Oxalate nephropathy in cattle associated with the consumption of Megathyrsus maximus in Argentina

Abstract

Over a 2-wk period, 20 cows that were grazing a Megathyrsus maximus (Guinea grass) pasture died after developing depression, respiratory difficulty, and recumbency. Affected animals had increased serum urea, phosphorus, and creatinine concentrations, and below-normal calcium concentrations. Autopsy revealed moderate ascites; mildly enlarged, pale, mottled kidneys; and perirenal edema. Microscopically, there was hyperplasia of mesangial cells in the renal glomeruli, renal tubular epithelial necrosis, and hyaline casts and refractive crystals in cortical and medullary renal tubular lumens. Samples of M. maximus from the affected pasture contained elevated concentrations of soluble oxalate (3.71%). Our findings suggest that oxalate produced by M. maximus caused acute tubular injury. Our case highlights the critical need for monitoring oxalate levels in pastures and managing grazing practices, particularly under drought conditions, to prevent similar outbreaks in the future.

Megathyrsus maximus (Guinea grass) is a plant native to Africa that has been introduced to several sub-tropical and tropical areas of the world, including the United States and Central and South America, as a forage crop. ¹² In the semi-arid Chaco region of South America, including parts of the Argentinean provinces of Santiago del Estero, Salta, Formosa, Chaco, and Córdoba, M. maximus covers >10 million hectares (Radrizzani A, Instituto Nacional de Tecnología Agropecuaria [INTA], pers. comm., 2024 Dec 12), and it is a very important resource for cattle farming due, in part, to its drought resistance. ⁹ Despite its benefits as a forage crop, toxicity risks are associated with the grazing of M. maximus. These include colic and cecal impaction in cattle and horses,^2,13,15 as well as photosensitization and a tremorgenic syndrome in cattle. ¹² However, although M. maximus may accumulate oxalates under certain environmental conditions, there are no documented cases of oxalate toxicity in livestock associated with consumption of this plant, to our knowledge. Secondary hyperparathyroidism has been reported in horses grazing M. maximus pastures, and these changes have been suggested to be associated with excessive oxalate intake.^5,7

Ruminants eliminate oxalates through various pathways, but if the concentration of oxalates in the blood becomes excessively high, oxalate may combine with Ca or Mg to form insoluble oxalate crystals. These crystals can block urine flow in the kidneys and cause renal failure.^4,10 Here we describe an outbreak of acute renal tubular injury in beef cattle grazing on a M. maximus pasture with high oxalate levels.

In November 2023, 2 of the authors (A. Avellaneda-Cáceres, J. F. Micheloud) visited a cattle farm with 40,000 Brangus and Braford cattle including cows, calves, steers, and heifers near the town of El Quebrachal, Salta, Argentina, to investigate the deaths of 20 cows in a group of 500 pregnant cows that had been introduced into a M. maximus paddock 90 d before. The farmer reported that, before death, the cows had shown apathy and weight loss.

The clinical course was 7–14 d, after which the animals either recovered or died. Due to the nonspecific nature of the clinical signs, it is difficult to estimate the total number of affected animals; however, based on the observations of the advising farmer, ~5 animals recovered from the total number of sick animals. At the time of the visit, a few cows had clinical signs. Five of these cows, which were pregnant, were clinically examined. They were depressed, recumbent, and thin, and had abdominal pain, increased respiratory effort, severe dehydration, and pale mucous membranes; the hindquarters were soiled with feces. Blood was collected from these 5 cows, and packed cell volume (PCV), calcium (Ca), phosphorus (P), urea, and creatinine were measured in a private clinical pathology laboratory (Alonso Lab Vet, Salta, Argentina). Briefly, serum P, urea, and creatinine were mildly or moderately increased, Ca was mildly decreased, and PCV was within its RI (Table 1).

Table 1.

Selected hematology and biochemistry results from 5 cattle intoxicated with Megathyrsus maximus.

