Pharmacologic Therapies
Loop Diuretics
There is significant controversy surrounding the use of loop diuretics in the prevention of AKI. Early experimental studies proposed that loop diuretics had the following theoretical advantages: decreased risk of tubular obstruction secondary to an increased urine flow and flushing out of debris; increased urine output that may be beneficial in itself, as nonoliguric AKI is associated with better outcomes than oliguric AKI; decreased risk of ischemic injury as the result of inhibition of the sodium/potassium chloride cotransporter and thus a reduction in oxygen demand; and enhanced renal blood flow due to increased availability of renal prostaglandins.63 However, clinical studies have been less favorable. Even though the majority of studies demonstrate that loop diuretics increase urine output, they lack beneficial effects on patient outcomes, such as mortality, need for RRT, and renal recovery.63–65 There is even some evidence of potential harm associated with their use, in particular, ototoxicity and possibly mortality in certain clinical settings.66 The proposed explanations for such lack of benefit are twofold. Loop diuretics may not be reaching the proximal tubule as their site of action due to tubular obstruction from debris, increased extrarenal clearance secondary to hypoalbuminemia, and increased urinary protein binding due to albuminuria. Also, loop diuretics may actually decrease renal blood flow by reducing effective circulating arterial volume, which, in turn, may stimulate the adrenergic and the renin-angiotensin systems.63
Sidebar: Clinical Controversy
Loop diuretics are widely used for the management of volume overload in critically ill patients, including those with concomitant AKI. Although volume overload is certainly an appropriate indication for loop diuretics, current evidence does not support their use for prevention of AKI or treatment of oliguria.
Dopamine Agonists
Dopamine is a nonselective dopamine receptor agonist that, in high doses, also stimulates the adrenergic receptors. Low doses of intravenous (IV) dopamine (2 mcg/kg/min) increase renal blood flow, induce natriuresis and diuresis, and might be expected to increase GFR. Theoretically, this could be considered beneficial, as an increase in renal perfusion and oxygenation might limit ischemic cell injury, inhibition of sodium transport might reduce oxygen demand, and an enhanced GFR might flush nephrotoxins and casts from the tubules. Despite these theoretical suggestions, controlled studies have found that low-dose dopamine did not prevent AKI, need for dialysis, or mortality compared with placebo.67,68 Thus, current evidence does not support the use of low-dose dopamine for prevention of AKI.
Sidebar: Clinical Controversy
Despite most studies not showing improved patient outcomes with its use, low-dose dopamine continues to be commonly used. The risks associated with dopamine (extravasation and the potential for significant dosing errors) suggest that its use should be avoided whenever possible.
Fenoldopam mesylate is a selective dopamine A-1 receptor agonist that increases renal blood flow, natriuresis, and diueresis. Although fenoldopam seems ineffective in preventing CIN, it may have some benefit in preventing AKI in critically ill patients or those undergoing surgery.