Unidad de Investigación, Hospital Universitario de Salamanca, Salamanca, Spain.
Kidney Int. 2011 Mar;79(5):518-28. doi: 10.1038/ki.2010.439. Epub 2010 Oct 27.
A key aspect for the clinical handling of acute kidney injury is an early diagnosis, for which a new generation of urine biomarkers is currently under development including kidney injury molecule 1 and neutrophil gelatinase-associated lipocalin. A further diagnostic refinement is needed where one specific cause among several potentially nephrotoxic insults can be identified during the administration of multidrug therapies. In this study we identified increases in regenerating islet-derived protein III beta (reg IIIb) and gelsolin as potential differential urinary markers of gentamicin's nephrotoxicity. Indeed, urinary levels of both reg IIIb and gelsolin distinguish between the nephrotoxicity caused by gentamicin from that caused by cisplatin where these markers were not increased by the latter. Reg IIIb was found to be overexpressed in the kidneys of gentamicin-treated rats and excreted into the urine, whereas urinary gelsolin originated from the blood by glomerular filtration. Our results illustrate an etiological diagnosis of acute kidney injury through analysis of urine. Thus, our results raise the possibility of identifying the actual nephrotoxin in critically ill patients who are often treated with several nephrotoxic agents at the same time, thereby providing the potential for tailoring therapy to an individual patient, which is the aim of personalized medicine.
急性肾损伤临床处理的一个关键方面是早期诊断，目前正在开发新一代尿液生物标志物，包括肾损伤分子 1 和中性粒细胞明胶酶相关脂质运载蛋白。在多药物治疗期间，需要进一步细化诊断，以便在几种潜在肾毒性损伤中确定特定的原因。在这项研究中，我们发现再生胰岛衍生蛋白 IIIβ（reg IIIβ）和凝胶蛋白的增加是庆大霉素肾毒性的潜在差异尿标记物。事实上，尿液中 reg IIIβ 和凝胶蛋白的水平可区分庆大霉素引起的肾毒性与顺铂引起的肾毒性，后者不会增加这些标志物。发现庆大霉素处理的大鼠肾脏中 reg IIIβ 过表达并分泌到尿液中，而尿液中的凝胶蛋白则通过肾小球滤过从血液中产生。我们的结果通过尿液分析说明了急性肾损伤的病因诊断。因此，我们的结果提出了一种可能性，即在经常同时接受几种肾毒性药物治疗的危重病患者中，可以通过分析尿液来确定实际的肾毒素，从而为针对个体患者量身定制治疗提供了可能性，这是个性化医疗的目标。
