Last Month's Most Accessed Feature: Dialysis membranes: Adsorbed proteins

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  • Published: Oct 3, 2017
  • Categories: Proteomics & Genomics / Proteomics
thumbnail image: Last Month's Most Accessed Feature: Dialysis membranes: Adsorbed proteins

Hemodialysis

The effects of protein adsorption on two types of hemodialysis membrane have been studied by Chinese scientists to identify the unwanted biochemical reactions that occur in an effort to design more efficient membrane materials.

Image: US Department of Veteran Affairs

Patients who are suffering from chronic kidney disease often develop the additional complication of uremia, in which urea and other toxic products build up in the kidney, rather than being eliminated as in healthy people. CKD is indicated by symptoms such as nausea, vomiting, fatigue, anorexia and weight loss but, as the disease progresses, more serious factors arise like the onset of spontaneous bleeding, seizures, coma and cardiac arrest. Eventually they may lead to death.

End-stage renal disease is the last stage of CKD before the kidneys fail and 58% of sufferers who reach that stage live in just five countries: the United States, Japan, Germany, Brazil and Italy. It has been estimated that ESRD will affect more than 750,000 Americans by 2020. The prognosis for patients with ESRD is poor unless their uremia is treated with renal replacement therapy, such as dialysis or transplantation. There is no cure.

However, dialysis is not without its complications. The main purpose is to filter the blood through dialysis membranes to remove these toxic compounds that have accumulated in the kidneys but high-molecular-weight toxins such as β2-microglobulin and tumor necrosis factor-α are not removed by low-flux membranes. High-flux analysis with membranes of large pore size are required to accomplish this. Nowadays, high-flux membranes are the norm.

When proteins are deposited on the membranes, they can induce unwanted biological processes. It has been recognised that the coagulation pathway and activation of the complement system can both be affected in this way, leading to potential problems for the patient such as insulin resistance, coronary heart disease and disorders in lipid metabolism.

Low-flux and high-flux membrane comparison

A number of studies have been reported that compare the adsorption of proteins on dialysis membranes of different compositions but scientists in China noted that there have been very few comparisons of adsorption on membranes of the same material. So Lihua Zhang, Jiuyang Zhao, Shuai Han, Kaiguang Yang, Jingdi Sun and Jianhui Liu from the National Chromatographic Research and Analysis Center, Dalian, and The Second Affiliated Hospital of Dalian Medical University, compared the performances of two Polyflux dialysers using proteomics techniques to identify the trapped proteins.

Two patients who were undergoing regular hemodialysis were treated with machines containing Polyflux 140H and 14L which are high-flux and low-flux materials, respectively. After treatment, the adsorbed proteins were desorbed with an ionic liquid before being solvent-exchanged into phosphate-buffered saline to allow them to be digested with trypsin.

The resulting peptides from the high- and low-flux membranes were isotope labelled with a light or heavy reagent so that they could be distinguished when they were mixed together and analysed by liquid chromatography-tandem mass spectrometry. After identifying the precursor proteins from the peptide data and comparing the abundances, the proteins fell into three distinct groups.

Coagulation and complement pathways affected

From a total of 668 proteins that were identified, 177 were preferentially adsorbed by the high-flux membrane, 320 by the low-flux membrane and 171 showed no clear differences in retention behaviour. Proteins of molecular mass 10-15 kDa tended to be adsorbed on the high-flux membrane with those of 30-90 kDa on the low-flux material. This might be expected as the larger proteins are more easily trapped on the membrane with the smaller pore size.

There was also a differential in the isoelectric points of the proteins on the membranes. The overall pI range was 4-11 but 42 and 38% of the pI values of 5-7 and 8-10, respectively, were more selectively retained on the high-flux membrane. Conversely, 57 and 16% of the pI values of 5-7 and 8-9, respectively, were preferentially adsorbed on the low-flux membrane. Knowledge of the individual properties of the adsorbed proteins like the pI and molecular mass will help in the future modification of dialysis membranes.

A closer look at the proteins revealed that they fell into different classes, with eight classes differing in abundance between the two membranes. The proteins were also associated with different biological processes. For instance, complement C4, MASP1 and MASP2, which are key proteins for activation of the complement system, were more strongly retained on the low-flux membrane. Other complement proteins (C6, C7, C8) were preferentially retained on the high-flux membrane. These variations might affect hemodialysis efficiency.

In a similar manner, proteins involved in coagulation were more adsorbed on the low-flux membrane but fibrinogen proteins were more adsorbed on the high-flux protein. These are associated with the formation of fibrin and cause blood clots, which could explain the need for higher doses of anticoagulation drugs for patients on high-flux dialysis.

Although the study is very limited, having low samples numbers and no calculation of the actual protein concentrations, the data will be useful for the development of more efficient dialysis membranes which will benefit hemodialysis patients.

Related Links

Proteomics – Clinical Applications 2017, online: "Proteomics Investigations into Serum Proteins Adsorbed by High-Flux and Low-Flux Dialysis Membranes"

Article by Steve Down

The views represented in this article are solely those of the author and do not necessarily represent those of John Wiley and Sons, Ltd.

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