Markers & Mediators of Disease
The Institute continues to seek better diagnostic tools to improve the early and accurate detection of renal disease.
The development of the now patented iohexol 'finger-prick' method for a safer more convenient method of measuring true GFR offers an excellent research tool for measuring GFR in subjects with GFR greater than 60 as well as patients in locations where in-patient facilities are not available. The iohexol "finger-prick" methodology was first published in 2006 and then validated in a non-renal population with the Oxford Clinical Trials Unit in 2007. The methodology has been further refined for greater sensitivity and is currently employed in collaborative projects with groups renal groups in India.
Urinary Retinol Binding Protein (RBP). Measurement of retinol-binding protein in urine (uRBP) is arguably the most sensitive biomarker for loss of function of the human proximal renal tubule. Receptor-mediated endocytosis by the megalin/cubilin system absorbs > 99% of protein filtered by the renal glomerulus. When this fails there is "tubular proteinuria," comprising uRBP, albumin, and many other proteins. In addition to its role as a biomarker for Fanconi syndrome uRBP is also proving an excellent marker of diabetic kidney disease and CKD in general. To improve the dynamic range and the sensitivity the Institute has developed a fluorescence based uRBP assay.
K-Cadherin (Cadherin 6) is a type II classical cadherin from the cadherin superfamily. In the human kidney K-cadherin is only expressed in the proximal tubule. It is expressed basolaterally and basally.
Work from the Institute has identified that its basal expression regulates kinase activities within proximal tubule cells. We have also identified that it is released from proximal tubule cells in extracellular vesicles. The presence of full-length k-cadherin in urine from patients with diabetes is a sensitive marker of progressive renal disease in patients with eGFR < and > 60.
The Institute works closely with Hellier Scientific Ltd in assessing the validity of urinary NAG activity in the diagnosis of different forms of renal impairment. Current projects include the use of urinary NAG and RBP in patients with amyloid in collaboration with the Royal Free Hospital London, NAG in acute renal injury in collaboration with Professor Lui Forni at the University of Surrey and NAG in pre-clinical evaluation of novel therapies targeting fibrosis in collaboration with KCL.