Reptiles, amphibians, and other non-mammalian vertebrates have a renal portal system, which functions to provide blood to the kidney's tubule cells during periods of water scarcity. This route of blood circulation directs venous blood returning from the caudal body wall and extremities through the iliac and femoral veins, to the renal portal vein and through the kidneys, before returning to the heart to be circulated through the rest of the body. (Fox, 1977; Holz, 1999; Murray, 1996) There is concern that when administering nephrotoxic drugs to reptiles and amphibians, injecting into the caudal third of the body (hind limbs and tail) may lead to kidney damage (i.e.: drug-induced renal failure) and that an amount of the drug could be excreted before being circulated, reducing its intended effect. (Klingenberg, 1996; Jenkins, 1996; Maxwell and Helmick, 2003; Wilson, 2002) Chelonians (Beck et al., 1995; Fox, 1977; Holz et al., 1997) and crocodilians (Fox, 1977) do not seem to be as affected by injecting nephrotoxic drugs into the caudal third of the body due to the presence of a hepatic portal system in addition to the renal portal system.

Source:
Drug-induced renal failure may occur if potentially nephrotoxic drugs are injected into the hind limbs or tail of reptiles and amphibians (excluding chelonians and crocodilians). (Klingenberg, 1996; Jenkins, 1996; Maxwell and Helmick, 2003) As mentioned above, this is due to the nature of the renal portal system. Nephrotoxic drugs include, but are not limited to, aminoglycosides, cephalosporins, tetracyclines, and acyclovir. (Merck and Co., Inc., 2005; Wanamaker and Massey, 2004)

Clinical Signs:
Renal failure may not have very specific clinical signs: Anorexia, bloat, lethargy, constipation, and paresis. When severe, polyuria and polydipsia often occur. If the illness progresses to the point where the animal displays ataxia and convulsions, the prognosis is typically poor. Plasma uric acid, total protein, and calcium:phosphorus ratios may be indicative, but a thorough history of the patient's nutrition, husbandry factors, and clinical history is vital. The kidneys may be enlarged and easily palpated. Visceral or articular gout usually occurs due to elevated levels of uric acid in the bloodstream. (Barten, 1996; Done, 1996; Frye, 1991; Kaplan, 2000; Wilson, 2002)

Pathophysiology:
Nephrotoxic drugs of concern are those that are directly damaging to cells, and are primarily eliminated through the urinary system via the kidneys. Each particular drug's action against the cells of the nephron varies. Antibiotics, such as aminoglycosides, cephalosporins and tetracyclines, are the most commonly used nephrotoxic drugs in reptiles and amphibians. These drugs will bind to cells in the glomerular tubules and inhibit their function. This compromises these cells' ability to function and decreases the kidney's overall ability to excrete wastes, which are then forced to accumulate in the bloodstream and cause a number of problems. (Merck and Co., Inc., 2005)

Treatment:
If renal failure occurs due to improper administration of nephrotoxic drugs, injections of the drug should cease and the animal should be treated according to symptoms. Keeping the animal within its preferred optimal temperature range is absolutely vital to promote proper bodily functions. (Hernandez-Divers, 1999; Done, 1996; Kaplan, 2000)

For acute kidney failure, rehydration using 0.18% saline and 4% glucose at 20-40 mL/kg/day IV or IO is suggested. Once the animal has been rehydrated, maintenance fluids of 2-10 mL/kg/day should continue to be administered, and overhydration should be avoided. If levels of uric acid in the blood are particularly elevated, allopurinol may be administered at 20 mg/kg PO once a day to attempt to reduce hepatic uric acid production. If the patient remains oliguric, diuresis may be induced by administering 20% dextrose IV or IO at 0.4-1.0 mL/kg/hr for 30-60 minutes then reduced to 0.2-0.5 mL/kg/hr. If the patient still remains oliguric, coelomic dialysis may be attempted. (Hernandez-Divers, 1999)

