Study On Factors Affecting The Adiponectin And Leptin Dialysate Concentrations In CAPD Patients

Chronic kidney disease was increasing year by year, the incidence statistics for CKD by country in the China up to10%,according to the Chinese population is estimated by the number of more than100million people. A conservative estimate of renal failure occurred in5%of this population, Accordingly estimates the number up to about650,000. Chronic kidney disease becomes another major disease hazard to human health after cardiovascular disease (CVD), diabetes, and tumors. Peritoneal dialysis (PD) has become an important choice of these patients with end-stage renal disease in china, However, the treatment of peritoneal dialysis is not carried out successfully due to various reasons. Less than10%of patients receiving dialysis treatment in China,and only10%received peritoneal dialysis dialysis in dialysis population. The situation is relatively optimistic abroad, the number of peritoneal dialysis patients in North America dialysis patients by45%, compared with40%in Europe, Hong Kong, up to a maximum of78%.It has the advantages of simple operation, small, effects on cardiovascular protection of residual renal function,patients do not need to make a round trip in order to receieve hospital treatment (what means the patient can be on their own dialysis at home).However, with the emergence of cardiovascular events, inflammation, malnutrition, complications such as residual renal dysfunction significantly increased mortality in patients undergoing peritoneal dialysis. In most mortalities,chronic kidney disease patients with cardiovascular disease was more than end-stage renal disease per se, may be due to risk factors for chronic kidney disease in patients with cardiovascular disease, common cardiovascular risk factors such as age, gender, race, diabetes, associated with chronic kidney disease risk factors such as anemia, oxidative stress, inflammation, hyperhomocysteinemia and others mutually reinforcing this result. Epidemiological studies have found that obesity and metabolic syndrome can promote rapid progression of chronic kidney disease to end-stage renal disease. Thus, it is a very meaningful work to find early clinical markers of cardiovascular disease, inflammation, malnutrition and other risk factors, and can be a method of intervention in peritoneal dialysis patients.Adipose tissue is widely being recognized as an active metabolic organ which secretes a variety of compounds with metabolic actions including cytokines (also termed adipocytokines or adipokines), such as tumor necrosis factor (TNF), leptin, resistin and adiponectin.ADPN is the most abundant adipokine in human body, is thought to have anti-atherogenic, anti-inflammatory, and insulin-sensitizing effects. Whereas lower levels of adiponectin are usually found in men and in patients with high cardiovascular risk, such as obesity, coronary artery disease, type-2diabetes, non-alcoholic fatty liver disease, and essential hypertension, higher plasma adiponectin concentrations are observed in another group with high cardiovascular risk, namely patients with chronic kidney disease (CKD). Adiponectin circulates as low-molecular weight (LWM), medium-molecular weight (MMW) and high-molecular weight (HMW) complexes. The percent of HMW adiponectin and HMW/LMW ratio have been postulated to be the most accurate measurements of biological activity. The relative importance of these different components of adiponectin has not been studied in patients with CKD. The increase in total adiponectin levels with progressive CKD2-4stage in children is associated with increasing HMW and decreasing LMW complexes,and LMW-ADPN plays a protective role in older people with a history of CAD. Total and HMW adiponectin are inversely associated with incident Peripheral Arterial Disease (PAD) among initially healthy womenin a prospective, nested case-control study. Calcium promotes the formation of HMW adiponectin,reduce the formation of MMW and LMW. The hypercalcemia is an independentl risk of malnutrition, inflammation, atherosclerosis and death. An elevated plasma adiponectin concentration was found in chronic kidney diease patients. Successful kidney transplantation was followed by a significant reduction (although not normalization) of plasma adiponectin concentration, this suggested us there may be other factors that affected the clearance of ADPN except clearance rate. Several clinical studies have confirmed an inverse association between circulating adiponectin and renal function. Because the gradual increase of plasma adiponectin concentration parallels the progression of CKD, the highest levels are usually found in end-stage renal disease (ESRD) patients. In hemodialysis (HD) and peritoneal dialysis (PD) patients, adiponectin concentrations are about three times higher than in healthy subjects. Of interest, nephrotic patients with normal renal