RESUMO
BACKGROUND: There are evidence indicating that some metabolites of arachidonic acid produced by cytochromes P450 (CYP) and epoxide hydroxylase (EPHX2), such as hydroxyeicosatetraenoic acids (HETEs), epoxyeicosatrienoic acids (EETs) or dihydroxyeicosatrienoic acids (DHETEs), play an important role in blood pressure regulation and they could contribute to the development of hypertension (HT) and kidney damage. Therefore, the main aim of the study was to evaluate whether the genetic polymorphisms of CYP2C8, CYP2C9, CYP2J2, CYP4F2, CYP4F11 and EPHX2, responsible for the formation of HETEs, EETs and DHETEs, are related to the progression of impaired renal function in a group of patients with hypertension. METHODS: 151HT patients from a hospital nephrology service were included in the study. Additionally, a group of 87 normotensive subjects were involved in the study as control group. For HT patients, a general biochemistry analysis, estimated glomerular filtration rate and genotyping for different CYPs and EPHX2 variant alleles was performed. RESULTS: CYP4A11 rs3890011, rs9332982 and EPHX2 rs41507953 polymorphisms, according to the dominant model, presented a high risk of impaired kidney function, with odds ratios (OR) of 2.07 (1.00-4.32; P=0.049) 3.02 (1.11-8.23; P=0.030) and 3.59 (1.37-9.41; P=0.009), respectively, and the EPHX2 rs1042032 polymorphism a greater risk according to the recessive model (OR=6.23; 95% CI=1.50-25.95; P=0.007). However, no significant differences in allele frequencies between HT patients and in normotensive subjects for any of the SNP analysed. In addition, the patients with diagnosis of dyslipidemia (n=90) presented higher frequencies of EPHX2 K55R (rs41507953) and *35A>G (rs1042032) variants than patients without dyslipidemia, 4% vs. 14% (P=0.005) and 16 vs. 27% (P=0.02), respectively. CONCLUSIONS: In this study has been found higher odds of impaired renal function progression associated with rs3890011 and rs9332982 (CYP4A11) and rs41507953 and rs1042032 (EPHX2) polymorphisms, which may serve as biomarkers for improve clinical interventions aimed at avoiding or delaying, in chronic kidney disease patients, progress to end-stage kidney disease needing dialysis or kidney transplant.
RESUMO
Chronic kidney disease (CKD) is a major health problem worldwide and, in Spain, it is present in 15.1% of individuals. CKD is frequently associated with some comorbidities and patients need to be prescribed multiple medications. Polypharmacy increases the risk of adverse drug reactions (ADRs). There are no published studies evaluating the prevalence of potential drug-drug interactions (pDDIs) among CKD patients in any European country. This study was aimed to determine the prevalence, pattern, and factors associated with pDDIs among CKD patients using a drug interactions program. An observational cross-sectional study was carried out at Plasencia Hospital, located in Spain. Data were collected among patients with CKD diagnoses and pDDIs were assessed by the Lexicomp® Drug Interactions platform. Data were obtained from 112 CKD patients. A total number of 957 prescribed medications were acknowledged, and 928 pDDIs were identified in 91% of patients. Age and concomitant drugs were significantly associated with the number of pDDIs (p < 0.05). According to the results, the use of programs for the determination of pDDIs (such as Lexicomp®) is recommended in the clinical practice of CKD patients in order to avoid serious adverse effects, as is paying attention to contraindicated drug combinations.
