eMedicine Specialties > Nephrology > Acute Kidney Failure
Acute Renal Failure: Treatment & Medication
Updated: Aug 17, 2009
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
- Multimedia
Treatment
Medical Care
The mortality rate for patients in the intensive care unit (ICU) is higher in those who have AKI, especially when AKI is severe enough to require dialysis treatment. In addition, evidence suggests that the relative risk of death is 4.9 in patients in the ICU who have renal failure that is not severe enough to require dialysis. This reflects that the high mortality rate in patients with AKI who require dialysis may not be related to the dialysis procedure or accompanying comorbidities and that AKI alone may be an independent indicator of mortality.
- Aggressive treatment should begin at the earliest indication of renal dysfunction. A large proportion of the renal mass is damaged before any biochemical evidence of renal dysfunction is appreciated because the relationship between the GFR and the serum creatinine level is exponential, not linear. The rise of serum creatinine may not be evident before 50% of the GFR is lost.
- At this point, recognizing the presence of AKI and promptly initiating therapy aimed at minimizing the damage to the remaining functional renal mass are important considerations. This may also aid in reversing the renal damage that has already occurred. Reversing renal damage can be accomplished only by identifying the underlying cause and directing the appropriate therapy.
- Maintenance of volume homeostasis and correction of biochemical abnormalities remain the primary goals of treatment. Furosemide can be used to correct volume overload when the patients are still responsive to it. Furosemide plays no role in converting an oliguric AKI to a nonoliguric AKI or to increase urine output when a patient is not hypervolemic. However, the response to furosemide can be taken as a good prognostic sign. At this stage, the kidneys remain vulnerable to the toxic effects of various chemicals. All nephrotoxic agents (eg, radiocontrast agents, antibiotics with nephrotoxic potential, heavy metal preparations, cancer chemotherapeutic agents, NSAIDs) are either avoided or used with extreme caution. Similarly, all medications cleared by renal excretion should be avoided or their doses should be adjusted appropriately.
- Correcting acidosis with bicarbonate administration is important. It cannot be overstated that the current treatment of AKI is mainly supportive in nature and no therapeutic modalities to date have shown efficacy in treating the condition. Therapeutic agents, such as dopamine, fenoldopam, and mannitol, are not indicated in the management of AKI and may be harmful for the patient.
- Hyperkalemia, which can be life-threatening, should be treated by decreasing the intake of potassium, delaying the absorption of potassium, exchanging potassium across the gut lumen using potassium-binding resins, controlling intracellular shifts, and instituting dialysis, as outlined in the eMedicine article Hyperkalemia.
- Correcting hematologic abnormalities (eg, anemia, platelet dysfunction) warrants appropriate measures, including transfusions and administration of desmopressin or estrogens.
Diet
- Dietary modulation is an important facet of the treatment of AKI. Diet and fluid restriction become crucial in the management of oliguric renal failure, wherein the kidneys do not adequately excrete either toxins or fluids.
- Because potassium and phosphorus are not excreted optimally in patients with AKI, blood levels of these electrolytes tend to be high. Frequent measurements are mandatory to achieve acceptable blood levels by modification of the diet or by intravenous supplementation.
- In the polyuric phase of AKI, potassium and phosphorus may be depleted and patients require dietary supplementation and intravenous fluids.
- Calculation of the nitrogen balance can be challenging, especially in the presence of volume contraction, hypercatabolic states, gastrointestinal bleeding, and diarrheal disease.
Medication
Pharmacologic treatment of 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.
A prophylactic strategy shown to decrease the incidence of contrast nephropathy is the IV administration of fluids. Although controversy exists regarding the ideal fluid, normal saline and isotonic NaHCO 3 have proven to be effective. Normal saline solution of 1 mL/kg/h administered 12 hours before the procedure and then 12 hours after the procedure is recommended. In patients who are at high risk for volume overload, isotonic NaHCO 3 solution should be administered before and after the procedure. It can be prepared by mixing 3 ampules of NaHCO 3 in a liter of D5W and can be given at a rate of 3 mL/kg/h for 1 hour prior to the procedure; 1 mL/kg/h during the procedure; and for 6 hours afterward.
