BackgroundCardiovascular events are frequent and vascular endothelial function is abnormal in patients with chronic kidney disease (CKD). We demonstrated endothelial dysfunction with vitamin D deficiency in CKD patients; however the impact of cholecalciferol supplementation on vascular stiffness and vasomotor function, endothelial and bone biomarkers in CKD patients with low 25-hydroxy vitamin D [25(OH)D] is unknown, which this study investigated.MethodsWe assessed non-diabetic patients with CKD stage 3/4, age 17–80 years and serum 25(OH)D <75 nmol/L. Brachial artery Flow Mediated Dilation (FMD), Pulse Wave Velocity (PWV), Augmentation Index (AI) and circulating blood biomarkers were evaluated at baseline and at 16 weeks. Oral 300,000 units cholecalciferol was administered at baseline and 8-weeks.ResultsClinical characteristics of 26 patients were: age 50±14 (mean±1SD) years, eGFR 41±11 ml/min/1.73 m2, males 73%, dyslipidaemia 36%, smokers 23% and hypertensives 87%.At 16-week serum 25(OH)D and calcium increased (43±16 to 84±29 nmol/L, p<0.001 and 2.37±0.09 to 2.42±0.09 mmol/L; p = 0.004, respectively) and parathyroid hormone decreased (10.8±8.6 to 7.4±4.4; p = 0.001). FMD improved from 3.1±3.3% to 6.1±3.7%, p = 0.001.Endothelial biomarker concentrations decreased: E-Selectin from 5666±2123 to 5256±2058 pg/mL; p = 0.032, ICAM-1, 3.45±0.01 to 3.10±1.04 ng/mL; p = 0.038 and VCAM-1, 54±33 to 42±33 ng/mL; p = 0.006. eGFR, BP, PWV, AI, hsCRP, von Willebrand factor and Fibroblast Growth Factor-23, remained unchanged.ConclusionThis study demonstrates for the first time improvement of endothelial vasomotor and secretory functions with vitamin D in CKD patients without significant adverse effects on arterial stiffness, serum calcium or FGF-23.Trial RegistrationClinicalTrials.gov NCT02005718

Journal WatchSerum-free immunoglobulin light chain evaluation as a marker of impact from intraclonal heterogeneity on myeloma outcome Brioli A, Giles H, Pawlyn C, et al. Blood 2014; 123: 3414-3419. In multiple myeloma (MM), an abnormal plasma cell clone secretes immunoglobulins, free light chains (FLCs), or both. Despite its 'monoclonal' nature, genetic and phenotypic variation within clones in MM is now recognised. Progression of such intraclonal heterogeneity (manifest as changes in immunoglobulin type over time) is the subject of this study.Data from 520 patients from the Myeloma IX trial who suffered relapse were analysed. Relapse was categorised as paraprotein only (49.6%), FLC and paraprotein (35.2%) and FLC only (10.4%). Patients whose relapse included increased FLC had decreased overall survival time by 13 months when compared with paraprotein only relapse (P ¼ 0.015), with the discrepancy mainly due to survival post relapse. The difference in survival time was suggested to be due to intraclonal heterogeneity, with greater resistance of FLC subclones to chemotherapy. A mechanism however was not suggested for this differing subclonal response.The authors suggest FLC monitoring in MM to assess intraclonal heterogeneity, and to aid detection of relapse. However, as many patients with FLC relapse also had elevated FLC at diagnosis (an adverse prognostic sign), it is not yet clear if FLC relapse provides independent prognostic information.

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