Supplementary Material for: Paricalcitol, Microvascular and Endothelial Function in Non-Diabetic Chronic Kidney Disease: A Randomized Trial

<br><strong><em>Background:</em></strong> Vitamin D deficiency, sympathetic activation and endothelial dysfunction are associated with increased cardiovascular risk in patients with chronic kidney disease (CKD). Studies have so far failed to establish the role of vitamin D and vitamin D receptor activator (VDRA) treatment in moderate CKD. This trial was designed to assess whether VDRA treatment can ameliorate sympathetic activation and macro- and microvascular dysfunction in non-diabetic patients with moderate CKD. <b><i>Methods:</i></b> We conducted a randomized controlled double-blind trial using placebo, 1 or 2 μg of paricalcitol, a VDRA, for 3 months. We assessed muscle sympathetic nerve activity (MSNA) by microneurography, pulse wave velocity (PWV) by tonometry, flow mediated vasodilatation (FMD) by brachial ultrasound, skin microcirculation assessed by iontophoresis and capillary blood velocity (CBV) by videophotometric capillaroscopy. <b><i>Results:</i></b> Thirty-six patients with a mean age of 65 years and mean estimated glomerular filtration rate of 40 ml/min/1.73 m² were included. We found a significant decline in endothelial function after 3 months, except in the group receiving 2 μg of paricalcitol. The higher dose (2 μg) seemed to attenuate the decline in microvascular endothelial function, assessed by iontophoresis of acetylcholine (p = 0.06 for all groups, p = 0.65 for the 2 μg group) and for FMD (p = 0.006 for all groups, p = 0.54 for the 2 μg group). We found a borderline significance (p = 0.05) for improved CBV in the treated groups. We found no significant changes between treatments in MSNA, PWV or albuminuria. <b><i>Conclusions:</i></b> Endothelial function declined significantly over 3 months in patients with moderate CKD, and this decline could be ameliorated by VDRA treatment (NCT01204528)

PowerPoint Slides for: Early Changes in Monocyte Adhesion Molecule Expression and Tumor Necrosis Factor-α Levels in Chronic Kidney Disease - A 5-Year Prospective Study

<i>Background:</i> Despite the absence of clinical symptoms, patients with chronic kidney disease (CKD) exhibit elevated levels of pro-inflammatory markers. To investigate whether it is possible to detect inflammatory activity and altered monocyte function at an early stage of renal disease, we studied patients with CKD stages 2-3 over 5 years. <i>Methods:</i> The expression of adhesion molecules on monocytes at resting state and after stimulation with formyl-methionyl-leucyl-phenylalanine (fMLP), as well as oxidative metabolism capacity was measured with flow cytometry in 108 CKD patients and healthy controls. Soluble markers of inflammation, such as cytokines, were analyzed using the Milliplex technique. <i>Results:</i> Patients showed significantly lower CD11b expression after stimulation during the 3rd (p = 0.002) and the 5th year (p < 0.001), together with a lower oxidative burst in response to fMLP over time (p = 0.02). The expression of CD62L on resting monocytes was lower during the 3rd (p = 0.001) and the 5th (p = 0.001) year in patients. Levels of tumor necrosis factor-α and RANTES were significantly increased (p = 0.001, p = 0.006) and interleukin-12 levels were also higher in CKD patients during the 5th year (p = 0.007). <i>Conclusion:</i>Monocytes in CKD stages 2-3 show emerging functional abrasions, with altered adhesion molecule expression and impaired fMLP response. These findings suggest that a transformation of monocyte function occurs at an early phase of renal impairment and may together with increased plasma levels of pro-inflammatory cytokines contribute to the higher vulnerability of CKD patients to comorbidities, such as infections and cardiovascular disease

Supplementary Material for: The Relationship of NT-proBNP and Dialysis Parameters with Outcome of Incident Haemodialysis Patients: Results from the Membrane Permeability Outcome Study

<b><i>Background/Aims:</i></b> The association of raised levels of natriuretic peptides with elevated risk of mortality was investigated in the present analysis of the Membrane Permeability Outcome study. <b><i>Methods:</i></b> N-terminal probrain type natriuretic peptide (NT-proBNP) was measured in 618 incident haemodialysis patients, randomised to either high-flux or low-flux. Characteristics of patients with NT-proBNP levels below or above the median were descriptively analysed and survival analysis was performed. <b><i>Results:</i></b> Median NT-proBNP value was 2,124 pg/ml, with 1,854 pg/ml in the high-flux and 2,919 pg/ml in the low-flux group. Survival probability was lowest in patients with both a history of cardiovascular disease and NT-proBNP values above the median (p < 0.001). A multivariate Cox proportional hazard model showed interaction between presence of cardiovascular diseases and NT-proBNP levels above the median. <b><i>Conclusions:</i></b> NT-proBNP is an independent predictor of mortality also in incident haemodialysis patients. Lower concentrations associated with high-flux dialysis suggest a possible biological link to improved survival in this group