In cases of chronic renal failure from long-term usage of nephrotoxic drugs, the patient should be stabilized as with acute renal failure, and long term therapy must be instigated. Reduction of protein intake, usage of phosphate binders, correcting hypocalcaemia through oral calcium supplements, taking extra measures to prevent dehydration, considering anabolic steroids and vitamin B complex every 7-28 days, avoiding undue stress through proper husbandry, and avoiding any further use of nephrotoxic drugs are all included in long term therapy for a reptile or amphibian that has suffered from chronic renal failure. (Hernandez-Divers, 1999)

Prevention:
The renal portal system should be avoided in reptiles and amphibians (possibly excluding chelonians and crocodilians) when administering potentially nephrotoxic drugs. This is accomplished by giving injections in the cranial half of the body, instead of the caudal half (including the hind limbs and tail). (Kaplan, 2000; Klingenberg, 1996; Maxwell and Helmick, 2003) Additionally, the use of any nephrotoxic drugs is contraindicated in any reptile or amphibian that has compromised kidney function. (Jacobson, 2001)


References

Barten, S.L. 1996. "Lizards" in Mader, D.M. (ed): Reptile Medicine and Surgery. W.B. Saunders Co., Philadelphia, PA. 324-332.

Beck, K., M. Loomis, G. Lewbart, L. Spelman and L. Papich. 1995. Preliminary comparison of plasma concentrations of gentamicin injected into the cranial and caudal limb musculature of the eastern box turtle (Terrapene carolina carolina). J Zoo Wildl Med. 26: 265-268.

Done, L.B. 1996. "Postural Abnormalities" in Mader, D.M. (ed): Reptile Medicine and Surgery. W.B. Saunders Co., Philadelphia, PA. 406-411.

Fox, H. 1977. "The urogenital system of reptiles," in Gans, C. and Parsons, T. (eds): Biology of the Reptilia: Morphology E. Vol. 6. Academic Press, London and New York. 1-157.

Frye, F. L. 1991. Reptile Care: An Atlas of Diseases and Treatments, Volume 1. T.F.H. Publications, Inc., New Jersey.

Hernandez-Divers, D.J. 1999. "Clinician's Approach to Renal Disease in Lizards." Proceedings of the ARAV, October 24-27, Sacramento, CA.

Holz, P.H., I.K. Barker, J.P. Burger, G.J. Crawshaw and P.D. Conlon. 1997. The effect of the renal portal system on pharmacokinetic parameters in the red-eared slider (Trachemys scripta elegans). J Zoo Wildl Med. 28 [4]: 386-393.

Holz, P.H. 1999. The Reptilian Renal Portal System - A Review. Assoc Reptilian Amphibian Vet. 9 [1]: 4-9.

Jacobson, E.R. 2001. "Antimicrobial Therapy in Reptiles." University of Florida College of Veterinary Medicine. <http://www.vetmed.ufl.edu/sacs/wildlife/antimicrobialtherapy> (April 6, 2005)

Jenkins, J.R. 1996. "Diagnostic and Clinical Techniques" in Mader, D.M. (ed): Reptile Medicine and Surgery. W.B. Saunders Co., Philadelphia, PA. 264-276.

Kaplan, M. 2000. "Protein, Gout and Renal Failure in Reptiles." Anapsid.org. <http://www.anapsid.org/kidney.html> (April 6, 2005)

Klingenberg, R.J. 1996. "Therapeutics" in Mader, D.M. (ed): Reptile Medicine and Surgery. W.B. Saunders Co., Philadelphia, PA. 299-321.

Maxwell, L.K. and K.E. Helmick. 2003. "Drug Dosages and Chemotherapeutics" in Jacobson, E.R. (ed): Biology, Husbandry and Medicine of the Green Iguana. Krieger Publishing Company, Malabar, FL. 133-151.

Murray, M.J. 1996. "Cardiology and Circulation" in Mader, D.M. (ed): Reptile Medicine and Surgery. W.B. Saunders Co., Philadelphia, PA. 95-104.

Wanamaker, B.P. and K.L. Massey. 2004. Applied Pharmacology for the Veterinary Technician. 3rd Edition. Saunders, St. Louis, MS.

Wilson, H. 2002. "Disease Management of the Green Iguana." <http://www.vetsoftware.com/acvc2002-wilson3.htm> (April 6, 2005)

Last modified: Friday, March 10, 2006