Novel Biomarkers in Patients with Chronic Kidney Disease: An Analysis of Patients Enrolled in the GCKD-Study

Abstract

Background: Chronic kidney disease (CKD) and cardiovascular diseases (CVD) often occur concomitantly, and CKD is a major risk factor for cardiovascular mortality. Since some of the most commonly used biomarkers in CVD are permanently elevated in patients with CKD, novel biomarkers are warranted for clinical practice. Methods: Plasma concentrations of five cardiovascular biomarkers (soluble suppression of tumorigenicity (sST2), growth differentiation factor 15 (GDF-15), heart-type fatty acid-binding protein (H-FABP), insulin-like growth factor-binding protein 2 (IGF-BP2), and soluble urokinase plasminogen activator receptor) were analyzed by means of enzyme-linked immunosorbent assay (ELISA) in 219 patients with CKD enrolled in the German Chronic Kidney Disease (GCKD) study. Results: Except for sST2, all of the investigated biomarkers were significantly elevated in patients with CKD (2.0- to 4.4-fold increase in advanced CKD (estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 m² body surface area (BSA)) and showed a significant inverse correlation with eGFR. Moreover, all but H-FABP and sST2 were additionally elevated in patients with micro- and macro-albuminuria. Conclusions: Based on our findings, sST2 appears to be the biomarker whose diagnostic performance is least affected by decreased renal function, thus suggesting potential viability in the management of patients with CVD and concomitant CKD. The predictive potential of sST2 remains to be proven in endpoint studies.

Insulin-Like Growth Factor Binding Proteins in Kidney Disease

“…Except LN, IGFBP-2 in the blood can be used as an early diagnostic marker for AKI, and its sensitivity is higher than creatinine, urea nitrogen and cystatin C ( Li et al, 2018 ), and this might be induced by hypoxia ( Minchenko et al, 2015 ). In studies related to chronic kidney disease, circulating IGFBP-2 increased in CKD patients with different conditions, including experimental uremia, CKD caused by heart failure, and children with CKD ( Powell et al, 1996 ; Tönshoff et al, 1997 ; Mahesh and Kaskel, 2008 ; Narayanan et al, 2012 ; Mirna et al, 2020 ; Ravassa et al, 2020 ). What’s more, clinical studies have also tracked the renal function level and plasma IGFBP-2 concentration of more than 400 patients with diabetic nephropathy over an 8-year period, suggesting that IGFBP-2 is a biomarker to predict longitudinal deterioration of renal function in patients with type 2 diabetes ( Narayanan et al, 2012 ).…”

Advances in the Progression and Prognosis Biomarkers of Chronic Kidney Disease

“…A head-to-head comparison study with Gal-3 in patients with chronic heart failure also demonstrated that sST-2 performed better than Gal-3 and could predict 5-year risk of cardiovascular death (Bayes-Genis et al, 2014). The significant correlation between plasma sST-2 levels and the progression of CKD to ESRD was also confirmed in a recent cohort study involving 219 patients who participated in the German Chronic Kidney Disease (GCKD) study (Mirna et al, 2020). All the evidence demonstrated the importance of sST-2 in evaluating the cardiovascular risk of CKD.…”

New Potential Biomarkers for Chronic Kidney Disease Management—A Review of the Literature

“…Growth differentiation factor-15 (GDF-15) is a member of the transforming growth factor beta cytokine superfamily, and its expression may be induced in response to ischemia. GDF-15 was significantly associated with increased risk of CKD progression in several studies [124][125][126][127]. Nair et al (2017) showed that circulating GDF-15 levels were strongly correlated with intrarenal expression of GDF-15, stating that GDF-15 may be a marker for intrarenal signaling pathways associated with CKD development and progression [124].…”