Patients with malfunctioning kidneys often need dialysis to rid their blood of unwanted molecules and excess water. Personalizing the settings of dialysis for each patient is crucial for their health, but it is complicated and error-prone. A group of Viennese scientists was awarded a competitive grant from the Vienna Science and Technology Fund to develop a precision medicine approach to dialysis treatment.
Our blood carries vital oxygen and nutrients to each of our organs, and transports by-products and toxins that the body needs to eliminate to the kidneys. The kidneys divert unwanted molecules and excess water to the bladder, from where they exit the body via urine.
Conditions such as diabetes and hypertension can cause kidneys to weaken or fail, thereby leading the body to accumulate toxic compounds and to produce less urine. Patients whose kidneys malfunction need their blood to be cleaned artificially through dialysis, which removes a set quantity of water and the unwanted compounds from the blood.
"Some dialysis patients cannot urinate at all and rely entirely on machines to regulate their level of hydration, which limits the amount of water they can drink and makes their lives very difficult," says Peter Pichler, a physician and proteomics specialist involved in the project. "Excess water in the blood needs to be removed, or patients may develop symptoms linked with overhydration and live shorter lives."
The nephrologist's ultimate goal is to find the right dialysis setting for each patient at any given time: how much water should be withdrawn from the body to keep the patient healthy? Adjustments are often based on a handful of variables and noticeable symptoms that only give a blurry picture of the patient's body fluids. As a result, dialysis follows an imprecise one-size-fits-all approach.
A group of scientists at the Vienna BioCenter, the Medical University of Vienna, and the Austrian Institute of Technology were recently awarded four years worth of funding by the Vienna Science and Technology Fund (WWTF) to research ways of improving and personalizing dialysis care.
Crossing disciplines to fine-tune dialysis
Ideally, one dialysis session would generate data about the patient's blood volume and composition that can be used to adjust the next session automatically, so that treatment changes dynamically at every session without a doctor's subjective input."
Manfred Hecking, Project Leader and Professor, Medical University of Vienna
Determining the optimal dialysis settings for a given patient requires a lot of experience and is often based on trial-and-error. Oftentimes, the settings do not progress as the patient's body changes.
"We want to transform the way dialysis is done and take some pressure off of clinicians with more rigorous practices," says Siegfried Wassertheurer, project leader and senior scientist at the Austrian Institute of Technology. "The idea is to orchestrate dialysis with a combination of clinical data and other measurements like the patient's absolute blood volume, body composition, and some of the proteins that are filtered out during dialysis." Combining data from a variety of sources would help customize dialysis for each patient at every session.
Proteins could give the beat
In collaboration with the Vienna General Hospital (AKH), the scientists will collect and analyze hundreds of dialysis and urine samples from patients.
"Our project aims to exploit an untapped source of information: the proteins that end up in the residual urine of dialysis patients versus in their dialysate," says Karl Mechtler, project leader and Head of Protein Chemistry, a service facility at the Vienna Biocenter. "Urine is the easiest body fluid to obtain, yet few have looked into its composition with a proteomics approach, and how it can inform dialysis."
The researchers' goal is to compare the protein composition of the fluids removed during dialysis to that of healthy urine, in diabetic and non-diabetic patients. "We'd like to know which proteins are eliminated during dialysis, and at some point, which proteins differ between the residual urine of diabetic and non-diabetic dialysis patients," says Manfred Hecking. "Some of these proteins could make a vital difference for care and we need to know which ones to filter out to give patients a healthier life."