Toxic Nephropathies of the Tubulointerstitium: Core Curriculum 2024.

Toxic Nephropathies of the Tubulointerstitium: Core Curriculum 2024.
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肾小管间质中毒性肾病:2024 年核心课程。

DOI:
10.1053/j.ajkd.2023.09.017
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发表时间:
2024
期刊:
American journal of kidney diseases : the official journal of the National Kidney Foundation
影响因子:
--
通讯作者:
Perazella,MarkA
Perazella,MarkA
中科院分区:
--
文献类型:
--
作者:
Krishnan,Namrata;Moledina,DennisG;Perazella,MarkA

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中毒性肾病是一组临床常见的疾病,其特征在于可影响肾小球、血管系统或肾小管的毒素诱导的肾损伤。涉及各种内源性(如肌红蛋白、血红蛋白、单克隆轻链和溶菌酶)和外源性毒素(如治疗药物、草药、重金属、放射性造影剂、麻醉剂和环境暴露)。肾脏的主要作用是通过肾小球滤过和肾小管分泌进行物质代谢和排泄,这增加了肾脏对这些物质不良反应的敏感性。药物/毒素通过肾脏的结构、剂量、代谢处理和排泄途径决定了其肾毒性风险。影响风险的患者特征包括药物代谢、转运和排泄的遗传决定因素、免疫应答基因和共病状况。临床表现取决于肾损伤的部位和严重程度。毒素诱导的肾小管间质损伤通常表现为肾功能下降和/或溶质转运缺陷和肾溶质消耗。在有限的毒素暴露下,损伤通常是可逆的;然而,长期暴露可能会发生不可逆的肾损伤。在本核心课程中,我们将重点讨论常见毒素引起的肾小管间质肾损伤的机制,并回顾其原因,临床表现,诊断和管理。
Toxic nephropathies are a clinically common group of disorders characterized by toxin-induced renal injury that can affect the glomerulus, vasculature, or tubulointerstitium. Various endogenous (eg, myoglobin, hemoglobin, monoclonal light chains, and lysozymes) and exogenous toxins (eg, therapeutic drugs, herbal medications, heavy metals, radiocontrast, intoxicants, and environmental exposures) have been implicated. The kidney’s primary role of metabolism and excretion of substances via glomerular filtration and tubular secretion increases its susceptibility to their adverse effects. The structure, dose, metabolic handling, and excretory pathway of the drug/toxin through the kidney determines its nephrotoxic risk. Patient characteristics that impact risk include genetic determinants of drug metabolism, transport and excretion, immune response genes, and comorbid conditions. Clinical manifestations depend on site and severity of renal injury. Toxin-induced tubulointerstitial injury often presents as a decline in renal function and/or solute transport defects and renal solute wasting. Injury is often reversible with limited toxin exposure; however, irreversible renal injury can occur with prolonged exposure. In this Core Curriculum, we will focus on discussing mechanisms of common toxin-induced tubulointerstitial renal injury and review their causes, clinical presentations, diagnosis, and management.
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