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Insufficiency of urinary acid excretion of overweight or obese patients with chronic kidney disease and its involvement with renal tubular injury
Author(s) -
Eguchi Koji,
Izumi Yuichiro,
Nakayama Yushi,
Inoue Hideki,
Marume Takahiro,
Matsuo Naomi,
Hiramatsu Akiko,
Ono Makoto,
Kakizoe Yutaka,
Kuwabara Takashige,
oguchi Hiroshi,
Mukoyama Masashi
Publication year - 2019
Publication title -
nephrology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 61
eISSN - 1440-1797
pISSN - 1320-5358
DOI - 10.1111/nep.13553
Subject(s) - medicine , endocrinology , overweight , excretion , kidney disease , urinary system , creatinine , metabolic acidosis , kidney , obesity
Aim Metabolic acidosis occurs due to insufficient urinary ammonium excretion as chronic kidney disease (CKD) advances. Because obese subjects tend to have excessive consumption of protein and sodium chloride, they are prone to chronic acid loading and may therefore be predisposed to acid‐induced kidney injury. We investigated the involvement of obesity in ammoniagenesis within damaged kidneys. Methods In the clinical study, urinary ammonium excretion was compared between 13 normal‐weight and 15 overweight/obese CKD outpatients whose creatinine clearance was higher than 25 mL/min. For animal experiments, NH 4 Cl was loaded to KKAy/TaJcl (KKAy), a metabolic syndrome model, and control BALB/c mice for 20 weeks. Kidney injury was evaluated through histological analysis and the expression of proinflammatory markers. Results Urinary ammonium excretion was lower in overweight/obese patients than in normal‐weight patients, while intakes of protein and sodium chloride were higher in overweight/obese patients, implying that subclinical metabolic acidosis occurs in overweight/obese patients. The increase in urinary ammonium excretion induced by NH 4 Cl loading was attenuated in KKAy mice after 16 weeks, whereas the increase was maintained in BALB/c mice throughout the study period. Histological study and real‐time polymerase chain reaction analysis showed proximal tubular injury and enhanced expression levels of neutrophil gelatinase‐associated lipocalin (NGAL) protein and messenger RNA, respectively, in KKAy mice but not in BALB/c mice. Finally, urinary NGAL concentration was higher in overweight/obese patients than in normal‐weight patients in the early stage of CKD. Conclusion Obesity could facilitate the induction of subclinical metabolic acidosis and acid accumulation in the kidney, which may potentially exacerbate kidney injury in CKD patients.