Abstract

The retention of a number of solutes that may cause adverse biochemical/biological effects, called uremic toxins, characterizes uremic syndrome. Uremia therapy is based on renal replacement therapy, hemodialysis being the most commonly used modality. The membrane contained in the hemodialyzer represents the ultimate determinant of the success and quality of hemodialysis therapy. Membrane’s performance can be evaluated in terms of removal efficiency for unwanted solutes and excess fluid, and minimization of negative interactions between the membrane material and blood components that define the membrane’s bio(in)compatibility. Given the high concentration of plasma proteins and the complexity of structural functional relationships of this class of molecules, the performance of a membrane is highly influenced by its interaction with the plasma protein repertoire. Proteomic investigations have been increasingly applied to describe the protein uremic milieu, to compare the blood purification efficiency of different dialyzer membranes or different extracorporeal techniques, and to evaluate the adsorption of plasma proteins onto hemodialysis membranes. In this article, we aim to highlight investigations in the hemodialysis setting making use of recent developments in proteomic technologies. Examples are presented of why proteomics may be helpful to nephrology and may possibly affect future directions in renal research.

Highlights

  • Uremia is a clinical syndrome resembling systemic poisoning [1], characterized by a variety of clinical symptoms that develop and worsen as kidney failure proceeds, due to the retention of various solutes, which are normally excreted by the kidney, called uremic toxins

  • Hemodialysis (HD) is by far the most commonly used modality for chronic renal replacement: more than 1.7 million patients are currently treated with HD worldwide, a number that is growing at a rate of approximately six-to-seven percent annually

  • Carbonylation of fibrinogen may be involved to the impaired clotting activity found in patients on HD [47]; carbonylation of ceruloplasmin and haptoglobin can impair the antioxidant properties of those proteins [48,49]; accumulation of advanced glycation end products (AGEs) may be a pathogenetic factor for low bone turnover [50]; oxidative alteration of albumin may adversely affect its vasculoprotective effects [39,51]; carbonyl stress may contribute in the pathogenesis of alteration in left ventricular geometry and function [46]; and, carbonylated albumin may play a role in the early atherogenic events of chronic uremia by directly damaging the endothelium [41]

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Summary

Introduction

Uremia is a clinical syndrome resembling systemic poisoning [1], characterized by a variety of clinical symptoms that develop and worsen as kidney failure proceeds, due to the retention of various solutes, which are normally excreted by the kidney, called uremic toxins. The principal aim of renal replacement therapies is the removal of uremic toxins, targeted at an improvement in quality of life and survival. ATnhdesreeparnoadlyusceibslaer,ehmoworeevecronthveeynipernotvaindde mreoplreocduulacribinlef,ohrmowateivoenratthtehyeppreopvtiiddeemleovleelcounlalyr,itnhfuorsmsuabtitolen daetfithneitipoenpotfidspeelceivfieclpornoltye,inthisuosfosrumbstleavdaeilfainbilteioinnthofe s2pDeEciifsicofpternotmeiinssiisnogf.oMrmosrearveacielanbtllye, tihnetdheefi2nDitEioins oofftteonp-mdoiswsinngst.raMteogrieesreincehnitglyh,rtehseoludteifoinniLtiCon-MoSf/tMopS-deoxwpenrimstreantteagliseest iunphiisgphrorvesidoliungtioanneLwC-gMroSu/MndS to define the specific proteoforms and their tentative association with specific biological states. These newly developed MS techniques have been successfully applied to research in uremic toxicity, with the discovery of novel uremic toxins and the potential to define a precise molecular approach to defining the biochemical nature of uremia. Proteomic investigations associate genomic information with functional insight into the mechanisms involved in the interactions between the artificial membrane material and blood, providing the basic knowledge for generation of third-generation HD biomaterials.

Dialytic Solute Removal
Proteomic and Uremic Toxicity
Characterization of Uremic Toxins
Characterization of Protein Damage Products
Other Investigations
Proteomic and Extracorporeal Blood Purification
Hemodialysis
Other Blood Purification Strategies
Proteomics and Protein Adsorption onto Dialysis Membrane
Findings
Conclusions
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