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

Moritz Mirna,Ulla T Schultheiss,Christian Jung,P Christian Schulze,Uta C Hoppe,Gunter Wolf,Martin Busch,Katharina Paul,Kristen Kopp,Bernhard Wernly,Claudia Sommerer,Hermann Salmhofer,Michael Lichtenauer,Markus P Schneider,Vera Paar,Richard Rezar,Albert Topf,Daniel Kretzschmar

doi:10.3390/jcm9030886

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.

Highlights

Chronic kidney disease (CKD) affects about 11.5% of the overall population with increasing age-dependent prevalence of up to 47% in persons older than 70 years [1]
Arterial hypertension was present in 90.4% (n = 198), diabetes mellitus type 2 in 39.3% (n = 86), heart failure in 26.0% (n = 57), and 49.3% had a history of smoking (n = 108)
The majority of patients was in CKD stages G3a (41.6% (n = 91), estimated glomerular filtration rate (eGFR) 45–59 mL/min/1.73 m2 body surface area (BSA)) and G3b (32.4% (n = 71), eGFR 30–44 mL/min/1.73 m2 BSA), followed by CKD stage 2 (13.7% (n = 30), eGFR 60–89 mL/min/1.73 m2 BSA) and CKD stages 4 and 5 (9.6% (n = 21), eGFR < 30 mL/min/1.73 m2 BSA); 2.7% (n = 6) of the patients had an eGFR above 90 mL/min/1.73 m2 BSA while having proteinuria

Summary

Introduction

Chronic kidney disease (CKD) affects about 11.5% of the overall population with increasing age-dependent prevalence of up to 47% in persons older than 70 years [1]. Some of the most common biomarkers in this field, such as troponin or brain natriuretic peptide (BNP), are chronically elevated in patients with CKD, which may in part be due to impaired renal clearance [5,6,7]. Their clinical applicability in patients with CKD is limited and novel biomarkers are warranted to improve diagnosis and risk stratification in these disease entities. The predictive potential of sST2 remains to be proven in endpoint studies

Methods

Results

Conclusion