Novel biomarkers of kidney injury and fibrosis in patients with different severity of hypertension: relation to vascular reactivity and stiffness

Abstract

Aim. To compare the relationships between conventional and new potentially more early investigational biomarkers (urine and ultrasound) of kidney injury and central aortic blood pressure, vascular stiffness and reactivity, endothelial dysfunction in patients with different severity of hypertension.Material and methods. Urine levels NGAL, KIM-1, L-FABP, albuminuria and serum levels of сystatin C and creatinine were measured in 92 hypertensive patients with mild and severe hypertension, 46 male (mean age 50,7±12,2 years). Glomerular filtration rate was estimated by the level of serum creatinine and cystatin C by MDRD and CKD-EPI formulas. Instrumental examination included measuring office blood pressure, 24-hour ambulatory blood pressure monitoring (SpaceLabs 90207), applanation tonometry (SphygmoCor, Artcor Medical) with the calculation of central aortic blood pressure, pulse wave velocity and augmentation index and Doppler ultrasonography with assessment of intraparenchymal renal arterial resistance indices — resistive index and pulsatility index (Vivid 7 dimension). Endothelial function was assessed by reactive hyperemia index with EndoPAT device (Itamar Medicals).Results. There were no differences in conventional levels of biomarkers between patients, however, cystatin C level increased and serum cystatin C estimated GFR and serum creatinine and cystatin C estimated GFR (CKD EPI formula) (sCr,Cys-estimated GFR) levels decreased with the severity of hypertension. These novel biomarkers were associated with increased central aortic blood pressure, arterial stiffness and intraparenchymal renal arterial resistance indices. Decreased sCr,Cys-estimated GFR levels were associated with lower reactive hyperemia index. There were no differences in NGAL, KIM-1 and L-FABP levels in patients with hypertension. However, NGAL levels were associated with increased augmentation index, resistive index in intralobular and pulsatility index in arcuate arteries, KIM-1 and L-FABP levels were associated with increased systolic and diastolic central aortic blood pressure, pulse wave velocity only in patients with severe and resistant hypertension.Conclusion. Serum cystatin C, NGAL, KIM-1 and L-FABP levels seem to be biomarkers of increased systemic and intrarenal vascular stiffness in patients with different severity of hypertension.

Significance of modern diagnostic methods in the early diagnosis of hypertensive nephropathy

“…Однако сведения по применению биомаркеров в диагностике поражения почек при АГ малочисленны и противоречивы. Кроме того, их использование ограничивается недостаточной специфичностью [23]. Так, в исследовании Kadioglu T, et al ( 2016) больные АГ и представители контрольной группы по уровню KIM-1 не различались, хотя была обнаружена положительная корреляция между уровнями KIM-1, систолическим АД, и продолжительностью заболевания (r=0,308, р=0,032 и r=0,339, р=0,032, соответственно) [24].…”