Improving Kidney Health by Targeting Urinary Biomarkers for Tubular Function

Project summary

Chronic kidney disease (CKD) affects one in ten people worldwide and is often progressive. Progressive CKD not only causes kidney failure, but also premature aging, cardiovascular disease, and loss of quality of life. Currently, progressive CKD can only be diagnosed after irreversible damage to the kidney has already occurred. There is therefore an urgent need for earlier biomarkers.

The kidney consists of filters and tubules, but diagnosis of progressive CKD is currently based on filter function alone. This is surprising, as it is tubular injury that drives CKD progression, and it is the tubule that is targeted by recently developed kidney protective treatments. U-Tube therefore aims to identify and apply next-generation biomarkers for kidney tubular function to facilitate the early detection and treatment of progressive CKD.

My central hypothesis is that the factors that cause tubular injury and CKD progression, are present in urine and therefore detectable as biomarkers. I will focus on urinary microcrystals and extracellular vesicles (EVs) as the drivers of tubular injury, which I will first study in tubuloids using a multi-omics approach. Subsequently, I will perform a large-scale analysis of crystallization and EVs in urine samples from people with stable or progressive CKD. I will then single out those biomarkers that can be targeted by kidney-protective treatment. These targetable biomarkers will be moved forward for the development of a high-throughput tubular panel that I will test for its potential to predict progressive CKD, compared to a gold standard test for tubular function.

U-Tube will use cutting-edge innovations to identify urinary biomarkers for tubular function that are targetable and implementable in clinical practice. If successful, it will advance the prediction of CKD progression, and as such redefine how we assess kidney health. By enabling early kidney-protective treatment, U-Tube has the potential to vastly improve CKD outcomes.