Uremic Toxin Concentrations are Related to Residual Kidney Function in the Pediatric Hemodialysis Population.

Evelien Snauwaert,Bruno Ranchin,Franz Schaefer,Charlotte Samaille,Fabio Paglialonga,Saoussen Krid,Sanne Roels,Rukshana Shroff,Johan Vande Walle,Maria Van Dyck,Claus Peter Schmitt,Ann Raes,Raymond Vanholder,Els Holvoet,Michel Fischbach,Griet Glorieux,Sunny Eloot,Nur Canpolat,Varvara Askiti,Koen Van Hoeck,Laure Collard,Constantinos J Stefanidis,Nathalie Godefroid,Wim Van Biesen,Mieczysław Litwin ,Aysun Karabay Bayazıt ,Karolis Ažukaitis ,Brankica Spasojević ,Łukasz Obrycki

doi:10.3390/toxins11040235

Abstract

Protein-bound uremic toxins (PBUTs) play a role in the multisystem disease that children on hemodialysis (HD) are facing, but little is known about their levels and protein binding (%PB). In this study, we evaluated the levels and %PB of six PBUTs cross-sectionally in a large pediatric HD cohort (n = 170) by comparing these with healthy and non-dialysis chronic kidney disease (CKD) stage 4–5 (n = 24) children. In parallel β2-microglobulin (β2M) and uric acid (UA) were evaluated. We then explored the impact of age and residual kidney function on uremic toxin levels and %PB using analysis of covariance and Spearman correlation coefficients (rs). We found higher levels of β2M, p-cresyl glucuronide (pCG), hippuric acid (HA), indole acetic acid (IAA), and indoxyl sulfate (IxS) in the HD compared to the CKD4–5 group. In the HD group, a positive correlation between age and pCG, HA, IxS, and pCS levels was shown. Residual urine volume was negatively correlated with levels of β2M, pCG, HA, IAA, IxS, and CMPF (rs −0.2 to −0.5). In addition, we found overall lower %PB of PBUTs in HD versus the CKD4–5 group, and showed an age-dependent increase in %PB of IAA, IxS, and pCS. Furhtermore, residual kidney function was overall positively correlated with %PB of PBUTs. In conclusion, residual kidney function and age contribute to PBUT levels and %PB in the pediatric HD population.

Highlights

Children in end-stage kidney disease (ESKD) are facing a multisystem disease with lifelong consequences, such as frequent hospitalizations, decreased quality of life, and a short expected lifetime compared to healthy children [1,2,3]
We found higher levels of β2M, p-cresyl glucuronide, hippuric acid (HA), indole acetic acid (IAA), and indoxyl sulfate (IxS) in the HD compared to the CKD4–5 group
We described the levels of eight uremic toxins with different physicochemical characteristics affecting their behavior during HD: one small water-soluble toxin (UA), one middle molecule (β2M), and six protein-bound uremic toxins covering a wide range of protein binding

Summary

Introduction

Children in end-stage kidney disease (ESKD) are facing a multisystem disease with lifelong consequences, such as frequent hospitalizations, decreased quality of life, and a short expected lifetime compared to healthy children [1,2,3]. PBUTs have the same molecular weight as small water-soluble uremic compounds, PBUTs’ accumulation and removal are far more complex [8] Due to their protein binding (PB), only the free fraction of PBUTs can diffuse to the dialysate, and their removal is strongly limited during dialysis [8]. In addition to greater removal of these compounds, residual kidney function has been associated with beneficial effects on pediatric and adult patient outcomes: e.g., improved albumin binding affinity, less inflammation; better growth; improved volume, mineral and electrolyte control; less myocardial stunning; decreased mortality; and most importantly a better quality of life [16,17,18,19,20,21,22]. The association between growth and residual kidney function is especially relevant for the pediatric population, since growth is an important clinical outcome due to its association with quality of life, risk of hospitalization, and death [23,24]

Methods

Results

Conclusion