Lapis ISSN 2398-2969

Kidney: nephrotoxicity

Synonym(s): Toxicity in the kidneys

Contributor(s): Sarah Pellett, Lesa Thompson

Introduction

  • Cause: compounds that cause renal damage and usually cause acute renal failure. Compounds that have accumulated over time can cause chronic renal failure.
  • Signs: anorexia, lethargy, depression, dehydration, secondary gastrointestinal stasis, bruxism (pain response), renomegaly, oliguria or anuria.
  • Diagnosis: hematology, biochemistry, electrolytes, lead and zinc serology, full urinalysis, abdominal radiographs and ultrasonography.
  • Treatment: discontinue any nephrotoxic drugs, treat appropriately for any ingested toxins, fluid therapy, supportive therapy for gastrointestinal stasis and ulceration.
  • Prognosis: depends on underlying cause, but if diagnosed and treated quickly may be reversible and prognosis is fair to good provided the rabbit survives the initial period. Tubular regeneration can occur within 3 days in response to treatment. A full recovery may take several months or may not be possible. If there are insufficient functional nephrons remaining, the prognosis is grave to poor.
Print off the Owner factsheet on Nephrotoxicity - toxicity in the kidneys to give to your clients.

Pathogenesis

Etiology

  • Antimicrobials: nephrotoxic antibiotics in the rabbit include aminoglycosides, particularly gentamicin, and sulfonamides.
  • NSAIDs: inappropriate use of NSAIDs, or chronic exposure to therapeutic doses if in pre-existing renal insufficiency.
  • Chemotherapeutic agents: cisplatin and doxorubicin have been used in rabbits.
  • Intravenous radiographic contrast agents.
  • Anesthetic agents: tiletamine in the tiletamine/zolazepam anesthetic combination. Acute renal failure characterized by azotemia, proteinuria and the presence of tubular casts can be seen within 24 h of administering tiletamine via the intramuscular route.
  • Heavy metal: house rabbits with free access may have exposure to ingestion and lead-containing items.
  • Antifreeze: ingestion of ethylene glycol.
  • Pesticides, herbicides and solvent: ingestion of these products.
  • Potentiators of nephrotoxins: dehydration, diuretics, general anesthesia.
  • Endogenous nephrotoxins: calcium, myoglobin, hemoglobin.

Predisposing factors

General

  • Dehydration.
  • Decreased renal perfusion.
  • Pre-existing renal disease.

Specific

  • Administration of nephrotoxic drugs.
  • Exposure to other nephrotoxic products.

Pathophysiology

  • Aminoglycosides: decreased available surface in the glomeruli for ultrafiltration and increased glomerular permeability for negative proteins. All aminoglycosides have the potential to induce acute tubular necrosis.
  • NSAIDs: decreased renal prostaglandin synthesis -> decreased renal blood flow.

Timecourse

  • Ethylene glycol ingestion: acute presentation, signs of acute renal failure are reported within 12-72 h in other species.
  • Gentamicin accumulation: can result in acute renal failure approximately 5 days after administration in other species.

Diagnosis

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Treatment

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Prevention

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Outcomes

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Further Reading

Publications

Refereed papers

  • Recent references from PubMed and VetMedResource.
  • Cigremis Y, Akgoz M, Ozen H et al (2015) Resveratrol ameliorates cisplatin-induced oxidative injury in New Zealand rabbits. Can J Physiol & Pharm 93 (8), 727-735 PubMed.
  • Murphy L A (2015) Environmental toxicology: considerations for exotic pets. J Exotic Pet Med 24 (4), 390-397 VetMedResource.
  • Welle K R (2015) Pharmaceutical toxicoses. J Exotic Pet Med 24 (4), 403-407 VetMedResource.
  • Patil A N, Arora T, Desai A et al (2014) Comparison of the species-sensitive effects of different dosages of calcium and verapamil on gentamicin-induced nephrotoxicity in rats and rabbits. Toxicol Int 21 (3), 225-231 PubMed.
  • Ullah N, Azam Khan M, Khan T et al (2014) Protective potential of Tamarindus indica against gentamicin-induced nephrotoxicity. Pharm Biol 52 (4), 428-434 PubMed.
  • Rehman K, Akash M S, Azhar S et al (2012) A biochemical and histopathologic study showing protection and treatment of gentamicin-induced nephrotoxicity in rabbits using vitamin C. Afr J Trad Comp & Alt Meds 9 (3), 360-365 PubMed.
  • Ferguson M A, Vaidya V S & Bonventre J B (2008) Biomarkers of nephrotoxic acute kidney injury. Toxicology 245 (3), 182-193 PubMed.
  • Johnston M S (2008) Clinical toxicoses of domestic rabbits. Vet Clin North Am Exotic Anim Pract 11 (2), 315-326 PubMed.
  • Melillo A (2007) Rabbit clinical pathology. J Exotic Pet Med 16 (3), 135-145 VetMedResource.
  • Fisher P G (2006) Exotic mammal renal disease: causes and clinical presentation. Vet Clin North Am Exotic Anim Pract (1), 33-67 PubMed.
  • Alvarez A, Martul E, Veiga F et al (1994) Functional, histological, and ultrastructural study of the protective effects of verapamil in experimental ischaemic acute renal failure in the rabbit. Renal Failure 16 (2), 193-207 PubMed.
  • Enriquez J I Sr., Schydlower M, O'Hair K C et al (1992) Effect of vitamin B6 supplementation on gentamicin nephrotoxicity in rabbits. Vet Hum Toxicol 34 (1), 32-35 PubMed.
  • Brammer D W, Doerning B J, Chrisp C E et al (1991) Anaesthetic and nephrotoxic effects of Telazol in New Zealand white rabbits. Lab Anim Sci 41 (5), 432-435 PubMed.

Other sources of information

  • Mancinelli E & Lord B (2014) Urogenital System and Reproductive Disease. In: BSAVA Manual of Rabbit Medicine. Eds: Meredith A & Lord B. BSAVA, Gloucester. pp 191-204.
  • Fisher P G & Vella D (2013) Renal Disorders. In: Clinical Veterinary Advisor Birds and Exotic Pets. Eds: Mayer J & Donnelly T M. Elsevier, St Louis. pp 412-415.
  • Oglesbee B (2011) Renal Failure. In: Blackwell’s Five Minute Veterinary Consult – Rabbits and Rodents. Wiley-Blackwell, Chichester. pp 506-508.
  • Oglesbee B (2006) Poisoning (Intoxication). In: Blackwell’s Five Minute Veterinary Consult – Rabbits and Rodents. Blackwell, Ames (IA). pp 324-325.
  • Varga M (2014) Urogenital Diseases. In: Textbook of Rabbit Medicine. 2nd edn. Butterworth Heinemann Elsevier, Edinburgh. pp 405-424.


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