Impaired blood flow in acute kidney injury: pathophysiology and potential efficacy of intrarenal vasodilator therapy.
OBJECTIVE
Acute kidney injury (AKI) is a common complication of hospitalized patients and associated with significant morbidity and mortality. Numerous studies have documented that acute reductions in glomerular filtration rates are associated with significant in-hospital mortality. Moreover, patients progressing to dialysis-dependent AKI can have mortality rates that exceed 60%. The pathophysiology of AKI is unknown, but marked reductions in corticomedullary blood flow leads to significant reductions in glomerular filtration rate during early phases of the disease. The recognition that hypoperfusion of the outer medulla is common to many forms of AKI and contributes to tubular ischemia has led many investigators to re-examine the use of vasodilators to restore blood flow and stabilize renal function.


RESULTS
Numerous prospective trials have studied the efficacy of various vasoactive compounds with primarily negative results. However, trial designs that failed to fully examine the dose response of many investigational agents contributed to the development of systemic hypotension, thus offsetting potential benefits of the treatment. Emerging devices that allow for intrarenal administration of drugs have led to the concept of 'targeted renal' prophylaxis and treatment. The rationale is that local renal administration can improve the safety profile of many vasoactive agents. Recent studies confirm that higher doses of fenoldopam or other vasodilators can be administered intrarenally without the development of systemic hypotension.


CONCLUSIONS
Previous trials utilizing vasodilator therapy to stabilize renal function in AKI have given conflicting results. This study will critically review trial design and dose selection used in previous studies of vasodilator therapy in AKI. Lastly, the potential for high-dose therapy using intrarenal drug delivery systems will be discussed.
Tumlin
James A
JA
University of Tennessee College of Medicine Chattanooga, Chattanooga, Tennessee 37404, USA. jamestumlinmd@nephassociates.com
D058186:Acute Kidney Injury / Q000097:blood / Q000503:physiopathology*; D002404:Catheterization; D018818:Fenoldopam / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D012079:Renal Circulation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use
D014665:Vasodilator Agents; D018818:Fenoldopam