Millions of kidney patients stand to benefit from early diagnosis and prevention thanks to the breakthrough by scientists at the CRCHUM.

In a world first, Canadian scientists at the CRCHUM, the hospital research centre affiliated with Université de Montréal, have identified microRNA able to protect small blood vessels and support kidney function after severe injury.

For the four million people diagnosed with chronic renal failure in Canada—and millions more abroad—this scientific advancement could have a major impact on early diagnosis and prevention of the disease.

Previously, there was no known reliable biomarker for evaluating the health of these capillaries and for developing targeted approaches to preserve kidney function.

In a study published last Thursday in JCI Insight, the CRCHUM research team shows that miR-423-5p microRNA is a promising marker in the blood for predicting the microvascular health of the kidneys.

UdeM medical professors Marie-Josée Hébert and Héloïse Cardinal, holders of the Shire Chair in Nephrology, Renal Transplantation and Regeneration, co-authored the study with Hébert’s research associate Francis Migneault.

Their specialty is studying the loss of peritubular capillaries, a conclusive indicator of chronic renal failure.

Located in the kidneys, millions of these small blood vessels filter waste products out of the blood and transport the oxygen and nutrients necessary for the organ’s functions.

Kidney injuries, caused by the temporary interruption and restoration of blood flow, can lead to a decrease in the number of small blood vessels, seriously disrupting kidney function.

“In people who have received a transplant, if kidney function is severely altered, the kidney’s survival is threatened,” said Hébert, a nephrology-transplant physician and UdeM’s outgoing vice-rector for research, discovery, creation and innovation.

“Using this biomarker, a test could be developed to evaluate the status of the small blood vessels much earlier,” she said. “Doctors in hospitals could then better evaluate the microvascular health of higher-risk patients.

“These could include elderly patients or those undergoing surgeries during which blood flow is temporarily stopped, as is the case for organ transplants or cardiovascular interventions.”

Of mice and… 51 transplant recipients

“We first observed fluctuating levels of miR-423-5p microRNA in the blood of mice with acute kidney injuries,” said Migneault, the study’s first author. “These results

were then confirmed in 511 transplant recipients who participated in the CHUM kidney transplant biobank.”

Thanks to this biomarker, clinical teams could confirm whether their interventions improve or diminish the health of small blood vessels.

“But what’s really incredible is that by injecting this microRNA into mice with kidney injuries, we were able to preserve the small blood vessels and limit the damage done to the kidneys,” said Migneault.

While direct injection into the kidney is a clinically feasible method during a transplant, to protect the remaining small blood vessels, the CRCHUM scientists are now focused on alternative techniques to transport the microRNA, or likely a microRNA cocktail, to the kidney.

Potentially useful for other patients

In terms of prevention, a test based on this miR-423-5p microRNA could be useful for patients with cardiac failure, pulmonary failure or certain neurodegenerative diseases.

“For these medical conditions, the loss of small blood vessels plays a key role, because of the association with normal or accelerated aging,” said Hébert. “Our discovery could, therefore, have a significant impact on the health of all Canadians.”

For those with pulmonary failure, several research projects are in progress under Emmanuelle Brochiero, a researcher and head of the Immunopathology research theme at the CRCHUM.

It may be also be possible, using the CHUM’s biological material biobank, to determine if existing medications, administered after a kidney transplant to treat another issue, impact small blood vessel health, added Hébert.

Author: Bruno Geoffroy