Acute renal failure (ARF) with fluid overload (FO) occurs often in stem cell transplant (SCT) recipients. We have previously demonstrated that an increased percentage of FO prior to the initiation of continuous renal replacement therapy (CRRT) is associated with mortality in children with ARF. Based on these data, we devised a protocol for the prevention of FO in SCT patients with ARF. SCT patients with ARF and 5% FO were started on furosemide and low-dose dopamine. To allow for nutrition, medication, and blood product administration, RRT was initiated for patients with > or =10% FO. There were 272 patients who received allogeneic SCT from 1999 to 2002. Of these, medical records of 26 SCT patients with a first episode of oliguric ARF were reviewed. The mean patient age was 13+/-5 years (range 2-23.5 years). Mean days to ARF after SCT were 28+/-29 days (range 2-90 days). Of the 26 patients, 11 (42%) survived an initial ARF episode. All 11 survivors either maintained <10% FO during their course or re-attained <10% FO with RRT treatment. Of the 15 non-survivors, 6 had <10% FO at the time of death. Of 14 patients who received RRT, 4 (29%) survived. Mechanical ventilation and pediatric risk of mortality score > or =10 at the time of admission to the intensive care unit were associated with lower survival ( P<0.05). The use of one or more pressors, the presence of graft-versus-host disease, and septic shock were not correlated with survival. Our data demonstrate that maintenance of euvolemia ( <10% FO) is critical but not sufficient for survival in SCT patients with ARF, as all non-euvolemic patients died. We suggest that aggressive use of diuretics and early initiation of RRT to prevent worsening of FO may improve the survival of SCT patients.