Another prophylactic agent, used with varying success, is N -acetylcysteine at a dosage of 1200 mg PO q12h. This is administered to high-risk patients the day before a contrast study is performed and is continued the day of the procedure. Diuretics, NSAIDs, and possibly ACEIs should be withheld near the time of the procedure.
Diuretics
Although diuretics seem to have no effect on the outcome of established AKI, they appear useful in fluid homeostasis and are used extensively. The use of isotonic sodium chloride solution in conjunction with diuretics is debatable. The only therapeutic or preventive intervention that has an established beneficial effect in the management of AKI is administration of isotonic sodium chloride solution to keep the patient euvolemic or even hypervolemic.
Furosemide (Lasix)
Increases excretion of water by interfering with chloride-binding cotransport system, which, in turn, inhibits sodium and chloride reabsorption in the thick ascending loop of Henle and the distal renal tubule. Potent and rapid-acting agent with peak action at 60 min and lasting 6-8 h.
In renal failure, higher doses must be used for greater diuretic effects. Doses as high as 600 mg/d may be needed under monitored conditions.
Frequently, IV doses are needed in AKI to maintain urine output. IV infusions are often helpful in ICU settings, in which larger doses are necessary. This method promotes a sustained natriuresis with reduced ototoxicity compared to conventional intermittent bolus dosing.
Adult
20-40 mg PO qd initially
Pediatric
Not established
Metformin decreases concentrations; interferes with hypoglycemic effect of antidiabetic agents and antagonizes muscle-relaxing effect of tubocurarine; auditory toxicity appears to be increased with coadministration of aminoglycosides or ethacrynic acid; hearing loss of varying degrees may occur; anticoagulant activity of warfarin may be enhanced when taken concurrently; increased plasma lithium levels and toxicity are possible when taken concurrently
Documented hypersensitivity; hepatic coma, anuria, and states of severe electrolyte depletion
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Perform frequent serum electrolyte, carbon dioxide, glucose, creatinine, uric acid, calcium, and BUN determinations during first few months of therapy and periodically thereafter; avoid using other nephrotoxic agents if possible
Vasodilators
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 prevent tubular cast obstruction. Most clinical studies have failed to establish this beneficial role of renal-dose dopamine infusion.
Dopamine (Intropin)
Stimulates both adrenergic and dopaminergic receptors. Hemodynamic effect is dose-dependent. Lower doses predominantly stimulate dopaminergic receptors, which, in turn, produce renal and mesenteric vasodilation. Cardiac stimulation and renal vasodilation produced by higher doses.
Adult
1-5 mcg/kg/min IV
Pediatric
Administer as in adults
Phenytoin, alpha-adrenergic and beta-adrenergic blockers, general anesthesia, and MAOIs increase and prolong effects
Documented hypersensitivity; pheochromocytoma or ventricular fibrillation
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Caution in hypertension, CVA, coronary heart disease, and dysrhythmias; closely monitor urine flow, cardiac output, pulmonary wedge pressure, and blood pressure during infusion; before infusion, correct hypovolemia with either whole blood or plasma, as indicated; monitoring central venous pressure or left ventricular filling pressure may be helpful in detecting and treating hypovolemia
Calcium channel blockers
Effective in animal models but efficacy not proven in humans. Effects are believed to be mediated through vasodilation, and calcium channel blockers increasingly are used to enhance the function of transplanted kidneys.
Nifedipine (Adalat, Procardia)
Relaxes smooth muscle and produces vasodilation, which, in turn, improves blood flow and oxygen delivery.
