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Role of Kidney Injury Molecule-1 in the Acute Kidney Injury to Chronic Kidney Disease Transition

Dr. Lakshman Gunaratnam, M.D.
The University of Western Ontario
Kidney Health Research Grant
2020 - 2022
Renal Failure

Lay Summary

In acute kidney injury, decreased blood flow, medication toxicity, or other causes suddenly damage the kidneys. While most people with acute kidney injury will eventually recover kidney function, some can develop chronic kidney damage and scarring, and would eventually need dialysis. Methods to predict who will recover and who will develop chronic kidney disease are imprecise. Moreover, there are no effective treatments to prevent the transition from acute to chronic damage. 

Dr. Gunaratnam will study the molecular mechanisms behind the transition from acute kidney injury to chronic damage. This knowledge will help us develop interventions to prevent end-stage kidney failure after an episode of acute kidney injury.

His team has identified a molecule called “Kidney Injury Molecule-1” (KIM-1) that would be critical for the body to repair damage during the first few weeks of acute kidney injury. However, preliminary data suggests that if KIM-1 remains “on” for prolonged periods of time – for example, when the acute kidney injury is very severe – KIM-1 can paradoxically lead to fibrosis (scarring) of the kidney and cause chronic kidney disease. They have found that KIM-1 activates a gene called TBX-1 after severe acute kidney injury and they suspect TBX-1 is involved in kidney scarring. In this study, they will confirm that TBX1 is responsible for causing kidney scarring after severe acute kidney injury; verify that TBX-1 is a key factor activated by KIM- 1 and test a previously unknown treatment strategy to prevent kidney scarring in severe kidney injury. This work will greatly increase our understanding of processes that cause chronic kidney disease after severe acute kidney injury and potentially identify an effective treatment.