Bariatric Surgery Reduces Elevated Urinary Mitochondrial DNA Copy Number in Patients With Obesity

Lee, Haekyung; Oh, Songhee; Yang, Wonmi; Park, Rojin; Kim, Hyoungnae; Jeon, Jin Seok; Noh, Hyunjin; Han, Dong Cheol; Cho, Kae Won; Kim, Yong Jin; Kwon, Soon Hyo

doi:10.1210/jc.2018-01935

Cited by 15 publications

(38 citation statements)

References 43 publications

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“…The inclusion criteria for patients with obesity were: bariatric surgery candidates, body mass index (BMI) >35 or >30 kg/m 2 for those with comorbidities related to obesity such as hypertension (HTN), obstructive sleep apnea and obesity-related arthropathy. 17 The specific surgical procedure performed was determined on an individual basis after interdisciplinary discussion with consideration of relevant patient information. Exclusion criteria were as follows: those who had experienced major cardiovascular or cerebrovascular events in the 6 months preceding the study, those who had undergone kidney transplantation and those with a serum creatinine (Cr) level >2.5 mg/dL.…”

Section: Research Design and Methods Subjectsmentioning

confidence: 99%

“…15 We previously observed decreased urinary mtDNA levels after bariatric surgery in patients with obesity and without diabetes. 17 In addition, the intracellular mtDNA copy number recovered in patients with obesity after weight reduction surgery, reaching the level of nonobese control subjects. 18 However, since T2DM induces higher degrees of mitochondrial dysfunction in patients with obesity, 4 18 the extracellular mtDNA copy number in patients with obesity with T2DM may differ from that of patients without diabetes.…”

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confidence: 95%

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Effect of bariatric surgery on circulating and urinary mitochondrial DNA copy numbers in obesity with or without diabetes

Seo

Kim

Noh

et al. 2020

BMJ Open Diab Res Care

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IntroductionRecent studies have suggested that extracellular circulating and urinary mitochondrial DNA (mtDNA) are associated with mitochondrial dysfunction in obesity and type 2 diabetes mellitus (T2DM). However, the changes to cell-free serum and urinary mtDNA after bariatric surgery in patients with obesity with T2DM have not been investigated to date.Research design and methodsWe prospectively recruited patients with obesity (n=18), and with obesity and T2DM (n=14) who underwent bariatric surgery, along with healthy volunteers (HV) as a control group (n=22). Serum and urinary mitochondrial nicotinamide adenine dinucleotide dehydrogenase subunit-1 (mtND-1) and cytochrome-c oxidase 3 (mtCOX-3) copy numbers were measured using quantitative PCR (qPCR). The mtDNA copy numbers of patients with obesity (with and without T2DM) were followed up 6 months after surgery.ResultsThe copy numbers of urinary mtND-1 and mtCOX-3 in patients with obesity, with or without T2DM, were higher than those in the HVs. Moreover, urinary mtCOX-3 copy number increased in patients with obesity with T2DM compared with patients with obesity without T2DM (p=0.018). Meanwhile, serum mtCOX-3 copy numbers in HV were higher in both obesity patient groups (p=0.040). Bariatric surgery reduced urinary mtND-1 and mtCOX-3 copy numbers, as well as serum mtCOX-3 copy numbers only in patients with obesity with T2DM.ConclusionThese results suggest that T2DM induces greater kidney mitochondrial dysfunction in patients with obesity, which can be effectively restored with bariatric surgery.

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Section: Research Design and Methods Subjectsmentioning

confidence: 99%

mentioning

confidence: 95%

Effect of bariatric surgery on circulating and urinary mitochondrial DNA copy numbers in obesity with or without diabetes

Seo

Kim

Noh

et al. 2020

BMJ Open Diab Res Care

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“…Third, the lack of systemic mtDNA levels is an important limitation. We measured urinary mtDNA levels, as previous studies have reported that urinary mtDNA levels, but not circulating mtDNA levels, are correlated with kidney dysfunction and the clinical outcomes of various kidney diseases, including acute kidney injury [32,33], chronic kidney disease [9,18], and obesity-related hyperfiltration [11]. Age-/sex-matched healthy volunteers were collected to minimize the effects of other factors that may increase circulating mtDNA levels.…”

Section: Discussionmentioning

confidence: 99%

“…4403326; Thermo Fisher Scientific), using human genomic DNA for the standard curve. The mtDNA copy numbers were calculated using Copy Caller software (Thermo Fisher Scientific, Carlsbad, CA, USA) and expressed as mtDNA/nDNA ratios [11].…”

