The Study Of Metabolic Disorder And Risk Factors In Peritoneal Dialysis Patients

The study of metabolic disorder and risk factors in peritoneal dialysis patientsBackgroundPeritoneal dialysis(PD) is one of the renal replacement therapy of end stage renal disease(ESRD) patients.The hemodynamic effect of PD is stable.But the prevalence of cardiovascular events in PD patients is high.Insulin resistance(IR) and dislipidemia is commonly encountered in uremic patients,and may be worsened in patients undergoing peritoneal dialysis because of a high peritoneal glucose load.Aside from classic risk factors such as hyperlipidaemia and insulin resistance,recent studies have demonstrated that systematic inflammation and adipocytokines,such as leptin, adiponectin and resistin,may play important roles in the development of IR and atherosclerosis.During our study we found that not all of the PD patients showed metabolic disorder.We supposed that genetic predisposition is one of the determinants of metabolic disorder in PD patients except for the overload of glucose.Uncoupling protein(UCP) is proposed to catalyze a mitochondrial inner-membrane H~+ leak that bypasses ATP synthase.UCP2 might play a role in energy balance,body weight regulation,insulin secretion,and etc.Genetic variation in CUP2 may have effects on the development of obesity and type 2 diabetes.ObjectiveTo compare the effect of different dialysis therapys on BMI,insulin resistance, plasma lipid levels and adipocytokines.To investigate the changes in fat mass,insulin resistance,plasma lipid levels and adipocytokines after initiation of maintenance peritoneal dialysis and the risk factors of metabolic disorder in peritoneal dialysis patients.To study the effects of UCP2 exon 8 insertion/deletion polymorphism on metabolic disorder in PD patients.Methods1.75 PD patients,37 hemodialysis patients and 73 CKD-V predialysis patients were enrolled.Parameters including body mass index(BMI),insulin resistance(IR) using HOMA-IR[Plasma insulin(mU/L)~* plasma glucose(mmol/L)/22.5] and serum lipid profile[including total cholesterol,triglyceride,LDL-C,HDL-C] were measured in the same situation.Adipocytokines such as leptin,adiponectin and resistin were measured by ABC-ELISA methods.2.50 PD patients were chosen at the time before,and 1 month,3months, 6months and 12months after they began the peritoneal dialysis therapy,to examine BMI,triceps skinfold thickness(TSF),abdominal circumference,HOMA-IR,the plasma lipid profile,CRP,ferritin and adipocytokines including leptin,adiponectin and resistin in the same situation.Peritoneal glucose absorption,Kt/V and creatinine clearance(Ccr) of peritoneal dialysis and residual kidney were estimated in these PD patients.3.Genotyping of a polymorphism in the 3' untranslated region of exon 8 of UCP2 was performed in 70 PD patients.All the patients were divided into DD group and DⅠ/Ⅱgroup to examine BMI,HOMA-IR,the plasma lipid profile,CRP,ferritin, peritoneal glucose absorption,and adipocytokines.50 PD patients were divided into DD group and DⅠ/Ⅱgroup.Parameters including BMI,triceps skinfold thickness(TSF),HOMA-IR,the plasma lipid profile, CRP,ferritin,peritoneal glucose absorption,and adipocytokines were measured at the time before,and 3 months,6months after they began the peritoneal dialysis.Results1.There was no difference in age,gender,duration of dialysis treatment and proportion of diabetic patients in three groups.The HOMA-IR(4.6187 vs 2.3143 vs 1.7622,P<0.01),CHO(5.5020 vs 3.9727 vs 4.6733,P<0.01),TG(2.3700 vs 1.3200 vs 1.6400,P<0.01) and serum leptin level(1.6000 vs 1.4900 vs 1.4280,P<0.05) of PD patients were significantly higher than that of HD and CKD-V predialysis patients. Serum adiponectin level in PD patients