PracticeUpdate: Conference Series | ADC 2018

Is Targeting Mitochondrial Dysfunction Worth Considering as a Prevention Strategy for Kidney Disease in T1D?

This possibility was raised after young adults with T1Dwho presented with early kidney damage also

had defects in themitochondria. BY THE PRACTICEUPDATE EDITORIAL TEAM

Y oung adults with type 1 diabetes (T1D) at high risk for diabetic kidney disease (DKD) and cardiovascular disease (CVD) have been found to have mitochondrial dysfunction and other factors suggestive of early chronic kidney disease. This raised the question of whether addressing mitochondrial dysfunction could form part of a strategy to prevent DKD in patients with T1D. Current evidence suggests that DKD and CVD develop early in diabetes, and it’s the young adults in the highest tertile of the urine albumin/creatinine ratio (uACR) who are at greatest risk. And while there is evidence of dysfunctional mitochondria late in DKD, Josephine Forbes, PhD, Program Leader in Chronic Disease at Mater Research Institute–The University of Queensland in Brisbane investigated if this was the case in early kidney disease. Among young adults with T1D, her team found that those at high risk for DKD and CVD – patients with uACR ≥1.17 – had persistent elevations in uACR since their diabetes diagnosis. And while almost all the patients (99.7%) presented with hyperfiltration (CKD EPI eGFR, 135.0 [13.8] mL/min/m 2 ), it was the high-risk patients who had the highest median eGFR (P<.031 vs low-risk patients), even after adjustment for age, gender, and diabetes duration. This cross-sectional study recruited 100 young adults with T1D. Patients were on average 20 years of age, similar proportion of female to male participants, HbA1c of 12.3 mmol/L, diabetes duration of 10.7 years, and BMI of 24.5 kg/m 2 . Patients were divided into three uACR tertiles: low-risk (uACR ≤0.66 mg/mmol; n=33), medium-risk (uACR 0.67–1.16; n=33), and high-risk (uACR ≥1.17; n=34) for DKD and CVD. Professor Forbes and colleagues also found that mitochondrial function in circulating leukocytes was lower in high-risk patients compared with the low- and medium-risk groups (P=.008). The high-risk patients also had characteristics of early chronic kidney disease, including elevated circulating kidney injury molecule-1.

" This early evidence of mitochondrial

dysfunction and early kidney damage in "at risk" 15- to 25-year-olds with T1D, may provide a novel target for therapies to prevent progression to overt DKD and lower risk for future CVD. "

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