Hernández-Marco Roberto, Codoñer-Franch Pilar, Pons Morales Sara, Del Castillo Villaescusa Cristina, Boix García Laura, Valls Bellés Victoria
Department of Pediatrics, Dr. Peset University Hospital, Valencia, Spain.
Pediatr Nephrol. 2009 Jan;24(1):121-7. doi: 10.1007/s00467-008-0961-4. Epub 2008 Sep 10.
Diabetic nephropathy (DN), a major cause of morbidity and mortality in diabetes, will develop within a subset of type 1 diabetes mellitus (T1DM) patients, and oxidative stress has been implicated in its pathogenesis. To investigate the relationship between indicators of early DN stages (hyperfiltration estimated by creatinine clearance > or =150 ml/min per 1.73 m(2), microalbuminuria) and oxidative stress, a prospective study was conducted in 29 T1DM patients (age 13.89 +/- 4.61 years) and 18 control subjects (age 13.23 +/- 3.99 years). Blood samples were collected to assay for biomarkers of oxidative stress (malondialdehyde and carbonyl groups) and antioxidants (glutathione peroxidase, reduced glutathione, alpha-tocopherol, and beta-carotene). With respect to control subjects, in T1DM patients, an increase was found in biomarkers of oxidative stress (p < 0.05), mainly due to the group of subjects with hyperfiltration, and a decrease in the ratio alpha-tocopherol/lipids (p < 0.05). In multiple regression analyses, age at disease onset, glycated hemoglobin, microalbuminuria, and oxidative stress biomarkers remained as explicative variables of hyperfiltration (R (2) adjusted = 0.731, p = 0.000). These findings support the importance of the oxidative damage to lipids and proteins, which is linked to hyperfiltration and which could contribute to the development of DN in patients with T1DM.
糖尿病肾病(DN)是糖尿病发病和死亡的主要原因,在一部分1型糖尿病(T1DM)患者中会发生,氧化应激被认为参与了其发病机制。为了研究早期DN阶段指标(通过肌酐清除率估计的超滤>或=150 ml/min per 1.73 m²,微量白蛋白尿)与氧化应激之间的关系,对29例T1DM患者(年龄13.89±4.61岁)和18例对照受试者(年龄13.23±3.99岁)进行了一项前瞻性研究。采集血样以检测氧化应激生物标志物(丙二醛和羰基)和抗氧化剂(谷胱甘肽过氧化物酶、还原型谷胱甘肽、α-生育酚和β-胡萝卜素)。与对照受试者相比,在T1DM患者中,氧化应激生物标志物增加(p<0.05),主要是由于超滤组,α-生育酚/脂质比值降低(p<0.05)。在多元回归分析中,发病年龄、糖化血红蛋白、微量白蛋白尿和氧化应激生物标志物仍然是超滤的解释变量(调整后的R²=0.731,p=0.000)。这些发现支持了脂质和蛋白质氧化损伤的重要性,其与超滤相关,可能有助于T1DM患者DN的发展。