Acute kidney injury biomarkers and hydration assessments following prolonged mild hypohydration in healthy young adults.

IF 3.7 2区 医学 Q1 PHYSIOLOGY American Journal of Physiology-renal Physiology Pub Date : 2023-08-01 Epub Date: 2023-06-15 DOI:10.1152/ajprenal.00086.2023
Christopher L Chapman, Sadie M Holt, Cameron T O'Connell, Shaun C Brazelton, William A B Howells, Hannah N Medved, Emma L Reed, Karen Wiedenfeld Needham, John R Halliwill, Christopher T Minson
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Abstract

The high prevalence of inadequate hydration (e.g., hypohydration and underhydration) is concerning given that extreme heat increases excess hospitalizations for fluid/electrolyte disorders and acute kidney injury (AKI). Inadequate hydration may also be related to renal and cardiometabolic disease development. This study tested the hypothesis that prolonged mild hypohydration increases the urinary AKI biomarker product of insulin-like growth factor-binding protein 7 and tissue inhibitor of metalloproteinase-2 ([IGFBP7·TIMP-2]) compared with euhydration. In addition, we determined the diagnostic accuracy and optimal cutoffs of hydration assessments for discriminating positive AKI risk ([IGFBP·TIMP-2] >0.3 (ng/mL)2/1,000). In a block-randomized crossover design, 22 healthy young adults (11 females and 11 males) completed 24 h of fluid deprivation (hypohydrated group) or 24 h of normal fluid consumption (euhydrated group) separated by ≥72 h. Urinary [IGFBP7·TIMP-2] and other AKI biomarkers were measured following the 24-h protocols. Diagnostic accuracy was assessed via receiver operating characteristic curve analysis. Urinary [IGFBP7·TIMP-2] [1.9 (95% confidence interval: 1.0-2.8) vs. 0.2 (95% confidence interval: 0.1-0.3) (ng/mL)2/1,000, P = 0.0011] was markedly increased in hypohydrated versus euhydrated groups. Urine osmolality (area under the curve: 0.91, P < 0.0001) and urine specific gravity (area under the curve: 0.89, P < 0.0001) had the highest overall performance for discriminating positive AKI risk. Optimal cutoffs with a positive likelihood ratio of 11.8 for both urine osmolality and specific gravity were 952 mosmol/kgH2O and 1.025 arbitrary units. In conclusion, prolonged mild hypohydration increased urinary [IGFBP7·TIMP-2] in males and females. Urinary [IGFBP7·TIMP-2] corrected to urine concentration was elevated in males only. Urine osmolality and urine specific gravity may have clinical utility for discriminating positive AKI risk following prolonged mild hypohydration.NEW & NOTEWORTHY This study found that prolonged mild hypohydration in healthy young adults increased the Food and Drug Administration approved acute kidney injury (AKI) biomarker urinary insulin-like growth factor-binding protein 7 and tissue inhibitor of metalloproteinase-2 [IGFBP7·TIMP-2]. Urine osmolality and specific gravity demonstrated an excellent ability to discriminate positive AKI risk. These findings emphasize the importance of hydration in protecting renal health and lend early support for hydration assessment as an accessible tool to assess AKI risk.

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健康年轻人长期轻度缺水后的急性肾损伤生物标志物和水合评估。
鉴于酷热会增加因液体/电解质紊乱和急性肾损伤 (AKI) 而住院治疗的人数,水合不足(如水份过低和水份不足)的高发病率令人担忧。水合不足还可能与肾脏和心脏代谢疾病的发展有关。本研究测试了这样一个假设:与缺水相比,长期轻度缺水会增加尿液中胰岛素样生长因子结合蛋白 7 和金属蛋白酶组织抑制剂-2([IGFBP7-TIMP-2])的急性肾损伤生物标志物产物。此外,我们还确定了诊断准确性和判别阳性 AKI 风险的最佳水化评估临界值([IGFBP-TIMP-2] >0.3 (纳克/毫升)2/1,000)。在分块随机交叉设计中,22 名健康的年轻成人(11 名女性和 11 名男性)完成了 24 小时的液体剥夺(低水合组)或 24 小时的正常液体消耗(高水合组),两组间隔时间≥72 小时。诊断准确性通过接收者操作特征曲线分析进行评估。尿液[IGFBP7-TIMP-2] [1.9 (95% 置信区间:1.0-2.8) vs. 0.2 (95% 置信区间:0.1-0.3) (ng/mL)2/1,000,P = 0.0011]在缺水组和缺水组明显增加。尿渗透压(曲线下面积:0.91,P < 0.0001)和尿比重(曲线下面积:0.89,P < 0.0001)在判别阳性 AKI 风险方面的整体表现最佳。尿渗透压和尿比重的最佳临界值分别为 952 mosmol/kgH2O 和 1.025 任意单位,阳性似然比均为 11.8。总之,长期轻度缺水会增加男性和女性的尿液[IGFBP7-TIMP-2]。根据尿液浓度校正的尿液[IGFBP7-TIMP-2]仅在男性中升高。尿渗透压和尿比重可能对鉴别长期轻度缺水后的急性肾损伤(AKI)阳性风险有临床用途。这项研究发现,健康年轻人长期轻度缺水会增加食品及药物管理局批准的急性肾损伤(AKI)生物标志物尿胰岛素样生长因子结合蛋白 7 和金属蛋白酶组织抑制剂-2 [IGFBP7-TIMP-2]。尿渗透压和尿比重在判别 AKI 阳性风险方面表现出色。这些发现强调了水合在保护肾脏健康方面的重要性,并为水合评估作为评估 AKI 风险的便捷工具提供了早期支持。
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来源期刊
CiteScore
8.40
自引率
7.10%
发文量
154
审稿时长
2-4 weeks
期刊介绍: The American Journal of Physiology - Renal Physiology publishes original manuscripts on timely topics in both basic science and clinical research. Published articles address a broad range of subjects relating to the kidney and urinary tract, and may involve human or animal models, individual cell types, and isolated membrane systems. Also covered are the pathophysiological basis of renal disease processes, regulation of body fluids, and clinical research that provides mechanistic insights. Studies of renal function may be conducted using a wide range of approaches, such as biochemistry, immunology, genetics, mathematical modeling, molecular biology, as well as physiological and clinical methodologies.
期刊最新文献
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