acute kidney injury

Acute kidney injury is a major health issue and is defined as an abrupt (within 48 hours) reduction in kidney function based on an elevation in serum creatinine level, a reduction in urine output, the need for renal replacement therapy or a combination of these factors. It is caused by a variety of factors, including ischemia (lack of oxygen), reperfusion (reintroduction of oxygen), drug and toxin exposures, sepsis, major trauma and/or hemorrhage, among others. There are no approved pharmacological treatments.1


Delayed graft function is a severe form of acute kidney injury resulting from ischemia-reperfusion injury following kidney transplantation. It is distinct from transplant rejection and is most commonly seen in recipients of deceased-donor kidneys. In delayed graft function, the kidney fails to adequately filter the blood and patients require dialysis within the first week after transplantation.2 Dialysis does not treat acute kidney injury, but instead is renal replacement therapy for impaired kidneys. Patients with delayed graft function are more likely to experience transplant failure and have higher mortality rate.3, 4, 5 Delayed graft function is expensive to the system. Increased hospitalization, re-admissions, and other care amounts to an increase in costs of approximately $20,000 per patient in the U.S. for the transplant center.6 Dialysis, for which Medicare spending per ESRD patient per year was approximately $90,000 in 2017, is also a contributing factor to the economic burden of delayed graft function.7


Acute kidney injury associated with cardiac surgery is another form of acute organ injury. During cardiac surgery, cardiopulmonary bypass (the use of a heart-lung machine) is often employed to support the patient’s heart and lung function. CSA-AKI is caused by many factors, including shear stress during cardiopulmonary bypass and injuries from nephrotoxic drugs and contrast agents. In addition, an important driver of CSA-AKI is ischemia-reperfusion injury, which is similar to the injury seen in delayed graft function.

CSA-AKI is a frequent complication of cardiac surgery, with approximately 150,000 patients per year in the United States and Europe, or nearly one-third of the approximately 450,000 coronary bypass and valve replacement surgeries performed annually in the United States and Europe.4,8,9,10


  1. Bellomo R, et al. “Acute kidney injury.” The Lancet (2012); 380: 756-766.
  2. Centers for Disease Control and Prevention. “Dialysis Safety.” October 2017.
  3. Shoskes D, et al. “Delayed Graft Function in Renal Transplantation: Etiology,cManagmeent and Long-term Significance.” The Journal of Urology (1996); 155: 1831-1840.
  4. Brown, et al., “Duration of acute kidney injury impacts long-term survival after cardiac surgery. The Annals of thoracic surgery. (2010); 90(4).
  5. Schnuellee, P et al., “Comparison of early renal function parameters for the prediction of 5-year graft survival after kidney transplantation.” Nephrology Dialysis Transplantation (2006); 22: 235–245.
  6. Mayne, et al. “Delayed Graft Function (DGF) in Kidney Transplantation Patients: An Analysis of Disease Burden”. American Society of Nephrology Annual Meeting 2019
  7. USRDS “US Renal Data System 2019 Annual Data Report: Epidemiology of Kidney Disease in the United States” (2019)
  8. Mannon, RB “Delayed Graft Function: The AKI of Kidney Transplantation.” Nephron (2018); 140 (2): 94-98.
  9. Benjamin et al. “Forecasting the future of cardiovascular disease in the United States; a policy statement from the American Heart Association.” Circulation. (2018);137:e67–e492.
  10. OECD/EU (2016), Health at a Glance: Europe 2016 – State of Health in the EU Cycle