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Medication

Medication Summary

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 kidney 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 crystalloid solution. It should be given in quantities sufficient to keep the patient euvolemic or even hypervolemic.

Class Summary

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 (Lasix)

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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 (Intropin)

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Dopamine stimulates adrenergic and dopaminergic receptors. Its hemodynamic effect is dose dependent. In small doses (eg, 0.5-3.0 mcg/kg/min), dopamine predominantly stimulates dopaminergic receoptors, which, in turn produce vasodilation 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. Higher doses produce cardiac stimulation and renal vasodilation. Potential complications of dopamine use include cardiac arrhythmias, myocardial ischemia, and intestinal ischemia.

Fenoldopam (Corlopam)

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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 renal blood flow to the cortex and medullary regions in the kidney, increases diuresis , and has minimal adrenergic effects. Fenoldopam is indicated for the treatment of severe hypertension, including patients with renal compromise.

Class Summary

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 (Adalat, Procardia, Afeditab CR, Nifediac CC, Nifedical XL)

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Nifedipine relaxes smooth muscle and produces vasodilation, which, in turn, improves blood flow and oxygen delivery.

N-acetylcysteine (Acetadote)

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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.

Questions

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Media Gallery

Pigmented, muddy brown, granular casts are visible in the urine sediment of a patient with acute tubular necrosis (400x magnification).
Photomicrograph of a kidney biopsy specimen shows renal medulla, which is composed mainly of renal tubules. Features suggesting acute tubular necrosis are the patchy or diffuse denudation of the renal tubular cells with loss of brush border (blue arrows); flattening of the renal tubular cells due to tubular dilation (orange arrows); intratubular cast formation (yellow arrows); and sloughing of cells, which is responsible for the formation of granular casts (red arrow). Finally, intratubular obstruction due to the denuded epithelium and cellular debris is evident (green arrow); note that the denuded tubular epithelial cells clump together because of rearrangement of intercellular adhesion molecules.

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Table 1. RIFLE Classification System for Acute Kidney Injury

Stage	GFR Criteria	Urine Output Criteria	Probability
Risk	SCreat increased × 1.5 or GFR decreased >25%	UO < 0.5 mL/kg/h × 6 h	High sensitivity (Risk >Injury >Failure)
Injury	SCreat increased × 2 or GFR decreased >50%	UO < 0.5 mL/kg/h × 12 h
Failure	SCreat increased × 3 or GFR decreased 75% or SCreat ≥4 mg/dL; acute rise ≥0.5 mg/dL	UO < 0.3 mL/kg/h × 24 h (oliguria) or 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		High specificity
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-F_C; 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).

Table 2. Acute Kidney Injury Network Classification/Staging System for AKI

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.

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Author

Biruh T Workeneh, MD, FASN Professor of Medicine, University of Texas MD Anderson Cancer Center

Biruh T Workeneh, MD, FASN is a member of the following medical societies: American Society of Nephrology, National Kidney Foundation

Disclosure: Nothing to disclose.

Coauthor(s)

Omar Mamlouk, MBBS Instructor, Division of Internal Medicine, The University of Texas MD Anderson Cancer Center

Omar Mamlouk, MBBS is a member of the following medical societies: American Society of Nephrology, American Society of Onconephrology, National Kidney Foundation, Texas Medical Association

Disclosure: Nothing to disclose.

Specialty Editor Board

Eleanor Lederer, MD, FASN Professor of Medicine, Chief, Nephrology Division, Director, Nephrology Training Program, Director, Metabolic Stone Clinic, Kidney Disease Program, University of Louisville School of Medicine; Consulting Staff, Louisville Veterans Affairs Hospital

Eleanor Lederer, MD, FASN is a member of the following medical societies: American Association for the Advancement of Science, American Society for Bone and Mineral Research, American Society of Nephrology, American Society of Transplantation, International Society of Nephrology, Kentucky Medical Association, National Kidney Foundation

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: American Society of Nephrology<br/>Received income in an amount equal to or greater than $250 from: Healthcare Quality Strategies, Inc.

Chief Editor

Vecihi Batuman, MD, FASN Professor of Medicine, Section of Nephrology-Hypertension, Deming Department of Medicine, Tulane University School of Medicine

Vecihi Batuman, MD, FASN is a member of the following medical societies: American College of Physicians, American Society of Hypertension, American Society of Nephrology, Southern Society for Clinical Investigation

Disclosure: Nothing to disclose.

Additional Contributors

Mahendra Agraharkar, MD, MBBS, FACP, FASN Clinical Associate Professor of Medicine, Baylor College of Medicine; President and CEO, Space City Associates of Nephrology

Mahendra Agraharkar, MD, MBBS, FACP, FASN is a member of the following medical societies: American College of Physicians, American Society of Nephrology, National Kidney Foundation

Disclosure: Nothing to disclose.

Rajiv Gupta, MD Assistant Professor, Department of Medicine, Texas A&M University College of Medicine; Consulting Staff, Veterans Affairs Medical Center

Rajiv Gupta, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Cardiology, Society for Cardiovascular Angiography and Interventions

Disclosure: Nothing to disclose.

Acknowledgements

Aruna Agraharkar, MD, FACP Consulting Staff, Department of Gerontology, Space Center Clinic

Aruna Agraharkar, MD, FACP is a member of the following medical societies: American Medical Assocation

Disclosure: Nothing to disclose.

Eleanor Lederer, MD Professor of Medicine, Chief, Nephrology Division, Director, Nephrology Training Program, Director, Metabolic Stone Clinic, Kidney Disease Program, University of Louisville School of Medicine; Consulting Staff, Louisville Veterans Affairs Hospital

Eleanor Lederer, MD is a member of the following medical societies: American Association for the Advancement of Science, American Federation for Medical Research, American Society for Biochemistry and Molecular Biology, American Society for Bone and Mineral Research, American Society of Nephrology, American Society of Transplantation, International Society of Nephrology, Kentucky Medical Association, National Kidney Foundation, and Phi Beta Kappa

Disclosure: Dept of Veterans Affairs Grant/research funds Research

Laura Lyngby Mulloy, DO, FACP Professor of Medicine, Chief, Section of Nephrology, Hypertension, and Transplantation Medicine, Glover/Mealing Eminent Scholar Chair in Immunology, Medical College of Georgia

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Acute Kidney Injury (AKI) Medication

Medication Summary

Diuretics, Loop