was significantly lower than that of HD and predialysis patients(9.0720 vs 14.2210 vs 13.7480,P<0.05).There was no remarkable difference in serum resistin level in three groups.2.A total of 50 PD patients(28 males,56%) with a mean age of 61.68±15.33 years were enrolled.After PD treatment for 12 months,these patients showed higher BMI(P<0.01),TSF(P<0.05),abdominal circumference(P<0.05),serum TG level(P<0.01),serum leptin level(P<0.01) and lower serum adiponectin level(P<0.01) than the values before commencing PD treatment.We found that HOMA-IR increased significantly in non-diabetic patients(P<0.01).There were no remarkable changes in serum CHO,HDL-C and LDL-C levels.The proportion of patients taken statin was significantly increased(P<0.01).HOMA-IR was associated with abdominal glucose absorption(P<0.01,OD value 2.917,95%CI(1.349,6.306)),leptin(P<0.01,OD value 2.694,95%CI(1.604,4.524)), ferritin(P<0.05,OD value 1.720,95%CI(1.038,2.852)),TG(P<0.01,OD value 2.9493, 95%CI(1.491,4.169)) and adiponectin(P<0.01,OD value 0.441,95%CI(0.264, 0.738)).Multiple logistic regression analysis showed that changes in abdominal glucose absorption,ferritin and serum leptin level were most significant predictive factors for the change in HOMA-IR.Serum TG level was positively related to ferritin and serum leptin level while negatively related to serum adiponectin level.Factors affecting serum TG level including IR(P<0.01,OD value 2.493,95%CI(1.491,4.169)) and adiponectin(P<0.01,OD value 0.409,95%CI(0.244,0.686)).CRP was positively related to serum leptin and resistin levels(r=0.127,P<0.05; r=0.218,P<0.01).Ferritin was positively related to serum resistin level and abdominal glucose absorption(r=0.133,P<0.05;r=0.222,P<0.05) while negatively related to serum aidponectin level(r=-0.139,P<0.05).Multiple logistic regression analysis showed that changes in TSF and IR were significant predictive factors for the change in serum leptin level(P<0.01,OD value 3.480,95%CI(2.049,5.911);P<0.01,OD value 2.694,95%CI(1.604,4.524)).Serum adiponectin level decreased as IR and TG increased(P<0.01,OD value 0.441,95%CI(0.264,0.738);P<0.01,OD value 0.409, 95%CI(0.244,0.686)).3.Pateints with DD genotype showed higher IR(3.7893 vs 2.0902,P<0.01), serum leptin level(1.8400 vs 1.5950,P<0.01) and peritoneal glucose absorption (104.8483 vs 86.2176,P<0.05) compared to those with DⅠ/Ⅱgenotype.Patients with DD genotype showed a significant increase in BMI(P<0.05),IR(P<0.01),serum TG(P<0.01) and leptin level(P<0.05) and a significant decrease in serum adiponectin level(P<0.05) after 6 months of PD treatment.We did correlation and logistic regression analysis in DD group.We found that IR was positively related to TG,CRP,ferritin,serum leptin level and abdominal glucose absorption while negatively related to serum adiponectin level.TG was positively related to serum leptin level while negatively related to serum adiponectin level.Abdominal glucose absorption was positively related to CRP and ferritin. Factors affecting IR including leptin(P<0.01,OD value 3.765,95%CI(1.664,8.515)) and TG(P<0.01,OD value 3.161,95%CI(1.483,6.737)).These correlations were not found in DⅠ/Ⅱgroup.ConclusionThere was critical metabolic disorder including dyslipidemia and insulin resistance in PD patients compared to that in HD and CKD-V predialysis patients. Body fat mass of PD patients increased significangly during the first year of peritoneal dialysis therapy.Metabolic disturbance including IR and dislipidemia gradually aggravated,which was associated with multiple factors including overweight,glucose absorption,adiponectin,leptin,inflammation,and etc.Patients with 45bp DD genotype in exon 8 ins/del polymorphism of the UCP2 gene prone to get metabolic disorder.