Calcium oxalate crystals in the kidneys.

As wildlife pathologists one of our goals is to determine the cause of death of wild animals submitted for necropsy. The first step of a necropsy is to do a macroscopic exam of the carcass, which is usually followed by a microscopic examination of organs sampled. Based on the findings from these, the pathologist will propose a cause of death. Depending of the severity and how extensive the observed lesions are, the pathologist will determine if these lesions are clinically significant or not. The causes of the lesions are attributed based on our knowledge and on the scientific literature in veterinary pathology. However, in some cases, the exact origin of the lesions found at necropsy remains unclear.

An example of these findings is the presence of microscopic calcium oxalate crystals, which can be observed occasionally in the kidney of different species of wild animals. The presence of calcium oxalate crystals in the kidneys of a sandhill crane (Grus canadensis) recently submitted for necropsy (Figure 1) made us wonder about the possible origins of these crystals.


Figure 1: A calcium oxalate crystal is seen in a renal tubule of a sandhill crane (Grus canadensis). These crystals, which have a broken glass appearance, are frequently associated with inflammatory cells. T: Normal renal tubules.

Calcium oxalate crystals are derived from oxalic acid which can precipitate in the renal tubules. When these crystals are present in large quantities, they can damage the renal cells and cause an acute renal failure, which could be fatal for the affected animal. Even if some causes of calcium oxalate depositions, such as ethylene glycol intoxication and the ingestion of oxalate-containing plants, are well documented, other causes, like Aspergillus spp. infections and contamination are not as well known. The objective of this short note is to explore the different causes for the calcium oxalate crystals formation in the kidneys of wild animals.

Ethylene glycol toxicity

Ethylene glycol is a substance mainly found in antifreeze liquids used in cooling systems of vehicles. This odourless substance has a sweet taste, making it palatable for some domestic and wild animal species. In domestic animals, this intoxication is often observed in dogs and is usually accidental. In wild animals, this intoxication can also be accidental, but voluntary poisonings are sometimes suspected, especially in raccoons, red foxes, coyotes and stripped skunks. Ethylene glycol toxicosis is mainly seen in the northern parts of North America where ethylene glycol containing products are widely used. Intoxicated animals can exhibit neurologic, cardiac and renal diseases.

Figure 2: Kidney of a racoon (Procyon lotor) with ethylene glycol toxicity. Note the large amount of calcium oxalate crystals in the renal tubules. The presence of these crystals is associated with renal tubular necrosis. T: Unaffected renal tubules. G: Renal glomerulus.

The most common clinical signs are incoordination, lethargy and staggering gait. Those clinical signs are caused by the deposition of calcium oxalate crystals in a variety of tissues, especially the brain, the liver and the kidneys. Ethylene glycol is rapidly metabolized via the liver into oxalic acid which precipitate in calcium oxalate in the renal tubules (Figure 2), causing acute renal insufficiency 24-72h after the ingestion.

Ingestion of plants containing oxalates

The consumption of oxalate-containing plants is another cause of deposition of calcium oxalate crystals in the kidneys. Several plants are known to contain either insoluble oxalates or soluble oxalates, which cause different toxic effects when ingested. Insoluble oxalates are found in a variety of house plants (Philodendron, Alocasia, Caladium and many others), but can also be found in indigenous plants. Intoxications by insoluble oxalates, which is rarely fatal in animals, cause mucosal and digestive irritations, vomiting and diarrhea. Soluble oxalates, which are found less frequently in plants, can be found in spinach, shamrock and rhubarb leaves (the stem does not contain oxalates). When ingested, soluble oxalates enter the blood circulation where they bind to serum calcium to form calcium oxalates. Then, calcium oxalates precipitate in the kidneys and create renal damage potentially leading to acute renal failure.

Aspergillus spp. infections and aflatoxins ingestion

Aspergillus spp. fungi can cause respiratory infections in domestic and wild animals. These fungi are ubiquitous, meaning that they are widely present in different environments. Animals become infected by inhaling spores. Birds are more susceptible to Aspergillus spp. infections because of their complex respiratory system, but infections are also reported in different species of mammals including people. In the majority of cases, infections by Aspergillus spp. affect immunocompromised animals (either caused by stress, emaciation, or concomitant infections). One of the metabolites produced by the aerobic metabolism of this fungi is called oxalic acid. In the animal’s body, the oxalic acid enters the blood flow where it binds to serum calcium and can precipitate in calcium oxalate at a physiologic pH, mainly in the lungs, liver, spleen, and kidneys. A correlation has been made between Aspergillus spp infections and calcium oxalate crystals in kidneys in different species, including in dogs, horses, cattle, dolphins and people.

In addition to systemic infection caused by Aspergillus spp, food contaminated with aflatoxins (produced by Aspergillus spp.) have been identified as a possible cause of calcium oxalate crystal depositions in the kidneys. This type of natural toxin can be found in mouldy food, such as cereal products left in fields.

Cause of calcium oxalate crystals in the sandhill crane

Even if the presence of calcium oxalate crystals in the kidneys of the submitted sandhill crane was associated with inflammatory changes, it was not believed that these renal changes were of clinical significance (no negative impact on this bird’s health). Nevertheless, the origin of this finding is intriguing. No evidence of infection with Aspergillus spp. was detected in this bird at necropsy. Ethylene glycol toxicity and ingestion of oxalate-containing plants are unlikely in this case considering the diet of this species. However, since cranes are known to eat large amount of grains, such as barley, in fields, ingestion of aflatoxin in mouldy grains could be a potential explanation for this finding. Interesting fact, the marked increased of the population of cranes in Quebec, which is actually good news, is also a source of growing conflicts with grains producers in some regions of the province due to the damages associated with the presence of these birds in the fields.

References

Franceschi VR, Nakata PA. Calcium oxalate in plants: formation and function. Annu Rev Plant Biol. 2005;56:41-71. doi: 10.1146/annurev.arplant.56.032604.144106. PMID: 15862089.

Kiser PK, Meritet DM, Bildfell RJ. Aspergillus Section Nigri-Associated Calcium Oxalate Crystals in an Eurasian Eagle Owl (Bubo bubo). Case Rep Vet Med. 2018;2018:3807059. Published 2018 Jun 12. doi:10.1155/2018/3807059

Payne CL, Dark MJ, Conway JA, Farina LL. A retrospective study of the prevalence of calcium oxalate crystals in veterinary Aspergillus cases. Journal of Veterinary Diagnostic Investigation. 2017;29(1):51-58. doi:10.1177/1040638716672254

Grauer, G. (2013) Overview of Ethylene Glycol Toxicity. Veterinary Merck Manual.

M. Rhaman et al. A Review of Oxalate Poisoning in Domestic animals: tolerance and performance aspects. Journal of Animal Physiology and Nutrition, 2012. DOI: 10.1111/j.1439-0396.2012.01309.x

Martin V. Dutton and Christine S. Evans. Oxalate production by fungi: its role in pathogenicity and ecology in the soil environment. Canadian Journal of Microbiology. 42(9): 881-895. https://doi.org/10.1139/m96-114

Contributors:

Marianne Thibodeau and Stéphane Lair, RCSF Québec

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