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Introduction: Vascular lesions and arterial stiffness appear at early stages of chronic kidney disease (CKD) and follow an accelerated course with disease progression, contributing to high cardiovascular mortality. There are limited prospective data on mechanisms contributing to progression of arterial stiffness in mild-to-moderate CKD (stages 2-3). Methods: We applied an affinity proteomics approach to identify candidates of circulating biomarkers with potential impact on vascular lesions in CKD and selected soluble cluster of differentiation 14 (sCD14), angiogenin (ANG), and osteoprotegerin (OPG) for further analysis. We studied their association with ankle-brachial index (ABI) and carotid intima-media thickness, as measures of arteriosclerosis and atherosclerosis, respectively, in 48 patients with CKD stages 2-3, who were prospectively followed and intensively treated for 5 years, and 44 healthy controls. Results: Concentrations of sCD14 (p < 0.001), ANG (p < 0.001), and OPG (p < 0.05) were higher in patients with CKD 2-3 at baseline, and sCD14 (p < 0.001) and ANG (p < 0.001) remained elevated in CKD patients at follow-up. There were positive correlations between ABI and sCD14 levels (r = 0.36, p = 0.01) and between ABI and OPG (r = 0.31, p = 0.03) at 5 years. The changes in sCD14 during follow-up correlated to changes in ABI from baseline to 5 years (r = 0.41, p = 0.004). Conclusion: Elevated levels of circulating sCD14 and OPG in patients with CKD 2-3 were significantly associated with ABI, a measure of arterial stiffness. An increase in sCD14 over time in CKD 2-3 patients was associated with a corresponding increase in ABI. Further studies are needed to examine if early intensive multifactorial medication to align with international treatment targets may influence cardiovascular outcomes., QC 20240115

Background: Chronic kidney disease (CKD) is associated with an increased risk of cardiovascular disease and infections. Both conditions share the same underlying cause comprising of changes in innate and adaptive immunity. Aim: The objective of this thesis was to contribute to an increased understanding of the dysregulation in the immune system in CKD and to evaluate if selected markers can add prognostic information about the presence of vascular changes and infection outcomes in CKD. Methods: In study I, we phenotyped subsets of monocytes, B and T cells in patients with IgA nephropathy (IgAN) using flow cytometry. We included a disease control group (patients with autosomal dominant polycystic kidney disease (ADPKD)) and healthy controls (HC). Cytokines were analyzed using ELISA. In study II, we measured levels of IgE anti double-stranded DNA (dsDNA) in patients with active lupus nephritis (LN), patients with a history of LN, SLE patients with no kidney involvement and population-based controls. Levels of IgE anti-dsDNA were measured using fluorescence enzyme immunoassay. In a subgroup of patients with active LN and healthy controls, we evaluated the effect of active LN serum on healthy donor granulocytes compared to control sera. Granulocytes were stained for markers involved in cell migration, adhesion and immune modulation and were analyzed by flow cytometry. In study III, affinity proteomics was used to detect potential biomarkers for early vascular changes in patients with CKD stages 2-3. Three proteins of interest, potentially involved in vascular lesions, were identified and further analyzed with Luminex. Vascular status was evaluated using ankle-brachial index (ABI) and carotid media-intima thickness (CIMT). In study IV, we evaluated monocyte related markers in relation to kidney function and mortality in hospitalized patients with COVID-19 infection. As controls we included healthy individuals and patients with CKD without infection. Results: In study I