function also have higher adiponectin concentrations, a phenomenon directly associated with degree of proteinuria. The reasons for the high adiponectin levels in the uremic milieu are not fully understood. However, potential explanations include the loss of balance between the ligand/receptor reactivity, reduced adiponectin clearance by the kidneys leading to impaired biodegradation and abolition, and metabolic derangements in uremia.. The higher adiponectin levels associated with gross proteinuria have been proposed to occur as a defense mechanism to mitigate endothelial damage triggered by the nephrotic syndrome. It should also be mentioned that other features of reduced renal function, such as volume overload with higher levels of natriuretic peptides. Tsukamoto et al. found natriuretic peptides not only enhance adiponectin production by human adipocytes in vitro, but also elevated ADPN level when injection of natriuretic peptides in vivo. Kamari found high salt intake in rats increases adiponectin levels independent of the increase in BP. This effect is mediated through the renin-angiotensin-aldosterone system. The lower adiponectin gene expression reported in ESRD may be partially explained by a feed-back mechanism due to renal retention of adiponectin. Although successful renal transplantation significantly decreases adiponectin levels, it does not normalize them,the biological effects of kidney on ADPN remains unclear.Leptin, the product of the ob gene, is a hormone secreted by adipocytes.Leptin is taken up into the central nervous system by a saturable transport system, and controls appetite in rodents and in healthy subjects. Leptin acts on peripheral tissue and increases the inflammatory response by stimulating the production of tumor necrosis factor alpha, interleukin-6and interleukin-12. The adipose tissue-derived hormone leptin acts via its receptor (LRb) in the brain to regulate energy balance and neuroendocrine function. Circulating leptin serves to communicate the state of body energy repletion to the central nervous system (CNS) in order to suppress food intake and permit energy expenditure. Many of the physiological adaptations triggered by prolonged fasting can be attenuated by exogenously administered leptin, which falsely signals to the brain that energy stores are replete. An absolute deficit of leptin does not underlie most cases of obesity: Indeed, most obese individuals exhibit elevated circulating leptin levels commensurate with their adipose mass. The apparent conundrum that this observation implies has given rise to the notion of the existence of physiological leptin resistance. Simply put, the failure of high levels of leptin to suppress feeding and decrease body weight/adiposity to prevent or mitigate obesity suggests a relative resistance to the catabolic effects of leptin action in obesity.A number of mechanisms have been proposed to explain leptin resistance; these include alterations in the transport of leptin across the Blood Brain Barrier, alterations in cellular LRb signaling, perturbations in developmental programming, and others. Indeed, each of these mechanisms may contribute to the totality of leptin resistance. Although the absolute lack or genetic alteration of LRb does not underlie most leptin resistance, the preponderance of data confirm that alterations in cellular LRb signaling, especially in the arcuate, play a crucial role in leptin resistance.The same as ADPN,Because the gradual increase of plasma leptin concentration parallels the progression of CKD, the highest levels are usually found in end-stage renal disease (ESRD) patients. In hemodialysis (HD) and peritoneal dialysis (PD) patients. In patients with intact renal function there is net renal uptake of12%of circulating leptin, whereas in patients with renal insufficiency there is no renal uptake of leptin. leptin modulates insulin sensitivity and high leptin triggers insulin resistance and vice versa. Obesity, a situation where circulating leptin attains very high levels is accompanied by increased bone mass, a phenomenon which may depend on direct stimulation of osteoblasts by leptin. However in animal models the stimulating effect of leptin on the osteoblast is counterbalanced by a strong inhibitor effect on bone formation in the central nervous system. The same as ADPN,ESRD patients’LEP gene expression is down-regulation.LEP(16KD) was a macromolecular toxins, difficult to removed by dialysis. The CAPD patients have higher leptin levels than those of HD patients, glucose load during CAPD may be important factor in increased in leptin levels in CAPD patients.Although varied factors affecting survival in peritoneal dialysis patients, but cardiovascular disease, malnutrition, inflammation and residual renal function reduced or loss is still the most important risk factor.ADPN and LEP are two major adipocytokine released from adipose tissue, is thought to in role of cardiovascular