Kidney Hyperfiltration and Mitochondrial Changes Are Associated With eGFR Decline in Young People With Type 1...

To examine the relationship between kidney hyperfiltration during adolescence and subsequent changes in estimated glomerular filtration rate (eGFR) and urinary albumin creatinine ratio (UACR) in a young cohort of participants with type 1 diabetes. Additionally, to explore urinary mitochondrial DNA to nuclear DNA ratio (mtDNA:nDNA) as a marker of metabolic stress and its association with early changes in kidney function.

Eighty adolescents were studied at baseline (mean [SD] age 14.2 [1.5] years; mean diabetes duration 6.7 [3.0] years) and at follow-up 9.2 (1.3) years later. Blood pressure, HbA1c, lipids, eGFR, UACR, and heart rate variability were assessed at each visit. Urinary mtDNA:nDNA was measured by quantitative PCR.

Overall, 4.2% of participants had diabetic kidney disease at follow-up. Hyperfiltration at baseline (>135 mL/min/1.73 m2) was seen in 31% of adolescents and was associated with a decline in eGFR at follow-up when adjusted for sex, diabetes duration, and HbA1c (hyperfiltration -1.46 [3.07] mL/min/1.73 m2/year vs non-hyperfiltration -0.51 [2.48] mL/min/1.73 m2/year, P = .02). Participants with hyperfiltration also had higher odds of undergoing rapid eGFR decline (>3 mL/min/1.73 m2/year) compared to those without hyperfiltration (odds ratio 14.11 [95% CI 2.30-86.60], P = .004). Baseline urinary mtDNA:nDNA was significantly associated with both greater annual rate of eGFR decline and rapid eGFR decline in univariable but not multivariable modeling.

Hyperfiltration during adolescence is significantly associated with greater reduction in eGFR and higher risk of rapid eGFR decline after ∼9 years, following transition into young adulthood in type 1 diabetes. Urinary mtDNA:nDNA measured during adolescence may be a novel predictor of early changes in kidney function.