Kliniese mededeling An outbreak of perirenal oedema syndrome in cattle associated with ingestion of pigweed ( Amaranthus hybridus L . )

INTRODUCTION Amaranthus hybridus L. (smooth pigweed) and Amaranthus retroflexus L. (redroot pigweed) are erect annual weeds which are members of the Amaranthaceae family and belong to the same genus Amaranthus L.. These plants occur in great abundance in the tropical and subtropical regions of Africa and the Americas . They grow prolifically on disturbed soil sites such as ploughed fields, gardens, fallow farm lands and waste areas. Both species commonly occur together and cross-hybridisation between species has been documented. Intoxication syndromes that have been described in animals associated with the ingestion of A. hybridus and A. retroflexus include renal disease, nitrate intoxication and oxalate poisoning. Clinically the renal condition in cattle is characterised by rapid-onset weakness, trembling, incoordination, knuckling of pasterns, recumbency and death within 10 days of having access to the plant. Gross pathology includes subcutaneous oedema, ascites, perirenal, perirectal and omental oedema and nephrosis. Renal histopathology is characteristic of a toxic nephrosis with widespread renal tubular degeneration and coagulative necrosis; however, tubular basement membranes remain intact. In the Americas, perirenal oedema syndrome is commonly reported in swine, infrequently in cattle and rarely in sheep and horses . In South Africa, A. hybridus and A. retroflexus have only been previously associated with nitrate and possibly oxalate poisoning in cattle. This report documents an outbreak of perirenal oedema syndrome in bovines in South Africa following ingestion of Amaranthus hybridus L..


INTRODUCTION
Amaranthus hybridus L. (smooth pigweed) and Amaranthus retroflexus L. (redroot pigweed) are erect annual weeds which are members of the Amaranthaceae family and belong to the same genus Amaranthus L. 8,24 .These plants occur in great abundance in the tropical and subtropical regions of Africa and the Americas 4,8,11,21 .They grow prolifically on disturbed soil sites such as ploughed fields, gardens, fallow farm lands and waste areas.Both species commonly occur together and cross-hybridisation between species has been documented 4,6,21 .Intoxication syndromes that have been described in animals associated with the ingestion of A. hybridus and A. retroflexus include renal disease, nitrate intoxication and oxalate poisoning 4,5,6,11,12,14 .

CASE HISTORY
One hundred and fifty head of 15month-old, long weaner cattle were introduced into an old maize land, which contained a full stand of Amaranthus spp.Eight days after entering this field the 1st animals presented sick and a day later 8 were found dead.The clinical syndrome included fairly sudden onset ataxia, knuckling of the pastern joints and recumbency.Ventral abdominal, perirectal, perineal and subcutaneous pitting oedema was severe.Forty seven of the 150 cattle eventually died and 8 autopsies were performed.

Pathology
Gross necropsy findings included a distinct urine odour on opening the abdominal cavity, subcutaneous oedema of the ventral abdomen, perirectal oedema, perivaginal oedema with vaginal prolapse, ascites, mesenteric oedema and marked perirenal oedema (Figs 1-3).Kidneys were markedly swollen with a diffuse pale discolouration and surface petechiation (Fig. 4).Various tissues from two animals were collected into 10% buffered formalin and submitted for histopathology.
Renal histopathology showed widespread renal tubular nephrosis with coagulative necrosis of clusters of tubules, intratubular hyaline casts and intertubular haemorrhage (Fig. 5).The coagulative renal tubular necrosis was most prominent in the proximal and distal straight tubules (Fig. 6).No oxalate crystals were observed under bright field or polarised illumination.Periodic acid-Schiff (PAS) staining confirmed that the tubular basement membranes of renal tubules examined remained intact.Masson trichrome staining revealed minimal interstitial fibrosis.
Implicated plant material collected from this farm was forwarded to the Natal University Herbarium, School of Biological and Conservation Sciences, University of KwaZulu-Natal, Scottsville, Pietermaritzburg, where it was identified as Amaranthus hybridus L.

DISCUSSION
Amaranthus hybridus/retroflexus poisoning in cattle is considered rare as these plants are only ingested in large quantities when other more suitable and palatable forage is not available 4,6,11,17,18 .All other reported outbreaks of pigweed toxicity in cattle in South Africa have been associated with nitrate and possibly oxalate poisoning 11 .Perirenal oedema has never been previously documented 11 .The causative mechanism of the renal syndrome remains undetermined, but nitrate and oxalate do not appear to be involved [4][5][6]10 .
Perirenal oedema syndrome in cattle and pigs follows ingestion of leafy mature fresh plants or regrowths of cuttings and signs develop after animals have been feeding on the leaves of the plants for several days or more (5-10 days) [4][5][6] .Nitrate poisoning is usually seen within 6 to 24 hours of ingesting toxic quantities of nitrate, which is at its highest level in the stems of the dried plant and is therefore more often associated with pigweedcontaminated hay [4][5][6]13,22 . Mortaity due to nitrate poisoning is generally limited to ruminants with swine rarely experiencing lethal nitrate toxicity.10,13,22 Nitrate poisoning involves the conversion of haemoglobin to methemoglobin with resultant tissue hypoxia/anoxia due to the inability of methaemoglobin to transport oxygen 4,10,11,13,22 .The clinical syndrome is usually peracute or acute and may be fatal within minutes to hours after ingestion, with few clinical signs 4,11,22 .
Oxalates, which are readily accumulated by Amaranthus spp plants, are known to have nephrotoxic effects through accumulation of calcium oxalate crystals within renal tubules [4][5][6]11 . Degneration, necrosis, and loss or renal tubules with intraluminal oxalate crystals, interstitial fibrosis, and multifocal mild lymphocytic interstitial nephritis, characterize the histopathological changes of oxalate nephrosis 10,11,13 .However, renal tubular oxalate crystal accumulation is not a feature of the histopathology of perirenal oedema 4,6,10,13 .In addition, perirenal oedema has been produced experimentally when animals were fed Amaranthus retroflexus, but the syndrome could not be reproduced when fed other oxalate-accumulating plants.4,10 Therefore, a plant-derived oxalate-induced nephrosis seems unlikely in the case of the perirenal oedema syndrome.
Owing to the extensive renal tubular necrosis induced in the perirenal oedema syndrome, there is tubular obstruction, damming back of urine resulting in increased transcapsular lymphatic drainage and leakage into the perirenal connective tissue and hence the marked perirenal oedema.This is the hallmark gross pathological feature of the syn-   drome 12 .This acute renal failure causes the clinical nephrotic syndrome with subcutaneous oedema, mesenteric oedema, perirectal oedema and accumulation of fluid in body cavities [4][5][6]10,13 . This udden loss of adequate renal function results in the inability to clear metabolic wastes and maintain normal fluid and electrolyte balance, with metabolic acidosis and hyperkalemia being the 2 most serious manifestations of this function loss 1,3,19 .Excretion of potassium ions is severely affected by renal tubular injury with marked hypercalaemia developing with increased risk of cardiac derived lethal toxicity 1,2,7 .Mortality in cattle is though to be the consequence of hyperkalaemic cardiotoxicosis and case fatality rates in excess of 50 % have been reported.4,13,23 A plant poisoning with a very similar clinical syndrome and pathology to the perirenal oedema syndrome in cattle is oak poisoning (Quercus sp.) 4,9,12 .The macroscopic pathological features of ascites, hydrothorax, hydroperitoneum, subcutaneous oedema, mesenteric oedema and gut mucosal oedema described are virtually identical to those of Amaranthus 4,5,10,13 .The renal histopathology of groups of tubules showing complete necrosis with intratubular haemorrhage and the presence of gastrointestinal erosion, distinguish Quercus sp. from the perirenal oedema syndrome 6,10,11,13 .

Fig. 4 :
Fig. 4: Kidney, cut surface, in situ within the abdominal cavity.Severe perirenal oedema encompasses the kidney (arrowheads) and the renal pelvis.Diffuse renal cortical necrosis (arrow) with diffuse pale discoloration of the full thickness of the cortex.