[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.

[Significance of the markers of endothelial dysfunction and hemorheological disorders for assessing the activity and prognosis of chronic glomerulonephritis].

AIM: to define the clinical value of changes in blood rheological properties and renal endothelial function in patients with hematuric and nephritic forms of chronic glomerulonephritis (CGN) and to ascertain whether the indices under study can be applied to assess the activity (progression) of nephritis and used as a prognostic criteria. SUBJECTS AND METHODS: Sixty-one patients, including 30 with hematuric nephritis (Group 1) and 31 with nephrotic nephritis (Group 2), were examined. A control group consisted of 12 healthy individuals. The rheological properties of blood, such as its viscosity; kinetics of spontaneous aggregation and disaggregation of red blood cells in shear flow; their deformability; urinary excretion of functionally active von Willebrandt factor (WF), a plasminogen activator inhibitor type 1 (PAl-1); urine total fibrinolytic activity (UTFA), activity of urinary urokinase-type plasminogen activator (UPA) were studied. RESULTS: The patients with CGN were found to have signs of impaired blood rheological properties (increased viscosity, an accelerated rapid phase of erythrocyte aggregation, increased strength of erythrocyte aggregates) and vascular endothelial dysfunction in the microcirculatory bed, among other factors, increased urinary excretion of functionally active WF, PA-1, which correlated with the activity of CGN. Data were obtained on the negative impact of the level of urinary PAl-1 excretion, red blood cell aggregation on the prognosis of CGN regardless of its form, the markers of endothelial damage/activation. Low urokinase activity and decreased red blood cell deformability in parallel with higher diurnal proteinuria are of poor prognostic value for hematuric nephritis. CONCLUSION: The findings illustrate two ways of the involvement of the endothelium in the mechanisms contributing to the development of tubular interstitial fibrosis, namely: endothelial dysfunction and as a substrate that links the processes of immune inflammation, hemorheology, and fibrinolysis/proteolysis in the kidney. The regularities revealed by clinical and laboratory comparison suggest that the indices under study may be used to determine the prognosis of the disease and may serve as a basis for the application of treatments aimed at correcting the detected disorders.

[The fibrinolytic system in uric acid dysmetabolism].

The subjects of the study were 50 first-degree relatives of patients with uric acid (UA) dysmetabolism. The subjects were divided into three groups: 15 with hyperuricosuria and normal UA blood level (group 1), 17--with hyperuricosuria and hyperuricemia (group 2), and 18--with hyperuricemia and lowered UA clearance (group 3). All of them displayed inhibited urine fibrinolytic activity (UFA) and reduced urokinase activity. The degree of UFA inhibition correlated with urokinase activity (r = 0.60) and grew from group 1 to group 3; the subjects in the latter had maximal manifestations of tubulointerstitial nephritis, which suggests that disorder of the local fibrinolytic mechanisms plays an important role in the development and progress of urate tubulointerstitial renal lesion. No changes of blood fibrinolysis were observed.

[Proteinuria-induced mechanisms of tubulointerstitial remodeling and possibilities of nephroprotection in glomerulonephritis].

The authors describe various mechanisms (including cellular and molecular ones) that mediate the realization of interstitial inflammation under the influence of proteinuria components. The paper covers epithelial cell transdifferentiation processes, the role of angiotensin II, transforming growth factor beta, nuclear transcription factor NFkB, chemokines, endothelial factors etc. The effects of drugs routinely used in nephrology at present (angiotensin converting enzyme inhibitors, statines etc.) are presented in a new way according to the modern conception of the mechanisms of proteinuria-induced renal interstitial tissue remodeling in glomerulonephritis. The authors consider administration of antichemokine agents, which influences chemokine/chemokine receptor system, to be a prospective independent immunotherapeutic direction in treatment, aimed at prevention of glomerulonephritis progression.

[The key role of tubulointerstitium remodeling in progression of chronic renal diseases]. / Kliuchevaia rol' remodelirovaniia tubulointerstitsiia v progressirovanii khronicheskikh zabolevanii pochek.

Tubulointerstitial fibrosis (TIF) is thought now to be a key factor in progression of renal failure in chronic nephropathies. A similar pattern of changes in glomerulonephritis and amyloidosis suggests common mechanisms operating in progression of renal failure in these nephropathies. Of importance in the process of interstitial inflammation is activation of the nuclear factor of transcription (NFkB) in tubular cells due to components of proteinuria and their secretion of some proinflammatory mediators, first of all chemokines with formation of inflammatory infiltrate and accumulation of interstitial myofibroblasts--the main source of extracellular matrix (ECM) components. Our findings are of interest in the light of current ideas that among ECM components the number of fibronectin deposites most of all reflects the severity of structural renal tissue damage including TIF and correlates with severity of renal failure.

[Urine fibrinolytic activity as an indicator of kidney damage in uric acid metabolic imbalance]. / Fibrinoliticheskaia aktivnost' mochi kak pokazatel' porazheniia pochek pri narushenii obmena mochevoi kisloty.

AIM: To determine functional fibrinolytic activity of the urine in patients with different forms of purine metabolism disorder. MATERIAL AND METHODS: Uricemia, 24-h uricosuria, serum creatinine, GFR, maximal urinary specific gravity, urokinase activity in the urine, total fibrinolytic activity of the urine (TFAU), activity of plasminogen activator inhibitor (PAI) in blood were studied in 33 patients with genetically determined purine metabolism disorders. RESULTS: Patients with purine metabolism disorders vs controls had decreased TFAU and urokinase activity. There was no significant difference between the study and control groups in the levels of PAI in blood. No statistically significant difference was found between the patients with hyperuricemia and patients with hyperuricosuria in the levels of TFAU and urokinase activity, while the group with hyperuricemia was characterized by a decreased maximal specific urinary gravity. CONCLUSION: A decrease in TFAU and urokinase activity in patients with purine metabolism disorder was observed in the isolated hyperuricosuric stage of urite renal damage.

[The computer support of hypoglycemic therapy in non-insulin-dependent diabetes mellitus]. / Komp'iuternoe obespechenie sakharosnizhaiushchei terapii pri insulinonezavisimom sakharnom diabete.

Computer program designed by the authors and described in the article is realized as a reference system providing data on combinations of drugs used for diabetes mellitus. The system supplies information on hypoglycemic effects of representatives from each of three groups (insulins, sulfonamides, biguanides) administered both separately and in association with second drug selected by user. Interface of the system (drug menus and output windows) is friendly and demand no special training and operating skill. The program is written in C language and compiled as a single executable module for IBM-compatible personal computers.