR]