CASE NOTES

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RENAL FAILURE IN CALVES CAUSED BYAMARANTHUS RETROFLEXUS

Lucienne Downs, District Veterinarian, Central Tablelands LLS andCharlotte Campbell, Final Year Veterinary Student, CSU Wagga Wagga

Posted Flock & Herd September 2015

Introduction

Ingestion of Amaranthus retroflexus (Figure 1) is associated with two syndromes of poisoning in cattle: toxic nephrosis and methaemoglobinaemia due to nitrate-nitrite poisoning. The plant contains an unidentified compound that damages kidneys and, in certain circumstances, toxic amounts of soluble oxalates and nitrate^1,2,3. Cattle, sheep, goats and pigs are susceptible to kidney failure from ingesting A. retroflexus. Renal failure may result from the effects of the nephrotoxin or soluble oxalates. Ruminants may succumb to nitrate-nitrite poisoning as nitrate is converted to nitrite in the rumen^1,2,3.

Cases of nephrotoxicity in cattle attributed to A. retroflexus have been reported infrequently in the veterinary literature in USA^4,5,6, Canada,⁷ Brazil,⁸ South Africa,⁹ and Slovenia.¹⁰ A literature search found no Australian reports of A. retroflexus poisoning cattle in the peer reviewed literature. At ANZCVS Science Week in 1986, a case of Amaranthus sp. poisoning in cattle causing the death of 21 of 23 dairy heifers was reported.¹¹ Case reports involving sheep have been recorded Mexico,¹² Canada,¹³ New Zealand¹⁴ and Australia.² There are a number of reports of Amaranthus species poisoning pigs.^14,15

In this case report the calves had renal failure attributed to the ingestion of A. retroflexus. Nitrate-nitrite poisoning was ruled out on the basis of history, clinical signs and laboratory findings.

Figure 1. Amaranthus retroflexus

History

Five of forty calves died in February 2015 on a property in Mandurama, in the Central Tablelands. The 4-5 month old calves weighed approximately 120-140kg and were still suckling mixed breed cows. The mob had been grazing a paddock for 10 days when the first calf was found dead. The next day another two calves were dead and the mob was moved. A number of calves appeared slow and weak. Their demeanor improved over the following two days and the District Veterinarian was contacted for advice. Another two calves died, four and seven days after they were removed from the at risk paddock. No adult cows died or appeared unwell. The stock had been vaccinated against clostridial diseases.

Pasture in the eight hectare paddock was predominantly cocksfoot (Dactylis glomerata) and phalaris (Phalaris aquatica) and had been spelled. The owner noted the presence of a mature stand of a plant known locally as “Prince of Wales Feather”. On inspection the plant was identified as A. retroflexus. This was confirmed by the National Herbarium of NSW. It comprised approximately 5% of the herbage mass of the paddock and had been heavily grazed.

The stock had not been denied feed prior to accessing the paddock and there was adequate alternative forage available. These animals had been purchased from outside of the area approximately four months earlier. The producer noted that the stock readily consumed the A. retroflexus and consumed this plant preferentially when moved to another paddock where there was less of this plant, appearing to be “addicted” to it which aroused his suspicions. In previous years, other stock had grazed this plant without apparent ill-effects.

CLINICAL EXAM

Three calves were selected by the owner for examination as they had been quiet, recumbent and reluctant to move. These calves stood with their heads down when left alone. They were otherwise normal on physical exam apart from pale gums seen in calf 2 and calf 3.

Laboratory Findings

Blood was taken from all three calves for a ruminant biochemistry, complete blood counts and nitrate and nitrite levels. The nitrite and nitrate levels for all animals were normal ruling out nitrate poisoning. Haemograms in all animals were normal. Calf 1 had normal blood biochemistry.

	Range	Calf 2	Calf 3
Urea	2.1-10.7 mmol/L	72.9	85.1
Creatinine	0-186 umol/L	1403	1867
Creatinine kinase	0-300 mmol/L	348	1033
Calcium	2-2.75 mmol/L	1.38	1.28
Protein	60-85 g/L		95
Phosphorus	0.8-2.8 mmol/L		5.54

Table 1. Biochemistry results for two affected calves

The specific gravity of calf 2 (post-mortem sample) was minimally concentrated at 1.015. No oxalate crystals were found in the urine.

Post-mortem findings

Calf 3 died the day after the blood samples were taken but was not made available for a post-mortem. Calf 2 was given supportive treatment consisting of oral electrolytes and fluids on two occasions after the blood samples were taken. More intensive treatment was discussed but not considered feasible. The calf was quite difficult to catch in the paddock and appeared to be improving. It was observed to be eating and nursing but died 6 days after the blood sample was taken. When found the calf, which was in a dam, was too decomposed to perform a meaningful necropsy. Calf 1 appeared to recover.

Discussion

The history, clinical signs, laboratory findings and identification of the plant that had been grazed implicated A. retroflexus as the cause of renal failure in these calves.

A. retroflexus, originally from tropical America, is now a weed in NSW, Victoria, Tasmania, SA and WA. It invades summer crops, cultivated fields, paddocks, gardens, disturbed habitats, open ground and roadsides.² It is a strong competitor and is capable of supplanting other species. All parts of the plant may induce kidney failure, oxalates are concentrated in the leaves and the stems and leaves can contain toxic amounts of nitrate.¹

Clinical signs in cattle due to consumption of A. retroflexus are variable and have been reported to include: depression,^6,8,11 dehydration,⁵ weakness,^5,6, inco-ordination,⁸ ataxia,^7,9 recumbency,^5,9 recumbency with signs resembling hypocalcaemia,⁶ trembling,^5,6 ventral subcutaneous oedema,^7,8,9 mild serosanguinous nasal discharge,⁸ diarrhoea (with or without blood)^8,11 and death within 10 days of exposure to the toxic plant.^{1,4,5,6,7,8,9,10} Affected cattle may partially or temporarily respond to treatments containing calcium borogluconate.^4,6 In cases reported in the literature, morbidity rates vary from 5-40% and of those, mortality rates range from 50-100%.

The biochemistry results indicate renal azotaemia in calf two and three. This is based on severe azotaemia, lack of clinical evidence of dehydration, no laboratory evidence of severe pre-renal azotaemia (mild hyperproteinaemia in calf three only) and no clinical or post-mortem evidence of post-renal azotaemia.¹⁶ Azotaemia is reported in cases of A. retroflexus toxicity in cattle when it has been measured.^4,5 The marked phosphorus disruptions seen in this case occur with renal failure due to the reduced glomerular filtration rate.¹⁶

A. retroflexus is known to contain potentially toxic amounts of soluble oxalates. Ruminants are able to detoxify some oxalate in the rumen thereby preventing the absorption of the soluble oxalates. Prior adaptation of the rumen microflora allows more soluble oxalates to be eaten safely. Poisoning occurs when the quantities of soluble oxalates eaten overwhelm the capacity of the rumen microflora to detoxify them.¹⁸ The oxalates chelate calcium and magnesium in the bloodstream resulting in hypocalcaemia and hypomagnesaemia.^2,18 The calcium oxalate crystals precipitate in a variety of tissues including the renal tubules and cause kidney failure.^1,2,18 Animals poisoned by soluble oxalates may be found dead or show signs suggestive of milk fever as a result of hypocalcaemia.² The presence of soluble oxalates in A. retroflexus in this case is considered the most likely explanation for the hypocalcaemia observed. Hypocalcaemia has been reported in one other case of cattle poisoned by A. retroflexus.⁶ Hypocalcaemia can also occur due to renal failure, alkalosis, milk fever, hypomagnesaemia and ethylene glycol toxicity.¹⁶ Hypercalcaemia has also been reported in A. retroflexus poisoning. ⁵

Calf one had normal blood results and ultimately survived. Greater than 75% of nephrons must be damaged before azotaemia will be detected.¹⁶ It is possible that calf one had a sub-lethal dose of A. retroflexus and was able to recover with or without ongoing subclinical renal insufficiency. It is also possible that this calf was incorrectly identified as a sickly calf as there were no management tags and the clinical signs were subtle.

In the report by Kessel et al. reduced rates of ultrasound confirmed pregnancy were found in the ewes that had been exposed to Amaranthus plants compared to the unexposed ewes (20% vs 88%).² The authors speculate that the cause of abortion/foetal resorption in the mob was due to the stress of illness and perhaps renal dysfunction following exposure. Amaranthus sp. poisoning in lambs from NZ caused the death of 13% of 4000 and the growth rate in the surviving lambs was reduced. The more subtle sequelae of Amaranthus sp. poisoning in cattle have not been investigated.

Urine of cattle poisoned by A. retroflexus has been reported to contain increased levels of protein and trace amounts of glucose.⁴ Urine from Calf 2 was slightly above isothenuric which is inappropriate in the face of azotaemia. However, the urine and blood samples were not contemporaneous. Urine specific gravity has not been recorded in the reports reviewed. Oxalate crystals were not observed. Oxalate crystals are often observed in cases of chronic oxalate toxicity.^16,18

Perirenal oedema is a characteristic feature of oxalate poisoning in pigs and cattle consuming Amaranthus retroflexus.^{1,2,4,5,6,7,8,9,10,11} The unknown nephrotoxic substance is believed to contribute to a profound perirenal oedema and tubular degeneration.^1,4,5,6,8 Kerr⁶ reported slightly swollen kidneys with petechial haemorrhages on their surfaces with no perirenal oedema. Some necropsied cases reported by Torres et al.⁸ had no perirenal oedema. Kessel et al² reported mildly enlarged, pale and turgid kidneys in lambs and perirenal oedema was not noted in this case or in the NZ case report.^2,14 Gross necropsy findings reported in cattle have also included perirenal haemorrhage⁸, pale, swollen kidneys,⁴ petechial haemorrhages on the kidneys,⁴ retroperitoneal oedema,^4,5,8,11 subcutaneous oedema,^5,7,8,11 hydrothorax,^4,5 ascites,^4,5 oedema of the rectum and omentum,^7,8,9 petechial haemorrhages on the visceral serosa,^7,8 and ulcerations of the alimentary mucosae.^8,11

Histopathology of the kidneys shows necrosis of the renal tubular epithelium, particularly the proximal tubules^4,5,6,7,8 with fluid and haemorrhage within the tubules^1,4,7 and cellular¹¹ and hyaline casts ^1,4,5,7,11 within them. There may be mild renal interstitial fibrosis.^1,5,7,8,11 Calcium oxalate crystals may be present in small numbers in some cases.⁵

Necropsy lesions seen in oxalate poisoning will depend on the duration and severity of the poisoning. In acute cases the kidneys may be oedematous and dark red in colour, whereas in chronic poisoning the kidneys may be pale and small.^1,6,18 The rumen may be haemorrhagic due to the presence of large quantities of oxalate in the rumen epithelial lining. Histopathology in chronic cases shows fibrosis, loss of renal tubules and blockage of tubules by rosettes of calcium oxalate crystals; calcium oxalate crystals may also be demonstrated in the rumen epithelium. ^1,5,18

Kerr⁶ considered the possibility that two agents existed in the A. retroflexus to induce the poisonings he observed. It is possible that the nephrotoxin and soluble oxalates contained in A. retroflexus contributed to the renal failure in this case. I was unable to get the soluble oxalate content measured in a specimen obtained. Further information from post-mortem findings and histopathology would have been invaluable in this case.

Treatment of animals with renal damage due to A. retroflexus is unlikely to be effective. Early and aggressive fluid therapy may be of benefit. Animals affected by acute oxalate poisoning can be treated with intravenous or subcutaneous calcium borogluconate. These animals are still at risk of dying from kidney failure days to weeks after successful treatment of the initial depressed blood calcium concentrations.^1,6,18

In the differential diagnosis of A. retroflexus poisoning in cattle, other plants causing renal damage should be considered including: Quercus (oaks), Isotropis sp (lamb poison and poison sage), Lilium sp (Oriental, Asiatic, Trumpet and Aureliun lillies), Hemerocallis sp (day lillies), Lythrum hyssopifolia (lesser loosestrife), Anagallis arvensis (scarlet pimpernel), other species of Amaranthus such as A. hybridus and Yellow wood (Terminalia oblongata). There are a large number of plants containing potentially dangerous amounts of soluble oxalates including but not limited to: Chenopodium sp (goosefoot family), Oxalis sp (soursob), Portulaca sp (pigweed), Rumex sp (docks) Rheum x cultorum (Rhubarb).^1,3,18 None of these were found in the paddock or known on the property.

Other potential causes of renal damage were excluded on the basis of the history: there was no history of antibiotic use, access to chemicals such as ethylene glycol, heavy metals or supplementary feed given potentially containing mycotoxins.

In this case only calves were noted to be clinically affected. Only three calves were blood tested, there may have been more animals, including adult cows, subclinically affected. McKenzie¹ reports that cattle fed 340g/kg bodyweight were poisoned. The lower bodyweight of the calves makes them more susceptible to poisoning however, they would also eat less. Another theory is that calves have less discriminating foraging habits. This may be the case but to refute this, the literature documents many cases in which adult cows have been poisoned. It has been postulated that the nephrotoxin may pass through the milk however there is no evidence in the literature to further this theory. The adult cattle may have previously adapted to the ingestion of soluble oxalates which enabled them to tolerate higher levels of oxalate containing plants. The combined effects of the neprohrotoxin and oxalates may have caused this outbreak of A. retroflexus poisoning.

It is uncertain as to why this common plant does not cause toxicity more frequently. It may be because large amounts of the plant must be consumed to cause toxicity and it is reported to be unpalatable. ^4,8,10 This is contrary to observations in this case. Kerr also reported that cattle appeared addicted to the A. retroflexus.⁶

Poisoning due to A.retroflexus is reported in late summer and early autumn,^{2,4,5,6,7,8,9,10,11} as occurred in this case, when the plant is in its seeding stage. It has been postulated that the plant may contain more toxic principle in its seeding stage.⁴ Another explanation is that during late summer and autumn, stock may be more likely to consume large amounts due to the lack of alternate fodder. A lack of forage was not found to be the case in this report. The variable pathogenesis of renal failure caused by A.retroflexus may be due to other unknown factors such as the presence of a metabolite at a certain stage of growth, or time of year, the presence of another factor such as a mycotoxin or the development of tolerance by some animals⁴ or a combined or synergistic effect of the nephrotoxin and soluble oxalates.

Conclusion

Farmers and veterinarians should be aware of the potential for renal toxicity leading to death when stock has access to Amaranth retroflexus in the late summer and autumn, especially when there is evidence of azotaemia on blood sampling, perirenal oedema is documented on necropsy or renal tubular necrosis is found microscopically.

References

1. McKenzie. Australia's Poisonous Plants, Fungi and Cyanobacteria. 2012. CSIRO publishing. Australia
2. Kesell AE, Boulton J, Krebs GL, Quinn JC. Acute renal failure associated with Amaranthus species ingestion by lambs. Australian Veterinary Journal 2015;93(6):208-213
3. Shepherd RCH. Is That Plant Poisonous? A Field Guide for livestock, pets and people. 2010. RG & FJ Richardson, Australia
4. Stuart BP, Nicholson SS, Smith JB. Perirenal edema and toxic nephrosis in cattle, associated with ingestion of pigweed. Journal of the American Veterinary Medical Association 1975; 167(10): 949-950
5. Casteel SW, Johnson GC, Miller MA, Chudomelka HJ, Cupps DE, Haskins HE, Gosser HS. Amaranthus retroflexus (redroot pigweed) poisoning in cattle. Journal of the American Veterinary Medical Association 1994; 207(4): 1068-1070
6. Kerr LA, Kelch WJ. Pigweed (Amaranthus retroflexus) toxicosis in cattle. Veterinary and Human Toxicology 1998; 40(4): 216-218
7. Spearman G. Redroot Pigweed Toxicoses in Cattle. Canadian Veterinary Journal 1989; 30:255-256
8. Torres MB, Kommers GD, Dantas AF, De Barros CL. Redroot pigweed (Amaranthus retroflexus) poisoning of cattle in southern Brazil. Veterinary and Human Toxicology 1997; 39(2): 94-96
9. Last RD, Hill JH, Theron G. An outbreak of perirenal syndrome in cattle associated with ingestion of pigweed (Amaranthus hybridus L.). Journal of the South African Veterinary Association 2007; 78(3):171-174
10. Zadnik T, Staric J, Klinkon M, Cigler T and Jezek. Poisoning Associated with Ingestion of Redroot pigweed (Amaranthus retroflexus) in Cattle - Case Report. The Open Access Veterinary Science Journal 2008, 2: 127-129
11. Links IJ, Salmon D. Amaranthus sp. Poisoning in Cattle. Case report for the Pathobiology Chapter Science Week Conference, Australian and New Zealand College of Veterinary Scientists, 1986
12. Gonzalez C. Tubular necrosis in sheep and goats after ingesting plants of the genus Amaranthus sp. Vet. Mex. 1983; 14:247-251
13. Rae CA, Binnington BD. Amaranthus retroflexus (redroot pigweed) poisoning in lambs. Can. Vet. J. 1995; 36:446
14. OertlyD, Black A. Amaranthus toxicity in lambs. Vetscript 2001;XIV:10-11
15. Osweiler GD, BuckWB, Bicknell EJ. Production of perirenal oedema in swine with Amaranthus retroflexus. American Journal of Veterinary Research 1969; 30:557-566
16. Salles MS, Lambardo de Borros CS, Lemas RA et al. Perirenal oedema associated with Amaranthus spp. Poisoning in Brazilian Swine. Vet. Hum. Toxicol. 1991; 33:616-617
17. Duncan JR, Prasse KW, Mahaffey EA. Veterinary Laboratory Medicine Clinical Pathology (3^rd edition). 1994. Iowa State University Press. Iowa USA
18. Knight AP and Walter RG. Plants Causing Renal Failure. A Guide to Plant Poisoning in North America. 2003. International Veterinary Information Service. New York USA