摘要目的 探讨溶酶体相关膜蛋白2(LAMP-2)及LAMP-2抗体与慢性肾脏病(CKD)患者肾功能变化的关系.方法 选择2016年8月至2017年8月湖北医药学院附属东风医院收治的CKD 3～5期患者80例(CKD组)和健康体检者50例(对照组).两组均抽取空腹肘静脉血检测血红蛋白、肌酐、尿素、白蛋白、LAMP-2和LAMP-2抗体水平,计算估算肾小球滤过率(eGFR).CKD患者随访1年,末次随访时若eGFR下降幅度超过平均eGFR下降幅度定义为肾功能恶化;若随访期间患者开始透析或死亡,则随访结束,并将此类患者判定为肾功能恶化.以入选时血清LAMP-2 及 LAMP-2 抗体水平中位数为依据将患者分为高水平组和低水平组.结果 CKD组eGFR、血红蛋白、白蛋白明显低于对照组[(24.60 ± 5.79)ml/min比(119.20 ± 9.52)ml/min、(111.36 ± 24.41)g/L比(144.60 ± 17.85)g/L、(36.83 ± 3.84)g/L比(45.92 ± 6.37)g/L],肌酐、尿素、LAMP-2、LAMP-2 抗体明显高于对照组[(306.17 ± 49.24)μmol/L 比(83.24 ± 5.55)μmol/L、(15.17 ± 3.39)mmol/L 比(5.57 ± 1.33) mmol/L、(24.76 ± 5.47)μg/L 比(12.93 ± 4.43)μg/L、(20.33 ± 4.89)μg/L比(9.98 ± 2.20)μg/L],差异有统计学意义(P<0.01).80例CKD患者均完成随访,随访时间3～12(8.14 ± 1.95)个月.末次随访时患者eGFR较入选时明显降低[(19.38 ± 7.30) ml/min比(24.60 ± 5.79)ml/min],肌酐、LAMP-2抗体较入选时明显升高[(397.56 ± 52.32)μmol/L比(306.17 ± 49.24)μmol/L和(22.35 ± 4.74)μg/L比(20.33 ± 4.89)μg/L],差异有统计学意义(P<0.01);末次随访时血红蛋白、白蛋白、尿素和LAMP-2与入选时比较差异无统计学意义(P＞0.05).80例CKD患者中,肾功能恶化患者42例,肾功能稳定患者38例.在肾功能恶化患者中,末次随访时eGFR、尿素明显降低[(18.28 ± 6.92)ml/min比(24.46 ± 5.76)ml/min和(13.51 ± 1.92) mmol/L比(14.81 ± 3.32)mmol/L],肌酐、LAMP-2和LAMP-2抗体明显升高[(412.47 ± 53.21)μmol/L比(303.16 ± 47.87)μmol/L、(29.07 ± 5.42)μg/L 比(25.89 ± 5.39)μg/L、(25.03 ± 3.30)μg/L 比(20.95 ± 4.86)μg/L],差异有统计学意义(P<0.01或﹤0.05);末次随访时血红蛋白和白蛋白与入选时比较差异无统计学意义(P＞0.05).在肾功能稳定患者中,末次随访时eGFR较入选时明显降低[(20.38 ± 7.58)ml/min比(24.73 ± 5.89)ml/min],肌酐较入选时明显升高[(381.07 ± 46.64)μmol/L比(309.49 ± 51.15)μmol/L],差异有统计学意义(P<0.01);末次随访时血红蛋白、白蛋白、尿素、LAMP-2和LAMP-2抗体与入选时比较差异无统计学意义(P＞0.05).CKD患者中,LAMP-2高水平组(≥24.75 μg/L)38例,LAMP-2低水平组(﹤24.75 μg/L)42例;LAMP-2抗体高水平组(≥20.33 μg/L)38例,LAMP-2抗体低水平组(﹤20.33 μg/L)42例.Kaplan-Meier曲线分析结果显示,LAMP-2高水平组肾功能恶化风险明显高于LAMP-2低水平组,LAMP-2抗体高水平组肾功能恶化风险明显高于LAMP-2抗体低水平组,差异有统计学意义(P﹤0.01).结论 CKD患者血清LAMP-2、LAMP-2抗体明显升高,高血清LAMP-2、LAMP-2抗体水平患者发生肾功能恶化的风险增加.

