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Kadomtseva L. V., Pulatova S. S., Tukhvatulina E. R., Tashkent Pediatric Medical Institute E-mail: mbshakur@mail.ru
CHARACTERISTICS OF RENAL DAMAGE EARLY STAGE IN HYPERTONIC DISEASE
Abstract: The damage of the kidney as the target organ of hypertensive disease in 40% of patients starts to form early - within 5 years from the debut of the disease. The early stage of hypertensive nephropathy is a dynamic process that has clinical and functional markers at each stage, so microalbuminuria, increased intrarenal vascular resistance, and changes in the total filtration function of the kidneys are the earliest.
Keywords: hypertensive disease, kidney damage, early diagnosis, dopplerometry.
Hypertonic disease (HD) is a widely spread disease the prevalence of which involves about 40% of adult population of Russia. According to statistic data HD occupies one of the leading places in the range of the causes of terminal renal failure in patients on dialysis [2; 11], and that makes the problem of the study of renal pathology linked with arterial hypertension to be extremely topical one [1; 10].
According to the modern notions the central part of the development of hypertonic nephropathy (HNP) is non-immune damage of renal vessels. Through hem dynamic factors (shift tension and circled stress) high hypertension activates/ damages renal endotheliocytes causing their dysfunction. Dysfunction of endothelium of internal renal vessels together with metabolic disorders, oxidative stress, neural humoral activation potentiate ischemia of renal tissue and fibroangio-genesis, realized through pathologic activation of local renal angiotensine II [3; 9]. Structural functional reconstruction linked with fibroangiogenesis is dysadaptation remodeling of micro vascular renal lumen, desolation of intraglomerular and peritubular capillaries with intensification of ischemia serve to be pathologic physiologic basis for hypertonic vascular nephropathy (HNP) [5; 10].
On the other hand, kidneys damaged by hypertension can produce the factors, intensifying the damage of systemic vascular lumen and create conditions for the involvement of other HD target-organs such as heart, central and peripheral vessels, and its complications (SVC) [6; 8]. Close interrelation of cardiac vascular pathologies and renal damage via arterial hypertension served to be premise for creation of a notion of renal-cardiac-vascular continuum on the basis of common mechanisms of organic damage in case of HD, and, first of all, endothelial dysfunction [4; 7].
Due to the mention concept, clarification of hem dynamic pathways of early HNP stage development gains primary importance for the definition of more effective measures of pathogenetic impact on the progress of the disease as a whole.
The objective: to characterize the early stage of renal damage in case of hypertonic disease - hypertonic nephropa-thy (HNP),
Materials and research methods: We examined 259 patients with hypertonic disease (HD): 186 (65%) men and 73 (35%) women in the age from 17 to 67 years old, who received therapy in the 5th city clinic in Tashkent. The control group involved 57 healthy people of the age and gender corresponding to the patients of the studied group: 38 men and 19 women in the age from 20 to 63 years old, with average age 42.1 ± 0.1 years old. Verification of HD diagnosis was performed in compliance with the WHO recommendations on the diagnostics and treatment of arterial hypertension. Diagnosis criterion was considered to be office AP > 140/90.
In the majority of the patients (76% of all the examined) duration of HD did not exceed 10 years; more than in half (75%) hypertension term was less than 5 years. Long-lasting progression of the pathology (> 16 years) was registered in less than 10% of the patients. Most of259 patients (73%) had 1(38%) and 2(35%) stages of HD, approximately 27% the 3rd (more severe) stage of hypertension.
Besides common clinical tests, patients passed special checkings. For the characteristics of alterations in kidneys all patients were checked for micro albuminuria (MAU) by means of enzyme immunoassay, calculation velocity of glomerular filtration (GFV) using Cokroft-Gowlt formula with correction for a standard square body surface (ml/ min/1.73m2). Stages of chronic renal pathology (CRP) were determined according to NKF K/DOKI criteria (2002).
