Matrix metalloproteinases in patients with resistant hypertension and type 2 diabetes mellitus: relation with renal blood flow and kidney function

Objective. To evaluate the plasma levels of metalloproteinases (MMP) and their inhibitor in patients with resistant hypertension (RHTN) and type 2 diabetes mellitus (DM2) and their relationship with renal blood flow and kidney function.

Design and methods. The study included 18 patients with RHTN and DM2 and 16 individuals with RHTN without DM, who underwent offce and 24-h ambulatory blood pressure measurements, renal Doppler ultrasound, and laboratory tests (daily albuminuria, estimated glomerular fltration rate calculated by CKD-EPI formula, HbА1c and basal glycaemia levels, MMP-9, MMP-2, tissue inhibitor of MMP type 1 (TIMP1), MMP/TIMP-1 ratios).

Results. Patients with RHTN and DM2 and subjects with RHTN without DM were comparable by mean levels of metalloproteinases, TIMP-1, and their ratios. The frequency of increased MMP-9 level was similar in both groups (61 % for RHTN + DM2 group and 75 % for RHTN without DM, p > 0,05). In patients with RHTN and DM2 the increase in MMP-9 and a decrease in TIMP-1/MMP-9 ratio were associated with a reduction in renal resistive indices (MMP-9 and RI in the main renal arteries: right-sided R = –0,60, p = 0,009, left-sided R = –0,60, p = 0,008; in segmental arteries: R = –0,49, p = 0,038 on the right and R = –0,59, p = 0,012 on the left; for TIMP-1/MMP-9 and segmental arteries: R = 0,51, p = 0,028 on the right; and R = 0,46, p = 0,04 on the left). The eGFR and MMP-9 signifcantly correlated (R = 0,55, p = 0,023). Patients with increased albuminuria showed higher values of TIMP-1/MMP-2 ratio than patients with normal albuminuria (2,97 ± 0,82 и 1,58 ± 0,33 ng/mL, respectively, p = 0,03). There was a direct correlation between TIMP-1/MMP-2 ratio and basal glycaemia (R = 0,59, p = 0,018).

Conclusions. Patients with RHTN and DM2 had comparable MMP levels and their inhibitor to those in patients with RHTN without DM, which may partly reflect that extracellular matrix formation is independent from carbohydrate disorders in RHTN. In patients with RHTN and DM2 an increase in MMP-9 and a decrease in TIMP-1/MMP-9 ratio may be adaptive, since it is accompanied by improved intrarenal blood flow and renal fltration function. The increase in basal hyperglycemia is associated with the suppression of the proteolytic activity of MMP-2 related to the progression of albuminuria.

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