Mitochondrial DNA Changes in Blood and Urine Display a Specific Signature in Relation to Inflammation in Normoalbuminuric Diabetic Kidney Disease in Type 2 Diabetes Mellitus Patients

• Published in: International journal of molecular sciences Vol. 24; no. 12; p. 9803
• Main Authors: Petrica, Ligia, Vlad, Adrian, Gadalean, Florica, Muntean, Danina Mirela, Vlad, Daliborca, Dumitrascu, Victor, Bob, Flaviu, Milas, Oana, Suteanu-Simulescu, Anca, Glavan, Mihaela, Jianu, Dragos Catalin, Ursoniu, Sorin, Balint, Lavinia, Mogos-Stefan, Maria, Ienciu, Silvia, Cretu, Octavian Marius, Popescu, Roxana
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01.06.2023; MDPI
• Subjects: Albuminuria - urine; Biomarkers; Biomarkers - urine; Blood; Chronic kidney failure; Creatinine; Cytokines; Diabetes; Diabetes mellitus; Diabetes mellitus (non-insulin dependent); Diabetes Mellitus, Type 2 - complications; Diabetes Mellitus, Type 2 - genetics; Diabetes therapy; diabetic kidney disease; Diabetic Nephropathies; Diabetic nephropathy; Diabetics; DNA, Mitochondrial - genetics; Glucosaminidase; Humans; Hypotheses; Inflammation; Inflammation - genetics; Inflammatory response; Injuries; Interleukin 10; Interleukin 18; Interleukin-17; Interleukin-18 - genetics; Kidney diseases; Mitochondria; Mitochondria - genetics; Mitochondrial DNA; normoalbuminuria; Oxidative stress; Patients; Peripheral blood; podocyte; proximal tubule; Regression analysis; Type 2 diabetes; Urine; Romania; diabetic kidney disease; inflammation; mitochondrial DNA; podocyte; type 2 diabetes mellitus; normoalbuminuria; proximal tubule
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms24129803

Mitochondrial dysfunction is an important mechanism contributing to the development and progression of diabetic kidney disease (DKD). Mitochondrial DNA (mtDNA) levels in blood and urine were evaluated in relation to podocyte injury and proximal tubule (PT) dysfunction, as well as to a specific inflammatory response in normoalbuminuric DKD. A total of 150 type 2 diabetes mellitus (DM) patients (52 normoalbuminuric, 48 microalbuminuric, and 50 macroalbuminuric ones, respectively) and 30 healthy controls were assessed concerning the urinary albumin/creatinine ratio (UACR), biomarkers of podocyte damage (synaptopodin and podocalyxin), PT dysfunction (kidney injury molecule-1 (KIM-1) and -acetyl-β-(D)-glucosaminidase (NAG)), and inflammation (serum and urinary interleukins (IL-17A, IL-18, and IL-10)). MtDNA-CN and nuclear DNA (nDNA) were quantified in peripheral blood and urine via qRT-PCR. MtDNA-CN was defined as the ratio of the number of mtDNA/nDNA copies via analysis of the CYTB/B2M and ND2/B2M ratio. Multivariable regression analysis provided models in which serum mtDNA directly correlated with IL-10 and indirectly correlated with UACR, IL-17A, and KIM-1 (R = 0.626; < 0.0001). Urinary mtDNA directly correlated with UACR, podocalyxin, IL-18, and NAG, and negatively correlated with eGFR and IL-10 (R = 0.631; < 0.0001). Mitochondrial DNA changes in serum and urine display a specific signature in relation to inflammation both at the podocyte and tubular levels in normoalbuminuric type 2 DM patients.