What is the Link between Poor Ultrafiltration and Increased Mortality in Anuric Patients on Automated Peritoneal Dialysis? Analysis of Data from Eapos

Abstract

Background Primary analysis of the European Automated Peritoneal Dialysis Outcomes Study (EAPOS) found that patients with daily ultrafiltration (UF) below a predefined target of 750 mL at baseline experienced increased mortality and continuing low UF over 2 years. Setting Multicenter, prospective observational study of prevalent, functionally anuric patients on automated peritoneal dialysis (APD) treated to predefined standards. Methods Secondary data analysis to determine clinical covariates that might support a link between poor UF and outcome, including pattern of comorbidity, prescription, nutrition as determined by Subjective Global Assessment (SGA), membrane function, and blood pressure (BP). Ultrafiltration was treated as a categorical (comparing patients above and below target at baseline) and continuous dependent variable in univariate and multivariate regression. The relationship between BP and survival was also explored. Results Of 177 patients recruited from 28 centers across Europe, 43 were below the UF target at baseline. Compared to those above target, there were no differences in the spread of comorbidity, type of APD prescription, SGA, BP, hemoglobin, HCO3, or parathyroid hormone, at baseline or at any later time. At baseline, plasma calcium and, at 12 months, plasma phosphate were lower in the low UF group. There was a weak positive correlation between baseline systolic or diastolic BP and UF, which remained on multivariate analysis but accounted for just 9% of the variability in BP. There was no clear relationship between baseline BP and survival, although, if anything, low BP was associated with earlier death. Poor UF was associated with lower mean dialysate glucose concentration during the first 4 months and with consistently worse membrane function. Conclusions The increased mortality associated with poor UF is likely multifactorial and not easily explained by clear differences in comorbidity, nutritional state, or other indices of treatment at baseline. The lower plasma phosphate suggests a subsequent fall in appetite. Poor BP control is unlikely to be the explanation, and a link between lower BP, reduced UF, and earlier death is suggested. Failure to achieve adequate UF due to worse membrane function remains an important and potentially reversible or preventable cause.

Does increased glucose exposure lead to increased body fat and reduced lean body mass in anuric peritoneal dialysis patients?

“…Previous reports have suggested that hunger profiles are blunted in peritoneal dialysis patients compared to both haemodialysis patients and normal healthy controls [8], as appetite may be reduced by a variety of factors including abdominal distension from larger in-fill volumes, and increased glucose absorption from hypertonic glucose dialysates. As such earlier studies reported reduced nutritional intake over time in anuric patients [4], and those patients with greater malnutrition, determined by subjective global assessment scoring were more likely to die or transfer to haemodialysis [3]. Despite changes in peritoneal dialysis prescriptions and exposure to greater amounts of dialysate glucose our cohort of patients did not reduce their dietary protein intake, as assessed by nPNA.…”

“…To compensate for the loss of residual renal function, peritoneal dialysis prescriptions are typically adjusted in clinical practice to increase both peritoneal small solute clearances and ultrafiltration, leading to larger infill volumes and additional cycles, with greater use of hypertonic glucose dialysates [3]. In keeping with this practice there was a greater prescription of both hypertonic glucose dialysates and icodextrin in our cohort of anuric patients maintained on peritoneal dialysis.…”

“…As such anuric peritoneal dialysate patients are typically prescribed more glucose containing dialysates once residual renal function has been lost. It has been suggested that the increased mortality associated with loss of residual renal function may be due to protein energy wasting (PEW), secondary to increased glucose absorption from the peritoneal dialysates with loss of appetite and reduced protein intake [3].…”

Mitigating peritoneal membrane characteristics in modern peritoneal dialysis therapy

“…There was a high penetration of icodextrin use (45%) in EAPOS; patients using it at the start of the study had worse membrane function as determined by higher solute transport and less good ultrafiltration capacity and yet they achieved as good daily ultrafiltration as those not on icodextrin. 28,51,60,61 Furthermore, in these patients there was no detectable adverse effect of solute transport on achieved daily ultrafiltration, whereas for the remaining patients high transport was negatively correlated despite the use of APD. Icodextrin did not have an independent beneficial effect on survival in EAPOS but it clearly had an additional beneficial effect and was of value to patients with worse membrane function.…”

“…In EAPOS, it was ultrafiltration capacity not solute transport that was the membrane characteristic associated with low baseline ultrafiltration and increased mortality risk. 28,51 In a subgroup analysis of the ANZDATA study, the increased risk of solute transport was seen in continuous ambulatory PD but not APD patients. 25 The problem with APD is that it still leaves the long daytime dwell to be managed.…”