血清农药残留水平与慢性肾脏病的相关性研究

Relationship between serum pesticide residues and chronic kidney disease

目的探讨机体血清农药残留水平与CKD发生、发展的相关性。方法回顾性分析上海交通大学医学院附属瑞金医院北院肾内科的110例CKD(CKD组)患者资料,另取同期来自体检中心的49名非CKD人群(对照组)的资料。采用气相色谱-质谱法检测受试者的血清农药残留水平,包括有机氯类农药滴滴涕(代谢产物为p,p’-DDE)等26种农药残留量。以血清p,p’-DDE检测值中位数(1.5\mg/L)为界,将CKD组患者分为p,p’-DDE<1.5\mg/L组(54例)和≥1.5\mg/L组(56例),比较两组患者临床特点。筛选出糖尿病肾病患者18例和慢性肾小球肾炎患者92例,分析患者血清p,p’-DDE残留水平与两种疾病发生的相关性。结果受试者农药残留种类以p,p’-DDE为主。CKD组患者血清p,p’-DDE残留检出率为60.0%(66/110),显著高于对照组的14.3%(7/49,χ~2=28.53,P<0.01)。p,p’-DDE<1.5\mg/L组与p,p’-DDE≥1.5\mg/L组间血清肌酐、EPI法估算的肾小球滤过率(EPI-eGFR)和BMI的差异均无统计学意义(P值均>0.05)。p,p’-DDE≥1.5\mg/L组患者年龄为(51.9±15.9)岁,显著高于p,p’-DDE<1.5\mg/L组的(37.7±13.7)岁(t=5.02,P<0.01)。糖尿病肾病亚组患者血清p,p’-DDE残留检出率为72.2%(13/18),显著高于对照组的14.3%(χ~2=21.10,P值<0.01);糖尿病肾病亚组患者年龄为(58.5±13.1)岁,显著高于对照组的(44.4±10.5)岁(t=4.56,P值<0.01)。校正年龄因素后,血清p,p’-DDE残留水平升高是糖尿病肾病患病的影响因素(OR=3.024,95%CI为1.313~8.181,P=0.028)。慢性肾小球肾炎亚组与对照组间的性别构成、年龄的差异均无统计学意义(P值均>0.05)。血清p,p’-DDE残留水平升高是慢性肾小球肾炎的危险因素(OR=3.030,95%CI为1.638~5.592,P<0.01)。80例行肾脏穿刺活组织病理学检查的患者以IgA肾病(32例)、膜性肾病(26例)、局灶节段硬化性肾小球肾炎(9例)为主要病理类型,3种类型患者血清p,p’-DDE水平秩平均值的差异无统计学意义(χ~2=5.51,P=0.06)。80例患者肾脏间质病变严重程度为无损伤(10例)、轻度损伤(47例)、中度损伤(16例)、重度损伤(7例),4个等级间患者血清p,p’-DDE水平秩平均值的差异无统计学意义(χ~2=2.53,P=0.24)。结论CKD患者血清p,p’-DDE残留检出率及其水平升高,提示机体p,p’-DDE残留可能与CKD的发生、发展相关;p,p’-DDE残留亦是患者发生糖尿病肾病和慢性肾小球肾炎的危险因素。

Objective To explore the relationship between the level of pesticide residues and the development and progession of chronic kidney disease(CKD).Methods The data of 110 patients with CKD in the department of Nephrology,Ruijin Hospital North Branch,Shanghai Jiao Tong University School of Medicine were collected,and the data of 49 non-CKD population from the physical examination center were enrolled in this case-control study.Gas chromatography-mass spectrometry was used to detect pesticide residues.Twenty-six types of pesticides,such as dichlorodiphenyltrichloroethane(DDT,its metabolite was p,p’-DDE)were tested.CKD patients were subdivided into two groups according to the median p,p’-DDE level(1.5\mg/L),and clinical manifestations were compared between the two groups.There were 54 cases in p,p’-DDE<1.5\mg/L group and 56 cases in p,p’-DDE≥1.5\mg/L group.Eighteen patients with diabetic nephropathy and 92 patients with chronic glomerulonephritis were screened,and the correlation between serum p,p’-DDE residual levels and the development of two diseases was analyzed.Results The most common pesticide detected was p,p’-DDE.It was detected in 60.0%(66/110)of CKD patients and 14.3%(7/49)of healthy controls(χ~2=28.53,P<0.01).No significant difference was found in the level of serum creatinine,estimated glomerular filtration rate(GFR)by EPI analysis(EPI-eGFR)or body mass indes(BMI,all P>0.05)between group p,p’-DDE<1.5\mg/L and group p,p’-DDE≥1.5\mg/L.But the patients of group p,p’-DDE≥1.5\mg/L were significantly older than group p,p’-DDE<1.5\mg/L([51.9±15.9]years vs.[37.7±13.7]years,t=5.02,P<0.01).Diabetic nephropathy patients had higher p,p’-DDE positive rate and were older than healthy controls(72.2%[13/18]vs.14.3%[7/49],χ~2=21.10,P<0.01;[58.5±13.1]years vs.[44.4±10.5]years,t=4.56,P<0.01).Logistic regression showed that serum p,p’-DDE level was a risk factor for diabetic nephropathy after age adjustment(OR=3.024,95%CI:1.313-8.181,P=0.028).There was no statistical difference in gender or age composition between chronic glomerulonephritis patients and healthy controls(both P>0.05).Serum p,p’-DDE level was a risk factor for chronic glomerulonephritis(OR=3.030,95%CI:1.638-5.592,P<0.01).Eighty patients received renal biopsy.The most common pathologic type was IgA nephropathy(32 cases),followed by membranous nephropathy(26 cases)and focal segmental glomerular sclerosis(FSGS,9 cases).There was no significant difference in serum p,p’-DDE level among different pathological types of glomerulonephritis(χ~2=5.51,P=0.06).In the 80 patients,the severity of renal tubulointerstitial lesions was as follows:no lesion in 10,mild in 47,moderate in 16 and severe in 7.There was no significant difference in serum p,p’-DDE level among different severities of renal tubulointerstitial lesions(χ~2=2.53,P=0.24).Conclusion Serum p,p’-DDE level is increased in CKD patients,indicating that p,p’-DDE may be associated with the development and progression of CKD.Serum p,p’-DDE may be a risk factor for diabetic nephropathy and chronic glomerulonephritis.