Tools for diagnosing kidney disease and assessing renal function

Glomerular filtration rate (GFR) is the most accurate measure of renal excretory function, but an estimated GFR based on serum creatinine (SCr) levels is typically used, rather than the actual measured GFR (mGFR). This is mainly because obtaining the mGFR requires repeated blood and/or continuous urine sampling over a prolonged period (5-24h), which is technically challenging in preclinical models and highly inconvenient for patients. There is thus a pressing need to develop a simple method for obtaining an accurate mGFR in animals and humans.

The University of Heidelberg has developed an electronic transcutaneous device that can give an accurate indication of GFR in preclinical models by measuring the half-life of intravenously administered FITC-sinistrin non-invasively1. However, this device is not suitable for clinical use because of the limited penetration depth of FITC. To address this, a near infrared (NIR) tracer for measuring GFR and a prototype device for measuring its half-life2 has been developed in collaboration with Cyanagen. The increased penetration depth of the NIR tracers means that the device could be suitable for clinical use. In this project, we will make the further innovations required to develop the prototype device as a marketable product and will develop the mathematical tools necessary to model the clearance of NIR tracers developed.

Apart from glomerular filtration, other important aspects of renal function include proximal tubule cell (PTC) secretion and re-absorption, both of which are difficult to assess. In some pathologies, including ischemia-reperfusion injury, damage to PTCs can precede a decline in GFR, and thus, a medical device for monitoring PTC function could facilitate earlier diagnosis, and help classify the nature of the pathology. Therefore, we will develop optical sensors and NIR tracers to permit monitoring of PTC secretory and re-absorptive function. These tracers will be assessed using an in vitro bioartificial renal tubule device developed by Utrecht University3.

These step-change innovations in electronics and NIR tracers, which go beyond the current state-of-the-art, will facilitate the development of a novel electronic device and new markers for the simultaneous monitoring of mGFR and PTC function. 

A lack of effective molecular biomarkers makes it difficult to accurately diagnose and stage CKD non-invasively, and also means that monitoring disease progression and regression is problematic. To address this, Utrecht University and the University of Liverpool will develop a panel of urinary biomarkers, including urinary miRNA biomarkers, that will indicate the health/disease state of the kidney. The development of this panel of molecular biomarkers will enable us to monitor the progression and regression of kidney disease more accurately.

1. Schock-Kusch et al (2011) Kidney Int 79:1254-8
2. EU patent EP 2 944 326A 2015; US patent US2015328342(A1) 2015
3. Jansen et al (2016) Sci. Rep. 6:26715


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