History
A 6-month-old approximately 125-kg (275-lb) female Black Angus calf was presented for necropsy. The calf had a history (duration unknown) of ill thrift. The calf had been treated by the owners with florfenicola (dosage and duration of treatment unknown) for suspected respiratory tract disease; however, 3 weeks later, the calf became recumbent and died shortly thereafter.
Gross Findings
The calf was in thin body condition (body condition score, 2/5), and the medial and lateral claws of both hind limbs were severely overgrown (Figure 1). The cranioventral portions of the left and right cranial lung lobes were dark red and floated when placed in formalin. Mineralization was present in the papillary muscles, myocardium, and an area ventral to the aortic valve. Both kidneys were small (3 × 8 × 5 cm), pale tan, and firm; on cut section, they had pale tan cortices and white, linear streaks near the corticomedullary junction. The splenic capsule was diffusely wrinkled and mineralized. A 36 × 38-cm sheet of plastic foreign material admixed with green roughage was present in the rumen, and the abomasum was filled with white to yellow, thick ingesta (digested milk) and approximately 500 mL of sand. The ventricles of the brain were dilated and contained an increased amount of CSF. No other notable abnormalities were found.
Photographs of the right hind foot (A) and cut section of a kidney (B) from a 6-month-old female Black Angus calf that did not thrive from birth and eventually died. Notice the overgrown medial and lateral claws of the right hind foot. The renal cortices are tan and the corticomedullary junction has pale streaks. Bar = 2.5 cm.
Citation: Journal of the American Veterinary Medical Association 258, 5; 10.2460/javma.258.5.463
Histopathologic Findings
Samples of the kidneys, heart, tongue, spleen, rumen, reticulum, small intestines, liver, lungs, brain, and a mesenteric lymph node were fixed in neutral-buffered 10% formalin, and sections were examined microscopically. The normal renal cortical parenchyma was segmentally to diffusely replaced by abundant fibrous connective tissue containing small, poorly developed tubules and glomeruli in close apposition (Figure 2). Glomeruli varied markedly in size with enlarged glomeruli (compensatory hypertrophy) in less affected sections of the cortex and small (juvenile and sclerotic) glomeruli in areas of fibrosis. Juvenile glomeruli were characterized by peripheral rowing of podocyte nuclei. Other small glomeruli had prominent periglomerular sclerosis. Interstitial inflammation was minimal as evidenced by small numbers of lymphocytes, plasma cells, and macrophages.
Photomicrograph of a section of the cortex of a kidney from the calf. Notice the variably sized glomeruli. The small glomeruli are within areas of interstitial fibrosis containing dysplastic tubules and mild inflammation (F). H&E stain; bar = 50 μm.
Citation: Journal of the American Veterinary Medical Association 258, 5; 10.2460/javma.258.5.463
Mineralization was found within cardiac and glossal myofibers and the splenic capsule (Figure 3) and diffusely within the keratin layer of the rumen and reticulum. Occasional vessel mineralization (affecting the tunica intima and lumen) was noted in most of these areas. Areas of myofiber mineralization were surrounded by multinucleated giant cells and epithelioid macrophages. The areas of mineralization in the heart also had surrounding myofiber degeneration characterized by atrophy, vacuolation, or fragmentation.
Photomicrograph of a section of the calf's spleen. Severe mineralization of the capsular collagen fibers (C) is present. H&E stain; bar = 100 μm.
Citation: Journal of the American Veterinary Medical Association 258, 5; 10.2460/javma.258.5.463
The lateral ventricles of the brain were severely dilated with the ependymal epithelium multifocally flattened to absent. Bovine viral diarrhea virus was not detected immunohistochemically in skin tissue sections. Sections of small intestines, liver, lungs, and a mesenteric lymph node had no notable findings.
Morphologic Diagnosis and Case Summary
Morphologic diagnosis: renal dysplasia with segmental interstitial fibrosis, tubular hypoplasia, and immature glomeruli; multifocal myofiber, collagen, and vessel wall mineralization of the heart, spleen, and skeletal muscle; severe diffuse intracorneal mineralization of the rumen and reticulum; severe hydrocephalus; and hind feet claw overgrowth.
Case summary: severe renal dysplasia and concurrent hind feet claw overgrowth in a 6-month-old Black Angus calf with mineralization of the heart, spleen, rumen mucosa, reticulum mucosa, and skeletal muscles, which was most likely attributable to renal dysfunction.
