Urinary levels of regenerating islet-derived protein III β and gelsolin differentiate gentamicin from cisplatin-induced acute kidney injury in rats.
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.
Ferreira
Laura
L
Unidad de Investigación, Hospital Universitario de Salamanca, Salamanca, Spain.
Quiros
Yaremi
Y
Sancho-Martínez
Sandra M
SM
García-Sánchez
Omar
O
Raposo
Cesar
C
López-Novoa
Jose M
JM
González-Buitrago
Jose M
JM
López-Hernández
Francisco J
FJ
D058186:Acute Kidney Injury / Q000139:chemically induced* / Q000175:diagnosis / Q000652:urine; D000818:Animals; D000900:Anti-Bacterial Agents / Q000633:toxicity*; D000951:Antigens, Neoplasm / Q000652:urine*; D000970:Antineoplastic Agents / Q000633:toxicity*; D014408:Biomarkers, Tumor / Q000652:urine*; D002945:Cisplatin / Q000633:toxicity*; D005260:Female; D018260:Gelsolin / Q000652:urine*; D005839:Gentamicins / Q000633:toxicity*; D037181:Lectins, C-Type; D000073718:Pancreatitis-Associated Proteins; D040901:Proteomics; D051381:Rats; D017208:Rats, Wistar
D000900:Anti-Bacterial Agents; D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D018260:Gelsolin; D005839:Gentamicins; D037181:Lectins, C-Type; D000073718:Pancreatitis-Associated Proteins; D002945:Cisplatin