Introduction: Hyponatremia is a common electrolyte disorder in critically ill patients. Rapid correction of chronic hyponatremia may lead to osmotic demyelination syndrome. Management of severe hyponatremia in patients with acute or chronic kidney disease who require continuous renal replacement therapy (CRRT) is limited by the lack of commercially available hypotonic dialysate or replacement fluid solutions. Methods: This was a single-center quality improvement project that consisted of the development and implementation of a multidisciplinary protocol for gradual correction of severe hyponatremia in patients who were admitted to the intensive care unit (ICU) and required CRRT. The protocol utilized a simplified method based on single-pool urea kinetic modeling and a hybrid technique of volume exchange, and addition of sterile water for sodium dilution of commercially available dialysate and replacement fluid solutions. Results: We report data of the first 3 ICU patients who required CRRT for acute kidney injury management, had severe hyponatremia (serum sodium <120 mEq/l), and were treated under the protocol. Targeted and gradual hyponatremia correction was achieved in all 3 patients. The observed versus the predicted serum sodium correction in each patient was concordant. No complications related to the protocol were reported. We detailed facilitators of and hindrances to the development and successful implementation of our multidisciplinary protocol. Conclusion: We demonstrated gradual and individualized rates of severe hyponatremia correction utilizing customized (sodium dilution) dialysate/replacement fluid solutions in ICU patients who required CRRT. It is not known whether the use of customized solutions to prevent hyponatremia overcorrection has a significant impact on patient outcomes. Further research in this susceptible population is needed.