#2853 MITOCHONDRIAL DNA DEREGULATED PATTERN PARALLELS INFLAMMATION IN EARLY DIABETIC KIDNEY DISEASE OF TYPE 2 DIABETES MELLITUS PATIENTS

Abstract Background and Aims Mitochondrial DNA (mtDNA) abnormalities, as well complex inflammatory processes involved in the pathogenesis of DKD may be detected early course DKD. The aim study was to evaluate a potential relation mtDNA modifications blood urine with podocyte injury proximal tubule (PT) dysfunction type 2 diabetes mellitus (DM) patients. hypothesis according which changes related specific response normoalbuminuric DM patients also questioned. Method A total 150 [52 normoalbuminuria, 48 microalbuminuria, 50 macroalbuminuria)] 30 age- gender-matched healthy controls were enrolled this case series study. All assessed concerning urinary albumin/creatinine ratio (UACR), biomarkers damage (synaptopodin, podocalyxin) PT (kidney molecule-1-KIM-1, N-acetyl-D-glucosaminidase-NAG), serum interleukins (IL-17A, IL-18, IL-10), eGFR (creatinine-cystatin C). MtDNA-CN nuclear (nDNA) quantified peripheral by qRT-PCR (ABI 7900-HT–Applied BioSystem). TaqMan assays utilized for assessment cytochrome b (CYTB) gene, subunit NADH dehydrogenase (ND2), beta microglobulin gene (B2M). mtDNA-CN defined number mtDNA/nDNA copies, through analysis CYTB/B2M ND2/B2M ratio. standards created plasmidial cloning vectors. Cloning verified PCR sequencing validation. Results Serum decreased, while increased all groups compared controls. In univariable linear analysis, correlated directly negatively UACR, synaptopodin, podocalyxin, KIM-1, NAG. Also, IL-17A IL-17A, IL-18 IL-10 IL-10. Urinary NAG, showed an inverse correlation IL-10, eGFR. Multivariable provided models indirectly KIM-1 (R2 = 0.626; p 0.0001). 0.631; This data suggests that levels attributed filtration circulating derive from filtered due lesions glomerular tubular structures. correlations proinflammatory cytokines anti-inflammatory cytokine could explain association these variations expression studied groups, even Conclusion MtDNA abnormalities occur DM. displays profile inflammation both at level These observations are independent renal function decline.