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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.

Chronic kidney disease, despite being a “silent epidemic” disease, represents one of the main causes of mortality in general population, along with cardiovascular disease, which is the leading cause of poor prognosis for these patients. The specific objective of our study was to characterize the relationship between the inflammatory status, the bone disorders markers, and kidney failure in chronic kidney disease patient stages 2–4, in order to design a novel biomarker panel that improves early disease diagnosis and therapeutic response, thus being further integrated into clinical applications. A panel of proteomic biomarkers, assessed by xMAP array, which includes mediators of inflammation (IL-6, TNF-α) and mineral and bone disorder biomarkers (OPG, OPN, OCN, FGF-23, and Fetuin-A), was found to be more relevant than a single biomarker to detect early CKD stages. The association between inflammatory cytokines and bone disorders markers, IL-6, TNF-α, OPN, OPG, and FGF-23, reflects the severity of vascular changes in CKD and predicts disease progression. Proteomic xMAP analyses shed light on a new approach to clinical evaluation for CKD staging and prognosis.

The association of NAFLD with chronic hepatitis C (CHC) has been extensively studied but little is known about its coexistence with chronic hepatitis B (CHB).To investigate the prevalence and determinants of steatosis and insulin resistance (IR) in CHB and its consequences on liver injury compared with CHC and NAFLD.Patients with CHB (N=110), CHC (N=111) and NAFLD (N=136) were evaluated by biomarkers of steatosis (SteatoTest0.38 as a surrogate for steatosis5%), IR (HOMA-IR2.7 as a surrogate for IR) and fibrosis (FibroTest0.48 as a surrogate for significant fibrosis, ≥F2).HOMA-IR gradually increased in CHB, CHC and NAFLD: 2.3±1.8; 3±2.6 and 3.8±2.7 (p0.001). The prevalence of steatosis5% was 21% (CHB), 43% (CHC) and 82% (NAFLD), (p0.001). The prevalence of fibrosis≥F2 was 10% (CHB), 42% (CHC) and 21% (NAFLD), p0.001. In CHB, IR was related to host and not viral factors. CHB patients with steatosis had higher BMI (29±5.7kg/m(2) vs. 24±4kg/m(2), p0.001), waist circumference (96±14cm vs. 84±11cm, p=0.001) and HOMA-IR (3.9±2.6 vs. 1.8±1.2, p0.001) than those without steatosis. HOMA-IR independently predicted steatosis in CHB (OR=1.9, 95% CI, 1.09-3.27, p0.05) and CHC (OR=1.38; 95% CI, 1.07-1.78, p0.02). In CHB, metabolic risk factors and HOMA-IR were not associated with significant fibrosis. HOMA-IR was an independent predictor of fibrosis in CHC.Steatosis may co-exist in CHB patients but with a lower prevalence than in CHC and NAFLD. In CHB steatosis is related to host and not viral factors, and is not associated with the severity of fibrosis.

Aim: To evaluate the prevalence of HBV, HCV, HDV and HEV infections in populations with different categories of risk and the seroprevalence of HBV and HCV infections in subjects asking for a medical examination.Method: We conducted a cross-sectional, epidemiological study in 2,851 subjects from the SubCarpathian and South-Eastern Romania (including 17 counties, 34% of the country area and 42% of the population). The subjects were divided into four groups: controls (n=2,540, i.e. consecutive subjects asking for a medical examination), subjects with very low risk (students; n=44), with low risk (doctors and nurses; n=93) and with high risk for viral hepatitis (hemodialysis patients; n=174). All subjects were screened for HBsAg, antiHCV and ALT level. In populations at risk, antiHBs, HBeAg, antiHBe, antiHBc (IgG), HBV-DNA, HCV-RNA, antiHDV(IgG) and antiHEV(IgG) were also assessed.Results: In controls, HBV seroprevalence was 5.59% and HCV seroprevalence 4.56%. The risk factors for HBV infection were: age, male gender and South-East region of Romania. The risk factors for HCV infection were: age, female gender, elevated ALT level and the South-East region of Romania. In the very low risk population HBV, HCV, HDV and HEV seroprevalence was: 2.27%, 0%, 0% and 12.5%, respectively. In low risk population the seroprevalence was 2.15%, 1.07%, 0% and 13.98%. In hemodialysis patients, HBV and HCV seroprevalence were 7.91%, respectively 39.26%. HCV-RNA was detectable in 20.69% cases.Conclusion: In the South and South-Eastern Romania the seroprevalence of viral hepatitis infections is intermediate, similar to other Romanian regions or the Balkans.