Insufficiency of urinary acid excretion of overweight or obese patients with chronic kidney disease and its involvement with renal tubular injury.
Insufficiency of urinary acid excretion of overweight or obese patients with chronic kidney disease and its involvement with renal tubular injury.
复制标题
超重或肥胖慢性肾脏病患者尿酸排泄不足及其与肾小管损伤的关系。
DOI：
10.1111/nep.13553
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发表时间：
2019
期刊：
影响因子：
2.5
通讯作者：
Mukoyama M.
中科院分区：
文献类型：
--
作者：
Eguchi K;Izumi Y;Nakayama Y;Inoue H;Marume T;Matsuo N;Hiramatsu A;Ono M;Kakizoe Y;Kuwabara T;Nonoguchi H;Mukoyama M.
随着慢性肾脏病（CKD）的进展，由于尿铵排泄不足而发生代谢性酸中毒。由于肥胖受试者倾向于过量摄入蛋白质和氯化钠，因此他们容易出现慢性酸负荷，因此可能易发生酸诱导的肾损伤。我们调查了参与ammoniagenesis在受损kidney.MethodsIn临床研究中，尿铵排泄进行了比较13正常体重和15超重/肥胖CKD门诊患者的肌酐清除率高于25 mL/min。动物实验，NH 4Cl加载到KKAy/TaJcl（KKAy），代谢综合征模型，和对照BALB/c小鼠20周。肾损伤进行了评估，通过组织学分析和表达的促炎markers.ResultsUrinary铵排泄低于超重/肥胖患者比正常体重的患者，而蛋白质和氯化钠的摄入量较高的超重/肥胖患者，这意味着亚临床代谢性酸中毒发生在超重/肥胖患者。NH 4Cl负荷诱导的尿铵排泄增加在KKAy小鼠中在16周后减弱，而在整个研究期间在BALB/c小鼠中保持增加。组织学研究和真实的实时聚合酶链反应分析显示，KKAy小鼠近端肾小管损伤和中性粒细胞明胶酶相关脂质运载蛋白（NGAL）蛋白和信使RNA的表达水平分别升高，但BALB/c小鼠未出现。最后，尿NGAL浓度高于超重/肥胖患者在CKD的早期阶段比在正常体重的患者。结论肥胖可以促进诱导亚临床代谢性酸中毒和酸在肾脏中的积累，这可能会加剧CKD患者的肾损伤。
AimMetabolic 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.MethodsIn 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, NH4Cl 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.ResultsUrinary 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 NH4Cl 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.ConclusionObesity could facilitate the induction of subclinical metabolic acidosis and acid accumulation in the kidney, which may potentially exacerbate kidney injury in CKD patients.