Peritoneal Protein Loss, Inflammation, and Nutrition: Refuting Myths

Abstract

Peritoneal protein loss (PPL) has been correlated with mortality, malnutrition and inflammation. More recently overhydration was brought to the equation. This study aims to review classic and recent factors associated with PPL. Prevalent and incident peritoneal dialysis (PD) patients were included. Dialysate and serum IL-6 was obtained during PET. Hydration and nutritional status were assessed by bio-impedance. Linear regression and Cox regression were performed. The 78 included patients presented median values of PPL 4.8 g/24 h, serum IL-6: 5.1 pg/mL, and IL-6 appearance rate 153.5 pg/min. Mean extracellular water excess (EWexc) was 0.88 ± 0.94 L, and lean body mass index (LBMI) 17.3 ± 2.4 kg/m2. After mean follow-up of 33.9 ± 29.3 months, 12 patients died. Linear univariable analysis showed positive associations between PPL and small solute transport, body composition (LBMI and EWexc), comorbidities and performing CAPD (vs. cycler). PPL correlated positively with dialysate appearance rate of IL-6, but not with serum IL-6. Linear multivariable analysis confirmed positive association between PPL and EWexc (p = 0.012; 95%CI: 4.162–31.854), LBMI (p = 0.008; 95%CI: 1.720–11.219) and performing CAPD (p = 0.023; 95%CI: 4.375–54.190). In survival analysis, no relationship was found between mortality and PPL. Multivariable Cox regression showed Charlson Comorbidity Index (HR: 1.896, 95%CI: 1.235–2.913), overhydration (HR: 10.034, 95%CI: 1.426–70.587) and lower PPL (HR: 0.576, 95%CI: 0.339–0.978) were predictors for mortality. Overhydration, was a strong predictor of PPL, overpowering variables previously reported as determinants of PPL, namely clinical correlates of endothelial dysfunction or local inflammation. PPL were not associated with malnutrition or higher mortality, emphasizing the importance of volume overload control in PD patients.

Increased Peritoneal Protein Loss and Diabetes: Is There a Link?

“…The tendency for overhydration in diabetics undergoing PD can be explained by lower capacities of ultrafiltration and sodium removal compared to their nondiabetic counterparts [ 27 ]. However, irrespective of DM, there is a growing number of studies assuming that overhydration associated with increased PPCl (rather than PPCl itself) is actually a risk for increased mortality [ 12 , 28 , 29 ]. This fact is especially important in light of new studies which show that increased PPCl did not affect the development of malnutrition and sarcopenia and even led to better removal of uremic toxins of medium molecular weight [ 29 , 30 ].…”

“…However, irrespective of DM, there is a growing number of studies assuming that overhydration associated with increased PPCl (rather than PPCl itself) is actually a risk for increased mortality [ 12 , 28 , 29 ]. This fact is especially important in light of new studies which show that increased PPCl did not affect the development of malnutrition and sarcopenia and even led to better removal of uremic toxins of medium molecular weight [ 29 , 30 ]. Unfortunately, we were not able to include ECW in the analysis since the study had a retrospective character and bioimpedance assessment or NT-proBNP measurement were not routinely performed.…”

Peritoneal Protein Loss With Time in Peritoneal Dialysis

“…Gender, male (%) 58% PPL with malnutrition [3,[17][18][19]. Better nutritional status have conversely been associated with higher [3].…”

“…Mortality was not associated with higher PPL in incident PD patients in the present study, and the long-term evolution showed a reduction in protein leakage. So, PPL should be regarded as an individual characteristic, integrated in the congestive and nutritional state of the patient plus membrane transport characteristics [3], that evolves with the acquired damage to the membrane, toward reduction, without affecting global or cardiovascular mortality.…”

“…Peritoneal dialysis (PD) protein loss has been presumed to be linked with detrimental effects, such as malnutrition, inflammation, and mortality [1,2]. Studies' results were often not consistent, but recently overhydration appeared to be the major drive for higher losses, and therefore a confounder for the worse outcome associated [3,4]. Longitudinal changes in protein clearance, predominantly a reflection of hydrostatic pressure-driven leak of plasma proteins through the large-pore pathway, are less clear [5].…”