特发性膜性肾病伴贫血患者的临床病理特征及预后分析

Clinicopathological features and prognostic analysis of idiopathic membranous nephropathy with anemia

目的 比较特发性膜性肾病(IMN)伴贫血患者与未伴贫血患者的临床病理特征,探讨其预后。方法 2011年1月—2018年4月中国人民解放军总医院诊治IMN伴贫血患者58例为贫血组,IMN未伴贫血患者344例为非贫血组。2组IMN治疗均依据改善全球肾脏病预后组织指南,贫血组根据贫血程度给予促红细胞生成素、琥珀酸亚铁片或蔗糖铁注射液。比较2组年龄、病程、体质量指数、血压、慢性肾脏病(CKD)分期、血尿评分;记录入院时血红蛋白、空腹血糖、血白蛋白、尿素、血肌酐、尿酸、胱抑素C、N-乙酰-β-氨基葡萄糖苷酶、估算肾小球滤过率、总胆固醇、三酰甘油、D-二聚体、C反应蛋白、IgA、IgG、IgM、补体C3、补体C4水平及24 h尿蛋白定量、肾组织病理指标;比较2组治疗24个月IMN完全缓解率。随访至2020年4月,比较2组终点事件发生率。结果 (1)贫血组病程[6(2,12)个月]长于非贫血组[3(1,6)个月](P<0.05),收缩压[(136.09±18.88)mmHg]、尿素[(6.07±3.27)mmol/L]、血肌酐[(88.64±43.98)μmol/L]、胱抑素C[(1.27±0.62)mg/L]、D-二聚体[1.06(0.47,2.70)mg/L]、C反应蛋白[0.36(0.32,0.41)mg/L]、24 h尿蛋白定量[(6.08±3.47)g]均高于非贫血组[(129.90±17.31)mmHg、(4.77±1.68)mmol/L、(73.89±19.80)μmol/L、(0.99±0.30)mg/L、0.55(0.36,1.31)mg/L、0.32(0.10,0.34)mg/L、(4.82±2.55)g](P<0.05),血红蛋白[105.0(94.5, 111.3)g/L]、尿酸[(294.29±92.20)μmol/L]、血白蛋白[(21.66±6.14)g/L]、IgA[(171.54±86.35)g/L]、补体C3[(98.24±25.64)g/L]及CKD 1期比率(51.7%)均低于非贫血组[140.0(130.0,150.0)g/L、(349.82±92.18)μmol/L、(26.07±6.32)g/L、(210.61±80.09)g/L、(115.37±28.42)g/L、73.8%](P<0.05)。(2)贫血组Ehrenreich-Churg分期、C3阳性率、肾小球球性硬化评分、肾小球节段硬化评分、肾小管萎缩/间质纤维化评分、炎症细胞浸润评分、肾血管病变评分、C1q阳性率、IgM阳性率与非贫血组比较差异均有统计学意义(P<0.05),IgA、C4阳性率与非贫血组比较差异均无统计学意义(P>0.05)。(3)贫血组接受肾素-血管紧张素-醛固酮系统抑制剂、糖皮质激素和/或免疫抑制剂治疗比率与非贫血组比较差异均无统计学意义(P>0.05)。治疗24个月,贫血组完全缓解率(34.5%)与非贫血组(39.5%)比较差异无统计学意义(P>0.05)。随访至2020年4月,贫血组终末期肾病发生率(6.9%)高于非贫血组(1.2%)(P<0.05),与治疗相关的严重不良反应死亡率(1.7%)与非贫血组(0.3%)比较差异无统计学意义(P>0.05)。结论 伴贫血的IMN患者肾脏损伤程度较未伴贫血者重,积极纠正贫血可提高IMN完全缓解率,降低终末期肾病发生率,改善预后。

Objective To compare the clinicopathological features of patients with idiopathic membranous nephropathy(IMN) complicated with anemia versus without anemia, and to explore the prognosis. Methods Totally 403 patients with IMN were treated in Chinese PLA General Hospital from January,2011to April,2018,and were divided into anemia group(n=58)and non-anemia group(n=344).The patients in two groups received standard treatment according to guidelines of Kidney Disease:Impioving Global Outcomes organization,and anemia group was treated with erythropoietin,ferrous succinate tablets or iron sucrose injections based on the severity of anemia.The age,course of disease,body mass index,blood pressure,stage of chronic kidney disease(CKD),and hematuria score were compared between two groups.The admission hemoglobin,fasting plasma glucose,albumin,blood urea,blood creatinine,uric acid,cystatin C,N-acetyl-β-glucosaminidase,estimated glomerular filtration rate,total cholesterol,triacylglycerol,D-dimer,C-reactive protein,immunoglobulin(Ig)A,IgG,IgM,complement C3,complement C4,24-h urinary protein quantification,and renal histopathological indexes were recorded in two groups.The 24-month complete remission rate was compared between two groups.The incidence of end event was compared between two groups.Results(1)The course of disease was longer in anemia group [6(2,12)months]than that in non-anemia group [3(1,6)months](P<0.05).The systolic blood pressure,blood urea,blood creatinine,cystatin C,D-dimer,C-reactive protein and 24-h urinary protein quantification were higher in anemia group[(136.09±18.88)mmHg,(6.07±3.27)mmol/L,(88.64±43.98)μmol/L,(1.27±0.62)mg/L,1.06(0.47,2.70)mg/L,0.36(0.32,0.41)mg/L,(6.08±3.47)g]than those in non-anemia group [(129.90±17.31)mmHg,(4.77±1.68)mmol/L,(73.89±19.80)μmol/L,(0.99±0.30)mg/L,0.55(0.36,1.31)mg/L,0.32(0.10,0.34)mg/L,(4.82±2.55)g](P<0.05).The levels of hemoglobin,uric acid,serum albumin,IgA and complement C3as well as proportion of CKD 1were lower in anemia group[105.0(94.5,111.3)g/L,(294.29±92.20)μmol/L,(21.66±6.14)g/L,(171.54±86.35)g/L,(98.24±25.64)g/L,51.7%]than those in non-anemia group[140.0(130.0,150.0)g/L,(349.82±92.18)μmol/L,(26.07±6.32)g/L,(210.61±80.09)g/L,(115.37±28.42)g/L,73.8%](P<0.05).(2)There were significant differences in the Ehrenreich-Churg stage,positive rate of complement C3,glomerular sclerosis score,glomerular segmental sclerosis score,tubular atrophy/interstitial fibrosis score,inflammatory cell infiltration score,renal vascular score,and positive rates of C1q and IgM between two groups(P<0.05),and the positive rates of IgA and complement C4showed no significant differences between two groups(P>0.05).(3)The proportions of patients receiving renin-angiotensinaldosterone system inhibitors,glucocorticoids and/or immunosuppressant therapy showed no significant differences between two groups(P>0.05).After 24-month treatment,the complete remission rate showed no significant difference between anemia group(34.5%)and non-anemia group(39.5%)(P>0.05).The follow-up till April,2020showed a higher incidence rate of end-stage renal disease in anemia group(6.9%)than that in non-anemia group(1.2%)(P<0.05),and no significant difference in the mortality from treatment-related serious adverse events between two groups(1.7%vs.0.3%)(P>0.05).Conclusions The kidney injury severity of IMN patients with anemia is higher than that of those without anemia,and active correction of anemia can improve the complete remission rate,lower the incidence of end-stage renal disease and improve the prognosis of IMN patients.