Efficacy of valsartan in the therapy of persistent microalbuminuria in normotensive patients with type 1 diabetes mellitus

Abstract

Aim. To determine the efficacy of AT1 receptor antagonist (valsartan) in decreasing of urinary excretion of albumin in normotensive patients with type 1 diabetes and incipient diabetic nephropathy (DN). Methods. This was a prospective, randomised, placebo-controlled study, which included 20 patients with insulin-dependent diabetes mellitus, mean age 25.15, and the duration of diabetes of 13.95 years. All the patients were normotensive, with persistent microalbuminuria (incipient phase of DN). Patients were randomly divided into two groups (10 patients each): valsartan group treated with 80 mg valsartan daily during 6 months, and the group treated with placebo during the same period. Both groups were similar and comparable concerning the observed parameters at the beginning of the study. Results. After 6 months therapy, valsartan caused significant decrease of urinary albumin excretion rate (UEAR) by 69.1% from 64.8 to 21.1 mg/24 h, while in placebo group there was an insignificant increase of UEAR by 29.8%. During the follow-up of UEA in the observed groups, at the beginning and the end of the mentioned period highly significant decrease of albumine secretion (p<0.001) was observed. Valsartan significantly lowered mean systolic blood pressure (from 122.0 ? 10.1 to 110.0 ? 11.8 mmHg). After 6 months therapy, the reduced values of total cholesterol and LDL-cholesterol fraction were registered in the valsartan group, while the difference in serum trigliceride values reached statistical significance (1.42 ? 0.79 vs. 1.21 ? 0.89 mmol/L; p<0.05). Neither significant difference in glycoregulation quality between the two groups, nor the occurence of hyperkalemia was detected throughout the study period. Conclusion. Valsartan's efficacy in the decrease of microalbuminuria after 6 months of therapy could justify the use of this group of renin/angiotensin blockers in delaying the clinically manifested DN. Valsartan was well tolerated and did not influence the quality of glycoregulation. It did not increase the level of serum lipids and could be recomended in the treatment of diabetic patients.Cilj. Utvrditi efikasnost antagonista AT1 receptora - valsartan u smanjivanju urinarne ekskrecije albumina kod normotenzivnih bolesnika sa tipom 1 secerne bolesti, u fazi pocetne dijabetesne nefropatije (DN). Metode. Sprovedena je prospektivna, randomizovana, placebom kontrolisana studija koja je obuhvatila 20 osoba obolelih od insulin-zavisnog dijabetesa, prosecne starosti 25,15 godina i trajanja dijabetesa 13,95 godina. Svi ispitanici bili su normotenzivni i u fazi pocetne DN, odnosno perzistentne mikroalbuminurije. Metodom slucajnog izbora, bolesnici su podeljeni u dve grupe od po 10: I ? valsartansku grupu, koja je tokom 6 meseci dobijala 80 mg valsartana dnevno i II ? placebo grupu, koja je u istom periodu dobijala placebo. Navedene grupe bile su komparabilne u bazalnim vrednostima ispitivanih parametara. Rezultati. Nakon 6 meseci terapije, valsartan je doveo do znacajnog snizenja stope urinarne ekskrecije albumina (SUEA) za 69,1% (od 64,8 na 21,1 mg/24 h) dok je u placebo grupi postojala tendencija nesignifikantnog porasta SUEA za 29,8% (od 75,9 na 98,5 mg/24 h). Poredjenjem procenta promene SUEA medju ispitivanim grupama, nadjena je visoka znacajnost u ispoljenom efektu valsartana u odnosu na placebo (p< 0,001). Osim toga, uoceno je da valsartan dovodi do nesignifikantnog smanjenja stope glomerulske filtracije (SGF) od 14,9%, dok je u placebo grupi SGF ostala prakticno nepromenjena (-1,4%). Nakon sestomesecne primene, valsartan je znacajno snizio srednju vrednost sistolnog krvnog pritiska (od 122,0 na 110,0 mm Hg), i nesignifikantno dijastolni pritisak. U toku lecenja ovim preparatom, doslo je do redukcije nivoa ukupnog holesterola i LDL frakcije, dok je smanjenje ukupnih triglicerida, u poredjenju sa placebo grupom, bilo statisticki znacajno (sa 1,42 na 1,21 mmol/l; p<0,05). Primenom ovog antagoniste AT1 receptora, nisu uocene promene u kvalitetu glikoregulacije (izrazene kao procenat HbA1c) niti je registrovana pojava hiperkalijemije. Zakljucak. Efikasnost antagoniste angiotenzin II receptora -valsartana u smanjenju mikroalbuminurije nakon 6 meseci terapije, opravdava primenu ove grupe blokatora renin-angiotenzin sistema, u odlaganju klinicki manifestne DN. Valsartan je dobro podnosljiv ne utice na kvalitet glikoregulacije, ne povecava nivo serumskih lipida, pa se moze smatrati metabolicki neutralnim i pogodnim za primenu kod bolesnika sa secernom bolesti.