Background. Chronic kidney disease is one of the most serious diabetic complications, which end-stage leads to a dramatic decline of renal function and needs for renal replacement therapy. Due to the progressive nature of CKD and the limited efficacy of treatment for advanced stages the prediction of risks and diagnostics on preclinical stage are of great importance. All of the above determines the high relevance of search for genetic markers predict the chronic kidney disease (CKD) development.The aim of our study was to investigate association between polymorphic marker (PM) of gene involved in insulin secretion with development of CKD in type 2 diabetic (T2D) patients. Polymorphism of KCNJ11 gene is associated with different phenotypes of glycemic disorders: neonatal diabetes, hyperinsulinemia, reduced insulin secretion and increased risk of type 2 diabetes. This gene coding Kir6.2 subunit of ATP-dependent potassium channels. The pathogenesis of it’s involvement in renal damage development referred to the fact that this type of potassium channels found not only in the beta- cells, but also in smooth muscle cells of blood vessels, and therefore might have an effect on risk of vascular complications, including CKD.Materials and methods. We enrolled 444 T2D patients. PM rs5219 in KCNJ11 gene was analysed among patients divided in 2 groups: with and without CKD (n=123/321) based on glomerular filtration rate (GFR) < and ≥ 60 ml/min/1,73m2 calculated by MDRD formula. PM studied using PCR. Differences in alleles/genotypes frequencies were assessed by χ² and odds ratio (OR) were calculated. The study was approved by local ethical committee; informed concern was obtained from all the patients.Results. We studied the main clinical parameters: age, HbA1c, serum levels of cholesterol and triglycerides, BP between the groups. We observed significant differences in alleles/genotypes distribution of rs5219 in KCNJ11 gene between groups with and without CKD: the prevalence of allele C and genotype CC in patients without CKD: OR=0,53, 95%CI: 0,40-0,72 and OR=0,46, 95%CI: 0,27-0,79, respectively; while allele T and genotype TT did as risk factors: χ²=17,33; р=0,0002; OR=1,87, 95%CI: 1,39-2,53; genotype TT OR=2,39, 95%CI: 1,52-3,76.Conclusions. We conclude that T2D patients might have genetic susceptibility to CKD development caused by polymorphism rs5219 of KCNJ11 gene with protective role of allele C and genotype CC and risk allelе/genotype is T/TT.
The purpose of the study was to evaluate the clinical efficacy and safety of dual RAAS blockage during treatment with angiotensin-converting enzyme (ACE) inhibitors in combination with a direct renin inhibitor (PIR) aliskiren versus combination therapy with ACE inhibitors and angiotensin receptor blocker II (ARB) valsartan in patients with type 2 diabetes mellitus (T2DM), arterial hypertension (AH) and obesity, without renal dysfunction. Materials and methods. The study included 26 patients with T2DM (10 men and 16 women, mean age 59,0±6,2 years) with inadequate control of blood pressure (over 130 and/or 80 mm Hg) on prior antihypertensive therapy and without renal dysfunctions (glomerular filtration rate (GFR) 60 ml/min/1, 73 m2 and the of albumin/creatinine (A/C) ratio in the morning urine sample 10 mg/mol). After screening with the continuation of the initial therapy, including ACE inhibitors, 14 patients were added aliskiren 150–300 mg/day, 12 patients – valsartan 80–160 mg/day. Evaluation of the treatment effectiveness in terms of blood pressure (mean of three consecutive measurements in the sitting position) and the parameters of renal function (serum creatinine and potassium, GFR, A/C ratio in the urine) was performed at 4, 12 and 24 weeks of therapy. Results. In the group of patients treated with aliskiren, after 4 weeks of treatment a significant decrease in systolic and diastolic blood pressure (SBP and DBP, respectively) was noted as compared to baseline: 146,1 and 138,9 mm Hg, p0,05, 87,1 and 81,1 mm Hg, p 0,05, respectively; with systolic BP after 24 weeks of treatment decreased to 127,8 (-18,2 mm Hg), p0,05, diastolic BP to 75,0 (-12, 1 mm Hg), p0,05, the target blood pressure (≤130/80 mm Hg) was achieved in 83% of patients. The group of patients treated with valsartan, after 4 weeks of therapy showed a significant reduction in systolic BP 148 and 141,6 mm Hg, p 0,05, diastolic BP - to 85,8 and 81,7 mm Hg, p=0,059; after 24 weeks systolic BP decreased to 128,7 (-19,3 mm Hg), p=0,05, diastolic BP – to 77,5 (-8,3 mm Hg), p=0,07, the target blood pressure was achieved in 78% of patients. When monitoring the safety of therapy in terms of potassium, serum creatinine, GFR, and A/C urine ratio statistically significant differences between the groups at 4, 12, 24 weeks of treatment were observed. Conclusion. Results of the study demonstrate the efficacy and safety of dual RAAS blockage in patients with T2DM and obesity with no prior renal impairment.
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