Artificial Kidney-Induced Kidney Injury (AKIKI)


Renal replacement therapy (RRT) is used for severe acute kidney injury (AKI). We published the first large trial on RRT timing (AKIKI). It showed no difference in mortality between 2 initiation strategies (early vs delayed) but the delayed one (allowing some patients to escape RRT) was associated with faster renal recovery. RRT might constitute a second hit, which would impair renal recovery by: 1/modifying renal hemodynamic; 2/activating platelets and neutrophils through contact with dialysis membrane; 3/removing plasma molecules involved in tubules regeneration (e.g. vit B3). To test these hypotheses, we set up a rat model of RRT after AKI. Kidney histology and function, tubular damage, hemodynamic, platelets/neutrophils activation/aggregation and NAD+ metabolites will be assessed. It will then be tested in blood/urine samples from patients included in AKIKI2 trial. We will also assess if plasma concentration of NAD+ metabolites is correlated with the time between AKI and recovery.

  1. Comparison of two delayed strategies for renal replacement therapy initiation for severe acute kidney injury (AKIKI 2): a multicentre, open-label, randomised, controlled trial. Gaudry S, Hajage D, …. and Dreyfuss D. Lancet. 2021. 397(10281):1293-1300. doi: 10.1016/S0140-6736(21)00350-0
  2. Timing of Initiation of Renal-Replacement Therapy in Acute Kidney Injury. STARRT-AKI Investigators, …, Gaudry S… and Zarbock A. N Engl J Med 2020. 383(3):240-251. doi: 10.1056/NEJMoa2000741.
  3. Timing of Renal Replacement Therapy for Severe Acute Kidney Injury in Critically Ill Patients. Gaudry S, Quenot JP…and Dreyfuss D. Am J Respir Crit Care Med 2019. 99(9):1066-1075. doi: 10.1164/rccm.201810-1906CP.
  4. Timing of Renal Support and Outcome of Septic Shock and Acute Respiratory Distress Syndrome. A Post Hoc Analysis of the AKIKI Randomized Clinical Trial. Gaudry S, Hajage D, …. and Dreyfuss D. Am J Respir Crit Care Med 2018. 198(1):58-66. doi:10.1164/rccm.201706-1255OC.
  5. Initiation of Renal-Replacement Therapy in the Intensive Care Unit. Gaudry S, Hajage D and Dreyfuss D. N Engl J Med 2016;375:122–133. doi: 10.1056/NEJMc1610500.