Adult
10-30 mg IR cap PO tid; not to exceed 120-180 mg/d
30-60 mg SR tab PO qd; not to exceed 90-120 mg/d
Pediatric
0.25-0.5 mg/kg/dose PO tid/qid prn
Caution with coadministration of any agent that can lower BP, including beta-blockers and opioids; H2 blockers (eg, cimetidine) may increase toxicity
Documented hypersensitivity
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
May cause lower extremity edema; allergic hepatitis has occurred rarely
N-acetylcysteine
Used for prevention of contrast toxicity in susceptible individuals such as those with diabetes mellitus.
N-acetylcysteine (Mucosil, Mucomyst)
May provide substrate for conjugation with toxic metabolites.
Adult
For prevention of nephrotoxicity: 600 mg PO bid on day preceding and day of procedure
Pediatric
Not established
None reported
Documented hypersensitivity
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
GI distress may occur
More on Acute Renal Failure |
| Overview: Acute Renal Failure |
| Differential Diagnoses & Workup: Acute Renal Failure |
 Treatment & Medication: Acute Renal Failure |
| Follow-up: Acute Renal Failure |
| Multimedia: Acute Renal Failure |
| References |
| Further Reading |
| « Previous Page | Next Page » |
References
Bellomo R, Ronco C, Kellum JA, Mehta RL, Palevsky P. Acute renal failure - definition, outcome measures, animal models, fluid therapy and information technology needs: the Second International Consensus Conference of the Acute Dialysis Quality Initiative (ADQI) Group. Crit Care. Aug 2004;8(4):R204-12. [Medline]. [Full Text].
[Best Evidence] Kheterpal S, Tremper KK, Heung M, Rosenberg AL, Englesbe M, Shanks AM, et al. Development and validation of an acute kidney injury risk index for patients undergoing general surgery: results from a national data set. Anesthesiology. Mar 2009;110(3):505-15. [Medline].
Goldberg R, Dennen P. Long-term outcomes of acute kidney injury. Adv Chronic Kidney Dis. Jul 2008;15(3):297-307. [Medline].
Feest TG, Mistry CD, Grimes DS, Mallick NP. Incidence of advanced chronic renal failure and the need for end stage renal replacement treatment. BMJ. Oct 20 1990;301(6757):897-900. [Medline]. [Full Text].
American College of Radiology. ACR Appropriateness Criteria® renal failure. National Guideline Clearinghouse. Available at http://www.guideline.gov/summary/summary.aspx?doc_id=8283&nbr=004615. Accessed May 20, 2009.
[Best Evidence] Ho KM, Morgan DJ. Meta-analysis of N-acetylcysteine to prevent acute renal failure after major surgery. Am J Kidney Dis. Jan 2009;53(1):33-40. [Medline].
[Best Evidence] Zacharias M, Conlon NP, Herbison GP, Sivalingam P, Walker RJ, Hovhannisyan K. Interventions for protecting renal function in the perioperative period. Cochrane Database Syst Rev. Oct 8 2008;CD003590. [Medline].
Agraharkar M, Safirstein RL. Pathophysiology of acute renal failure. In: Greenberg A, Coffman T, eds. Primer on Kidney Diseases. 3rd ed. San Diego, Calif: Academic Press; 2001:243-86.
Chertow GM, Christiansen CL, Cleary PD, et al. Prognostic stratification in critically ill patients with acute renal failure requiring dialysis. Arch Intern Med. Jul 24 1995;155(14):1505-11. [Medline].
Donohoe JF, Venkatachalam MA, Bernard DB, Levinsky NG. Tubular leakage and obstruction after renal ischemia: structural-functional correlations. Kidney Int. Mar 1978;13(3):208-22. [Medline].
[Best Evidence] Marenzi G, Assanelli E, Marana I, et al. N-acetylcysteine and contrast-induced nephropathy in primary angioplasty. N Engl J Med. Jun 29 2006;354(26):2773-82. [Medline].
Merten GJ, Burgess WP, Gray LV, et al. Prevention of contrast-induced nephropathy with sodium bicarbonate: a randomized controlled trial. JAMA. May 19 2004;291(19):2328-34. [Medline].
