Post-Market Observation Study of Intra-Renal Drug Delivery (PROVIDE)

Acute kidney injury, or AKI, is a rapid decline in renal function characterized by a
decrease in urine output and/or an increase in serum creatinine (Cr), and is associated with
worsened clinical outcomes and increased healthcare costs. AKI may be caused by numerous
factors including interruptions or perturbations of renal blood flow or toxins, and often
these factors are extra-renal in origin. AKI diagnoses in hospitalized patients are over
one million per year and are projected to continue to grow, due largely to the aging
population and increasing numbers of medical and invasive procedures performed on the
elderly and the ever-increasing prevalence of diabetes mellitus and its medical
complications, as well as increasing awareness within the medical community.

Treatment options for established acute kidney injury are limited and consist mainly of
fluid and electrolyte balance (diuretics and/or IV fluids) supportive care up until the
point that dialysis or other renal replacement therapy (RRT) is required. Despite the advent
of newer drugs, more sophisticated RRT equipment, and increased awareness of the problem,
little has changed relative to patient outcomes, which remain poor. Similarly, limited
options exist in patients with known risk factors for AKI to prevent its development due to
iatrogenic causes (e.g., major surgery, exposure to contrast media).

Targeted Renal Therapy allows for direct delivery of therapeutically relevant doses of
various pharmacological agents directly to the renal bed, potentially reducing dose limiting
side effects of traditional IV therapy. With Targeted Renal Therapy, or TRT, the kidney can
metabolize, conjugate, and/or clear a substantial portion of many agents immediately (known
as the "renal first-pass" effect), reducing the amount that is returned to the systemic
circulation via the renal veins, thus potentially reducing untoward side effects. While the
existence of a renal first-pass effect has been hypothesized in the medical literature for
some time, it has not been possible to take clinical advantage of this important
physiological function prior to the advent of AngioDynamics' TRT. Thus, TRT has the
potential to offer an additional preventative or treatment opportunity in those patients at
risk for AKI, or with established AKI, respectively.