Continuous Renal Replacement Therapy Doses in Critically Ill Patients With Acute Kidney Injury

Overview

Acute kidney injury in critically ill patients admitted to the ICU is a common complication associated with high mortality or long-term chronic kidney damage. Some of these patients require continuous renal replacement therapy (low-intensity hemodialysis for 24 hours) until renal function recovery is achieved. Continuous Renal Replacement Therapy (CRRT) is a crucial treatment for ICU patients with acute renal failure. It offers continuous toxin removal and prevents fluid accumulation in the patient's body. The therapy not only eliminates toxins but also physiological substances, including micronutrients and essential elements for cellular metabolism and organ function. Currently, there is limited information available to adjust the renal therapy dose and avoid or balance the loss of these substances without causing toxin accumulation. Some studies suggest that high doses of therapy do not provide benefits and increase complications. The objective of this study is to evaluate two doses of continuous renal therapy in terms of internal environment control (sodium, potassium, and acids and bases), micronutrient loss, and toxin elimination. After 48 hours of therapy, patients will be assigned to continue with a dose equal to the initial dose or a decrease in the initial dose. These two options are part of the current standard practice in our center. Patients participating in the study will be randomly assigned one of the continuous renal therapy doses. The study is open, so treating physicians will always know the therapy the patient is receiving and can freely adjust it if deemed necessary. The intervention duration is 96 hours, after which the dose will be at the discretion of the treating medical team. A follow-up will be conducted through medical records or phone calls approximately 90 days after starting therapy. The risks for the patient are minimal, as toxin elimination monitoring will be even more intensive than usual. The study plans to include approximately 100 patients.

Interventions

• Procedure continuous renal replacement therapy
  Intervention Arm: Effluent dose schedule of 10-20 ml/kg/h after 48 hours of starting dose of 25-35 ml/kg/h, until completing 96 hours Control Arm Effluent dosage schedule of 25-35 ml/kg/h fixed for 96 hours

Primary outcome measures

• Control of biochemical parameters (natremia, kalemia, and base excess) [Time frame: From enrollment to the end of follow-up at 90 days]

Eligibility criteria

Inclusion criteria

• Patients 18 years of age or older
• Acute renal failure (AKIN 3) requiring Continuous Renal Replacement Therapy
• Requirement of vasoactive drugs (norepinephrine > 0.1 mcg/kg/min)
• Written informed consent (patient or family)

Exclusion criteria

• Lack of informed consent.
• Possibility of using plasma exchange or MARS therapy at the at the time of inclusion.
• Baseline renal function with an estimated glomerular filtration rate (CKD-EPI) less than 30 ml/min.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Publications

• Koekkoek KWA, Berger MM. An update on essential micronutrients in critical illness. Curr Opin Crit Care. 2023 Aug 1;29(4):315-329. doi: 10.1097/MCC.0000000000001062. Epub 2023 Jun 8. PMID 37306546
• Karkar A, Ronco C. Prescription of CRRT: a pathway to optimize therapy. Ann Intensive Care. 2020 Mar 6;10(1):32. doi: 10.1186/s13613-020-0648-y. PMID 32144519
• Fayad AI, Buamscha DG, Ciapponi A. Intensity of continuous renal replacement therapy for acute kidney injury. Cochrane Database Syst Rev. 2016 Oct 4;10(10):CD010613. doi: 10.1002/14651858.CD010613.pub2. PMID 27699760
• Jun M, Heerspink HJ, Ninomiya T, Gallagher M, Bellomo R, Myburgh J, Finfer S, Palevsky PM, Kellum JA, Perkovic V, Cass A. Intensities of renal replacement therapy in acute kidney injury: a systematic review and meta-analysis. Clin J Am Soc Nephrol. 2010 Jun;5(6):956-63. doi: 10.2215/CJN.09111209. Epub 2010 Apr 15. PMID 20395356
• RENAL Replacement Therapy Study Investigators; Bellomo R, Cass A, Cole L, Finfer S, Gallagher M, Lo S, McArthur C, McGuinness S, Myburgh J, Norton R, Scheinkestel C, Su S. Intensity of continuous renal-replacement therapy in critically ill patients. N Engl J Med. 2009 Oct 22;361(17):1627-38. doi: 10.1056/NEJMoa0902413. PMID 19846848
• Hoste EA, Bagshaw SM, Bellomo R, Cely CM, Colman R, Cruz DN, Edipidis K, Forni LG, Gomersall CD, Govil D, Honore PM, Joannes-Boyau O, Joannidis M, Korhonen AM, Lavrentieva A, Mehta RL, Palevsky P, Roessler E, Ronco C, Uchino S, Vazquez JA, Vidal Andrade E, Webb S, Kellum JA. Epidemiology of acute kidney injury in critically ill patients: the multinational AKI-EPI study. Intensive Care Med. 2015 Au PMID 26162677
• Maynar Moliner J, Honore PM, Sanchez-Izquierdo Riera JA, Herrera Gutierrez M, Spapen HD. Handling continuous renal replacement therapy-related adverse effects in intensive care unit patients: the dialytrauma concept. Blood Purif. 2012;34(2):177-85. doi: 10.1159/000342064. Epub 2012 Oct 24. PMID 23095418
• Chawla LS. Permissive azotemia during acute kidney injury enables more rapid renal recovery and less renal fibrosis: a hypothesis and clinical development plan. Crit Care. 2022 Apr 28;26(1):116. doi: 10.1186/s13054-022-03988-0. PMID 35484549

Identifiers

NCT: NCT06901011 · HCB/2024/0228

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