Clinical Research Of Incidence And Pathogenesis Of Metabolic Syndrome In Recipients After Kidney Transplantation

[BACKGROUND]Metabolic syndrome was proposed by Herberg at the first time in 1972 and its definition made by WHO in 1999. MS is a clinical syndrome which was based on insulin resistance and its characteristics are central obesity, diabetes mellitus or the damaged regulation of glucose, the disorder of lipid metabolism and hypertension.According to National Cholesterol Education Program/Adult Treatment Panel, every moity of MS including central obesity, the metabolic disturbance of lipid and glucose, hypertension etc. is an important risk factor of cardiovascular disease, especially when they are concomitant. Obesity associated nephropathy, dyslipidemia associated renal damage, diabetic nephropathy and hypertensive nephropathy could be resulted by a different moity of the syndrome, meanwhile renal damage could also result to the occurrence and aggravation of MS. So, MS and chronic kidney disease can be caused and promoted by each other.In a sense, the recipients of renal transplantation were also patients of chronic kidney disease at the same time. In another word, short-term graft survival had been raised significantly, but long-term graft survival not. All kinds of immunological and non-immunological factors could lead to renal lesion and allograft dysfunction at last. A lot of research proved that metabolic syndrome was not only a risk factor of cardiovascular disease but could lead to renal lesion. Our aim in the study was to analyze the pathogenesis, consequences and impact of metabolic syndrome on recipient and allograft survival by investigating the incidence and risk factors of metabolic syndrome in recipients after renal transplantation.As the basis of metabolic syndrome, insulin resistance can lead to many kinds of pathologicical status, such as type 2 diabetes mellitus, dyslipidemia, obesity. The pathogenesis of insulin resistance was not clear until now. The aim of the study was to investigate the risk factors and its relationship with metabolic syndrome and chronic allograft nephropathy in recipient after renal transplantation.PARTⅠClinical Study of the Incidence and Pathogenesis ofMetabolicSyndrome in Recipients after Kidney TransplantationObjective To investigate the incidence and risk factors of metabolic syndrome (MS)in patients after renal transplantation. Methods 292 renal transplant recipients who hadnot undergone acute rejection, calcinurine intoxication and severe infection, and had normal renal function and no proteinuria at the 6th month post-transplantation, were involved in the study. They had a history of chronic glomerulonephritis as the primary disease of ESRF but no diabetes mellitus. One year after, blood and urine biochemical determinations and physical examination were performed in the recipients, and BMIcalculated. 200 community residents were randomized selected as controls. Result Theincidence of MS in the recipients was 25.7%, significantly higher than controls (15%). There was no difference between the incidence of MS in recipients treated with cyclosporine+MMF+prednisone and recipients treated with tacrolimus+MMF+prednisone. The incidence in recipients respectively treated with cyclosporine at a maintain dosage >200mg.d-l or tacrolimus at a maintain dosage >2mg.d-1 was markedly higher, compared to cyclosporine at a maintain dosage≤200mg.d-l or tacrolimus at a maintain dosage≤2mg.d-1. There was no significant difference between the incidence of obesity oroverweight in the recipients and community residents. Conclusion It is suggested by thesignificantly increased incidence of MS that MS might increase the non-immune risk factors of CAN. It is indicated that, after renal transplantation, male sex and maintain dosage of cyclosporine >200mg.d-1 or a maintain dosage of tacrolimus >2mg.d-1 are the risk factors of MS after renal transplantation, while obesity and overweight are not the main factors related to the increased incidence of MS in the sutdy.PartⅡClinical Study of the Risk Factors ofInsulin-resistance and itsrelationship with Metabolic Syndrome and CAN in Recipientsafter Kidney TransplantationObjective To investigate the risk factors of insulin resistance (IR) and itsrelationship with metabolic syndrome in patients after renal transplantation. Methods133 renal transplant recipients who had not undergone acute rejection, calcinurine intoxication and severe infection, and had normal renal function and no proteinuria at the 6th month post-transplantation, were involved in the study. They had a history of chronic glomerulonephritis as the primary disease of ESRF but no diabetes mellitus. One year after, blood and urine biochemical determinations and physical examination were performed in the recipients, and HOMA calculated. 200 community residents were randomized selectedas controls. Result The incidence of MS in the recipients was 33.1%, significantly higherthan controls (15.0%). There was no significant difference between the incidence of obesity and overweight in recipients (29.3%) and controls (37.5%). While in recipients with obesity or overweight, the insulin-resistance level and urine albumin level, and the incidence of MS and microalbuminuria were significantly higher than recipients without obesity or overweight. The insulin-resistance level in Tacrolimus-treated recipients was markedly higher than CsA-treated recipients, and there was a positive correlation between the blood concentration of Tacrolimus and insulin-resistance level. Micoralbuminuria-positive recipients had higher insulin-resistance levels. Metabolic syndrome-complicating recipients had higher insulin-resistance levels, compared to recipients without metabolic syndrome, and higher insulin-resistance levels existed in recipients with hypertriglyceridemia or hypercholesterolemia, hypertension. ConclusionIt is shown in the study that obesity or overweight, Tacrolimus (especially when blood concentration was higher) were risk factors resulting in insulin-resistance in kidney transplant recipients. It is suggested by the study that insulin-resistance might be involved in the pathogenesis of metabolic syndrome including hypertriglyceridemia, hypercholesterolemia and hypertension, and simultaneously the pathogenesis of CAN, in kidney transplant recipients.