Overhydration May Be the Missing Link between Peritoneal Protein Clearance and Mortality

<b><i>Introduction:</i></b> Peritoneal protein loss (PPL) has been associated with mortality. Inflammation was assumed a putative cause with malnutrition as a consequence. Hydrostatic convection is a major drive for microvascular protein transport, but most studies in peritoneal dialysis (PD) patients overlooked this mechanism. An association between peritoneal protein clearance (PPCl) and venous congestion has been reported recently. The aim of this study was to explore the importance of fluid overload in PPCl in PD. <b><i>Methods:</i></b> Sixty-seven prevalent PD patients were assessed with peritoneal equilibration test and multifrequency bioelectrical impedance assessment (BIA). PPL and PPCl were calculated from simultaneously obtained 24-h peritoneal effluent. <b><i>Results:</i></b> PPL averaged 5.2 g/24 h. It was higher in patients on continuous treatment than in those without a long dwell. Significant associations between PPCl and BIA parameters of overhydration were found in both univariable and multivariable analyses. Lean mass index, partly dependent on hydration status, was associated with PPCl in univariable but not in multivariable analysis. A multiple linear model identified extracellular water excess and higher D/P creatinine as predictors of higher PPCl, independent of PD duration, type of PD, age, gender, albumin, cardiovascular disease, C-reactive protein, or lean mass index. <b><i>Conclusions:</i></b> The uni- and multivariable strong associations between fluid overload and PPCl support the importance of hydrostatic pressure-induced convection for PPCl. Also, peritoneal small solute transport was associated with PPCl. Both are amenable by adjusted dialysis prescription, especially focused on fluid status and avoidance of overhydration. The assumption of an association with inflammation and malnutrition was not confirmed.

Relationships between Peritoneal Protein Clearance and Parameters of Fluid Status Agree with Clinical Observations in other Diseases that Venous Congestion Increases Microvascular Protein Escape

Background Peritoneal effluent from peritoneal dialysis (PD) patients contains proteins, mainly transported from the circulation through large pores in the venular part of the peritoneal micro-vessels. Hydrostatic convection is the major driver for peritoneal protein transport, although in PD there is additional diffusion. Consequently, venous pressure may have a role in peritoneal protein transport. The aim of the study was to investigate the importance of venous congestion on the magnitude of peritoneal protein clearance in incident PD patients using non-invasive measurements. Methods A total of 316 adult PD patients, on PD for 8 - 12 weeks and collecting 24-hour urine and dialysate for total protein determination, underwent standard peritoneal equilibration testing (PET) along with measurement of N terminal pro-brain natriuretic peptide (NT-proBNP) and C-reactive protein (CRP), multifrequency bioimpedance analysis, and a transthoracic echocardiogram. Results Statistically significant univariate relationships for peritoneal protein clearance with a Spearman correlation coefficient > 0.25 were present for 4-hour dialysate/plasma (D/P) creatinine, NT-proBNP, extracellular/total body water, extracellular water excess, left ventricular mass, and right atrial area. Negative correlations were found with serum total protein and residual renal function. On multivariate analysis, logNTproBNP (β 0.11, p = 0.007) and right atrial area (β 0.01, p = 0.03) were significant independent predictors of peritoneal protein clearance. Conclusion Indicators of venous congestion showed the most important relationships with peritoneal protein clearance. These indicators have not been assessed in previous studies on the presence or absence of relationships between peritoneal protein clearance and mortality.

Association of Lean Body Mass Index and Peritoneal Protein Clearance in Peritoneal Dialysis Patients

Background/Aims: The relationship between peritoneal protein clearance (PPCl) and nutritional status in peritoneal dialysis (PD) population have not been clarified. This study aims to investigate the relationship between PPCl and nutritional status in PD population. Methods: Prevalent PD patients were enrolled in the cross-sectional survey in a single center from April to November 2013. The total amount of protein loss in the dialysate was calculated. PPCl reflects the individual differences of peritoneal protein loss, and is calculated by the formula, that PPCl (ml/day)=24-h dialysate protein loss / (albumin/0.4783). Nutritional status measured by lean body mass index (LBMI) was assessed by multi-frequency bioelectrical impedance analysis (BIA). Results: Totally 351 PD patients (55% male, 17.1% with diabetes, mean age 47.7±14.3 years) were included. The median PPC l was 58 ml/day. Patients were divided into four groups for comparison according to the PPC quartiles. Compared with lower PPCl quartiles, patients with higher PPCl had higher body mass index (BMI) (P< 0.001), body surface area (BSA) (P < 0 .001), LBMI (P<0.001), 4-hour D/P creatinine ratio (P< 0.001), and lower residual renal CCl (P<0.001). Compared with conventional body index (BMI and BSA) in ROC analysis, LBMI (area under curve: 0.71, 95% confidence interval [CI]: 0.66-0.77) had better performance in predicting higher PPCl. After adjustment in logistic regression models, each 1 kg/m2 increase of LBMI (odd ratio[OR] =1.37; 95% CI: 1.17-1.60), each 0.1 increase of 4-hour D/P creatinine ratio (OR =1.47; 95% CI: 1.11-1.93), and every 1 L/week/1.73m2 decrease of residual renal CCl (OR =0.98; 95% CI: 0.96-0.99) were independently associated with higher PPCl (> 58 ml/day). Conclusion: Higher LBMI was independently associated with higher , indicating that better nutritional status dominates peritoneal protein metabolism in PD patients.

Peritoneal Protein Clearance Rather than Faster Transport Status Determines Outcomes in Peritoneal Dialysis Patients

Faster peritoneal transport has been associated with an increased risk of therapy failure and patient mortality. However, faster transport can the result of many factors. Peritoneal protein clearance (PPC) has been proposed to distinguish faster peritoneal transport attributable to inflammatory conditions, as protein clearance reflects large-pore flow, which increases during inflammation. We followed a cohort of 300 peritoneal dialysis patients, and after adjustments for age and comorbidity, higher PPC was associated with increased risk of death (hazard ratio: 1.81; 95% confidence interval: 1.11 to 2.95), even after patients underwent transplantation or transferred to hemodialysis.