The Relationship Between The Level Of Leptin And Microinflammation In Chronic Kidney Disease And Their Roles In Atherogenesis

Objective : 1.To investigate the changes of the concentration of serum leptin and C-reaction protein (CRP) with chronic kidney disease (CKD);2.To investigate the changes of the level of IMT of carotid artery with chronic kidney disease(CKD);3.To investigate the relationship between the level of the serum leptin , C-reaction protein (CRP) and each of the parameter for clinic with chronic kidney disease (CKD);4.To explore the relationship among the serum leptin, C-reaction protein (CRP) and chronic kidney disease (CKD),and the possible mechanism of leptin to atherosclerosis seen in chronic kidney disease (CKD).Methods:We collected 79 patients with chronic kidney disease (51 males and 28 females) aged 44.22±13.47 (mean±SD). The standard of diagnosis by using K/DOQI guideline[1]. The primary diseases: 53 patients were chronic glomerulo- nephritis, 5 patients were hypertention nephritis, 3 patients were polycystic kidney,4 patients were obstructive nephropathy and 12 patients were etiology unknown. 79 patients with chronic kidney disease were classified into three groups according to glomerular filtration rate (GFR): (1) CKD2~3 stage groups included 26 patients (GFR30~90ml/min /1.73m2), (18 males and 8 females),the average age is 44.69±14.13 years; (2) CKD4 stage groups included 22 patients (GFR15~30ml/min/1.73m2), (16 males and 6 females),the average age is 42.7±12.63 years;(3) CKD 5stage groups included 31 patients (GFR<15ml/min /1.73m2), (17 males and 14 females),the average age is 45.19±13.78 years;(4) Healthy control group included 13 healthy volunteers (8 males and 5 females), aged 40.07±18.51 (mean±SD). Excluding standards:①Those who were infected, operated on and had trauma in recently one month;②To have acute cardiovascular disease (CVD) in recently one month;③Those who have used the cortical hormone or other immunity conditioner in recently six months ;④To affiliate malignancy, pregnancy;⑤diabetic nephropathy;⑥To have dialysis or renal transplantation. All the patients starved for 12 hours and the vein blood 6ml was sampled in the morning. The blood samples were tested by the automatic biochemical machine to measure the blood routine, blood creatinine, urea nitrogen, blood sugar, the cholesterol, triglyceride, high dense lipoprotein cholesterol, low dense lipoprotein, very low density lipoproteintotal protein, albumin. At the same time, the serum was centrifugally separated and saved in -70℃refrigerator to measure the leptin and CRP, The leptin was tested by the radio-immunity method and the reagents were provided by the Beijing Puer Weiye Biotechnical Institute. The CRP was tested by the rate-scatter turbidimetry method and the antiserum was provided by Shanghai Sun Biotechnical Institute. Seventy nine CKD patients and 13 healthy volunteers were involved in the study. The serum leptin was tested by the radio-immunity method;The CRP was tested by the rate-scatter turbidimetry method. Intima-medial thickness (IMT) of extracranial common carotid artery and the presence of atherosclerotic plaques were determined by using noninvasive high-resolution B-mode ultrasonography. To calculate body mass index (BMI) and glomerular filtration rate (GFR).Results:1. Levels of leptin in the chronic kidney disease (CKD) patients were significantly higher than those in the healthy groups, and to elevate along with the deteriorate of kidney function;Levels of CRP in the chronic kidney disease (CKD) patients were significantly higher than those in the healthy groups, and to elevate along with the deterioration of kidney function;2. The IMT in carotid artery were significantly higher in CKD patients compared with the healthy groups, and to elevate along with the deteriorate of kidney function;3. It was found that patients with chronic kidney disease in the high IMT of carotid artery groups had serum CRP and serum leptin concentrations significantly increased compared with the normal IMT of carotid artery groups;4. It was found that patients with chronic kidney disease in the high CRP groups had serum leptin concentrations and IMT of carotid artery significantly increased compared with the normal CRP groups;5. It was found that patients with chronic kidney disease in hyperleptin groups had serum CRP concentrations and IMT of carotid artery significantly increased compared with the lowleptin groups; 6. It was found that patients with chronic kidney disease in the Alb <35g/L groups had serum CRP concentrations and IMT of carotid artery significantly increased compared with the Alb >35g/L groups;7. The linear correlations were found between the leptin and parameters in patients with chronic kidney disease (CKD) as follows:①The serum leptin levels were correlated positively with urea nitrogen serum creatinine C-reaction body mass index (BMI) (r=0.293,P<0.01;r=0.324,P<0.01;r=0.539,P<0.01;r=0.312,P<0.05);②The serum leptin levels were correlated negatively with glomerular filtration rate hemoglobin albumin (r=-0.389,P<0.01;r=-0.454,P<0.01;r=-0.246, P< 0.05),and were not correlated with age cholesterol triglyceride (r=0.014, P>0.05;r=0.051, P>0.05;r=-0.055, P>0.05) 8.The linear correlation regression analyses for IMT and serum leptin, serum CRP, TG, Hb, showed that serum leptin and serum CRP participated straightly in the atherosclerosis of vessel and the forming of atherosclerosis spot mass. 9. Logistic regression analysis further indicated that Leptin (β=1.527, 95%CI :1.028~1.438 , P<0.05) was an independent risk factor of atherosclerosis-related cardiovascular events in chronic disease (CKD).Conclusions:①There is hyperleptin and micro inflamma- tory state in the chronic kidney disease (CKD) patients.②The leptin and microinflammatory state might be in close correlation with atherosclerosis-related cardiovascular events in chronic kidney disease (CKD).③The serum leptin and microinflamma- tion may result in accelerated atherosclerosis seen in chronic kidney disease (CKD).