高尿酸血症与老年特发性膜性肾病患者预后的关系

Relationship between hyperuricemia and prognosis of elderly patients with idiopathic membranous nephropathy

目的分析老年(年龄>60岁)特发性膜性肾病(IMN)患者发生高尿酸血症的影响因素,探讨高尿酸血症对老年IMN患者预后的影响。方法2011年1月—2018年4月中国人民解放军总医院诊治老年IMN患者336例,其中发生高尿酸血症者80例为高尿酸血症组,血尿酸水平正常者256例为尿酸正常组。比较2组体质量指数、肾脏病病程、合并症(高血压、糖尿病)、慢性肾脏病分期及入院时血压、血红蛋白、空腹血糖、血肌酐、血白蛋白、血尿酸、血清尿素和总胆固醇等临床资料。2组均行经皮肾穿刺活检组织病理检查,记录Ehrenreich-Churg分期、肾小球球性硬化评分、肾小球节段硬化/球囊粘连评分、肾小管萎缩/间质纤维化评分、肾间质炎症细胞浸润评分、肾小管间质评分、肾血管病变评分及补体C3沉积情况。采用多因素logistic回归分析老年IMN患者发生高尿酸血症的影响因素。2组均采用肾素-血管紧张素-醛固酮系统(RAAS)抑制剂、糖皮质激素和钙调磷酸酶抑制剂治疗,高尿酸血症患者给予降尿酸治疗,随访6~24个月,记录末次随访时总缓解率。采用多因素Cox回归分析老年IMN患者治疗后未缓解的影响因素。结果(1)高尿酸血症组体质量指数[(26.52±3.83)kg/m^(2)]及血清尿素[6.52(5.38,8.69)mmol/L]、总胆固醇[(6.90±2.34)mmol/L]水平均高于尿酸正常组[(25.11±4.53)kg/m^(2)、5.52(4.39,7.24)mmol/L、(6.21±2.07)mmol/L](P<0.05),肾脏病病程、高血压及糖尿病比率、慢性肾脏病分期、肾病综合征发生率,入院时收缩压、舒张压、血红蛋白、空腹血糖、血肌酐、血白蛋白、估算肾小球滤过率、磷脂酶A2受体抗体阳性率、24 h尿蛋白定量、胱抑素C、N-乙酰葡萄糖苷酶、IgA、IgG、IgM、补体C3、补体C4、三酰甘油、高密度脂蛋白胆固醇水平与尿酸正常组比较差异均无统计学意义(P>0.05)。(2)高尿酸血症组肾间质炎症细胞浸润评分0分比率(6.3%)低于尿酸正常组(16.8%)(χ^(2)=5.537,P=0.019),肾间质炎症细胞浸润评分1分(86.2%)、补体C3沉积强度++(20.0%)比率均高于尿酸正常组(74.2%、10.6%)(χ^(2)=4.995,P=0.025;χ^(2)=4.881,P=0.027),治疗方案、Ehrenreich-Churg分期、肾小球球性硬化评分、肾小球节段硬化/球囊粘连评分、肾小管萎缩/间质纤维化评分、肾小管间质评分、肾血管病变评分及肾间质炎症细胞浸润评分2分和3分、补体C3沉积强度0和+比率与尿酸正常组比较差异均无统计学意义(P>0.05)。(3)体质量指数(OR=1.076,95%CI:1.003~1.048,P=0.045)、血清尿素(OR=3.424,95%CI:1.275~9.195,P=0.015)是老年IMN患者发生高尿酸血症的影响因素。(4)随访至2018年4月,失访221例,余115例(高尿酸血症组27例、尿酸正常组88例)随访8(6,17)个月,高尿酸血症组总缓解率(59.3%)低于尿酸正常组(81.8%)(χ^(2)=5.852,P=0.016)。(5)血清总胆固醇(HR=0.781,95%CI:0.612~0.996,P=0.047)、补体C3沉积强度(HR=0.259,95%CI:0.075~0.892,P=0.032)是老年IMN患者治疗后未缓解的影响因素。结论体质量指数和血清尿素水平升高的老年IMN患者易发生高尿酸血症,高尿酸血症可影响老年IMN患者预后,血清总胆固醇水平和补体C3沉积强度升高时预后不良的风险增大。