abstractsObjective To investigate the correlation between serum lysosomal- associated membrane protein 2 (LAMP-2), LAMP-2 antibody levels and the progression of renal function in patients with chronic kidney disease (CKD). Methods A total of 80 patients with CKD 3 to 5 stage (CKD group) and 50 healthy controls (control group) from August 2016 to August 2017 in Affiliated Dongfeng Hospital, Hubei University of Medicine were enrolled. The levels of hemoglobin, creatinine, urea, albumin, LAMP-2 and LAMP-2 antibody in fasting elbow venous blood of 2 groups were detected, and the estimate glomerular filtration rate (eGFR) was calculated. The CKD patients were followed up for 1 year, and renal function deterioration was defined as eGFR declined more than average value; the follow-up was over when the patients started dialysis or died, and those patients also defined as renal function deterioration. The patients were divided into high level group and low level group according to the serum LAMP-2 and LAMP-2 antibody levels. Results The eGFR, hemoglobin and albumin in CKD group were significantly lower than those in control group: (24.60 ± 5.79) ml/min vs. (119.20 ± 9.52) ml/min, (111.36 ± 24.41) g/L vs. (144.60 ± 17.85) g/L and (36.83 ± 3.84) g/L vs. (45.92 ± 6.37) g/L, the creatinine, urea, LAMP-2 and LAMP-2 antibody were significantly higher than those in control group: (306.17 ± 49.24) μmol/L vs. (83.24 ± 5.55) μmol/L, (15.17 ± 3.39) mmol/L vs. (5.57 ± 1.33) mmol/L, (24.76 ± 5.47) μg/L vs. (12.93 ± 4.43) μg/L and (20.33 ± 4.89) μg/L vs. (9.98 ± 2.20) μg/L, and there were statistical differences (P﹤0.01). All 80 patients with CKD patients completed follow-up, and the follow-up time was 3 to 12 (8.14 ± 1.95) months. The eGFR at the end of followed-up was significantly lower than that at enrolment:(19.38 ± 7.30) ml/min vs. (24.60 ± 5.79) ml/min, the creatinine and LAMP-2 antibody at the end of followed- up were significantly higher than those at enrolment: (397.56 ± 52.32) μmol/L vs. (306.17 ± 49.24) μmol/L and (22.35 ± 4.74) μg/L vs. (20.33 ± 4.89) μg/L, and there were statistical differences (P﹤0.01); there were no statistical differences in hemoglobin, albumin, urea and LAMP-2 between the end of follow-up and enrollment (P＞0.05). Among the 80 patients with CKD, renal function deterioration was in 42 cases, and renal function stability was in 38 cases. In renal function deterioration patients, the eGFR and urea at the end of followed up were significantly lower than those at enrolment:(18.28 ± 6.92) ml/min vs. (24.46 ± 5.76) ml/min and (13.51 ± 1.92) mmol/L vs. (14.81 ± 3.32) mmol/L, the creatinine, LAMP-2 and LAMP-2 antibody at the end of followed up were significantly higher than those at enrolment: (412.47 ± 53.21) μmol/L vs. (303.16 ± 47.87) μmol/L, (29.07 ± 5.42) μg/L vs. (25.89 ± 5.39) μg/L and (25.03 ± 3.30) μg/L vs. (20.95 ± 4.86) μg/L, and there were statistical differences (P﹤0.01 or﹤0.05); there were no statistical differences in hemoglobin and albumin between the end of follow-up and enrolment (P＞0.05). In renal function stability patients, the eGFR at the end of follow-up was significantly lower than that at enrolment: (20.38 ± 7.58) ml/min vs. (24.73 ± 5.89) ml/min, the creatinine at the end of follow-up was significantly higher than that at enrolment: (381.07 ± 46.64) μmol/L vs. (309.49 ± 51.15) μmol/L, and there were statistical differences (P﹤0.01); there were no statistical differences in hemoglobin, albumin urea, LAMP-2 and LAMP-2 antibody between the end of follow-up and enrolment (P＞0.05). In CKD patients, 38 cases were in LAMP-2 high level group (≥24.75 μg/L), and 42 cases were in LAMP-2 low level group (﹤24.75 μg/L); 38 cases were in LAMP-2 antibody high level group (≥20.33 μg/L), and 42 cases were in LAMP-2 antibody low level group (﹤20.33 μg/L). Kaplan-Meier curve analysis result showed that the renal function deterioration risk in LAMP-2 high level group was significantly higher than that in LAMP-2 low level group, LAMP-2 antibody high level group was significantly higher than that in LAMP-2 antibody low level group, and there were statistical differences (P﹤0.01). Conclusions Serum LAMP-2, LAMP-2 antibody levels are increased in patients with CKD, and higher serum LAMP-2 and LAMP-2 antibody levels may be associated with high risk of adverse kidney outcomes and become a promising marker to predict CKD progression.