Section: Urinary Mtdna Copy Number Quantificationmentioning

confidence: 99%

“…The kidney is an organ with high energy demands and a consequent abundance of mitochondria. Mitochondrial injury plays an important role in the pathogenesis of various kidney diseases, including acute kidney injury [6], chronic kidney disease [7][8][9][10], obesity-related hyperfiltration [11], and glomerulonephritis (GN) [12][13][14][15][16]. Recently, we demonstrated that mitochondrial injury is involved in early-stage glomerular inflammation prior to pathological changes in immunoglobulin A nephropathy (IgAN) by measuring urinary mitochondrial DNA (mtDNA) [17], which is used as a surrogate marker of mitochondrial injury in various kidney diseases [18][19][20].…”

Section: Introductionmentioning

confidence: 99%

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Minor Glomerular Abnormalities are Associated with Deterioration of Long-Term Kidney Function and Mitochondrial Injury

Cho

Park

et al. 2019

JCM

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Minor glomerular abnormalities (MGAs) are unclassified glomerular lesions indicated by the presence of minor structural abnormalities that are insufficient for a specific pathological diagnosis. The long-term clinical outcomes and pathogenesis have not been examined. We hypothesized that MGAs would be associated with the deterioration of long-term kidney function and increased urinary mitochondrial DNA (mtDNA) copy numbers. We retrospectively enrolled patients with MGAs, age-/sex-/estimated glomerular filtration rate (eGFR)-matched patients with immunoglobulin A nephropathy (IgAN), and similarly matched healthy controls (MHCs; n = 49 each). We analyzed the time × group interaction effects of the eGFR and compared mean annual eGFR decline rates between the groups. We prospectively enrolled patients with MGAs, age-and sex-matched patients with IgAN, and MHCs (n = 15 each) and compared their urinary mtDNA copy numbers. Compared to the MHC group, the MGA and IgAN groups displayed differences in the time × group effects of eGFR, higher mean annual rates of eGFR decline, and higher urinary mtDNA copy numbers; however, these groups did not significantly differ from each other. The results indicate that MGAs are associated with deteriorating long-term kidney function, and mitochondrial injury, despite few additional pathological changes. We suggest that clinicians conduct close long-term follow-up of patients with MGAs.

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Dapagliflozin Reduces Urinary Kidney Injury Biomarkers in Chronic Kidney Disease Irrespective of Albuminuria Level

Cho,

Doo,

Song

et al. 2024

Clin Pharma and Therapeutics

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The beneficial effects of sodium–glucose cotransporter 2 (SGLT2) inhibitors in patients with chronic kidney disease (CKD) with low albuminuria levels have not been established. This study aimed to compare the effects of dapagliflozin on kidney injury biomarkers in patients with CKD stratified by albuminuria level. We prospectively enrolled healthy volunteers (HVs; n = 20) and patients with CKD (n = 54) with and without diabetes mellitus. Patients with CKD were divided into two age‐matched and sex‐matched subgroups according to urinary albumin–creatinine ratio (uACR) levels (<300 mg/g and ≥300 mg/g). The CKD group received dapagliflozin (10 mg/day). Urine samples were collected before treatment and after 3 and 6 months of dapagliflozin. Urinary kidney injury molecule‐1 (KIM‐1), interleukin‐1β (IL‐1β), and mitochondrial DNA nicotinamide adenine dinucleotide dehydrogenase subunit‐1 (mtND1) copy number were measured. The estimated glomerular filtration rate (eGFR) of patients with CKD was lower than that of HVs (P < 0.001). During the study period, eGFR decreased and uACR did not change in the CKD group. Kidney injury markers were significantly elevated in patients with CKD compared with those in HVs. Dapagliflozin reduced urinary KIM‐1, IL‐1β, and mtDNA copy number in patients with CKD after 6 months of treatment. In further, the levels of urinary KIM‐1 and IL‐1β, patients with CKD decreased after 6 months of dapagliflozin treatment regardless of albuminuria level. Dapagliflozin reduced urinary kidney injury biomarkers in patients with CKD, regardless of albuminuria level. These findings suggest that SGLT2 inhibitors may also attenuate the progression of low albuminuric CKD.

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Bariatric Surgery Reduces Elevated Urinary Mitochondrial DNA Copy Number in Patients With Obesity

Cited by 15 publications

References 43 publications

Effect of bariatric surgery on circulating and urinary mitochondrial DNA copy numbers in obesity with or without diabetes

Effect of bariatric surgery on circulating and urinary mitochondrial DNA copy numbers in obesity with or without diabetes

Minor Glomerular Abnormalities are Associated with Deterioration of Long-Term Kidney Function and Mitochondrial Injury

Dapagliflozin Reduces Urinary Kidney Injury Biomarkers in Chronic Kidney Disease Irrespective of Albuminuria Level

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