原发性干燥综合征合并肾脏损伤的临床病理特征研究

Clinical and pathological characteristics of 141 patients of primary Sjogren's syndrome with renal involvement

目的:研究原发性干燥综合征合并肾脏损伤患者临床表现、免疫学特征、病理表现及疗效,以期对患者进行更好的诊断及治疗,改善预后。方法:收集2002年1月1日至2016年3月31日在我院肾脏内科就诊,并符合2002欧美共识小组(AECG)诊断标准的141例原发性干燥综合征肾脏损伤患者,回顾性分析其临床表现、免疫学特征、病理表现及疗效。结果:141例患者中抗干燥综合征抗原A(SSA)抗体(+)92例(65.3%),抗干燥综合征抗原B(SSB)抗体(+)62例(44.0%),血清免疫球蛋白G(Ig G)升高122例(86.5%),抗核抗体(ANA)(+)75例(53.2%),类风湿因子(RF)升高37例(26.2%)。确诊非霍奇金淋巴瘤1例[腮腺黏膜相关淋巴组织(MALT)淋巴瘤]。肾小管酸中毒(RTA)94例(66.7%),其中Ⅰ型(远端)RTA 82例(58.2%),以低钾乏力或麻痹为首发症状59例(41.8%)。蛋白尿93例(66.0%),其中24 h蛋白尿<1 g者69例(48.9%)。肾功能处于慢性肾脏病(CKD)1期38例(27.0%),2期44例(31.2%),3期41例(29.1%),4期16例(11.4%),5期2例(1.4%)。56例患者接受肾活检,其中肾小管间质性肾炎41例(73.2%),肾小球病变以Ig A肾病及局灶节段性肾小球硬化为最常见的2种类型。89例伴肾功能不全、高血清免疫球蛋白或肾脏病理提示炎细胞重度浸润的患者接受单纯激素或激素联合免疫抑制剂治疗,肌酐由(118.50±72.55)μmol/L降至(98.19±41.55)μmol/L(P=0.025),24 h尿蛋白定量由901.50(509.25,1 577.00)mg降至206.50(94.75,328.75)mg(P<0.001),血清Ig G水平由(24.54±9.92)g/L降至(16.81±4.93)g/L(P<0.001)。结论:远端RTA是干燥综合征肾累及患者常见临床表现,且常以低钾乏力或麻痹为首发症状。肾功能不全发生率也较高,在肾功能不全、高免疫球蛋白血症或肾脏病理提示炎细胞浸润较重的患者中进行适当的免疫抑制治疗可减少患者蛋白尿,改善其免疫学状况及肾功能。

Objective To study the clinical and pathological characteristics of patients of primary Sjogren＇ s syndrome with renal involvement for improving the diagnosis and treatment of such patients. Methods All the patients admitted from 1st January 2002 to 31st March 2016 who fulfilled the 2002 American-European Consensus Group （AECG） criteria were enrolled. Records of clinical presentations, laboratory and pathologic findings were analyzed retrospectively. Results A total of 141 cases were enrolled in this study. Antibodies for anti-Sjogren＇s syndrome A antigen （SSA） and anti-Sjogren＇s syndrome B antigen（SSB） were found in 92（65.3%） and 62（44.0%） patients, respectively; hypergrammaglobulinemia was observed in 122（86.5%） patients; and autoantibody to nuclear antigen（ANA）（＋） and abnormally increased rheumatoid factor （RF） were found in 75（53.2%） and 37（26.2%） patients, respectively. One patient developed parotid gland mucosa-associated lymphoid tissue （MALT） lymphoma. Renal tubular acidosis （RTA） was detected in 94 （66.7%） patients, 82 （58.2%） of whom were confirmed as type I （distal） RTA, with hypokalaemia as the presenting symptom in 59（41.8%） patients. Proteinuria was observed in 93（66.0%） patients, 69（48.9%） patients had urine protein 〈1 g/24 h. For renal function, 38（27.0%） patients were in chronic kidney disease（CKD） stage 1, 44（31.2%） in stage 2, 41 （29.1%） in stage 3, 16（11.4%） in stage 4 and 2（1.4%） in stage 5. There were 56 patients undergoing renal biopsy, with 37（73.2%） patients diagnosed as tubulointerstitial nephritis （TIN）, and IgA nephropathy as well as focal segmental glomerular sclerosis being the two most common glomerular injures. Eighty-nine patients received treatment of steroid alone or in combination with cytotoxic drugs. Mean creatinine of these patients declined from（118.50±72.55） μmol/L to （98.19±41.55） μmol/L （P=0.025）, mean 24 hour urinary protein excretion from 901.50（509.25, 1577.00） mg to 206.50 （94.75, 328.75） mg （P〈0.001）, and mean serum IgG level from（24.54±9.92） g/L to （16.81±4.93） g/L （P〈0.001）. Conclusions Distal RTA was a dominant clinical presentation in our patients, and often with hypokalaemia as the presenting symptom. Prevalence of renal dysfunction was high. In patients with renal dysfunction or hypergrammaglobulinemia, and with renal biopsy findings indicating severe infiltration of inflammatory cells, immunosuppressive therapy could reduce urine protein excretion and improve the immunological status and renal function.