Endocrinol Metab.  2021 Dec;36(6):1298-1306. 10.3803/EnM.2021.1226.

Clinical Value of Serum Mitochondria-Inhibiting Substances in Assessing Renal Hazards: A Community-Based Prospective Study in Korea

• Choi HS
• Kim JT
• Lee HK
• Park WH
• Kim Pak Y
• Lee SW

• KMID: 2523498
• DOI: http://doi.org/10.3803/EnM.2021.1226

Abstract

Background
Mitochondrial dysfunction is strongly associated with several kidney diseases. However, no studies have evaluated the potential renal hazards of serum mitochondria-inhibiting substance (MIS) and aryl hydrocarbon receptor ligand (AhRL) levels.
Methods
We used serum level of MIS and AhRL and clinical renal outcomes from 1,511 participants of a prospective community-based cohort in Ansung. MIS was evaluated based on intracellular adenosine triphosphate (MIS-ATP) or reactive oxygen species (MIS-ROS) generation measured using cell-based assays.
Results
During a mean 6.9-year follow-up, 84 participants (5.6%) developed a rapid decline in kidney function. In the lowest quartile group of MIS-ATP, patients were older and had metabolically deleterious parameters. In multivariate logistic regression analysis, higher MIS-ATP was associated with decreased odds for rapid decline: the odds ratio (OR) of 1% increase was 0.977 (95% confidence interval [CI], 0.957 to 0.998; P=0.031), while higher MIS-ROS was marginally associated with increased odds for rapid decline (OR, 1.014; 95% CI, 0.999 to 1.028; P=0.055). However, serum AhRL was not associated with the rapid decline in kidney function. In subgroup analysis, the renal hazard of MIS was particularly evident in people with hypertension and low baseline kidney function.
Conclusion
Serum MIS was independently associated with a rapid decline in kidney function, while serum AhRL was not. The clinical implication of renal hazard on serum MIS requires further evaluation in future studies.

Keyword

Mitochondria; Renal insufficiency, chronic; Receptors, aryl hydrocarbon; Endocrine disruptors

Figure

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  Fig. 1 Subgroup analysis for the relationship between (A) aryl hydrocarbon receptor ligand (AhRL), (B) mitochondria-inhibiting substance (MIS)-adenosine triphosphate (ATP), and (C) MIS-reactive oxygen species (ROS) with rapid estimated glomerular filtration rate (eGFR) decline. Odd ratios (ORs) and 95% confidence intervals (CIs) were calculated by logistic regression. Covariates were age, sex, smoking, drinking, and exercise status, fasting glucose, systolic and diastolic blood pressure, body mass index, waist circumference, total cholesterol, high-sensitivity C-reactive protein, estimated glomerular filtration rate and proteinuria. When covariates were chosen as subgroup, they were excluded from the model. HTN, hypertension; DM, diabetes mellitus.

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