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 currently exist. 1

ACUTE KIDNEY INJURY AFTER RENAL
TRANSPLANTATION

Donor kidneys often undergo ischemic damage during the transplantation process resulting in acute kidney injury, which can lead to a condition known as delayed graft function. In delayed graft function, the kidney 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 rate. 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 470,000 coronary artery bypass graft and valve repair and replacement surgeries are performed annually in the United States. 5,8

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 SCIENCE BEHIND

ANG-3777

ANG-3777 is engineered to mimic the biological activity of HGF in order to address the timing mismatch of HGF levels and c-MET availability, which may activate this important repair pathway subsequently promoting tissue repair and possible improved organ function.*

*ANG-3777 is currently being studied in clinical trials to determine if it is safe and effective. It is not approved by any regulatory authority.

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 binding to the c-MET receptor, which is expressed on the surface of cells of an injured organ, activating processes preventing 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 physiological challenge is 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.

REFERENCES

  1. Bellomo R, et al. “Acute kidney injury.” The Lancet (2012); 380: 756-766.
  2. Perico N, et al. “Delayed graft function in kidney transplantation.” The Lancet (2004); 364:1814-1827.
  3. Centers for Disease Control and Prevention. “Dialysis Safety.” October 2017.
  4. Shoskes D, et al. “Delayed Graft Function in Renal Transplantation: Etiology,cManagmeent and Long-term Significance.” The Journal of Urology (1996); 155: 1831-1840.
  5. Brown, et al., “Duration of acute kidney injury impacts long-term survival after cardiac surgery. The Annals of thoracic surgery. (2010); 90(4).
  6. 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.
  7. Mannon, RB “Delayed Graft Function: The AKI of Kidney Transplantation.” Nephron (2018); 140 (2): 94-98.
  8. 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.
  9. O’Neal JB, et al., “Acute kidney injury following cardiac surgery; current understanding and future directions.” Critical Care (2016); 20:187.
  10. Liu Y, et al. Up-regulation of hepatocyte growth receptor: an amplification and targeting mechanism for hepatocyte growth factor action in acute renal failure.” Kidney International (1999); 55: 442–453.
  11. Homsi E, et al. “Endogenous hepatocyte growth factor attenuates inflammatory response in glycerol-induced acute kidney injury. American journal of nephrology (2009); 29(4):283-91.
  12. Rabkin R, et al. “Hepatocyte growth factor receptor in acute tubular necrosis.” Journal of the American Society of Nephrology. (2001). 12(3): 531–540.
  13. Joannidis M, et al. “Regional expression of hepatocyte growth factor/c-met in experimental renal hypertrophy and hyperplasia.” AJP Renal (1994); 267(2): F231-F236.
  14. Funakoshi, N & Nakamura T, “Hepatocyte growth factor: diagnosis to clinical applications.” Clinica Chimica Acta. (2003); 327:1 – 23.
  15. Nakamura T, et al. “Hepatocyte growth factor twenty years on: Much more than a growth factor.” Journal of Gastroenterology and Hepatology (2011); 26: Suppl. 1; 188–202.
  16. Liu Y, et al. Up-regulation of hepatocyte growth receptor: an amplification and targeting mechanism for hepatocyte growth factor action in acute renal failure.” Kidney International (1999); 55: 442–453.
  17. Dai C, et al. “Intravenous administration of hepatocyte growth factor gene ameliorates diabetic nephropathy in mice.” J Am Soc Nephrol. (2004); 15 (10): 2637-2647.
  18. Zhou D, et al. “Activation of hepatocyte growth factor receptor, c-met, in renal tubules is required for renoprotection after acute kidney injury.” Kidney International. (2013); 84(3): 509–520.