Fluid overload is a frequent finding in critically ill patients suffering from acute kidney injury (AKI). To assess the impact of fluid overload on the mortality of AKI patients treated with continuous renal replacement therapy (CRRT), we used a registry of 81 critically ill patients with AKI initiated on CRRT assembled over an 18-month period to conduct a cross- sectional analysis using volume-related weight gain (VRWG) of > or =10% and > or =20% of body weight and oliguria (< or =20 ml/h) as the principal variables, with the primary outcome measure being mortality at 30 days. Mean Apache II scores were 27.5 +/- 6.9 with overall cohort mortality of 50.6%. Mean (+/-SD) VRWG was 8.3 +/- 9.6 kg, representing a 10.2% +/- 13.5% increase since admission. Oliguria was present in 65.4% of patients. Odds ratio (OR) for mortality on univariate analysis was increased to 2.62 [95% confidence interval (CI): 1.07-6.44] by a VRWG > or =10% and to 3.22 (95% CI: 1.23-8.45) by oliguria. VRWG > or =20% had OR of 3.98 (95% CI: 1.01-15.75; p = 0.049) for mortality. Both VRWG > or =10% (OR 2.71, p = 0.040) and oliguria (OR 3.04, p = 0.032) maintained their statistically significant association with mortality in multivariate models that included sepsis and Apache II score. In conclusion, fluid overload is an important prognostic factor for survival in critically ill AKI patients treated with CRRT. Further studies are needed to elicit mechanisms and develop appropriate interventions.