Definition

Renal injury caused by a pharmacologic agent used to diagnose or treat a medical disorder.

Pathophysiology

• Drugs can cause nephrotoxicosis by interfering with renal blood flow, glomerular function, tubular function, or interstitial inflammation.
• Many drugs are nephrotoxic because they are excreted primarily by the kidneys.
• Most nephrotoxic drugs cause proximal renal tubular necrosis.
• If renal injury is severe, acute kidney failure develops.

Systems Affected

• Renal/Urologic.
• Gastrointestinal-inappetence, vomiting, diarrhea, or melena due to gastrointestinal irritation or uremic ulceration.
• Endocrine/Metabolic-metabolic acidosis due to decreased elimination of acid by kidneys and inability to reclaim bicarbonate filtered into tubules by glomeruli.
• Hemic/Lymphatic/Immune-anemia due to blood loss or decreased red blood cell survival in patients with uremia; increased susceptibility to infections because of immune dysfunction in patients with uremia.
• Nervous-depression, lethargy associated with effect of uremic toxins on the central nervous system.
• Neuromuscular-weakness due to systemic effects of uremia.
• Respiratory-tachypnea or respiratory distress due to uremic pneumonitis or compensatory response for metabolic acidosis.

Signalment

Signs

Causes

Risk Factors

• Dehydration.
• Advanced age, probably because older patients have preexisting kidney disease.
• Kidney disease, inactive or active.
• Renal hypoperfusion; potential causes include any disorder associated with hypovolemia (e.g., vomiting, hemorrhage, hypoadrenocorticism), low cardiac output (e.g., congestive heart failure, pericardial disease, cardiac arrhythmias, inhalational anesthesia), or renal vasoconstriction (e.g., NSAID administration).
• Electrolyte and acid-base abnormalities including hypokalemia, hyponatremia, hypocalcemia, hypomagnesemia, and metabolic acidosis.
• Concurrent drug therapy-administration of furosemide increases nephrotoxicosis of aminoglycosides; treatment with cytotoxic drugs (e.g., cyclophosphamide) may increase nephrotoxic potential of drugs.
• Fever.
• Sepsis.

Differential Diagnosis

• Must differentiate from other causes of acute kidney injury (e.g., ethylene glycol toxicosis, raisin/grape ingestion [dogs], lily toxicosis [cats], renal ischemia, leptospirosis).
• Most patients have a history of recent treatment (i.e., within the previous 2 weeks) with a potentially nephrotoxic drug; acute kidney injury may occur several days after discontinuation of an aminoglycoside.
• Accidental ingestion of large doses of medications may occur, especially with palatable chewable formulations (prescribed for this patient or other animals).
• Determine all drugs that have been administered to the patient, including over-the-counter preparations (e.g., aspirin, ibuprofen, and naproxen) and medications prescribed for human use (e.g., NSAID or ACE inhibitor).

CBC/Biochemistry/Urinalysis

• Hemogram-usually normal unless concomitant problems exist (e.g., gastrointestinal hemorrhage associated with administration of NSAIDs).
• Biochemistry-normal in early stages of drug-induced nephrotoxicosis or reveals signs consistent with acute kidney injury including azotemia, hyperphosphatemia, and metabolic acidosis.
• Urinalysis-may reveal low urinary specific gravity (often <1.025), proteinuria, glucosuria, or cylindruria. Casts may be one of the earliest indicators of acute kidney injury.

Other Laboratory Tests

N/A

Imaging

N/A

Diagnostic Procedures

Renal biopsy may be indicated to determine cause of acute kidney injury and potential for reversibility, especially in patients that do not favorably respond to treatment as expected. The magnitude of renal morphologic changes may appear mild compared to the magnitude of azotemia.

Pathologic Findings

Most nephrotoxic drugs cause proximal renal tubular necrosis.

Appropriate Health Care

• Manage patients with acute kidney injury as inpatients.
• Manage patients without azotemia that can eat, and drink enough to maintain hydration, as outpatients.

