高尿酸血症与不同性别膜性肾病肾脏预后的相关性分析

Correlation between hyperuricemia and renal prognosis of patients with membranous nephropathy between different genders

目的探讨尿酸水平对不同性别膜性肾病患者肾脏预后的影响和预测价值。方法回顾性分析上海中医药大学附属龙华医院肾内科优势病种临床研究生物样本库自2007年1月—2019年1月经肾脏活组织检查(简称活检)明确诊断为原发性膜性肾病并长期接受随访的386例患者的临床资料,其中男223例、女163例。观察患者的年龄、性别、血压值、血红蛋白、白蛋白、高密度脂蛋白(HDL)、低密度脂蛋白(LDL)、TG、TC、肌酐、尿素氮、尿酸(高尿酸血症定义:男性空腹血尿酸>420μmol/L,女性>357μmol/L)、24 h尿蛋白定量、EPI法估算的肾小球滤过率(EPI-eGFR),以及患者服用药物的情况。根据患者血尿酸水平,将不同性别患者分入高尿酸血症亚组和尿酸正常亚组;并结合随访资料判断患者肾脏预后。结果本研究中,176例患者(45.6%)出现过完全缓解,114例(29.5%)未出现缓解,发生终点事件的患者共39例(10.1%)。与女性组膜性肾病患者相比,男性组患者白蛋白、HDL、EPI-eGFR水平更低,肌酐、尿素氮、尿酸、24 h尿蛋白定量水平更高,在随访期间达到部分或完全缓解的患者比例更低(P值均<0.05)。男性组膜性肾病患者中合并高尿酸血症的比例为42.2%(94/223),女性组为36.2%(59/163)。男性组尿酸正常与高尿酸血症患者肾脏累积生存率的差异无统计学意义(P=0.708)。女性组尿酸正常患者的肾脏累积生存率显著高于高尿酸血症患者(P=0.018)。在男性组膜性肾病患者中,校正白蛋白、血红蛋白、EPI-eGFR、尿素氮因素后,经多因素Cox回归分析显示,尿酸并非影响男性膜性肾病患者预后的危险因素(P=0.238);在女性患者中,校正血红蛋白、EPI-eGFR、尿素氮后,经多因素Cox回归分析显示,尿酸是影响女性膜性肾病患者肾脏预后的危险因素(HR为1.039,95%CI为1.014~1.065,P=0.002)。女性基线尿酸水平预测终点事件的AUC为0.745(95%CI为0.619~0.870),显著大于男性的0.537(95%CI为0.440~0.634,P=0.011)。结论尿酸水平是女性膜性肾病患者肾脏预后不良的独立危险因素,且在一定程度上可以预测女性膜性肾病患者的肾脏预后,而对男性患者疾病预后的预测效能欠佳。

Objective To investigate the influence and predictive value of uric acid level on the renal prognosis of patients with membranous nephropathy between different genders.Methods A total of 386 patients from the clinical research biobank of dominant diseases in the Department of Nephrology,Longhua Hospital,Shanghai University of Traditional Chinese Medicine from January 2007 to January 2019 were retrospectively analyzed.They were clearly diagnosed as primary membranous nephropathy by renal biopsy and were followed up for a long time.There were 223 males and 163 females.The age,gender,blood pressure,hemoglobin,albumin,high-density lipoprotein(HDL),low-density lipoprotein(LDL),triacylglycerol,cholesterol,creatinine,urea nitrogen,uric acid(defined by hyperuricemia:male fasting blood uric acid>420μmol/L,female>357μmol/L),24-hour urine protein quantification,glomerular filtration rate estimated by EPI method(EPI-eGFR),and medication status were recorded.According to serum uric acid level,male and female patients were divided into hyperuricemia group and normal uric acid group,respectively.Results In this study,176 patients(45.6%)had a complete remission,114 patients(29.5%)had no remission,and 39 patients(10.1%)had an endpoint event.Compared with female patients with membranous nephropathy,male patients had lower albumin,HDL and EPI-eGFR levels,higher creatinine,urea nitrogen,uric acid and 24-hour urine protein quantitative levels,and a higher proportion of partial or complete remissions during follow-up(all P<0.05).The proportion of hyperuricemia was 42.2%(94/223)in male patients and 36.2%(59/163)in female patients.There was no statistically significant difference in the cumulative survival rate of the kidney between male patients with normal uric acid and hyperuricemia(P=0.708).The cumulative renal survival rates of female patients with normal uric acid was significantly higher than that of female patients with hyperuricemia(P=0.018).After adjustment for serum albumin,hemoglobin,EPI-eGFR and urea nitrogen,multivariate Cox regression analysis showed that uric acid was not a risk factor affecting the prognosis of male membranous nephropathy(P=0.238).After adjustment for hemoglobin,EPI-eGFR and urea nitrogen,multivariate Cox regression analysis showed that uric acid was a risk factor affecting the prognosis of female membranous nephropathy(HR=1.039,95%CI:1.014-1.065,P=0.002).The AUC of the endpoint predicted by baseline uric acid level in women was 0.745(95%CI:0.619-0.870),which was significantly greater than that of men’s 0.537(95%CI:0.440-0.634,P=0.011).Conclusion Uric acid level is an independent risk factor for poor renal prognosis in women with membranous nephropathy,and to a certain extent can predict the renal prognosis in women with membranous nephropathy,but the predictive power of the prognosis is not good in male patients.