慢性阻塞性肺疾病患者血清低氧诱导因子-1α水平与早期肾损伤相关性分析

Correlation of serum level of hypoxia-inducible factor-1α with early renal injury in patients with chronic obstructive pulmonary disease

目的：探讨慢性阻塞性肺疾病（COPD）患者血清低氧诱导因子-1α（HIF-1α）的水平与早期肾损伤的相关性及其临床意义。方法 COPD组：收集2012年1月至7月新入住宁夏人民医院呼吸内科首次确诊为COPD稳定期、无急性重症感染、非吸氧患者58例；对照组：同期该院体检中心年龄、性别相匹配的健康体检者50例。COPD组再依据氧分压（PaO2）分为3个亚组：Ⅰ级（60mmHg＜PaO2≤80mmHg，1mmHg＝0.133kPa）、Ⅱ级（40mmHg＜PaO2≤60mmHg）、Ⅲ级（PaO2≤40mmHg）。两组均采集静脉血，COPD组同时采集动脉血做血气分析，采用ELISA方法检测血清HIF-1α、胱抑素C（CysC）、血清结缔组织转化生长因子-β（TGF-β）水平。采用全自动生化分析仪检测血清肌酐（SCr），根据慢性肾脏病流行病学合作研究（CKD-EPI）公式计算估算肾小球滤过率（eGFR）。分析比较两组上述指标的变化。结果（1）与对照组比较，COPD组患者血清HIF-1α、CysC水平明显升高，差异有统计学意义（P＜0.05），eGFR、SCr、TGF-β升高不明显，差异无统计学意义（P＞0.05）。（2）亚组分析：与对照组及Ⅰ级缺氧亚组比较，血清HIF-1α在Ⅱ、Ⅲ级缺氧亚组明显升高。与对照组比较血清CysC在各级缺氧亚组均明显升高，而eGFR则仅在Ⅲ级缺氧亚组明显降低，差异均有统计学意义（P＜0.05）。血清SCr、TGF-β在3个不同缺氧亚组中均无明显升高，差异无统计学意义（P＞0.05）。（3）Pearson相关性分析显示，血清HIF-1α与CysC呈正相关（r＝0.665， P＝0.001），血清CysC、HIF-1α与eGFR呈负相关（r＝-0.827，r＝-0.739，P＜0.001）。结论血清HIF-1α可能是评估慢性低氧患者早期肾损伤较好的生物标志物，其与CysC联合检测可能有更好的临床实用价值。

Objective To evaluate the correlation between the serum level of hypoxia-inducible factor-1α（HIF-1α） and early renal injury in the patients with chronic obstructive pulmonary disease （COPD） and investigate its clinical value. Methods A total of 58 patients with freshly diagnosed stable COPD in the Department of Respiratory Disease, Ningxia People’s Hospital from January to July 2012 were subjected and prospectively analyzed in this study. Another 50 sex- and age-matched healthy individuals receiving physical examination during the same period served as normal controls. The COPD patients were all at stable phase, without severe acute infection, and with no need for oxygen inhalation, and were assigned into 3 subgroups according to hypoxia degrees： subgroupⅠ（60mmHg〈PaO2≤80mmHg, 1mmHg=0.133kPa）, subgroup Ⅱ （40mmHg〈PaO2≤60mmHg）, and subgroup Ⅲ （PaO2≤40mmHg）. Routine renal function and laboratory markers of kidney injury were detected by EILSA, including serum creatinine （SCr）, and cystatin C （CysC）, HIF-1α and transforming growth factor-β（TGF-β）. Estimated glomerular filtration rate （eGFR） was calculated by chronic kidney disease epidemiology collaboration （CKD-EPI） formula. Statistical analysis was carried out to compare the differences of above indices between these groups. Results The serum levels of HIF-1αand CysC were significantly higher in the COPD group than in control group （P〈0.05）, but the levels of SCr and TGF-β and eGFR were increased though without significant difference between the 2 groups （P〉0.05）. Further comparison among subgroups showed that the level of HIF-1αwas significantly higher in subgroups Ⅱ and Ⅲ than in the control group and subgroupⅠ（P〈0.05）. The level of CysC in subgroups Ⅰ, Ⅱ and Ⅲ was significantly higher than that in the control group （P〈0.05）. The eGFR was significantly lower in subgroup Ⅲ than in the control group （P〈0.05）. There was no significant difference in the serum levels of SCr and TGF-βamong the 3 subgroups of COPD patients compared with the control group （P〉0.05）. Pearson analysis showed that the serum level of HIF-1αhad positive correlation with CysC （r=0.665, P=0.001）, and those of CysC and HIF-1αhad negative correlation with eGFR （r=-0.827, r=-0.739, P〈0.001）. Conclusion Serum HIF-1α might be a good predictive biomarker for early renal injury in chronic hypoxia patients, and it might have better clinical value when combined with serum level of CysC.