EARLY MARKERS OF THE KIDNEYS DAMAGE IN PATIENTS WITH RESISTANT HYPERTENSION

Abstract

Objective: To define early specific markers for assessing the degree of kidney damage in patients with resistant hypertension (RH). Design and method: We examined 235 patients with RH confirmed by the office and ambulatory BP monitoring despite the use of 3 antihypertensive medications with diuretic. Chronic kidney disease (CKD) was diagnosed using estimated glomerular filtration rate (eGFR) according to the CKD-EPI equation. Microalbuminuria (MAU) was defined as levels of albumin ranging from 30 to 300 mg in a 24-h urine collection. In all pts plasma levels of citrulline, creatinine, matrix metalloproteinase-12 (MM-12), C-reactive protein (CRP), fibrinogen, uric acid were measured. Results: Patients were assigned to 3 groups: without CKD (Gr.I pts), CKD stage 1 (GFR more than 90 ml/ min/ 1.73 m2) (Gr.II pts), and CKD stages 2–3 (GFR 30–90 ml / min/1.73 m2) (Gr.III pts). Plasma citrulline content was significantly higher in Gr.II pts and Gr.III pts than that in Gr.I pts: 92.2 ± 4.3 and 116.50 ± 5.06 mol/l vs 71.0 ± 6.2 mol/l (p < 0.05 in both cases). The difference between Gr.II and Gr.III pts was also significant (p < 0.05). Patients with kidney damage had a significantly (p < 0.05) higher level of markers of systemic inflammation (CRP, fibrinogen, MM-12) compared with the group of patients without CKD. There was no significant difference in creatinine or uric acid content between pts without CKD (Gr.I) and CKD stage 1 pts. (Gr.II). There was negative correlative relationship between blood levels of citrulline, CRP, MM-12, fibrinogen and eGFR (r = -0,532; P < 0.04; r = -0,384; P < 0.05; r = -0,332; P < 0.05; r = -0,331; P < 0.05 accordingly). Conclusions: Citrulline level could be used to estimate the early degree of renal damage in RH pts that in conjunction with identifying inflammatory markers may be useful in developing effective strategies for the prevention or early detection and treatment of impaired renal function. Relationship between citrulline, CRP, MM-12, fibrinogen and eGFR may indicates on underlying tubulointerstitial dysfunction and chronic inflammation in mechanism of kidney damage of hypertensive nephropathy in patients with RH.