Improving protein bound uremic toxin removal in hemodialysis for kidney patients by combining novel methods

Background
Patients with end-stage chronic kidney disease (CKD) undergo dialysis to replace kidney function. However, current dialysis techniques only partially replace glomerular filtration, but not tubular function of the kidney. It is extremely difficult to remove the protein-bound uremic toxins (PBUTs), due to their strong binding with plasma proteins like albumin. PBUT accumulation has been linked to the uremic syndrome, cardiovascular morbidity and cognitive function decline in CKD patients, so there is a need to develop new methods which can improve the removal of PBUTs in dialysis. There are several methods currently under study that aim to weaken the binding between albumin and PBUTs, in order to increase the removal of toxins. Among these are increased ionic strength, pH, competitive binders or adsorbents.

Project
We are studying several techniques such as elevated blood temperature (outside the body) and chemical displacers (e.g. ibuprofen and fatty acids) during dialysis to check their effectiveness in increasing the removal of toxins.

For this, we propose a hands-on MSc major research project (~9 months) in which you will test these techniques using a hemodialysis machine setup. You will use a combination of several chemical displacers and temperatures with different thermal cycles. Samples will be measured mostly using High Performance Liquid Chromatography (HPLC), while others can be performed by the UMC Utrecht Central Diagnostics Lab (CDL). Some of the tasks you can expect include preparing albumin samples with uremic toxin, learning how to use the hemodialysis machine and performing full dialysis tests (up to 4h), sample preparation and measurement with HPLC and finally data analysis of both toxin removal and sample stability.

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What should you bring

  • A background in Drug Innovation, Pharmacology, Molecular Life Sciences or related field;     
  • A proactive approach to problem solving, experiment planning and data analysis;
  • An interest and enthusiasm for research, particularly within nephrology.

What you can learn

  • Collaborate in a multi-disciplinary team with diverse backgrounds (engineering, medicine, biology)
  • Hands-on experience with building experimental setups, measurement techniques and data analysis.

Project Length
Internship/ Graduation Project (6 to 9 months)

Location
Artificial Kidney Innovation Lab, Department of Nephrology, UMC Utrecht

Have any further questions? Feel free to contact us!

Contact:

  • João Brás (J.GarciaBras@umcutrecht.nl)
  • Dr. ir. Jeroen Vollenbroek (j.c.vollenbroek@umcutrecht.nl)
  • Dr. Karin Gerritsen (K.G.F.Gerritsen@umcutrecht.nl)

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