Cow	Hematocrit, L/L	Calcium, mmol/L	Phosphorus, mmol/L	Urea, mmol/L	Creatinine, μmol/L
1	25	2.0	2.0	40.0	10,900
2	36	1.6	2.2	23.2	29,600
3	43	1.9	2.5	31.8	21,700
4	42	2.0	2.2	42.8	21,700
5	29	1.6	2.5	8.2	14,800
x̅ ± SD	35±8	1.8 ± 0.2	2.3 ± 0.2	29.3 ± 13.9	19,700 ± 7,200
RI 10	24–46	2.4–3.0	1.8–2.1	2.1–9.6	442–1,680

Values in bold are outside their RI.

An autopsy was performed 2–3 h after the death of 2 affected cows that were 4–5 mo pregnant. Postmortem examination revealed perirenal edema (Fig. 1), as well as edema of the renal pelvis and ureters, which had thickened walls. The most striking lesions were observed in the kidneys, which were mildly enlarged, pale, and had a mottled appearance (Fig. 2). The renal cortex had multifocal-to-coalescing irregular pale areas, and the medulla was yellow. There was also moderate ascites (Fig. 1), hydrothorax, hydropericardium, and abomasal edema and hemorrhage. No other gross lesions were observed.

Figures 1–4.

Findings in cattle with oxalate-induced acute tubular injury associated with the consumption of Megathyrsus maximus. Figure 1. Moderate ascites and perirenal edema. Figure 2. Mildly enlarged, pale, mottled kidneys. Figure 3. Mild glomerular mesangial hyperplasia (white arrowhead), tubular epithelial necrosis (asterisk), and protein casts (black arrowhead). H&E. Figure 4. Oxalate crystals in the tubular lumen (arrowhead). Inset: birefringent crystals under polarized light. H&E.

Samples of liver, kidneys, lungs, heart, spleen, lymph nodes, brain, adrenal glands, pancreas, skeletal muscle, small and large intestine, reticulum, omasum, abomasum, urinary bladder, thyroid gland, esophagus, and brain were collected, fixed by immersion in 10% neutral-buffered formalin for 48 h, and processed routinely to produce 4-µm H&E-stained sections. All slides were examined under conventional light microscopy, and kidney sections were also examined under polarized light. The most significant microscopic changes were observed in the kidneys. The glomeruli had mild hyperplasia of mesangial cells and proliferation of the mesangial stroma (Fig. 3), and there were variable numbers of refractile crystals in cortical and medullary tubular lumens forming rosettes (Fig. 4) that were birefringent under polarized light (Fig. 4). Most proximal renal tubules were dilated, and the epithelium had hydropic degeneration or was necrotic. Additionally, multifocal interstitial fibrosis was noted around distal tubules. Pale, amorphous, granular and hyaline casts were present in the lumen of several proximal and distal renal tubules (Figs. 3, 4). No other microscopic abnormalities were observed in any of the other tissues examined.

Samples of M. maximus were collected from the pasture where the affected cows had been grazing and were analyzed for soluble oxalate concentrations as described previously. ⁶ Briefly, air-dried, finely ground M. maximus plant material was incubated in 30% sulfuric acid–methanol at 60°C for 1 h. The reaction was then partitioned between distilled water and chloroform. The chloroform fraction containing the methylated oxalic acid was removed and analyzed via gas chromatography–flame ionization detection and quantified against a 5-point dimethyl oxalate standard curve prepared from oxalic acid dihydrate in the same manner as the M. maximus sample, and over the range equivalent of 0.625–10 mg oxalic acid. The oxalic acid concentration of the plant material was 37 mg/g (3.71%).

A diagnosis of oxalate nephropathy (ON) associated with consumption of M. maximum was established based on clinical history and signs, the gross, microscopic, and clinical pathologic findings, and detection of oxalates in samples of M. maximum.

