22 July 2019

Mechanism for expelling waste identified

New opportunities for treating kidney failure

Our kidneys can sense when we need them to work a bit harder. As the intestines begin to produce more waste products, the kidneys start to work harder to excrete it. Researchers at, among others, Utrecht University and University Hospital Leuven published an article on this process in PNAS on July, 22. Insight into this mechanism could lead to new treatments for kidney failure. 

Kidneys filter waste products from the blood, and they can increase their filtering activity when necessary. But until now, scientists had not known exactly how this mechanism worked. The research group led by Roos Masereeuw has now shown that certain kidney cells have receptors that can observe higher concentrations of waste products. The group then identified how this observation stimulates the production of a transport protein, which results in increased excretion of the waste substances. 

New treatments for kidney failure

According to Prof. Masereeuw, insight into this mechanism could lead to new treatments for kidney failure. This is because the mechanism plays a vital role in stimulating the excretion of waste; a process that fails in kidney disease. “By hijacking that mechanism, we think that we might be able to treat early-stage kidney failure”, Masereeuw explains. “We are going to continue to study how we can manipulate that process.”

Made possible by artificial kidney tubules

One of the steps towards identifying this mechanism involved using artificial kidney tubules, that Masereeuw had previously developed together with other researchers. This allowed the group to study which receptors and signalling molecules are involved in monitoring the waste products produced by the gut and in regulating the transport proteins that facilitate their excretion in urine.

Successful partnership with Metabolomics

During this study, Masereeuw’s research group worked closely together with the group led by Celia Berkers, Professor of Metabolomics at the Faculty of Veterinary Medicine and the Faculty of Science’s Chemistry department. The researchers were very positive about the partnership: “We gradually began collaborating more over time, because we wanted to learn more about cellular processes. We’ve since found that it’s a successful combination of both fields, because our knowledge and expertise complement one another.” 

Publication

Title: Remote sensing and signaling in kidney proximal tubules stimulates gut microbiome-derived organic anion secretion

Authors: Jitske Jansen, Katja Jansen, Ellen Neven, Ruben Poesen, Amr Othman, Alain van Mild, Joost Sluijter, Javier Sastre Torano, Esther A. Zaal, Celia R. Berkers, Diederik Esser, Harry J. Wichers, Karin van Ede, Majorie van Duursen, Stéphane Burtey, Marianne C. Verhaar, Björn Meijer, en Rosalinde Masereeuw.

PNAS July, 22 2019, DOI: 10.1073/pnas.1821809116