diseases, malnutrition and inflammation. At present, their roles in peritoneal dialysis is not clear, as the search for better prevention and treatment of clinical risk factors for peritoneal dialysis, providing a theoretical basis for intervention studies, to improve survival in patients with peritoneal dialysis and life relationship quality, it’s necessary to research the relationship between adiponectin, leptin and nutritional status, cardiovascular status, residual renal function, peritoneal function in peritoneal dialysis patients.The reduction of renal function will contribute to retention of adipokines, thus generating adipokine imbalance. Such an imbalance may, via effects on the central nervous system and the vasculature, contribute to wasting, atherosclerosis, and insulin resistance. Patients maintenance peritoneal dialysis (PD) trend to exacerbate this situation,partially because of continuous absorption of glucose from dialysate.In PD patients, Conventional PD fluid (PDF) contains dextrose as the osmotic agent. Long-term exposure to glucose has been well recognized to cause peritoneal fibrosis and ultrafiltration (UF) failure, especially metabolic and cardiovascular abnormalitiesthe, and the leptin/adiponectin ratio is markedly elevated, which is consistent with their increased cardiovascular risk. With the consideration of the relatively smaller tissue mass of the peritoneal cavity compared with the entire body, serum concentrations of cytokines and adipokines are usually higher than those in effluent by factors of10—100. Interestingly,the dialysate concentrations of cytokines and adipokines are close to serum concentrations.And the effluent-to-serum ratio didn’t exhibit an inverse correlation with the molecular weight of these mediators. So the high effluent concentrations are a result of local synthesis rather than of size-selective peritoneal transport.It is important to find out the factors affact peritoneum synthesis.Lai et al. demonstrated that PD with conventional or low glucose degradation products(GDP) PDF induces synthesis of selected proinflammatory cytokines, chemokines, and adipokines in the peritoneum. Further more, compared with patients using conventional PDF, patients using neutral pH and low-GDP PDF showed lower interleukin8(IL-8),leptin and higher adiponectin effluent concentrations. This suggests that PDF biological incompatibility may affect the leptin and adiponectin effluent concentrations.In vitro studys, adiponectin secretion was significantly reduced by PD41.36%vs glucose-free dialysates.,and glucose concentration in PD fluids was shown to determine leptin secretion. In addition,both effluent concentrations of adiponectin and leptin were markedly elevated during acute peritonits. These change were not consequences of changes in their plasma levels. Increased concentration of leptin and especially adiponectin in peritoneal effluent seems to be a valuable and new early marker of high peritoneal membrane permeability due to acute peritonitis. However, their correlation with inflammation, residual renal function (RRF) and peritoneal characteristics have never been investigated.The aim of our study was to evaluate the relationship between concentrationss of adipokins(adiponectin,leptin) and transforming growth factor-β1(TGF-β1), RRF, peritoneal solute clearance (Kt/V(urea)) and solute transport rate in continuos peritoneal dialysis (CAPD) patients.Objective Recent research shows that the dialysate concentrations of adiponectin and leptin are close to serum concentrations. And the high effluent concentrations are considered as a result of local synthesis rather than of size-selective peritoneal transport. The aim of our study was to evaluate whether nutritional status,inflammation,residual ranal function,dialysis adequacy and peritoneal transport character affect the dialysate concentrations of adiponectin and leptin in CAPD patients.Methods Forty-one patients received CAPD therapy more than three months were recruited in this study. Their clinical and laboratory data were collected, serum and dialysate concentrations of adiponectin,leptin,TGF-β1and IGF-1were estimate by ELISA. Patients grouped according to absence or presence of RRF, high or low PTR.Results There was no difference in serum and effluent adipokine levels was observed dependent on grouped by RRF or PTR.. Multivariate forward stepwise linear regression analysis shows effluent TGF-β1concentration(R2change=0.483,p<0.001) and peritoneal solute clearance (Kpt/V(urea))(R2change=0.094,p<0.001) were independently associated with effluent ADPN concentration. and explained57.7%of variance. However, HsCRP and IGF-1were independently associated with effluent LEP concentration.Conclusion The peritoneal chronic inflammation and dialysis adequacy may affact the dialysate concentrations of adiponectin, malnutrition and inflammation might be related to the dialysate concentrations of leptin.