NOVEL BIOMARKERS OF KIDNEY CELL PATHOLOGY, INFLAMMATION AND FIBROSIS IN CONTROLLED AND UNCONTROLLED HYPERTENSION

Abstract

Objective: A significant reduction in kidney function is needed to detect a decrease in estimated glomerular filtration rate (eGFR), and only a minority of patients with hypertension (HT) have elevated urinary albumin excretion (UAE), leaving these biomarkers insensitive for early hypertensive organ damage. Low-grade inflammatory processes and fibrosis may have a key role in the pathogenesis of HT and HT-mediated kidney damage. Finding a panel of biomarkers related to HT and kidney damage at an early stage, that varies with modifiable risk factors, may aid targeted treatment. Several biomarkers of kidney cell pathology, markers of inflammation and fibrosis are of interest. In this nationwide cross-sectional multicentre study, we aimed to assess the associations between biomarkers and hypertension in four groups of patients; (1) healthy controls, (2) controlled HT, (3) uncontrolled HT, (4) uncontrolled HT with presence of kidney damage based on UAE and eGFR. We hypothesized that: (1) plasma levels of biomarkers are different between the 4 groups, (2) plasma levels of biomarkers are associated with the different HT groups. Design and method: Hypertensive patients (n = 183) were > = 18 years old with eGFR >30 mL/min/1.73m2, prescribed > = 2 antihypertensive agents and on a stable treatment regimen for at least 4 weeks. Age and sex matched healthy controls had undergone kidney donation assessment (n = 39). Biomarkers were analyzed in duplicate by a custom made Luminex bead-based immunoassay. The ethics committee approved the studies. All patients signed written informed consent. Results: Plasma levels of IL-1RA, NGAL and uromodulin were significantly different between healthy controls (n = 39) and hypertensive patients (n = 183). Levels of IL-1RA and NGAL were significantly different between the three groups of hypertensive patients. In multivariable models on hypertensive subjects none of the biomarkers were associated with uncontrolled HT (n = 126). IL-18, vWF-A2, NGAL and uromodulin were associated with uncontrolled HT with presence of kidney damage (n = 65). None of the biomarkers were associated with any of the HT groups after adjustment for eGFR. Conclusions: Selected biomarkers may add information to identify hypertensive patients at risk for kidney damage, but further and longitudinal analysis are needed.