Mitch WE, Klahr S. Handbook of Nutrition and the Kidney. 4th ed. Philadelphia: Lippincott Williams & Wilkins.
Safirstein R, Bonventre JV. Molecular response to ischemic and nephrotoxic acute renal failure. In: Schlondorff D, Bonventre JV, eds. Molecular Nephrology. New York: Marcel Dekker; 1995:839-54.
Schrier RW, Wang W, Poole B, Mitra A. Acute renal failure: definitions, diagnosis, pathogenesis, and therapy. J Clin Invest. 114(1):5-14. [Medline].
Solomon R, Werner C, Mann D, et al. Effects of saline, mannitol, and furosemide to prevent acute decreases in renal function induced by radiocontrast agents. N Engl J Med. Nov 24 1994;331(21):1416-20. [Medline].
Thadhani R, Pascual M, Bonventre JV. Acute renal failure. N Engl J Med. May 30 1996;334(22):1448-60. [Medline].
Tonelli M, Manns B, Feller-Kopman D. Acute renal failure in the intensive care unit: a systematic review of the impact of dialytic modality on mortality and renal recovery. Am J Kidney Dis. Nov 2002;40(5):875-85. [Medline].
van Bommel E, Bouvy ND, So KL, et al. Acute dialytic support for the critically ill: intermittent hemodialysis versus continuous arteriovenous hemodiafiltration. Am J Nephrol. 1995;15(3):192-200. [Medline].
Further Reading
Related eMedicine topics:
Acute Tubular Necrosis [Nephrology]
Acute Tubular Necrosis [Pediatrics: General Medicine]
Glomerulonephritis, Acute [Emergency Medicine]
Glomerulonephritis, Acute [Nephrology]
Glomerulonephritis, Rapidly Progressive
Hemolytic Uremic Syndrome [Emergency Medicine]
Hemolytic-Uremic Syndrome [Hematology]
Hemolytic Uremic Syndrome [Neurology]
Hemolytic-Uremic Syndrome [Pediatrics: General Medicine]
Renal Cortical Necrosis
Renal Failure, Acute
Clinical guidelines:
ACR Appropriateness Criteria® renal failure. American College of Radiology - Medical Specialty Society. 1995 (revised 2005). 8 pages. [NGC Update Pending] NGC:004615
Clinical practice guidelines for managing dyslipidemias in chronic kidney disease. National Kidney Foundation - Disease Specific Society. 2003 Apr. 91 pages. NGC:003133
Clinical trials:
A Dose Escalation and Safety Study of I5NP to Prevent AKI in Patients Undergoing Major Cardiovascular Surgery (QRK.002)
Cystatin C as a Marker for Detecting Early Renal Dysfunction in a Pediatric Emergency Department (CARING)
Phase I Study of Alpha-Melanocyte Stimulating Hormone in Patients With Acute Renal Failure
The Use of Nesiritide in Thoracic Aneurysm Repair to Prevent Acute Renal Failure
Use of Bicarbonate to Reduce the Incidence of Acute Renal Failure After Cardiac Surgery
Keywords
acute renal failure, kidney disease, renal failure, kidney failure, renal disease, acute renal, glomerulonephritis, dialysis renal, oliguria, anuria, hypotension, acute kidney failure, acute tubular necrosis, chronic renal failure, tumor lysis syndrome, ethylene glycol poisoning, vasculitis, intrinsic renal failure, interstitial renal disease, renal dysfunction, renal artery occlusion, urethral stricture, bladder outlet obstruction, prostate enlargement, interstitial nephritis, renovascular disease, bladder cancer, epigastric bruit, diabetic ketoacidosis, pancreatitis, hypercalcemia, prostaglandin inhibition, ischemic tubular necrosis, crescentic glomerulonephritis, postinfective glomerulonephritis, lupus nephritis, hepatitis, vasculitis-associated glomerulonephritides, prostatic hypertrophy
