Lauren M. Aleksunes

Since the discovery of calbindin release into the urine during renal injury, there has been growing interest in the utility of this protein as a biomarker of nephrotoxicity. However, little is known about the intrarenal regulation of the release and expression of this calcium‐regulating protein during kidney injury. We sought to characterize the time‐dependent expression and excretion of the protein calbindin in the distal tubule in comparison to kidney injury molecule‐1 (Kim‐1), a protein in the proximal tubule, in mice treated with cisplatin. Urine, blood, and kidneys were collected from male C57BL/6 mice treated with vehicle or cisplatin (20 mg/kg ip). Urinary concentrations of calbindin and Kim‐1 were elevated by 11.6‐fold and 2.5‐fold, respectively, within 2 days after cisplatin. Circulating creatinine and blood urea nitrogen levels increased in cisplatin‐treated mice by 3 days, confirming the development of acute kidney injury. Time‐dependent decreases in intrarenal calbindin protein were observed on Days 3 and 4 and a 200‐fold upregulation of calbindin ( CALB1) and KIM‐1 messenger RNAs (mRNAs) was observed on Day 3. These data suggest that early loss of calbindin protein into the urine along with declines in renal calbindin levels initiates a compensatory induction of mRNA expression at later time points (Days 3 and 4). Understanding the regulation of calbindin during cisplatin nephrotoxicity further enhances its utility as a potential urinary biomarker of kidney damage. The results of the current study support the combined use of a proximal (Kim‐1) and distal tubule (calbindin) marker to phenotype acute kidney injury secondary to cisplatin administration.