The elevated serum P, creatinine, and urea are consistent with the changes previously observed in other cases of nephrotoxic plant intoxications, in which azotemia and elevated serum P levels are common. ¹² In such cases, the compromised ability of the kidneys to excrete waste products and maintain electrolyte balance leads to the accumulation of nitrogenous waste and hyperphosphatemia. ⁵ In addition, serum Ca levels were below the RI, which were likely a consequence of Ca and oxalic acid combining to form calcium oxalate.

The clinical signs and lesions of oxalate toxicity vary between species and are influenced by different levels of exposure and disease duration. Monogastric animals are generally more sensitive, with intoxication typically occurring when oxalates exceed 0.5% in dry matter, as is the case with fibrous osteodystrophy in horses. ⁷ Conversely, ruminants have a greater ability to adapt and tolerate higher levels of oxalates because they can metabolize oxalate at the ruminal level. ¹⁴ Because of this, levels of oxalates that may cause toxicity under certain circumstances may not do so under others. In cattle and sheep, hypocalcemia is observed at oxalate levels >2% of dry matter. ¹⁰ However, in cattle, chronic exposure to lower levels can lead to ON. ¹⁴ ON occurs when calcium oxalate crystals accumulate within the renal tubules, particularly in the proximal convoluted tubules, causing tubular epithelium necrosis, renal atrophy, and interstitial fibrosis, ultimately resulting in renal failure. In ruminants, ON is commonly linked to the consumption of plants containing oxalates.^11,14 Less frequently, the condition has been associated with the ingestion of ethylene glycol, as reported in Jersey calves. ¹

The mechanism of oxalate toxicity involves the formation of calcium oxalate monohydrate and insoluble calcium oxalate. The latter damages mitochondria, leading to increased reactive oxygen species and decreased activity of tricarboxylic acid cycle enzymes, such as succinate dehydrogenase, isocitrate dehydrogenase, and malate dehydrogenase. This disruption results in mitochondrial dysfunction and reduces oxidative phosphorylation. ³ Oxalates also disrupt specific metabolic pathways, including Ca homeostasis, which explains the observed disturbances in serum Ca and P levels. Clinically, this manifests as renal failure. The form, dose, and duration of oxalate exposure are critical for disease progression. ¹² Acute poisonings at high doses can result in sudden death before ON develops. Pasture plants containing more than 0.5% oxalates in dry matter are generally considered dangerous. Levels exceeding 2% are associated with acute hypocalcemia.^11,14 In our cases, oxalate levels were >2%, yet no signs of acute hypocalcemia were observed. This suggests that oxalate levels may have increased progressively, allowing the rumen to adapt to these conditions. Over time, the persistent exposure to elevated oxalate levels likely led to the development of ON.

M. maximus is a highly valued pasture species for livestock in South America. It is widely used in cattle farming due to its ability to produce large quantities of palatable and nutritious feed, even in semi-arid environments. ⁸ Extensive drought periods are common in several regions of South America where M. maximus has successfully adapted. ⁷ In several parts of Argentina, M. maximus plays a fundamental role in silvo-pastoral systems, particularly during prolonged droughts (Radrizzani A, pers. comm., 2024 Dec 12). It should be noted that a prolonged drought occurred in the region during the summer of 2023. The problem on this cattle farm was observed ~15 d after the first rains, coinciding with the early regrowth of the plant, a factor that may have led to an accumulation of oxalates. Stressful conditions and the regrowth of such species have been associated with elevated oxalate levels in various forage plants.^11,14 However, no reports of M. maximus–associated ON in cattle have been published, although anecdotal evidence suggests that horses grazing on this plant in northwestern Argentina developed ON (Micheloud JF, pers. observation, 2025 March 5).

Cases of osteodystrophy in horses grazing M. maximus have been reported in Brazil, where high oxalate levels were suspected, although not measured.^5,13 In Paraguay, cases of ON have been recorded in Arabian and Quarter Horses grazing M. maximus. ⁶

Given the widespread use and importance of M. maximus as a forage resource, understanding its potential toxicity is crucial for maintaining the health and productivity of livestock that rely heavily on this forage.