FEATURES OF THE DYNAMICS OF URINARY EXCRETION OF TUBULAR DAMAGE BIOMARKERS IN PATIENTS WITH ARTERIAL HYPERTENSION AND CHRONIC KIDNEY DISEASE DURING TREATMENT WITH 2ND AND 3RD GENERATION CALCIUM CHANNEL BLOCKERS

Abstract

Backgraund : The renoprotective activity of angiotensin-converting enzyme inhibitors (ACE inhibitors), angiotensin II receptor antagonists (ARBs), beta-blockers (BBs), and diuretics has been proven, preventing kidney damage in patients with hypertension (HTN) and chronic kidney disease (CKD). However, the protective effects of calcium channel blockers (CCBs) in patients with hypertension and CKD have not been clearly defined. Aims : To compare the effect of the third-generation CCB lercanidipine and the second-generation CCB amlodipine on the dynamics of the levels of urinary markers of tubulointerstitial damage, neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1), in patients with arterial hypertension (AH) of varying severity and CKD with stage C2 and C3a during 6 months of treatment. Materials and methods: A total of 77 patients (21 men and 56 women, aged 40 to 78, mean age 57.0±9.9 years) with essential and nephrogenic hypertension and C2,C3a stage CKD were examined. They were divided into 2 groups according to the severity of hypertension: patients with stage 2 hypertension (SBP not higher than 179 mmHg) and with stage 3 hypertension (SBP 180 mmHg and higher). To compare the nephroprotective effect of CCBs of two generations, subgroups of patients prescribed amlodipine or lercanidipine were identified in each of these categories. The nephroprotective effect of the drugs was assessed by changes in the urinary levels of biomarkers NGAL, KIM-1 and albumin initially and after 6 months of antihypertensive treatment using standard methods and commercial reagent kits for ELISA diagnostics. Results : The decrease in the concentration of NGAL and KIM-1 in urine during antihypertensive therapy with amlodipine in patients with stage 2 and 3 hypertension combined with CKD was 65.6% (p<0.001) and 54.3% (p<0.001) for KIM-1, and 58.5% (p<0.001) and 65.8% (p<0.001) for NGAL compared with baseline, respectively. The dynamics of these biomarkers in patients receiving lercanidipine was similar and was characterized by a significant decrease in KIM-1 by 60.8% (p<0.001) and 67.6% (p<0.001), and NGAL by 80.5% (p<0.001) and 65.8% (p<0.001), respectively, from baseline values. Moreover, the degree of reduction in urinary NGAL concentration was 17.2% (p = 0.042) higher with lercanidipine therapy. A 25.7% (p = 0.017) reduction in albuminuria from baseline was observed in patients with stage 2 hypertension after 6 months of treatment with lercanidipine. Conclusions : In groups of patients with hypertension and CKD who took amlodipine and lercanidipine for 6 months, a significant decrease in urinary excretion of KIM-1 and NGAL was observed. However, the decrease in urinary NGAL concentration was more pronounced with lercanidipine therapy. A decrease in albuminuria was observed with the administration of lercanidipine in patients with stage 2 hypertension.