Objective To analyze the influencing factors of hyperuricemia in elderly patients(aged>60 years)with idiopathic membranous nephropathy(IMN),and to explore the influence of hyperuricemia on the prognosis of elderly patients with IMN.Methods Totally 336 elderly patients with IMN in Chinese PLA General Hospital from January 2011to April 2018 were divided into hyperuricemia group(n=80)and normal uric acid group(n=256).The clinical data of body mass index,duration of nephropathy,comorbidities(hypertension,diabetes),stage of chronic kidney disease,blood pressure,hemoglobin,fasting plasma glucose,serum creatinine,blood albumin,blood uric acid,serum urea and total cholesterol at admission were compared between two groups.Percutaneous renal biopsy was performed in both groups.Ehrenreich-Churg stage,glomerular sclerosis score,glomerular segmentosclerosis/balloon adhesion score,renal tubular atrophy/interstitial fibrosis score,renal interstitial inflammatory cell infiltration score,renal tubular interstitial score,renal vascular lesion score and complement C3 deposition were recorded.Multivariate logistic regression analysis was conducted to analyze the influencing factors of hyperuricemia in elderly IMN patients.Hyperuricemia group received urate-lowering therapy besides the administrations of renin-angiotensin-aldosterone system inhibitors,glucocorticoids and calcinurin inhibitors in two groups.The follow-up survey was done for 6 to 24 months,and the overall response rate at the latest follow-up was recorded.Multivariate Cox regression was used to analyze the influencing factors of non-response in elderly IMN patients.Results(1)The body mass index,serum urea and total cholesterol were higher in hyperuricemia group[(26.52±3.83)kg/m^(2),6.52(5.38,8.69)mmol/L,(6.90±2.34)mmol/L]than those in normal uric acid group[(25.11±4.53)kg/m^(2),5.52(4.39,7.24)mmol/L,(6.21±2.07)mmol/L](P<0.05),and there were no significant differences in the duration of nephropathy,rates of hypertension and diabetes,stage of chronic kidney disease,incidence of nephrotic syndrome and admission baseline data including systolic blood pressure,diastolic blood pressure,hemoglobin,fasting plasma glucose,creatinine,albumin,estimated glomerular filtration rate,phospholipase A2 receptor antibody positive rate,24-h urine protein,cystatin C,N-acetylglucosidase,IgA,IgG,IgM,complement C3,complement C4,triacylglycerol,high-density lipoprotein cholesterol levels between two groups(P>0.05).(2)The rate of renal interstitial inflammatory cell infiltration score 0 was lower in hyperuricemia group(6.3%)than that in normal uric acid group(16.8%)(χ^(2)=5.537,P=0.019.),the rates of renal interstitial inflammatory cell infiltration score 1 and complement C3 deposition intensity++were higher in hyperuricemia group(86.2%,20.0%)than those in normal uric acid group(74.2%,10.6%)(χ^(2)=4.995.P=0.025;χ^(2)=4.881,P=0.027),and there were no significant differences in the treatment plan,Ehrenreich-Churg stage,glomerular sclerosis sore,glomerular segmentosclerosis/balloon adhesion score,renal tubular atrophy/interstitial fibrosis score,renal tubular interstitial score,renal vascular lesion score,renal interstitial inflammatory cell infiltration score 2 and 3,and rates of complement C3 deposition intensity 0 and+between two groups(P>0.05).(3)Body mass index(OR=1.076.95%CI:1.003-1.048,P=0.045)and serum urea(OR=3.424,95%CI:1.275-9.195,P=0.015)were the influencing factors of hyperuricemia in elderly patients with IMN.(4)Till April 2018,221 patients were lost to follow-up,and the average follow-up lasted for 8(6,17)months in the other115 patients including 27 patients in hyperuricemia group and 88 in normal uric acid group.The overall response rate was lower in hyperuricemia group(59.3%)than that in normal uric acid group(81.8%)(χ^(2)=5.852,P=0.016).(5)Total cholesterol(HR=0.781,95%CI:0.612-0.996,P=0.047),complement C3 deposition intensity(HR=0.259,95%CI:0.075-0.892,P=0.032.)were the influencing factors of non-response in elderly IMN patients.Conclusions The elderly IMN patients with increased body mass index and urea level are prone to hyperuricemia.Hyperuricemia can affect the prognosis of elderly IMN patients.The high total cholesterol level and complement C3 deposition intensity increase the risk of poor prognosis.