A Risk Uncovered

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Researchers have uncovered why only a subset of diabetic patients develop kidney disease.
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Because there are no obvious symptoms for kidney disease, long-term diabetic patients must be constantly monitored for worsening kidney function.
Almost one in every two Canadians with diabetes will develop kidney disease, a leading cause of illness and death. A new study by Drs. David Cherney, Julie Lovshin and Bruce Perkins (Toronto General Hospital Research Institute) has shed light on why this is the case by identifying one of the factors that influence the progression of kidney disease in diabetes patients.
Higher than normal blood sugar levels, which are often observed in patients with diabetes, can damage the small blood vessels within the kidney. These fine blood vessels are critical for the organ’s ability to function and to filter out toxins from the body. When these vessels become compromised, serious complications can arise, including the accumulation of toxins in the body, high blood pressure and even heart failure.
In the study Drs. Cherney, Lovshin and Perkins explored the activation of a pathway—known as the renin-angiotensin-aldosterone system (RAAS)—that plays a role in kidney function. Persistent activation of the RAAS system has been linked to kidney disease and medications that block the RAAS can prevent kidney dysfunction.
The researchers looked at the effect of giving RAAS hormones to three groups of study participants: healthy individuals, those with long-term diabetes and those with long-term diabetes and signs of kidney damage. They then looked at changes in kidney function to determine how the participants had responded to the RAAS hormone activation.
They found that individuals with diabetes, but no signs of kidney failure, had comparable RAAS activity to healthy nondiabetic patients. In contrast, individuals with diabetes that showed signs of kidney disease had higher levels of RAAS hormone activity in the arteries that supply blood to the kidney. This response to RAAS hormone activation suggested that the microscopic arteries that supply the kidney—called glomeruli—may play an important role in kidney disease development. 
“These observations strongly suggest that RAAS activation could be an important marker for kidney dysfunction, especially in patients with long-term diabetes” explains Dr. Cherney. “Importantly, it suggests that other available methods for modifying RAAS activity may be required for a subset of patients. Further research is required to identify new medications that act at the inflow arteries in the kidney to lower pressure and strain on kidney glomeruli.”
This work was supported by JDRF and the Toronto General & Western Hospital Foundation.
Lovshin JA, Boulet G, Lytvyn Y, Lovblom LE, Bjornstad P, Farooqi MA, Lai V, Cham L, Tse J, Orszag A, Scarr D, Weisman A, Keenan HA, Brent MH, Paul N, Bril V, Perkins BA, Cherney DZ. Renin-angiotensin-aldosterone system activation in long-standing type 1 diabetes. JCI Insight. 2018 Jan 11. doi: 10.1172/jci.insight.96968