Ultra sound Doppler of peripheral and internal renal arteries (USD) was performed on SSD-5500 (Aloka, Japan). We studied internal renal arteries (segment and interlobular) in the proj ection of three segments ofboth kidneys. According to our data, among the studied Doppler parameters such as resistance index (RI) and pulsation index (PI), the value of RI of inter-
CHARACTERISTICS OF RENAL DAMAGE EARLY STAGE IN HYPERTONIC DISEASE
lobular renal arteries was the most descriptive (sensitivity 0.75, specificity 0.67, and positive prognostic value 90%), and that provided its usage in the further work for the assessment of internal renal hem dynamics, taking RI 0.65 for a threshold value.
In the statistical analysis the results of the study were evaluated by means of parametric and non-parametric methods with the help of applied software pack STATISTICA 7.0.
Results of the study: day excretion of albumin with urine in 259 examined patients with HD varies from 10.3 to 288 mg/day. In the group of patients with MAU (186.72%) its rate was average 51.73 mg/day; in the rest (73.28%) of the patients with HD the rate of albuminuria did not reach MAU stage and was average 22.4(12.1 28) mg/day. Distribution of the patients with HD dependently on the term of the disease in the groups with and without MAU was approximately similar, and that provided performance of the further analysis of specific renal lesions without taking into account the term of the disease. The group of patients with HD with MAU was characterized, as a whole, by a higher prevalence of expressed AH, than the group of patients without MAU: the 3rd stage of AP rise was revealed in 37% of the patients with MAU and only 12% without MAU.
Besides that, we revealed statistically significant increase of the average MAU rate among the people with more expressed (2nd and 3rd stages) AH. We did not determine a reliable link of MAU with traditional risk factors (RF) such as disorder of lipid exchange (total cholesterol, high and low density lipoproteids) and carbohydrate exchange (starving glycemia).
At the same time we revealed a reliable close correlation of MAU with the age of the patients and their BMI. Among the examined 212 patients with HD summary filtration function of kidneys was higher in 59 patients without MAU, then in 153 patients with MAU, 108(94-125) and 96.2(79-116) ml/min/1.73 ml, respectively (P < 0.05). for the clarification of the character of GFV alteration dependently on MAU we compared the prevalence of normal filtration (GFV from 90 to 130 ml/min/1.73m2), hyper filtration (GFV > 130 ml/ min/1.73ml) and hypo filtration (GFV < 90 ml/min/1.73ml) in the groups of HD patients with and without MAU. Prevalence of normal and increased GFV in these groups had no
statistically significant difference, while decreased GFV -hypo filtration was revealed reliably more often in the group of patients with MAU.
Calculation of the probability (chance) of renal function deterioration showed that the chance of hypo filtration reveal in the patients with MAU was 2.2 folds higher that in the group of patients without MAU (59:94 versus 13:46, ratio of chances = 2.21).
Among 224 patients with HD, internal renal blood flow of which was checked by Doppler, RI value of interlobular renal arteries, as a whole, was statistically higher than among 57 healthy people. Analysis of average RI and prevalence of RI high values (> 0.65) dependent on the severity of hypertension syndrome showed that both values were higher among the patients with the 2nd and 3rd stages of AH, then among the patients with the 1st stage AH. Thus, average RI in the patients with the 1st stage AH was 0.63 ± 0.001 (0.6-0.665), 2nd stage AH 0.65 ± 0.001 (0.61-0.665), 3rd stage AH 0.67 ± 0.002 (0.64-0.7); prevalence of RI high values revealing (> 0.65) in the groups 38%, 59% and 69%, respectively (p < 0.05).
Among the patients with pathology term above 5 years increased RI values (> 0.65) were revealed 2.3 times more often than normal ones. At the same time among HD patients with short term disease (less than 5 years) the frequency of increased RI values revealing was 1.6 times less, than the frequency of revealing normal RI values. Though, 40% of the patients of that group also had increase of internal renal vascular resistance (RI > 0.65), testifying probability of earlier involvement of kidneys as HD target-organ requiring active revealing.
Conclusion. Thus, degree of internal renal vascular resistance increase evaluated according to interlobular renal arterial RI (> 0.65) correlated with AP value, term, MAU and decrease of GFV, and it can be considered to be an indicator of further development of HNP early stage. Pathological physiological basis of these alterations is considered to be hypertonic remodeling of internal renal vessels, desolation of micro circulation lumen, leading to the decrease of renal blood flow and ischemia of renal tissue.
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