Biomarkers of kidney injury in hypertension: conventional versus novel

Abstract

Objective. The aim of the present study was to compare conventional and novel, potentially earlier biomarkers of kidney injury in patients with different severity and duration of arterial hypertension (HTN) and healthy controls. Design and methods. Urine levels of neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule‑1 (KIM‑1), liver fatty-acid binding protein (L‑FABP), albuminuria and serum levels of cystatin C and creatinine were measured in 92 hypertensive patients (46 male, mean age 50,7 ± 12,2 years) and 34 healthy control subjects (16 male, mean age 49,9 ± 11,4 years). Hypertensive patients were divided into four age- and sex-matched groups according to HTN severity: 1st grade (n = 24), 2nd grade (n = 26), 3rd grade (n = 17) and resistant hypertension (n = 25). Glomerular filtration rate (GFR) was estimated by the level of serum creatinine and cystatin C by MDRD and CKD-EPI formulas. Instrumental examination included measuring office blood pressure (BP), 24‑hour ambulatory BP monitoring (ABPM, SpaceLabs 90207), applanation tonometry (SphygmoCor, Artcor Medical) with the calculation of central aortic pressure. Results. As compared to healthy control subjects, hypertensive patients were characterized by higher creatinine and albuminuria levels, and lower GFR, however, creatinine levels remained within the normal range despite the increase in the severity of HTN. Levels of albuminuria increased only in patients with severe HTN. Also as compared to healthy controls, HTN patients had significantly higher levels of cystatin C, which already was found in patients with 1st and 2nd stages of HTN, which occurs more often than an increase of creatinine and albuminuria levels. Patients with HTN had significantly lower sCys-estimated GFR and creatinine-sCys-estimated GFR. In HTN patients these biomarkers were associated with office systolic BP (SBP), central aortic systolic and diastolic (CAP) and mean 24‑hour BP level. There were no differencesin NGAL, KIM‑1 levels between the groups, however, KIM‑1 levels were associated with office SBP, mean daily 24‑hour of diastolic BP (DBP) and systolic and diastolic CAP in patients with severe HTN. At the same time, as compared with healthy controls, patients with initial HTN were characterized by higher levels of urine L‑FABP and its concentration increased in patients with severe HTN. In addition, L‑FABP levels were associated with office SBP and DBP, mean 24‑hour BP and systolic and diastolic CAP. Conclusions. The simultaneous assessment of creatinine and cystatin C levels, and the calculation of GFR using the formula CKD-EPI seems to be more accurate method for CKD stage classification in general and, in particular, in hypertensive patients; in hypertensive patients L‑FABP appears to be earlier biomarker of kidney injury, reflecting the progression of tubulointerstitial injury.