[Clinical value of the determination of markers for endothelial dysfunction (endothelin-1, microalbuminuria) and tubulointerstitial tissue lesion (ß2-microglobulin, monocyte chemotactic protein-1) in hypertensive patients with uric acid metabolic disorders].

AIM: To identify the risk factors of kidney injuries in hypertensive patients with uric acid (UA) metabolic disorders in order to choose the optimal management tactics, by analyzing the changes in markers for endothelial dysfunction (endothelin-1 (ET-1), microalbuminuria (MAU), intima-media thickness (IMT)) and tubulointerstitial tissue lesion (beta2-microglobulin (beta2-MG, monocyte chemotactic protein-1 (MCP-1)). SUBJECTS AND METHODS: Eighty-one patients with grade 1 hypertension without associated diseases, diabetes mellitus, or metabolic syndrome were examined. There were 3 study groups: 1) hyperuricosuria (n = 7); 2) hyperuricemia (n = 53); 3) hyperuricemia and renal failure (n = 6); and a control group of 15 hypertensive patients without UA metabolic disorders who were matched for age and gender with the patients of the study groups. RESULTS: The hypertensive patients with hyperuricemia, as compared with those without UA metabolic disorders, showed higher plasma concentrations of ET-1 (p = 0.003) and MAU (p = 0.009) and more marked increases in common carotid IMT (p = 0.044), urinary excretion of beta2-MG (p = 0.010), and MCP-1 (p = 0.030). There were direct correlations between all the examined biomarkers and the degree of uricemia (Rs = 0.453; p < 0.001; Rs = 0.411; p < 0.001; Rs = 0.322; p = 0.067; Rs = 0.537; p < 0.001; and Rs = 0.318; p = 0.004, respectively) and between the markers of endothelial dysfunction and those of tubulointerstitial tissue lesion (Rs = 0.295 for ET-1 and MCP-1; p = 0.008; Rs = 0.399 for ET-1 and beta2-MG; p < 0.001; Rs = 0.462 for MAU and beta2-MG; p < 0.001; and Rs = 0.188 for MAU and MCP-1; p = 0.094). Multivariate analysis of the clinical and laboratory parameters under study confirmed the role of serum MCP-1, beta2-MG, MAU, creatinine levels as independent predictors for decreased relative urinary gravity, the clinical sign of tubulointerstitial tissue lesion/fibrosis, and that of a wider range of the indicators, such as MAU, ventricular septal thickness, glomerular filtration rate, relative urinary gravity, systolic blood pressure, MPC-1, low-density lipoproteins, as risk factors for renal filtrating dysfunction.

[Hyperuricemia and the problem of chronic kidney disease].

The paper reviews the literature on the role of hyperuricemia as a risk factor for chronic kidney disease and as one of the factors for the progression of existing kidney disease. It gives epidemiological information on a relationship between hyperuricemia and kidney lesion. The mechanisms for the damaging action of uric acid on kidney tissue, which have experimentally and clinically observed, are considered. The main areas of hyperuricemia correction and its place in the total nephroprotection strategy are defined.

[Antihypertensive therapy optimization and endothelial function in patients with gout and chronic urate tubulointerstitial nephritis].

AIM: to characterize the markers of endothelial dysfunction and the effect of antihypertensive drugs on them in patients with chronic urate tubulointestinal nephritis (UTIN) and articular gout. SUBJECTS AND METHODS: The study enrolled 81 patients aged 39 to 59 years with gout and urate nephropathy. All the patients were diagnosed as having grade 1-2 arterial hypertension. A lower glomerular filtration rate (GFR) was noted in 49.9%; microalbuminuria (MAU) and elevated serum endothelin-1 (ET-1) levels were recorded in all the patients. Combination antihypertensive therapy based on the use of angiotensin-converting enzyme (ACE) inhibitors and/or an angiotensin II receptor blocker (ARB) in combination with calcium channel blockers was performed during 12 months. The time course of changes in blood pressure, the parameters of target organ lesion, and the markers of endothelial dysfunction were monitored. RESULTS: Before the study, all the examinees were found to have MAU and increased serum ET-1, which are regarded simultaneously as signs of renal lesion and as markers of endothelial function. A combination of an ACE inhibitor or an ARB could diminish albuminuria and reduce ET-1 concentrations, lower systolic and diastolic blood pressure significantly, and increase GFR. CONCLUSION: The patients with articular gout and chronic UTIN are observed to have signs of endothelial dysfunction eliminated by combination antihypertensive therapy.

[Endothelial function in patients with arterial hypertension and impaired uric acid metabolism].

The aim of the study was to investigate endothelial function in patients with arterial hypertension and impaired uric acid metabolism in comparison with patients having arterial hypertension and normal uric acid metabolism. 46 patients aged 32-56 yr with grade I-II AH were included in the study. A group of 36 patients (27 male, 9 female) presented with AH and impaired uric acid metabolism (hyperuricemia), the control group included 10 patients with AH and unaffected uric acid metabolism. Inclusion criteria in the two groups were identical. Endothelial dysfunction was documented in all patients and confirmed by increased levels of serum endothelin-1 and microalbuminuria, qualitative and quantitative changes in the intima-media complex and its thickening. These changes were much more pronounced in patients with hyperuricemia It is concluded that impaired uric acid metabolism in patients with AH leads to rapid onset and progression of endothelial dysfunction. This fact should be taken into consideration by doctors practicing antihypertensive treatment and for the evaluation of cardiovascular risks.