Study Shows Altered Mitochondrial DNA Changes Precede Bioenergetic Dysfunction in Diabetic Nephropathy

Results from a recent study published in the journal EBioMedicine showed that altered mitochondrial DNA changes precede bioenergetic dysfunction and that patients with diabetic nephropathy (DN) have impaired mitochondrial metabolism compared to kidney disease. The results indicate that systemic mitochondrial dysfunction initiated by glucose induced altered mitochondrial DNA damage may be involved in the development of DN.

In the study titled “Altered Mitochondrial Function, Mitochondrial DNA and Reduced Metabolic Flexibility in Patients With Diabetic Nephropathy,” Anna Czajka and colleagues aimed to determine if mitochondrial dysfunction plays a role in diabetic nephropathy (DN), a kidney disease which affects > 100 million people worldwide and is a leading cause of renal failure despite therapy.

Mitochondrial dysfunction can affect key cellular functions and result in a variety of diseases, as altered mitochondrial DNA (MtDNA) levels have been reported in a wide range of human diseases.

Diabetes results in increased risk of numerous other complications that affect major organs, including the eyes (retinopathy), heart (diabetic cardiomyopathy), blood vessels (peripheral vascular disease) and brain (dementia). The multi-organ impact of diabetes complications resembles mitochondrial genetic disease and suggests a systemic dysfunction in the body.

For the cross-sectional study, the researchers compared 3 groups of subjects: healthy controls (HCs, n = 39) were volunteers with no history of any disease, diabetes controls (DCs, n = 45) comprised of patients with ≥ 20 years diabetes duration, normal renal function and no history of albuminuria, and diabetic nephropathy patients (DN, n = 83) with a history of or current albuminuria.

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Peripheral blood mononuclear cells (PBMCs) from patients were used as surrogates as various parameters associated with DN can be detected in these cells. The results showed that the PBMCs from DN patients had reduced reserve capacity and maximal respiration, loss of metabolic flexibility and reduced Bioenergetic Health Index (BHI) compared to DC. Based on the results, the researchers suggested that metabolic dysfunction can be detected in peripheral blood samples of patients with DN.

Using renal cells in-vitro, the researchers determined that hyperglycemia affects mitochondria, with MtDNA levels changing before other indicators of mitochondrial dysfunction. According to the researchers, the results indicate that the BHI formula can indicate mitochondrial dysfunction in live PBMCs from patients, and therefore could be developed into a non-invasive translational measure of mitochondrial function.