Validation of novel non-invasive diagnostic and prognostic methods in chronic kidney disease and kidney transplantation

Abstract

There is an emerging need to accurately detect chronic kidney disease (CKD) at an early stage so timely intervention can be implemented to optimize clinical outcomes. There remains a critical unmet requirement to develop non-invasive methodologies for early CKD diagnosis and prognostication. Using human urine samples, our group developed novel approaches based on indirect immunomagnetic extraction of urinary exfoliated proximal tubule cells (PTCs), to assess if urinary exfoliated PTCs can be assessed as an approach to inform CKD severity; and whether CKD staging and progression can be determined by utilizing multispectral autofluorescence in exfoliated PTCs. We have also assessed cell-free urine samples to evaluate their urinary volatile organic compound profiles and demonstrated this could potentially be applied as a novel metabolomic biomarker to assess CKD progression.

In the scenario when CKD progresses to kidney failure, patients may elect to receive kidney replacement therapy in the form of dialysis or kidney transplantation. Although kidney transplantation is often the preferred option of treatment for kidney failure, optimal outcomes following kidney transplantation may be challenged due to various post-transplant complications. There is no strongly validated method apart from transplant kidney biopsy which can definitively predict the cause of delayed or deteriorating graft function currently. Hence, there is also an unmet need for accurate non-invasive diagnostic approaches to identify the cause of kidney dysfunction following transplantation. This thesis also provides novel proof of concept data supporting the application of urinary exfoliated PTCs multispectral autofluorescence to non-invasively differentiate between individuals with different causes of kidney transplant dysfunction.