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Metabolic Complications of Peritoneal Dialysis
The removal of solute and water for the management of kidney failure with peritoneal dialysis (PD) is achieved by exposing the naturally occurring peritoneal lining of the abdomen to 6 to 15 L of dialysate every day. It is widely believed that the exposure of the peritoneum to large volumes of dialysate has significant and wide-ranging deleterious systemic effects. This chapter reviews the evidence for and the clinical implications for the purported systemic metabolic effects of PD.
Weight Gain
Every patient treated with PD uses glucose-based solutions either exclusively or for most of the treatment through the day, with the remaining time with either icodextrin- or amino acid-based solutions. Treatment with glucose- or icodextrin-based solutions is associated with an obligatory absorption of 50 to 150 g of carbohydrates daily. As a result, it is widely believed that patients treated with PD are significantly more likely to gain body weight than those undergoing hemodialysis (HD). At times, this may be an important consideration in the selection of dialysis modality for some patients because of either the effects on body image or future eligibility for transplantation.
Caution must be exercised in interpreting data on changes in body weight over time because they may result from alterations in volume status, fat mass, or fat-free edema-free body mass. Initiation of dialysis is associated with two competing events—improvement in volume status by correction of hypervolemia with dialysis as well as an improvement in appetite from the amelioration of anorexia, a cardinal manifestation of the uremic state. This results in a net decrease in body weight in the first few months of initiation of dialysis followed by weight gain in most patients irrespective of dialysis modality. Three large multicenter studies have compared the change in body weight after initiation of dialysis and demonstrated either no significant difference in the trajectory of change in body weight over time for patients treated with HD, PD, or a higher probability of significant weight gain for patients treated with HD. Hence, the notion that patients are more likely to gain significant body weight with PD is not supported by the available evidence. Limited evidence suggests that the magnitude of weight gain with PD may at least in part be determined genetically. Small single-center studies also seem to indicate that patients treated with PD may be more likely to gain visceral fat mass than those undergoing HD. These findings need to be validated in larger studies, but their clinical implications are unclear.
Thus, after the first few months of treatment with maintenance dialysis, patients gain body weight irrespective of modality, and concerns about a higher probability of weight gain with PD are not supported by the available evidence. It follows then that concerns about weight gain should not be an important consideration in the selection of dialysis modality.
Metabolic Syndrome
Metabolic syndrome is defined as the presence of a cluster of risk factors that are associated with a significantly higher risk for cardiovascular disease in the general population. The definitions for metabolic syndrome from different expert groups are somewhat different but generally include measures of adiposity, dyslipidemia, hypertension, and abnormal fasting blood glucose levels. Insulin resistance is the dominant but not the only condition underlying the pathogenesis of metabolic syndrome. The different components of the metabolic syndrome are independent risk factors for the development and progression of chronic kidney disease (CKD); hence, patients with metabolic syndrome are significantly more likely to have CKD. Conversely, metabolic syndrome is highly prevalent in patients with kidney failure, including those undergoing maintenance dialysis.
Several studies have demonstrated that half or more of patients undergoing PD meet the criteria for metabolic syndrome by one or more expert groups. However, there is only a fair to modest agreement in the diagnosis of metabolic syndrome using the various criteria. A small longitudinal cohort study has demonstrated an increase in the prevalence of metabolic syndrome over time when treated with PD, and another study that made a head-to-head comparison concluded that metabolic syndrome was significantly more prevalent in patients undergoing PD compared with in-center HD. These observations have raised concerns that PD therapy may contribute to the development of metabolic syndrome. This is thought to be biologically plausible given the obligatory carbohydrate absorption with PD. However, the data are preliminary at best for several reasons. The prevalence of metabolic syndrome for patients undergoing in-center HD in the only study with head-to-head comparison was substantially lower than in other studies. Also, there are at least two challenges with the diagnosis of metabolic syndrome in patients undergoing PD. First, the intraperitoneal instillation of dialysate with PD results in an increase in waist circumference, an important component for the diagnosis of metabolic syndrome. Second, there is continuous systemic absorption of glucose from intraperitoneal dialysate, and hence, patients undergoing PD are never in a postabsorptive state. This results in an overestimation of fasting glucose and lipid parameters. These challenges likely also explain, in part, the variability in who is diagnosed (or not) with metabolic syndrome based upon the expert group criteria used. Finally, the results from studies examining the association of metabolic syndrome with cardiovascular events or all-cause mortality have been inconsistent and may depend upon the diagnostic criteria used. This is not surprising because the individual components of metabolic syndrome themselves do not portend a higher risk for death or cardiovascular events in patients with kidney failure, including those undergoing PD.
For these reasons, the contribution of PD to the development of metabolic syndrome and its clinical relevance for these patients is at best uncertain. Notwithstanding these uncertainties, it remains prudent to minimize daily glucose exposure with PD prescription.
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