Acute Kidney Injury
Unmet Medical Need
Acute kidney injury (AKI), also referred to as acute renal failure, the sudden loss of the kidneys’ ability to eliminate excess fluid and waste material from blood. When the kidneys lose their filtering ability, dangerous levels of fluid and waste accumulate in the body. AKI is a serious condition that generally requires intensive care; however, the kidneys can regain function such that AKI can be reversed. In other circumstances, AKI can progress to chronic kidney disease, dialysis or need for transplantation.
AKI is most common in people who are already hospitalized, particularly in people who need intensive care. Research suggests that there are more than 550,000 cases of AKI a year.1 One percent of all hospitalizations in the US have AKI at the time of admission, and there is an estimated additional 2-5 percent who experience AKI during hospitalization. AKI also contributes to increased hospitalization time (two days on average) and increased mortality (20% or more). Currently, there is no therapeutic treatment for AKI. Renal replacement therapy (dialysis) is used to simulate kidney filtration, and the kidney may or may not regain function. AKI can occur in patients both with and without a history of renal problems, but tends to occur after complicated surgery, after a severe injury, or when blood flow to the kidneys is disrupted.
AKI can also occur when a kidney is transplanted and has not yet begun to function in the organ recipient, a condition called delayed graft function. Damage resulting from the sequence of cold and warm ischemia and subsequent reperfusion of donor kidneys prior to transplantation can lead to delayed graft function in the recipient in up to 25% of all kidney transplant procedures and higher if high-risk cadaveric donor kidneys are employed. Recipients of a transplant that exhibits delayed function are at increased risk of developing chronic allograft nephropathy and graft failure.
Renoprotective HIF-PHI
FibroGen is developing renoprotective HIF-PHI for acute treatment of AKI to reduce renal cell death, promote cellular recovery, and reduce the incidence or severity of renal damage. Previous studies demonstrated that brief periods of hypoxic preconditioning are renoprotective against ischemic insult and correlate with activation of HIF and induction of HIF-dependent gene expression. FibroGen’s nonclinical research and that of several collaborators has demonstrated the ability of HIF-PHI to preserve renal function in experimental models of acute kidney injury,2 attenuate proximal3 and distal tubular injury,4 and increase long-term graft survival in a kidney transplant model.5
References
- Liangos, O. et al., Epidemiology and outcomes of acute renal failure in hospitalized patients: a national survey. Clin J Am Soc Nephrol. 2006 Jan;1(1):43-51.
- Wang, Q. et al. Renoprotective and Therapeutic Efficacy of the HIF Prolyl Hydroxylase Inhibitor FG-4539 in Experimental Ischemia-Reperfusion Induced Acute Kidney Injury. JASN 2006;17:325A (abstract).
- Rosenberger et al. Activation of Hypoxia Inducible Factors (HIF) Ameliorates Hypoxic Distal Tubular Injury in the Isolated Perfused Rat Kidneys. Nephrol Dial Transplant. 2008 May 29. [Epub ahead of print]
- Bernhardt W, et al. Preconditional activation of hypoxia inducible factors ameliorates ischemic acute renal failure. J Am Soc Nephrol 2006; 17: 1970-1908.
- Bernhardt, W. et al., Donor Pre-treatment with an HIF-Prolylhydroxylase-Inhibitor Improves Function and Increases Long-Term Graft Survival in an Allogenic Rat Transplant Model JASN 2007;18:64A (abstract).
