[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.

[Ischemic disease of the kidneys and combined chronic nephropaties: clinical and prognostic features].

AIM: To characterize clinical features and course of ischemic renal disease (IRD) combined with other chronic nephropathies. MATERIAL AND METHODS: We examined 102 patients with IRD treated in the E. M. Tareev clinic of the I. M. Sechenov Moscow Medical Academy in 2001-2006. We made a general clinical examination, clinical and biochemical blood tests. Glomerular filtration rate (GFR) was calculated according to Cockroft-Gault formula. Arterial hypertension was assessed according to ESH. RESULTS: IRD associated with other chronic nephropathies was detected in 35 (34.3%) patients. Association of atherosclerotic stenosis of the renal arteries (ASRA) with diabetic, urate nephropathies was diagnosed in 9 and 8 patients, respectively; chronic pyelonephritis--in 7 cases, chronic glomerulonephritis--in 4 patients. The age of IRD patients associated with other chronic renal diseases was younger than of those with isolated IRD. Systolic arterial pressure was significantly higher in patients with isolated IRD, body mass index and total cholesterol--in the groups of IRD association with other chronic nephropathies. Aggravation of renal failure in patients with CRD association with other chronic nephropathies was provoked by ACE inhibitors and blockers of angiotensin II receptors. Revascularization of the kidneys in IRD associated with other chronic nephropathies leads to significant lowering of systolic blood pressure and stabilization of creatininemia. CONCLUSION: Development of IRD is possible in the presence of other chronic nephropathies. Diagnosis of IRD arising in patients suffering from other chronic renal diseases often requires radical change of therapeutic policy, but renal revascularization is not contraindicated.

[Relationships between arterial hypertension, metabolic disturbances and uric acid nephropathy].

AIM: To study effects of uric acid disbolism in combination with other metabolic disturbances on prevalence and clinical symptoms of arterial hypertension; contribution of uric acid nephropathy to its development. MATERIAL AND METHODS: A cohort of 243 representatives from a general population (107 males, 136 females, age 19-59 years) was studied in 1986 and 15 years later. At the beginning and end of the trial the participants were examined for arterial hypertension, microalbuminuria, uric acid nephropathy, blood biochemical tests were made. RESULTS: For 15-year follow-up prevalence of arterial hypertension doubled, incidence of hyperuricemia and hyperuricosuria, hypertriglyceridemia increased considerably. The number of hypertensive subjects was maximal in the group with the greatest number of signs of uric acid nephropathy. CONCLUSION: The population studied exhibited increasing frequency of some risk factors, especially of uric acid metabolism, contributing to formation of arterial hypertension.

[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.

[The features of uric acid metabolism in women in climacterium].

The purpose of the study was to establish the prevalence of uric acid (UA) metabolism disturbances as a possible risk factor of urate nephropathy in women of various age groups. The authors carried out a retrospective analysis of 757 case histories and performed uricemia and uricosuria screening in women aged 18 to 69 years. The study revealed significant age-dependent elevation of uricemia, with hyperuricemia (HUE) at the age of 60 to 69 years old. The study also found age-dependent increase of HUE rate with its significant elevation in postmenopausal women (older than 50 years), compared with HUE rate in reproductive age women (18 to 49 years old) -37.9% vs. 11.4%. For the first time the researchers established UA excretion level and found a significant tendency of uricosuria to decrease with age (p < 0.016 between the groups of 40 to 49 and 50 to 59 years old). The highest rate of hyperuricosuria was revealed in women of 40 to 49 years old (22.2%), while in women of 18 to 29 and 60 to 69 years old it was 10.1% to 12.1%. For the first time the authors established the rate of hypouricosuria in women, which culminated in women older than 50 (22% of cases). The increase of HUE rate, which is most prominent in postmenopausal women, is associated with the decrease in UA excretion, accompanied by the decrease of hyperuricosuria rate and increase of hypouricosuria rate. Taking into account high prevalence of UA metabolism disturbances in women older than 50, menopause may be considered a risk factor of HUE and urate nephropathy.

[Clinical implication of the body mass and waist/thigh indices in hypertensive patients: correlations with blood uric acid levels]. / Klinicheskoe znachenie indeksa massy tela i indeksa taliia/bedro u patsientov s arterial'noi gipertoniei: sviaz' s urovnem mochevoi kisloty v krovi.

Body mass index (BMI) and waist/thigh circumference (WTC) were estimated in 104 patients with mild and moderate arterial hypertension (AH) lasting for 8.4 +/- 3.2 years (63 men, 41 women, mean age 50.2(+)-9.6 years). Blood concentration of uric acid was tested with enzymes (Boehringer Mannheim kits). Only 5 of 104 examinees had BMI under 25. The majority of the patients (79%) had high WTC. Hyperuricemia was detected in 32 of 104 patients. Uric acid level in the blood correlates (r = 0.43) with WTC but not with BMI.

[Relationship between mass of the left ventricular myocardium and uric acid metabolic imbalance in patients with arterial hypertension]. / Sviaz' mezhdu massoi miokarda levogo zheludochka i narusheniem obmena mochevoi kisloty u bol'nykh arterial'noi gipertoniei.

AIM: To analyse relationships between left ventricular myocardium mass (LVMM) and imbalance of uric acid metabolism in patients with arterial hypertension (AH). MATERIAL AND METHODS: Body mass index, waist/hip circumference index, levels of uric acid in the blood and urine, urinary excretion of albumin, LVMM were estimated in 106 patients with mild and moderate AH (70 males and 36 females, mean age 51 +/- 8.5 years). RESULTS: Hypertensive patients with and without metabolic imbalance of uric acid differ significantly by LVMM index. The latter was higher in metabolic imbalance of uric acid, being the highest if this imbalance combined with microalbuminuria. CONCLUSION: Imbalance of uric acid metabolism in AH patients may indicate affection of both the kidneys and the heart.

