New blood marker can predict individuals most at risk of kidney failure
In a study published recently in Nature Communications, Dr Laura Denby and collaborators at the University of Edinburgh and Queen’s University Belfast, with funding from Kidney Research UK, have discovered a new biomarker in the blood for chronic kidney disease (CKD). This marker identified patients at a higher risk of faster chronic kidney disease progression, which in the future could be used to inform earlier interventions to help protect kidney health.
What are the tests for kidney function?
CKD is usually diagnosed with a blood test, to measure the level of creatinine, and a urine test, to look at the level of protein. Higher levels of these markers suggest reduced kidney function, which is used to identify the stage of CKD and inform any interventions, such as lifestyle changes, medications, dialysis and transplant.
What is microRNA?
MicroRNAs (miRNAs) are small molecules that are guardians of whether or not certain proteins are made from the instructions contained in our DNA. They are found throughout the body, including in the kidneys.
Better tests are needed to identify patients at risk of CKD progression
For patients with CKD, normal levels of creatinine in the blood and low protein in the urine can indicate that their kidneys appear to be working well and their risk of disease of progression low. However, CKD has many different causes and will affect patients differently.
Some patients with CKD can have no or little protein in their urine but still go on to lose kidney function and in some cases reach kidney failure. By identifying these at-risk patients early, this new biomarker could support the most appropriate treatments for their long-term kidney health.
Blood microRNA predicts CKD progression
Laura and the team began by looking at the genes expressed in blood samples of 33 patients with type 2 diabetes. They found a specific type of microRNA, called miR-190a-5p, was lower in patients who had worse kidney function.
By testing the levels of this miRNA in a larger group of 298 patients with CKD, they were able to identify lower levels in patients with worse kidney function, this time due to a variety of causes. When they followed up these patients around four years later, they found that amongst patients who would normally be considered at low risk of CKD progression as they had a low or medium level of protein in the urine, those with a lower miR-190a-5p blood level, had an increased risk of CKD progression, with some patients reaching kidney failure by this time.
Laura and her collaborators then went on to look at where miR-190a-5p is found and what role it could have in the kidney. By examining 24 biopsy samples they could look at how much miR-190a-5p was present in the kidney. They found that lower levels were seen in biopsy samples with more scarring and fewer/smaller tubules (tiny tubes important for producing urine in the kidney). Using a laboratory model they found restoring the levels of miR-190a-5p in kidney injury both reduced scarring and improved kidney health.
What could this mean for patients?
This new blood marker could in the future help healthcare providers to identify patients with a high likelihood of CKD progression, who may not be identified using current kidney function tests.
This could mean more regular monitoring, and earlier interventions for these patients, such as medications to try and protect kidney health and slow the progression of CKD.
In the longer term, therapies could be developed to restore the level of miR-190-5p in the kidneys of patients with CKD which may reduce renal scarring and preserve kidney function.
“This research has been supported by Kidney Research UK throughout its journey, from discovery of this microRNA molecule in the lab, to translating this into patients.
"My interest in miRNAs goes back to my post-doctoral fellowship, and the CKD patient samples used in this study came from seNSOR, both of these projects as well as my senior fellowship were funded by Kidney Research UK.
"We’re now at the stage where these results could inform better testing for CKD and improve things for patients which is why I do the research I’m doing.
"I am very grateful to Kidney Research UK’s supporters for making this possible.” Dr Laura Denby
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