Nursing Care

• Administer balanced polyionic fluid (e.g., lactated Ringer's solution).
• Correct hydration deficits rapidly (i.e., over 6–8 hours) to minimize further renal injury. Calculate volume of fluid to administer as follows: volume (mL) = body weight (kg) ×% dehydration × 1,000 mL.
• In addition to correcting hydration deficits, administer maintenance requirements (∼66 mL/kg/day) unless the patient is oliguric or anuric, and replace any ongoing losses caused by vomiting and diarrhea. As a minimum, assume that patients with acute kidney failure are losing 3–5% of their body weight because of ongoing losses.

Activity

Reduce

Diet

• Outpatients can be fed their regular food.
• Avoid oral feeding until vomiting is controlled, but initiate nutritional support as early as possible with acute kidney injury.
• If oral feeding is not possible initially, consider total or partial parenteral nutrition.
• The appropriate nutritional composition for patients with severe acute kidney injury has not been determined.
• Patients that recover from drug-induced nephrotoxicosis may develop chronic kidney disease, which should be managed by feeding a therapeutic renal diet indefinitely.

Client Education

• Provide unlimited access to clean, fresh water at all times.
• If any signs of illness such as inappetence, vomiting, or diarrhea develop, return the patient immediately for veterinary care to minimize worsening of renal function.

Surgical Considerations

• Avoid elective surgery until kidney disease is resolved.
• If surgery is necessary, administer fluids (5–20 mL/kg/h) during anesthesia to maintain adequate mean arterial blood pressure (>60 mmHg) and renal perfusion. Monitor urine output and adjust rate of fluid administration to maintain urine production of 1–2 mL/kg/h.

Drug(s) Of Choice

None

Contraindications

Do not use furosemide to promote diuresis in patients with aminoglycoside nephrotoxicosis.

Precautions

• Avoid drugs that may worsen renal injury in patients with nephrotoxicosis, including NSAIDs, vasodilators, and ACE inhibitors.
• Use less toxic drugs when possible (e.g., carboplatin instead of cisplatin, other effective antimicrobials instead of aminoglycosides).

Possible Interactions

N/A

Patient Monitoring

• Weigh hospitalized patients several times daily to detect changes in fluid balance and adjust fluid therapy accordingly.
• Perform biochemical analysis, including electrolytes, every 1–2 days to evaluate severity of azotemia and to detect electrolyte and acid/base abnormalities.
• Patients receiving aminoglycosides-perform urinalysis every 1–2 days to detect early signs of nephrotoxicosis such as glucosuria, increased proteinuria, and cylindruria; discontinue aminoglycoside if any of these signs are observed.
• Measure urine output to determine if patient is polyuric or oliguric; adjust fluid therapy on the basis of these findings and determine need for additional treatment to stimulate urine production. Do not overhydrate patient with parenteral fluids.

Prevention/Avoidance

• Avoid or correct risk factors that predispose to development of drug-induced nephrotoxicosis.
• Initiate saline diuresis to all dogs receiving cisplatin.
• Avoid using nephrotoxic drugs unless they are necessary (e.g., use aminoglycosides only if patient has overwhelming sepsis and culture results indicate aminoglycosides are the only effective antimicrobial).
• Monitor serum aminoglycoside concentration and perform frequent urinalyses while administering an aminoglycoside.
• Do not administer furosemide with an aminoglycoside as this combination is likely to enhance nephrotoxiccty of the aminoglycoside.

Possible Complications

• Acute kidney injury
• Chronic kidney disease

Expected Course and Prognosis

• Patients without azotemia may develop acute kidney injury after several days of exposure, especially to aminoglycosides.
• Renal injury caused by nephrotoxic drugs may lead to development of chronic kidney disease months to years after recovery from drug-induced renal injury.

Associated Conditions

N/A

Age-Related Factors

N/A

Pregnancy/Fertility/Breeding

N/A

See Also

Renal Failure, Acute

Abbreviations

• ACE = angiotensin converting enzyme
• NSAID = nonsteroidal anti-inflammatory drug

Authors Cathy E. Langston and Allyson C. Berent

Consulting Editor Carl A. Osborne

Acknowledgment The authors and editors acknowledge the prior contribution of S. Dru Forrester.