Association of Plasma Uremic Solute Levels with Residual Kidney Function in Children on Peritoneal Dialysis

Abstract

Background and objectives. Residual native kidney function confers health benefits in dialysis patients. It can facilitate control of extracellular volume and inorganic ion concentrations. Residual kidney function can also limit the accumulation of uremic solutes. This study assessed whether lower plasma concentrations of uremic solutes were associated with residual kidney function in pediatric patients on peritoneal dialysis. Design, setting, participants, and measurements. Samples were analyzed from 29 pediatric peritoneal dialysis patients including 13 without residual kidney function and 10 with residual kidney function. Metabolomic analysis by untargeted mass spectrometry compared plasma solute levels in patients with and without residual kidney function. Dialytic and residual clearances of selected solutes were also measured by assays employing chemical standards. Results. Metabolomic analysis showed that plasma levels of 256 uremic solutes in patients with residual kidney function averaged 64 (51-81 IQR) percent of the values in patients without residual kidney function who had similar total Kt/Vurea. The plasma levels were significantly lower for 59 of the 256 solutes in the patients with residual kidney function and significantly higher for none. Assays employing chemical standards showed that residual kidney function provides a higher portion of the total clearance for non-urea solutes than it does for urea. Conclusions. Concentrations of many uremic solutes are lower in peritoneal dialysis patients with residual kidney function than in those without residual kidney function receiving similar treatment as assessed by Kt/Vurea.

The Removal of Uremic Solutes by Peritoneal Dialysis

“…Metabolomic data from anuric children treated by PD and by HD revealed no average differences in the plasma levels of solutes with molecular masses from 75 to 400 Da as detailed in Supplemental Tables 2 and 3. 59 Data for solutes with mass between 400 and 2000 Da are not available. Despite their low PD clearances, reported plasma levels of ß 2 M and cystatin C (mass 13.5 kDa) are not much higher in PD than in HD patients.…”

“…Metabolomic data from anuric children treated by PD and HD however revealed no average differences in the plasma levels of solutes with free fraction <0.2 as detailed in Supplemental Tables 2 and 4. 59…”

“…Metabolomic data from anuric children treated by PD and HD however revealed no average differences in the plasma levels of solutes with free fraction ,0.2 as detailed in Supplemental Tables 2 and 4. 59 The available data comparing solute removal by PD and HD thus present a riddle. PD provides lower clearances for both large solutes and protein-bound solutes.…”

“…Plasma levels of p-cresol sulfate and indoxyl sulfate are no higher in anuric PD patients than anuric HD patients. 59,61 Instead, the generation of these solutes is hypothesized to be lower in anuric PD patients. The extent to which other protein-bound solutes behave in the same manner has been less studied.…”

Rationale for a New Classification of Solutes of Interest in Chronic Kidney Disease and Hemodialysis

“…The current classification of uremic toxins was published in 2003 [8] and included 90 solutes that were categorized based on their molecular weight and on protein affinity. As a comparison, a report published in 2021 detected 256 retention solutes in patients with kidney failure [9]. Currently, the discovery of new retention solutes is currently guided by proteomics and metabolomics analysis.…”