[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.

[Some approaches to raising quality of treatment for arterial hypertension (experience of school for arterial hypertension patients)]. / Nekotorye podkhody k povysheniiu kachestva lecheniia patsientov s arterial'noi gipertoniei (opyt "Shkoly patsienta s arterial'noi gipertoniei").

AIM: To investigate involvement of patients into control of their pressure to improve quality of treatment for arterial hypertension (AH). MATERIALS AND METHODS: 134 hypertensive patients (76 females and 58 males) were interviewed. Criteria of efficacy of AH control were ability and motivation of self-measurement of blood pressure and its maintenance at the optimal level. RESULTS: For the past year, 40% of the patients measured pressure regularly (once a day or more frequently), 34%--1-3 times a week, 9%--1-3 times a month, 17%--rarely, mostly, males. Most of the patients controlled their pressure insufficiently. This is explained by "working pressure" (high in many cases) which was registered in most of the examinees. When part of the patients reached that working pressure they discontinued treatment. CONCLUSION: Involvement of hypertensive patients and members of their families into control of hypertension is a feasible and valuable method of improving quality of hypertension treatment.

[Urate affection of kidneys and metabolic disturbances in hypertensive patients]. / Uratnoe porazhenie pochek i metabolicheskie sdvigi u patsientov s arterial'noi gipertoniei.

AIM: To detect urate renal affection and correlations between purine metabolism, hyperinsulinemia, obesity, dyslipidemia in patients with arterial hypertension (AH). MATERIALS AND METHODS: 78 patients with mild, moderate and severe hypertension have undergone 24-h monitoring of arterial pressure and microalbuminuria test. RESULTS: Hyperuricemia was diagnosed in 21 of 78, hyperuricosuria in 27 patients. 13 patients had combination of hyperinsulinemia with obesity, dyslipidemia, arterial hypertension. Renal symptoms occurred in almost half of the patients with hyperuricemia. Disturbed 24-h rhythm and variability of arterial pressure were encountered more frequently in patients with hyperuricemia and hyperinsulinemia than in patients with normal purin metabolism and no other metabolic shifts. CONCLUSION: Renal abnormalities were found more frequently in hypertensive patients with hyperuricemia and those free of urate disturbances and metabolic changes. A positive correlation exists between body mass index and insulinemia (r = 0.58, p < 0.01), body mass index and uricemia (r = 0.37, p < 0.01), insulinemia and uricemia (r = 0.32, p < 0.01).

[Detection of urate tubulointerstitial nephritis: contribution of diagnostic questionnaire]. / Raspoznovanie uratnogo tubulointerstitsial'nogo nefrita s ispol'zovaniem diagnosticheskoi ankety.

AIM: To develop a diagnostic questionnaire to identify individuals with uric acid hyperproduction and risk of urate tubulointerstitial nephritis (UTIN). MATERIALS AND METHODS: Clinical symptoms of 650 patients with verified hyperuricemia or hyperuricosemia have been summarized to design a special questionnaire which will be able to identify subjects to whom test for uricemia and uricosuria may be recommended to prevent onset and/or progression of UTIN. RESULTS: The questionnaire has been compiled which has rather high sensitivity and specificity in identification of persons with hyperuricemia and/or hyperuricosuria at risk to develop UTIN. CONCLUSION: The designed questionnaire allows to select subjects with existing UTIN or at UTIN risk both in population and individual studies.

[Clinical and diagnostic significance of microalbuminuria and activity of tubular enzyme N-acetyl-beta-D-glucosaminidase (NAG) determination in patients with hyperuricosuria]. / Kliniko-diagnosticheskoe znachenie opredeleniia mikroal'buminurii i aktivnosti kanal'tsevogo fermenta N-atsetil-beta-D-gliukozaminidazy u lits s giperurikozuriei.

AIM: Development of the approaches to detection of hyperuricosuric stage of purin metabolism derangement and specification of methods for early diagnosis of urate damage to the kidney. MATERIALS AND METHODS: The study included 115 young subjects whose parents suffer from gout with renal involvement or isolated urate nephropathy. Each patient was examined clinically with evaluation of family history for gout risk factors. Three times for 9 months measurements were made of uricemia and uricosuria, microalbuminuria and activity of tubular enzyme NAG. RESULTS: 45 (39.1%) patients had neither disturbances of purin metabolism nor renal affection. 70 (60.9%) patients had hyperuricosuria. In 23 (32.9%) of them microalbuminuria increased to > 20 mg/day, NAG activity to 5 u/l. Chronic tubulointerstitial nephritis was diagnosed in 17 (73.9%) patients. Six patients (26.1%) developed asymptomatic affection of the kidneys. The rest 47 patients had normal levels of microalbuminuria and NAG. There were 3 cases of hyperuricemia with microalbuminuria rising to 160-200 mg/day and further development of urinary syndrome. Hyperuricemia in them was registered at microalbuminuria higher that 160 mg/day. CONCLUSION: Microalbuminuria higher than 20 mg/day and NAG activity higher than 5 u/day are important diagnostic indicators of renal affection in hyperuricosuria including asymptomatic one. Microalbuminuria above 160 mg/day gives grounds to discuss the role of morphological changes prior to proteinuria.