Acute Kidney Injury Medication
- Author: Biruh T Workeneh, MD, PhD; Chief Editor: Vecihi Batuman, MD, FACP, FASN more...
Pharmacologic treatment of acute kidney injury (AKI) has been attempted on an empiric basis with varying success rates. Several promising experimental therapies in animal models are awaiting human trials. Experimental therapies include growth factors, vasoactive peptides, adhesion molecules, endothelin inhibitors, and bioartificial kidneys. Aminophylline has also been used experimentally for prophylaxis against renal failure.
There is no specific pharmacologic therapy proven to treat AKI secondary to hypoperfusion and/or sepsis. The only therapeutic or preventive intervention that has an established beneficial effect in the management of AKI is the intravenous (IV) administration of isotonic sodium chloride solution. It should be given in quantities sufficient to keep the patient euvolemic or even hypervolemic.
Although diuretics seem to have no effect on the outcome of established AKI, they appear to be useful in fluid homeostasis and are used extensively. They have also been used to reduce the requirement for renal replacement therapy. The use of isotonic sodium chloride solution in conjunction with diuretics is debatable.
Furosemide increases the excretion of water by interfering with the chloride-binding cotransport system, which, in turn, inhibits sodium and chloride reabsorption in the thick ascending loop of Henle and the distal renal tubule. It is a potent and rapid-acting agent with peak action at 60 minutes and a 6- to 8-hour duration of action.
In renal failure, higher doses must be used for greater diuretic effect. Doses as high as 600 mg/day may be needed under monitored conditions.
Frequently, IV doses are needed in AKI to maintain urine output. IV infusions are often helpful in intensive care settings, in which larger doses are necessary. This method promotes a sustained natriuresis with reduced ototoxicity compared with conventional intermittent bolus dosing.
Dopamine in small doses (eg, 1-5 mcg/kg/min) causes selective dilatation of the renal vasculature, enhancing renal perfusion. Dopamine also reduces sodium absorption, thereby decreasing the energy requirement of the damaged tubules. This enhances urine flow, which, in turn, helps to prevent tubular cast obstruction. The clinical benefit of low-dose dopamine remains uncertain.
Dopamine stimulates adrenergic and dopaminergic receptors. Its hemodynamic effect is dose dependent. Lower doses (0.5-3.0 mcg/kg/min) predominantly stimulate dopaminergic receptors, which, in turn, produce renal and mesenteric vasodilation. Higher doses produce cardiac stimulation and renal vasodilation. Potential complications of dopamine use include cardiac arrhythmias, myocardial ischemia, and intestinal ischemia.
Fenoldopam decreases systemic vascular resistance and increases renal blood flow to the cortex and medullary regions in the kidney. It has been noted to improve renal function in patients with severe hypertension.
Fenoldopam is a selective dopamine-receptor agonist that acts as a rapid-acting vasodilator. It is 6 times more potent than dopamine in producing renal vasodilation. It increases diuresis and has minimal adrenergic effects. Fenoldopam is indicated for the treatment of severe hypertension, including patients with renal compromise.
Calcium Channel Blockers
These drugs are effective in animal models of AKI, but their efficacy has not been proven in humans. The effects of calcium channel blockers are believed to be mediated through vasodilation, and they are increasingly used to enhance the function of transplanted kidneys.
Nifedipine relaxes smooth muscle and produces vasodilation, which, in turn, improves blood flow and oxygen delivery.
N -acetylcysteine is used for the prevention of contrast toxicity in susceptible individuals, such as those with diabetes mellitus. The mechanism by which it prevents contrast-induced nephropathy is presumed to be its ability to scavenge free radicals and improve endothelium-dependent vasodilation.
This drug may provide substrate for conjugation with toxic metabolites.
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|Stage||GFR** Criteria||Urine Output Criteria||Probability|
|Risk||SCreat† increased × 1.5
GFR decreased >25%
|UO‡ < 0.5 mL/kg/h × 6 h||High sensitivity (Risk >Injury >Failure)|
|Injury||SCreat increased × 2
GFR decreased >50%
|UO < 0.5 mL/kg/h × 12 h|
|Failure||SCreat increased × 3
GFR decreased 75%
SCreat ≥4 mg/dL; acute rise ≥0.5 mg/dL
|UO < 0.3 mL/kg/h × 24 h
anuria × 12 h
|Loss||Persistent acute renal failure: complete loss of kidney function >4 wk||High specificity|
|ESKD*||Complete loss of kidney function >3 mo|
|*ESKD—end-stage kidney disease; **GFR—glomerular filtration rate; †SCreat—serum creatinine; ‡UO—urine output
Note: Patients can be classified by GFR criteria and/or UO criteria. The criteria that support the most severe classification should be used. The superimposition of acute on chronic failure is indicated with the designation RIFLE-FC; failure is present in such cases even if the increase in SCreat is less than 3-fold, provided that the new SCreat is greater than 4.0 mg/dL (350 µmol/L) and results from an acute increase of at least 0.5 mg/dL (44 µmol/L).
|Stage||Serum Creatinine Criteria||Urine Output Criteria|
|1||Increase of ≥0.3 mg/dL (≥26.4 µmol/L) or 1.5- to 2-fold increase from baseline||< 0.5 mL/kg/h for >6 h|
|2||>2-fold to 3-fold increase from baseline||< 0.5 mL/kg/h for >12 h|
|3*||>3-fold increase from baseline, or increase of ≥ 4.0 mg/dL (≥35.4 µmol/L) with an acute increase of at least 0.5 mg/dL (44 µmol/L)||< 0.3 mL/kg/h for 24 h or anuria for 12 h|
|*Patients who receive renal replacement therapy (RRT) are considered to have met the criteria for stage 3 irrespective of the stage they are in at the time of RRT.|