Aims: Determine if mitochondrial dysfunction in adolescents with T1D contributes to an increased risk of developing DKD.

Background: Diabetic kidney disease (DKD), affecting ~1/3 of people with type 1 diabetes (T1D), is the leading cause of chronic kidney disease and kidney failure. DKD begins as early as adolescence, with the highest tertile of urinary albumin-to-creatinine ratio (uACR) predicting those at greatest future risk. This study tested the hypothesis that.

Methods: This cross-sectional cohort study recruited 100 young adults with T1D. Mean uACR was determined and the cohort was then divided into low (uACR ≤0.66 mg/mmol; n = 33), middle (uACR 0.67–1.16; n = 33) and high-risk groups for DKD (uACR ≥1.17; n = 34). Mitochondrial stress tests were performed in PBMCs using Seahorse. Flow cytometry quantified mitochondrial intensity in various blood derived T cells. Human kidney cells (PTECs) were exposed to participant serum and mitochondrial stress tests and fatty acid oxidation assays were performed using Seahorse. Mitochondrial intensity and collagen IV levels were measured using confocal microscopy and SGLT2 levels by flow cytometry.

Results: PBMCs from the high-risk group had greater mitochondrial intensities in CD3+ and CD4+/FOXP3+ T cells and lower basal and ATP-linked respiration (p < 0.05). PTECS treated with high-risk serum had higher collagen IV and SGLT2 expression (p < 0.05). PTECs also showed less ability for non-fatty acid dependent respiration compared to the cells treated with serum from low-risk patients (p < 0.0001).

Conclusion: Both the PBMCs of participants in the high-risk group and kidney cells treated with their serum demonstrated altered mitochondrial function, with serum-treated cells also having increased levels of collagen IV and SGLT2. These results may help better inform clinicians and patients regarding early risk factors for the development of DKD.