RESUMEN
BACKGROUND: As renin-angiotensin system (RAS) activity may affect the severity of oxidative stress and inflammatory markers, we assessed the effects of enalapril (E) and/or losartan (L) on these markers in renal transplant recipients with RAS polymorphisms. PATIENTS AND METHODS: After determination by PCR of RAS genotypes, consisting of the angiotensin-converting enzymes (ACE I/D), angiotensinogens (AGT M235T) and angiotensin II type 1 receptors (ATR1 A1166C), 76 recipients were recruited randomly and assigned 4 groups. The first (n = 17) and second (n = 24) groups were treated with E (E(+): 10 mg/d) and L (L(+): 50 mg/d) alone, respectively. The third positive control group (n = 17) received E + L (E(+)L(+): 10 mg/d + 50 mg/d) and the fourth negative control group (n = 18) received no medication (E(-):L(-)). High-sensitivity C-reactive protein (hs-CRP) and total antioxidant (TA) inflammatory and antioxidative markers were measured after 2 months. After a 2-week washout period, the E(+) group was changed to L(+) and vice versa in a crossover design. They were followed for another 8 weeks before retesting hs-CRP and TA. A value of P < or = .05 was considered significant. RESULTS: After 2 and 4 months of treatment with the drug regimen, hs-CRP and TA levels were significantly decreased and consequently increased among the E(+)L(+), L(+) and E(+) groups (P < .05). On analyzing the relationship between RAS polymorphisms and baseline hs-CRP or TA levels, CC genotype of ATR1 showed lower hs-CRP levels (P = .04). However, none of the RAS polymorphisms predicted the antioxidant and anti-inflammatory response rates to the drugs (P > .05). CONCLUSION: Although hs-CRP was lower in the CC genotype patients of ATR1 polymorphisms E and/or L reduced hs-CRP and increased TA regardless of the RAS genotype.
Asunto(s)
Antioxidantes/uso terapéutico , Proteína C-Reactiva/metabolismo , Enalapril/uso terapéutico , Trasplante de Riñón/inmunología , Losartán/uso terapéutico , Polimorfismo Genético , Sistema Renina-Angiotensina/genética , Adulto , Antihipertensivos/uso terapéutico , Proteína C-Reactiva/efectos de los fármacos , Creatinina/sangre , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estrés Oxidativo , Reacción en Cadena de la Polimerasa , Sistema Renina-Angiotensina/efectos de los fármacosRESUMEN
INTRODUCTION: In this study, hemoglobin (Hb) concentrations secondary to enalapril (E) or losartan (L) therapy were evaluated with respect to renin-angiotensin system (RAS) polymorphisms in renal transplant recipients. MATERIALS AND METHODS: After determination of RAS polymorphisms [angiotensin-converting enzyme (DD, non-DD), angiotensinogen (TT, non-TT), and angiotensin receptor type 1 (CC, non-CC)] by polymerase chain reaction, 70 renal transplant recipients were recruited to four groups randomly: first and second groups were treated with E (10 mg/d, 15 patients) and L (50 mg/d, 20 patients) alone, respectively. The third group received E+L (10 mg/d + 50 mg/d, 13 patients) and the fourth group (22 patients) received no medication. The treatment protocol was followed for 16 weeks. Complete blood counts were checked before treatment and every 2 months. P<.05 was considered to indicate statistical significance. RESULTS: Treatment for 4 months decreased the Hb level in the E+L (14.15 +/- 0.94 to 12.06 +/- 0.66 g/dL, P=.000), E (14.00 +/- 0.86 to 13.11 +/- 0.82 g/dL, P=.02), and L (14.12 +/- 0.90 to 12.10 +/- 2.35 g/dL, P=.01) groups, but not in the control group (13.55 +/- 0.70 to 13.36 +/- 0.69 g/dL, P>.05). None of these regimens showed greater Hb reduction than the others (P>.05). None of the RAS polymorphisms predicted the intensity of the reduced Hb according to the type of treatment (P>.05). Any other sets of RAS polymorphisms (alone or together) did not impact on Hb levels pre- or post-intervention (P>.05). CONCLUSION: Our findings suggest that low dosages of E and/or L decrease Hb levels regardless of the RAS polymorphisms.