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.
Highlights
When we prospectively evaluated mitochondrial injury using urinary mitochondrial DNA (mtDNA) copy numbers, we observed that proteinuria levels were higher in the minimal change disease (MCD) group than in the
To the best of our knowledge, this is the first study to investigate the role of mitochondrial injury in MCD pathogenesis and stimulator of interferon genes (STING) pathway activation in GN
Since urinary mtDNA levels are one of the most validated surrogate markers for mitochondrial injury in the kidney, and its clinical usefulness has been established in various kidney diseases [17,18,22,23,27], we used it to confirm that mitochondrial injury is involved in the MCD pathogenesis
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Minimal change disease (MCD) is the cause of nephrotic syndrome in approximately. T-cell dysregulation has been proposed as a major contributor to podocytopathy [3,4,5], and the effectiveness of B-cell depletion therapy suggests B-cells role as drivers of disease [6,7]; MCD pathogenesis remains unknown. Corticosteroid (CS) treatment is the first-line treatment for patients with MCD and is often effective [8], the mechanism is unclear, and response patterns vary between patients. The overall steroid responsiveness rate approached 70% to 90% after 12 weeks of treatment [9,10,11].
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
