ABOUT ACUTE KIDNEY INJURY

ACUTE KIDNEY INJURY

Acute kidney injury impairs kidney function, and when severe, can result in kidney failure and death. Although acute kidney injury commonly occurs after kidney transplantation and cardiac surgery, no effective therapies exist. 1

Acute kidney injury after renal transplantation

Donor kidneys often undergo ischemic damage during the transplantion process resulting in acute kidney injury, which can lead to a condition known as delayed graft function. In delayed graft function, the kidney then fails to adequately filter the blood and patients require dialysis within the first week after transplantation. 2

Dialysis is expensive and associated with risks, including infection. 3 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. 4, 5, 6 Delayed graft function is expensive, adding more than $18,000 to hospitalization costs in the first three months post- transplantation. 7

Acute kidney injury after cardiac surgery

More than 350,000 coronary artery bypass graft surgeries are performed annually in the United States. 8

As many as 30% of these patients develop acute kidney injury, making it the most common significant complication of cardiac surgery.9  Two to five percent of patients who have acute kidney injury following cardiac surgery experience kidney failure, and among those patients mortality can be as high as 50%. 5,6

The body’s hepatocyte growth factor/c-MET repair pathway

Decades of research have led to a deep understanding of the hepatocyte growth factor (HGF)/c-MET pathway and the role it plays in the repair of injured organs.

When an organ is injured, the body releases HGF into the blood. 10, 11, 12, 13 HGF is a protein that binds to the c-MET receptor, expressed by cells of an injured organ, activating processes that prevent cell death and increase cell reproduction and scattering. 14, 15, 16, 17, 18 This ultimately results in the repair of injured tissue and return of organ function.

HGF begins to rise and peaks at two hours and then slowly declines. The challenge is that while levels of HGF peak at two hours, the expression of c-MET receptors on injured tissue peaks at 24 to 36 hours, creating a mismatch between the availability of HGF and the c-MET receptor it binds to. 10

Angion’s founder, Dr. Itzhak Goldberg, has made seminal discoveries related to the HGF/c-MET pathway and how it can be targeted in drug development.

  • 1Bellomo R et al. “Acute kidney injury.” The Lancet (2012); 380: 756-766.
  • 2Perico N, et al. “Delayed graft function in kidney transplantation.” The Lancet (2004); 364;1814-1827.
  • 3Centers for Disease Control and Prevention. “Dialysis Safety.” October 2017.
  • 4Shoskes D, et al. “Delayed Graft Function in Renal Transplantation: Etiology, Managmeent and Long-term Significance.” The Journal of Urology (1996): 155; 1831-1840.
  • 5Brown et al., Ann ThoracSurg. 2010 October ; 90(4).
  • 6Schnuelleet al., NephrolDial Transplant (2007) 22: 235–245.
  • 7Mannon, Roslyn B. “Delayed Graft Function: The AKI of Kidney Transplantation.” Nephron vol. 140,2 (2018): 94-98.
  • 8Benjamin et al. Circulation. 2018;137:e67–e492
  • 9O’Neal et al., Critical Care 2016 20:187.
  • 10Liu Kidney International, Vol. 55 (1999), 442–453
  • 11Am J Nephrol. 2009;29(4):283-91.
  • 12Rabkin J Am Soc Nephrol 12: 531–540, 2001.
  • 13Joannidis M, et al. Regional expression of hepatocyte growth factor/c-met in experimental renal hypertrophy and hyperplasia. AJP Renal 1994; 267(2): F231-F236.
  • 14Funakoshi, Nakamura; Clinica Chimica Acta 327 (2003) 1 – 23
  • 15Nakamura; Journal of Gastroenterology and Hepatology 26 (2011) Suppl. 1; 188–202.
  • 16Kidney International, Vol. 55 (1999), 442–453.
  • 17Dai et al. J Am Soc Nephrol 13: 411–422, 2002.
  • 18Zhou et al. Kidney Int. 2013 September ; 84(3): 509–520.