Comments
The small and fibrotic kidneys with segmental fibrosis, dysplastic tubules, and asynchronous glomerular maturity were consistent with renal dysplasia. Renal dysplasia is defined as disorganized development of renal parenchyma owing to anomalous differentiation.1 Renal dysplasia is characterized grossly by small, often misshapen kidneys and histologically by immature tubules and glomeruli, large amounts of interstitial connective tissue, and minimal interstitial inflammation. The calf of the present report's failure to thrive was likely associated with renal dysfunction, secondary to the malformation of the kidneys.
Severe mineralization across multiple organ systems is, presumptively, metastatic mineralization as a result of a calcium-phosphorus imbalance secondary to renal failure.1 In the case described in the present report, no clinicopathologic analyses were performed to confirm a high serum calcium concentration–phosphorus concentration product and renal failure, but the gross and histologic findings strongly supported mineralization secondary to renal impairment. The mineralization of the rumen and reticulum likely hindered absorptive functions, thereby exacerbating the calf's poor condition. Chronic kidney disease can cause excessive parathyroid hormone production owing to an inability of the kidneys to synthesize calcitriol. Normally, calcitriol inhibits parathyroid hormone function. Unregulated parathyroid hormone concentration causes calcium mobilization into the circulation. Additionally, a decreased glomerular filtration rate associated with chronic kidney disease can result in increased serum phosphorus concentration because of decreased phosphorus excretion. Increases in circulating phosphorus and calcium concentrations can result in metastatic tissue mineralization, as seen in the calf of the present report.2 It is worth noting that decreased glomerular filtration rate in cattle does not always result in hyperphosphatemia because of other routes of phosphate excretion (eg, saliva), and the serum phosphate concentration in this calf was not known.
Renal dysplasia in cattle has been linked to genetic mutations in multiple breeds, including the Japanese Black cattle (Wagyu) breed. With certain genetic mutations, this condition is often associated with overgrown hooves,3 a gross finding for the calf of the present report. To the authors' knowledge, the cause for overgrowth of hooves associated with renal dysplasia in cattle has not been elucidated. In Japanese Black cattle, renal tubular dysplasia is associated with homozygous deletion of the claudin-16 gene, which is important in tight junction formation. This gene has autosomal recessive inheritance. The phenotype of that disease is associated with slowed growth, diarrhea, and elongated hooves.4,5 Genetic background information was not available for the calf of the present report.
Hydrocephalus is one of many congenital lesions associated with fetal infection with bovine viral diarrhea virus, bluetongue virus, or Schmallenberg virus.6 Additionally, bovine viral diarrhea virus has been speculated to be the cause of development of renal dysplasia in some cases.1 However, bovine viral diarrhea virus was not detected immunohistochemically in skin tissue sections from the calf of the present report. Therefore, a genetic cause for the identified renal lesions was considered more likely.
Footnotes
Nuflor, Merck Animal Health, Madison, NJ.
References
- 1. ↑
Cianciolo RE, Mohr FC. Urinary system. In: Maxie MG, ed. Jubb, Kennedy, and Palmer's pathology of domestic animals. Vol 2. 6th ed. St Louis: Elsevier, 2007;376–464.
- 2. ↑
Rosol TJ, Grone A. Endocrine glands. In: Maxie MG, ed. Jubb, Kennedy, and Palmer's pathology of domestic animals. Vol 3. 6th ed. St Louis: Elsevier, 2007;300–301.
- 3. ↑
Sugiyama A, Ozaki K, Miyazaki TY, et al. Renal dysplasia unrelated to claudin-16 deficiency in Japanese Black cattle. J Comp Pathol 2007;137:71–77.
- 4. ↑
Okada K, Ishikawa N, Fujimori K, et al. Abnormal development of nephrons in claudin-16-defective Japanese Black cattle. J Vet Med Sci 2005;67:171–178.
- 5. ↑
Testoni S, Mazzariol S, Drögemüller C, et al. Renal dysplasia in grey Alpine breed cattle unrelated to CLDN16 mutations. Vet Rec 2012;170:22.
- 6. ↑
Agerholm JS, Hewicker-Trautwein M, Peperkamp K, et al. Virus-induced congenital malformations in cattle. Acta Vet Scand 2015;57:54.
