Project Overview

Diabetic kidney disease (DKD) is the most common form of end-stage kidney disease in Canada. Current treatments for DKD have been largely ineffective with little change in the rate of progression to end-stage kidney disease over the past 20 years so that its numbers continue to rise. DKD has a highly variable course, ranging from a kidney function (eGFR) loss from 1%/year to 20%/year. This rate of function loss cannot, however, be predicted at diagnosis.

The prevalence and rate of progression of DKD are highest among Indigenous Canadians (~8-fold higher than Canadians of European origin). Mary Beaucage, one of our patient partners, wondered whether what we call DKD in Indigenous Canadians and Canadians of European descent may not be the same disease. There is substantial evidence to support this contention in Māori peoples of New Zealand, and Aboriginal and Torres Strait Islanders in Australia. Accordingly, this will be a major focus of the current initiative.

We are working to establish a personalized medicine methodology to provide:

(i) far greater accuracy in predicting the rates of kidney function loss at first presentation.
(ii) a means of identifying responders and non-responders to specific drug treatments.
(iii) clarity as to whether what has been labelled as the same disease in Indigenous Canadians is in fact the same as that in Canadians of European ancestry once the molecular profile has been obtained. This information will assist with (i) and (ii).

This proposal takes advantage of new techniques that allow molecular analysis of archival biopsies. The resulting information is then combined with patient demographic and laboratory data in this trans-Canada initiative to develop a molecular-clinical-histological map that can greatly assist with therapeutic decision-making and prognosis. Each of the 4 sites (Vancouver, Winnipeg, Ottawa, Toronto) will provide data from 75-100 patients. Ethics committee approval has already been obtained in both Toronto and Vancouver, and our protocol is under review by the Ethics boards of our two remaining sites. Proof-of-feasibility studies have already been conducted.

Precision medicine in diabetic kidney disease

Project lead(s):

Dr. Darren Yuen, Dr. Kevin Burns

Patient lead(s):

Gwen Herrington, Mary Beaucage, Dwight Sparkes

Research theme(s):

Diabetes

Publications

  • Overexpression of the Severe Acute Respiratory Syndrome Coronavirus-2 Receptor, Angiotensin-Converting Enzyme 2, in Diabetic Kidney Disease: Implications for Kidney Injury in Novel Coronavirus Disease 2019

    Canadian Journal of Diabetes

    Gilbert RE, Caldwell L, Misra PS, Chan K, Burns KD, Wrana JL, Yuen DA

  • Renal histology in diabetic nephropathy predicts progression to end-stage kidney disease but not the rate of renal function decline

    BMC Nephrology

    Misra PS, Szeto SG, Krizova A, Gilbert RE, Yuen DA

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