Longitudinal Study of Small Solute Transport and Peritoneal Protein Clearance in Peritoneal Dialysis Patients

Abstract

SummaryBackground and objectives Peritoneal protein clearance (Pcl) is determined by both effective (small pores) membrane area and relative capillary leakiness (large pores). It is not known how these two components change with duration of peritoneal dialysis (PD) in the context of progressive membrane injury and differential attrition of patients with higher Pcl, which has been associated with increased mortality risk in several studies.Design, setting, participants, & measurements Patients treated continuously from 2000 to 2011 for a minimum of 4 years were selected from the longitudinal prospective Stoke PD Study. Pcl, membrane area (peritoneal solute transport rate [PSTR]), dialysis prescription, and residual renal function were measured every 6 months, along with comorbidity and peritonitis events. Multilevel multivariate analysis was used to determine associations with Pcl over time, taking into account within-subject correlations.Results From 280 incident patients, 335 datasets were analyzed from 49 patients receiving treatment for 4 years. Pcl correlated with PSTR at baseline (R=0.61; P,0.01), but over time there was progressive uncoupling of this relationship (year 4, R=0.28; P=0.05) with increasing PSTR (0.66-0.74; P,0.01) and stable Pcl (78.4-81.9 ml/d; P=0.7). Multivariate analysis found that age, PSTR, daily ultrafiltration, and sodium removal were significant predictors of Pcl when adjusted for sex, comorbidity, glucose exposure, and residual renal function. Peritonitis was associated with increased PSTR but a similar pattern of uncoupling. ConclusionThere is a progressive dissociation of the small-and large-pore pathways with time on PD, which would be in keeping with a switch from local inflammation early on to progressive fibrosis, combined with increased vascular surface area. Measuring longitudinal changes in Pcl may complement membrane function tests used to monitor progressive injury.

Does Peritoneal Protein Transport Increase with Peritoneal Dialysis Therapy Duration and Lead to Extracellular Water Overload in Peritoneal Dialysis Patients?

“…One explanation for this could be that local mediators affect both the small and large pore permeability in the peritoneum. Changes in permeability would be expected to lead to an expansion in ECW, rather than expansion in plasma volume , and as such would lead to reports of both increased peritoneal protein and creatinine transport being linked to PD technique failure and patient mortality . However, we found no association between peritoneal protein transport and ECW excess over time.…”

Peritoneal Fluid Transport rather than Peritoneal Solute Transport Associates with Dialysis Vintage and Age of Peritoneal Dialysis Patients

“…In the current study, fluid transport parameters correlated with the age of the patients and dialysis vintage (though these two factors were not correlated), but in general no such dependency was observed for the transport of small solutes and proteins (Tables 1 and 2 ). In our cross-sectional study we did not find any consistent increase in small solute transport with dialysis vintage (except for urea PS, Table 2 ) that was observed in a few previous cohort studies [ 30 – 37 ]. The relations of fluid transport with patient age and dialysis vintage were similar suggesting that the time on PD had a similar effect on the peritoneal tissue transport system as patients' age.…”

“…Recently, detailed mechanistic analyses of peritoneal changes during long-term PD were presented shedding light on underlying alterations in the pore system [ 35 ] although some indirect information was discussed previously [ 31 ]. In contrast, data on changes related to patients' age are scarce [ 37 – 39 ].…”

An Open, Randomized, Single-Center, Crossover Pharmacokinetic Study of Meropenem after Intraperitoneal and Intravenous Administration in Patients Receiving Automated Peritoneal Dialysis

“…However, it should be emphasized that in the present study, only patients with chronic PD treatment were included. It was shown that ongoing exposition of the peritoneum to peritoneal dialysis fluid leads to changes of intraperitoneal blood flow and permeability (18). It is noteworthy that one patient enrolled in the present study demonstrated an intraperitoneal C max after i.v.…”