Inflammation-Related Patterns in the Clinical Staging and Severity Assessment of Chronic Kidney Disease

Abstract

Chronic kidney disease (CKD) is an irreversible loss of kidney function, and it represents a major global public health burden due to both its prevalence and its continuously increasing incidence. Mineral bone disorders (MBDs) constitute a hallmark of CKD, and alongside cardiovascular complications, they underlie a poor prognosis for these patients. Thus, our study focused on novel CKD biomarker patterns and their impact on the clinical staging of the disease. As a first testing approach, the relative expression levels of 105 proteins were assessed by the Proteome Profiler Cytokine Array Kit for pooled CKD stage 2–4 serum samples to establish an overall view regarding the proteins involved in CKD pathogenesis. Among the molecules that displayed significant dysregulation in the CKD stages, we further explored the involvement of Dickkopf-related protein 1 (Dkk-1), a recognised inhibitor of the Wnt signalling pathway, and its crosstalk with 1,25OH2D3 (calcitriol) as new players in renal bone and vascular disease. The serum levels of these two molecules were quantified by an ELISA (76 samples), and the results reveal decreasing circulating levels of Dkk-1 and calcitriol in advanced CKD stages, with their circulating expression showing a downward trend as the CKD develops. In the next step, we analysed the inflammation and MBD biomarkers' expression in CKD (by xMAP array). Our results show that the molecules involved in orchestrating the inflammatory response, interleukin-6 (IL-6) and tumour necrosis factor alpha (TNFα), as well as the mineral biomarkers osteoprotegerin (OPG), osteocalcin (OC), osteopontin (OPN), and fibroblast growth factor 23 (FGF-23), correlate with Dkk-1 and calcitriol, raising the possibility of them being potential useful CKD biomarkers. These results reveal the impact of different biomarker patterns in CKD staging and severity, thus opening up novel approaches to be explored in CKD clinical management.

Association between serum osteoprotegerin level and renal prognosis in nondialysis patients with chronic kidney disease in the Korean Cohort Study for Outcomes in Patients with Chronic Kidney Disease (the KNOW-CKD Study)

“…Because serum OPG level is a marker of vascular damage, many recent studies have focused on the relationship between it and cardiovascular outcomes, including coronary artery calcification and cardiovascular disease-related mortality [12,13,26,27]. This disorder of the kidney-vas-cular-bone axis can be related to mineral metabolism; however, it can also result from local inflammation [28]. OPG is expressed in various organs and cell types, including the heart, kidney, liver, osteoblasts, and vascular smooth muscle cells, and it is related to many cytokines and growth factors, such as interleukin (IL)-1, IL-6, IL-11, IL-17, TNF-α, transforming growth factor-β (TGF-β), and platelet-derived growth factor [29][30][31][32].…”

Cytokine changes during treatment of anti-Caspr2 encephalitis: a case report

“…In this case report, we used a commercial protein blotting membrane-based multiplexing immunoassay kit (cytokine array, R&D) to screen cytokines with significant changes during treatment and verified the changes using the fluorescent bead-based multiplexing immunoassay (Luminex assay, R&D). The cytokine array has been applied to identify immune status modifications by comparing diseased people with healthy controls [ 37 ], to identify chronic disease in different clinical stages [ 38 ], and to compare changes before and after treatment [ 39 ].…”

Relationship of phase angle and peak torque of knee extensors with the performance in six-minute step test in haemodialysis patients

“…Hospital Sírio-Libanês, Rehabilitation Centre, Dona Adma Jafet Street, 91 -Bela Vista, São Paulo, SP 01308-050, Brazil. 2 Hospital Sírio-Libanês, Haemodialysis Centre, Dona Adma Jafet, 91 -Bela Vista, São Paulo, SP 01308-050, Brazil.…”

“…Chronic kidney disease (CKD) is a multi-factorial syndrome that affects not only renal function, but also cardiovascular, respiratory, endocrine and musculoskeletal functions [ 1 ]. In advanced stages, hydroelectrolytic imbalance occurs, culminating in systemic changes in CKD: metabolic acidosis, systemic inflammation, anaemia, oedema and uraemia, causing major changes in body composition and peripheral muscle function [ 2 ]. At this point, sometimes it is necessary to initiate kidney replacement therapy (KRT), which tends to increase life expectancy in this population; however, individuals in KRT commonly present worsening of peripheral muscle function, reduced cellular integrity, reduced exercise tolerance, and worse quality of life [ 3 , 4 ].…”