Dexamethasone Modifies Cystatin C-Based Diagnosis of Acute Kidney Injury During Cisplatin-Based Chemotherapy.
OBJECTIVE
Plasma cystatin C (pCysC) may be superior to serum creatinine (sCr) as a surrogate of GFR. However, the performance of pCysC for diagnosing acute kidney injury (AKI) after cisplatin-based chemotherapy is potentially affected by accompanying corticosteroid anti-emetic therapy and hydration.


METHODS
In a prospective observational study pCysC, sCr, urinary kidney injury molecule-1 (KIM-1), and urinary clusterin were measured over 2 weeks in 27 patients given first-cycle chemotherapy. The same variables were measured over 2 weeks in Sprague-Dawley rats given a single intraperitoneal injection of dexamethasone, cisplatin, or both, and in controls.


RESULTS
In patients, pCysC increases were greater than sCr 41% vs. 16%, mean paired difference 25% (95% CI: 16-34%)], relative increases were ≥ 50% in 9 patients (35%) for pCysC compared with 2 (8%) for sCr (p = 0.04) and increases in sCr were accompanied by increased KIM-1 and clusterin excretion, but increases in pCysC alone were not. In rats, dexamethasone administration produced dose-dependent increases in pCysC (and augmented cisplatin-induced increases in pCysC), but did not augment histological injury, increases in sCr, or KIM-1 and clusterin excretion.


CONCLUSIONS
In the presence of dexamethasone, elevation of pCysC does not reliably diagnose AKI after cisplatin-based chemotherapy.
Prince of Wales Clinical School, University of New South Wales, Sydney, New South Wales, Australia.|Northern Clinical School, University of Melbourne, Melbourne, Victoria, Australia.
Timothy J
TJ
Pianta
Medicine, University of Otago, Christchurch, New Zealand.
John W
JW
Pickering
Prince of Wales Clinical School, University of New South Wales, Sydney, New South Wales, Australia.
Lena
L
Succar
Prince of Wales Clinical School, University of New South Wales, Sydney, New South Wales, Australia.
Melvin
M
Chin
Anatomical Pathology, SEALS, Prince of Wales Hospital, Randwick, New South Wales, Australia.
Trent
T
Davidson
Prince of Wales Clinical School, University of New South Wales, Sydney, New South Wales, Australia.|Clinical Pharmacology, University of Sydney, Sydney, New South Wales, Australia.
Nicholas A
NA
Buckley
Prince of Wales Clinical School, University of New South Wales, Sydney, New South Wales, Australia.|Clinical Pharmacology, University of Sydney, Sydney, New South Wales, Australia.
Fahim
F
Mohamed
Prince of Wales Clinical School, University of New South Wales, Sydney, New South Wales, Australia.|Medicine, University of Otago, Christchurch, New Zealand.
Zoltan H
ZH
Endre
D058186:Acute Kidney Injury / Q000175:diagnosis*; D000368:Aged; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D002945:Cisplatin / Q000627:therapeutic use*; D003404:Creatinine / Q000097:blood; D055316:Cystatin C / Q000097:blood / Q000187:drug effects*; D003907:Dexamethasone / Q000008:administration & dosage*; D003951:Diagnostic Errors; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D017207:Rats, Sprague-Dawley
D000970:Antineoplastic Agents; D055316:Cystatin C; D003907:Dexamethasone; D003404:Creatinine; D002945:Cisplatin
Acute kidney injury; Biomarkers; Creatinine; Cystatin C; Dexamethasone