Dexamethasone Modifies Cystatin C-Based Diagnosis of Acute Kidney Injury During Cisplatin-Based Chemotherapy

• Main Authors: Timothy J. Pianta (Author), John W. Pickering (Author), Lena Succar (Author), Melvin Chin (Author), Trent Davidson (Author), Nicholas A. Buckley (Author), Fahim Mohamed (Author), Zoltan H. Endre (Author)
• Format: Book
• Published: Karger Publishers, 2017-03-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.
• Notes: 1420-4096; 1423-0143; 10.1159/000469715
• Keywords: Cystatin C; Creatinine; Acute kidney injury; Biomarkers; Dexamethasone; Dermatology; RL1-803; Diseases of the circulatory (Cardiovascular) system; RC666-701; Diseases of the genitourinary system. Urology; RC870-923
• Source: Kidney & Blood Pressure Research, Vol 42, Iss 1, Pp 62-75 (2017)

Background/Aims: 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.