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Background Guidelines recommend saline hydration for prophylaxis of contrast-induced acute kidney injury (CI-AKI) in patients with chronic kidney disease (CKD) undergoing intravenous contrast media-enhanced CT (CE-CT). The safety and efficacy of a brief hydration protocol using sodium bicarbonate in this population is unknown. We analysed whether 1-h sodium bicarbonate hydration prior to CE-CT is non-inferior to saline hydration prior to and after CE-CT in CKD patients. Methods We performed an open-label multicentre randomized trial. Patients were randomized to 250 mL of 1.4% sodium bicarbonate hydration prior to CE-CT or 1000 mL of 0.9% saline hydration prior to and, once again, after CE-CT. Primary outcome was the relative increase in serum creatinine 48–96 h post-CE-CT. Secondary outcomes were incidence of CI-AKI [serum creatinine increase >25%/>44 µmol/L (0.5 mg/dL)], recovery of renal function, the need for dialysis and 2-month hospital costs. Results Five hundred and seventy adult CKD patients undergoing CE-CT were randomized between 2010 and 2012, of whom 548 were included in the intention-to-treat population. Mean relative serum creatinine increase was 1.2% for sodium bicarbonate and 1.5% for saline (mean difference −0.3%; 95% confidence interval −2.7 to 2.1, P-value for non-inferiority <0.0001). CI-AKI occurred in 22 patients (4.1%); 8 (3.0%) randomized to sodium bicarbonate versus 14 (5.1%) to saline (P = 0.23). Renal function recovered in 75 and 69% of CI-AKI patients, respectively (P = 0.81). No patients developed a need for dialysis. Mean hydration costs per patient were €224 for the sodium bicarbonate and €683 for the saline regime (P < 0.001). Other healthcare costs were similar. Conclusions Short hydration with sodium bicarbonate prior to CE-CT was non-inferior to peri-procedural saline hydration with respect to renal safety and may result in healthcare savings. [Netherlands Trial Register (http://www.trialregister.nl/trialreg/index.asp), Nr 2149, date of registration 23 December 2009.] [ABSTRACT FROM AUTHOR]