PS 02-49 ASSOCIATION OF MATRIX METALLOPROTEINASES WITH THE RENAL BLOOD FLOW AND RENAL FUNCTION IN PATIENTS WITH RESISTANT HYPERTENSION AND TYPE 2 DIABETES MELLITUS

Abstract

Objective: We wished to assess the relationship between the plasma concentrations of matrix metalloproteinases (MMP) and their tissue inhibitors with intrarenal vascular resistance level, renal function and development of microalbuminuria in patients with resistant hypertension (RH) and type 2 diabetes mellitus (DM). Design and Method: A total of 18 patients with RH and type 2 DM were included in the study (mean aged 58.6 ± 7.5 years, 6 male, office blood pressure (BP) 174.4 ± 20.2/94.1 ± 15.2 mmHg, basal glycaemia 8.8 ± 2.3 mmol/L, HbA1c 6.8 ± 0.7%, an estimated glomerular filtration rate (eGFR) 74.2 ± 27.9 mL/min/1.73m 2), which submitted to office BP measurements, renal Doppler ultrasound and laboratory tests to assess microalbuminuria (defined as 30–300 mg/24 h), eGFR (MDRD formula), HbA1c and basal glycaemia levels, plasma concentrations of MMP-9, MMP-2, tissue inhibitor of MMP type 1 (TIMP-1). Results: Decreased MMP-9 concentration was linearly associated with increased resistive index (RI) in renal arteries (in the main renal arteries: R = −0.60, p = 0.009 (right), R = 0.−60, p = 0.008 (left); in segmental arteries: R = −0.49, P = 0.038 (right) and R = −0.59, P = 0.012 (left)), while growth of TIMP-1/MMP-9 ratio was positively correlated with RI at segmental arteries (R = 0.51, R = 0.028- on the right, R = 0.46, P = 0.04- on the left). Additionally, decreased MMP-9 concentration was linearly associated with decreased eGFR (R = 0.53, P = 0.029). No correlation was observed between MMP-2, MMP-9, TIMP-1, TIMP-1/MMP-9, TIMP-1/MMP-2 ratios and microalbuminuria, however, microalbuminuric patients had a higher TIMP-1/MMP-2 ratio than normoalbuminuric patients (2.97(2.15–3.80) and 1.58(1.39–1.99)ng/mL, accordingly, P = 0.026). Besides, microalbuminuric patients had a higher TIMP-1/MMP-2 ratio than normoalbuminuric patients [2.97 (2.15–3.80) and 1.58 (1.39–1.99), accordingly, P = 0.026)]. Conclusions: In patients with RH and type 2 DM the decreased MMP-9 activity and increased TIMP-1/MMP-9 ratio are associated with growth of intrarenal vascular resistance and decline of renal filtration function. Furthermore, increased TIMP-1/MMP-2 ratio in these patients was due primarily to increase in basal glycaemia level and linked to development of microalbuminuria.