Acute Kidney Injury
Acute kidney injury is the sudden loss of the kidney’s ability to filter wastes without losing electrolytes. Most often AKI (also termed acute renal failure) is caused by reduced blood flow to the kidneys (prerenal), though about 20% of the cases are due to infections or toxins affecting the kidneys directly (intrinsic), and about 5% are due to blockages downstream of the kidneys (postrenal obstruction).
Most cases of AKI are acquired in the hospital as a result of complications from other illnesses or interventions. The most common causes are sepsis, hypovolemia, surgery, imaging contrast agents, chemotherapy drugs, NSAIDS and some antibiotics.
When AKI occurs the kidneys show multiple pathologies. Tubule flow decreases, epithelial cells depolarize and many are shed into the lumen where they can lodge and block flow downstream. Some tubules swell compressing adjacent tissue and tubules. Capillary perfusion also decreases and many capillaries collapse, while arteries constrict. Following an ischemic event the renal vasculature remains constricted for days. Blood flow is only 65% of normal after 48 hours and 85-90% after 7 days. Renal vasculature auto-regulation is also abnormal for about a week after ischemia with inappropriate vasoconstriction in response to arterial pressure variations that can lead to additional ischemia. Cell death is widespread presumably caused by reduced perfusion. However, surviving cells spread, proliferate, and reestablish polarity so that in many cases patients recover without notable consequences.
In the US approximately 40 million people a year experience conditions or treatments that put them at risk for developing AKI. Of these 7 million develop AKI with 3.2 million severe cases and 790,000 deaths. The added cost of treating a patient with severe AKI is $33,000.
In pilot animal studies of severe ischemic AKI, a one-time administration of HFT-012 produced a statistically significant improvement in kidney function within 24 hours. At the end of the 3 day experiment the HFT-012 treatment had cut the death rate in half and improved the recovery rate 5-fold.