Minimal Change Disease Is Associated with Mitochondrial Injury and STING Pathway Activation

Abstract

We hypothesized that minimal change disease (MCD) pathogenesis may be associated with mitochondrial injury, and that the degree of mitochondrial injury at the time of diagnosis may serve as a valuable prognostic marker. We compared urinary mitochondrial DNA (mtDNA) at the time of diagnosis in patients with MCD and age- and sex-matched healthy controls (MHC) (n = 10 each). We analyzed the site and signal intensity of immunohistochemical (IHC) staining of stimulator of interferon genes (STING) using kidney tissues at the time of diagnosis in patients with MCD. Patients with MCD were divided into high (n = 6) and low-intensity (n = 14) subgroups according to the signal intensity. Urinary mtDNA levels were elevated in the MCD groups more than in the MHC group (p < 0.001). Time-averaged proteinuria and frequency of relapses during the follow-up period were higher in the high-intensity than in the low-intensity subgroup (1.18 ± 0.54 vs. 0.57 ± 0.45 g/day, p = 0.022; and 0.72 ± 0.60 vs. 0.09 ± 0.22 episodes/year, p = 0.022, respectively). Mitochondrial injury may be associated with MCD pathogenesis, and the signal intensity of STING IHC staining at the time of diagnosis could be used as a valuable prognostic marker in MCD.

Roles of Mitochondrial DNA Damage in Kidney Diseases: A New Biomarker

“…Therefore, urinary mtDNA may be considered a valuable biomarker for determining the development of AKI and mitochondria-targeted therapy following sepsis-induced AKI [ 70 ]. Compared to healthy controls, the expression of STING in kidney was increased and urinary mtDNA levels were elevated in minimal change disease (MCD) patients, which could be used as a valuable prognostic marker in MCD [ 71 ]. Urinary mtDNA levels were significantly elevated in both diabetic patients and mice, which was negatively correlated with glomerular filtration rate and positively correlated with interstitial fibrosis [ 63 , 72 ].…”