RESUMO
Background: Type 2 diabetes mellitus (T2DM) and high blood pressure (HBP) are the main risk factors for chronic kidney disease (CKD). Relationships between variants within the NFE2L2 gene and the presence of environmental risk factors for CKD, such as HBP and hyperglycemia have been suggested; however, their interactions remains unclear. Aim: To analyze the association of NFE2L2 variants with metabolic and kidney parameters. Materials and Methods: Six-hundred and fifty-one patients grouped according to the diagnosis of T2DM (n =166), T2DM+HBP (n =348) and HBP (n =137) were included. Metabolic characteristics were evaluated to identify risk factors and presence of CKD. Genotyping was performed by polymerase chain reaction (PCR) using two pairs primers for rs35652124 and rs6721961 and by real-time PCR for rs2364723. Logistic regression analyses, adjusted for confounding factors and correction for multiple tests were performed. Results: Significant associations between decreased risk for presenting with CKD and the rs35652124 (A allele) and the rs2364723 (G allele) variants were detected. Other variables consistently associated with these alleles were HBP, BMI, waist circumference, uric acid and triglycerides. Haplotypes AAC and GCG (loci order: rs35652124-rs6721961-rs2364723) showed similar trends. After adjustment for age and sex and correction for multiple tests, only rs35652124 (Odds Ratio [OR] = 0.5; Confidence Interval at 95% (CI95%), 0.3-0.9; p = 0.04) and rs2364723 (OR = 0.3; CI95%, 0.1-0.8; p = 0.009) variants remained associated with deceased risk for CKD in T2DM patients. Conclusion: This study showed for the first time that NFE2L2 variants are associated with decreased risk for CKD in the presence of environmental/metabolic risk factors related to kidney damage, including HBP, hyperuricemia and albuminuria in Mexican patients with diabetes.
Assuntos
Diabetes Mellitus Tipo 2 , Insuficiência Renal Crônica , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/metabolismo , Humanos , Hipertensão , Hiperuricemia , Rim , Fator 2 Relacionado a NF-E2 , Insuficiência Renal Crônica/genética , Fatores de RiscoRESUMO
BACKGROUND: The aim of this paper is to determine prevalence and risk factors of chronic kidney disease (CKD) in the comprehensive care program DiabetIMSS. METHODS: Cross-sectional study in 488 patients with type 2 diabetes mellitus (DM2) included in the program DiabetIMSS. Sociodemographic, clinical, biochemical, and kidney function variables were collected. RESULTS: Prevalence of CKD was 32% [early nephropathy (EN) 19% and overt nephropathy (ON) 13%]. Patients with more severe nephropathy significantly (p < 0.05) had: older age [normal kidney function (NKF) 54±11, EN 54±10, ON 63±9, years)], cardiovascular disease (NKF 1%, EN 5%, ON 11%), hypertension (NKF 65%, EN 63%, ON 85%), longer duration of DM2 (NKF 5%, EN 5%, ON 9%,) and of hypertension (NKF 5%, EN 6%, ON 9%), glycemic lack of control (NKF 46%, EN 62%, ON 60%), hyperuricemia (NKF 7%, EN 13%, ON 23%), anemia (NKF 1%, EN 4%, ON 10%) and metabolic syndrome (NKF 79%, EN 82%, ON 93%). Uncontrolled hypertension and DM2, cardiovascular disease and hyperuricemia significantly predicted the presence of nephropathy CONCLUSIONS: A third of patients attending to DiabetIMSS had CKD and has not been previously diagnosed. Multiple risk factors are present in this high-risk population; their identification and control are extraordinarily important. Moreover, educative interventions for primary health-care professionals to improve health of this kind of patients are needed.
INTRODUCCIÓN: el objetivo de este trabajo es determinar la prevalencia de enfermedad renal crónica (ERC) e identificar factores de riesgo para nefropatía en el programa DiabetIMSS. MÉTODOS: estudio transversal analítico en 488 pacientes con diabetes mellitus tipo 2 (DM2) atendidos en el programa de atención integral DiabetIMSS. Se recolectaron variables sociodemográficas, clínicas, bioquímicas y de función renal. RESULTADOS: la prevalencia de ERC fue 32% [nefropatía temprana (NT) 19% y nefropatía establecida (NE) 13%]. A nefropatía más avanzada, los pacientes tenían significativamente (p < 0.05): mayor edad [función renal normal (FRN) 54 ± 11, NT 54 ± 10, NE 63 ± 9 años)], enfermedad cardiovascular (FRN 1%, NT 5%, NE 11%), hipertensión (FRN 65%, NT 63%, NE 85%), mayor evolución de DM2 (FRN 5%, NT 5%, NE 9%,) y de hipertensión (FRN 5%, NT 6%, NE 9%), descontrol glucémico (FRN 46%, NT 62%, NE 60%), hiperuricemia (FRN 7%, NT 13%, NE 23%), anemia (FRN 1%, NT 4%, NE 10%) y síndrome metabólico (FRN 79%, NT 82%, NE 93%). La hipertensión y DM2 descontroladas, la enfermedad cardiovascular y la hiperuricemia predijeron significativamente la presencia de nefropatía. CONCLUSIONES: un tercio de los pacientes atendidos en DiabetIMSS tenían ERC y no habían sido identificados. Múltiples factores de riesgo están presentes en esta población de alto riesgo; su identificación y control son de extraordinaria importancia. Son necesarias, además, intervenciones educativas para el personal del primer nivel de atención médica para mejorar la salud de este tipo de pacientes.