5-month-old female Sprague-Dawley rat (Rattus norvegicus).Tissues are from three rats that were part of a group of 60 rats receiving a trial diet that contained a single protein source. Rats within the group did not gain weight as rapidly as expected.

Gross Description:  

Rats were in a poor state of nutrition and weighed less than would be predicted for their age. Examination of the urinary system revealed pitted kidneys with white streaks within the cortex.

Histopathologic Description:

Lesion severity is variable within the sections. The predominant lesion is visible within the renal pelvis. Here, mild to marked dilation of the pelvis is visible. Inflammation is visible surrounding the pelvis. This inflammation consists predominantly of lymphocytes and plasma cells with some sections also containing significant numbers of neutrophils. Small foci of mineralization are visible surrounding the pelvis in some sections. The transitional epithelium within the renal pelvis has undergone squamous metaplasia. Inflammation and necrosis is visible extending from the renal pelvis into the cortex. Tubules that are dilated by neutrophils are visible within the sections. Areas of fibrosis indicate previous episodes of nephritis within the cortex.

Morphologic Diagnosis:  

Kidney. Pyelonephritis, moderate, subacute, neutrophilic, with marked squamous metaplasia of the transitional epithelium.

Lab Results:  

A pure growth of Escherichia coli was cultured from a sample of kidney from one of the rats.


Pyelonephritis, hypovitaminosis A

Contributor Comment:  

The high mortality within the group of rats receiving this experimental diet suggested a dietary toxin or deficiency. In addition to the renal pelvis, squamous metaplasia of the transitional epithelium was also visible within the ureters and bladder suggesting vitamin A deficiency. Subsequent analysis revealed that the experimental diet that these rats were receiving contained an inadequate concentration of vitamin A. Overall within the 60 rats, 27% had visible uroliths and 5% had nephroliths. Bilateral pyelonephritis was detected histologically in 43% of rats and unilateral pyelonephritis in 25%.

Vitamin A regulates epithelial cell growth and differentiation, enables production of visual pigment, is necessary for normal function of the immune system, and influences skeletal development(8). When rats are fed diets that contain no vitamin A, the most commonly reported clinical signs of deficiency are weight loss, corneal keratinization and ulceration, respiratory or skin disease, and salivary gland enlargement.(1) An 80% mortality rate due to inanition or bacterial infection of the skin or respiratory tract is expected after 15 weeks.(1) In the present case, the rats received some vitamin A, albeit in inadequate quantities. The restriction of the lesions to the transitional epithelium in these rats suggests that the transitional epithelium is the most susceptible to squamous metaplasia due to moderate vitamin deficiency(6). The squamous metaplasia of the transitional epithelium then predisposed to the development of ascending bacterial infections and urolith and nephrolith formation.

While squamous metaplasia of the transitional epithelium lining the renal pelvis can occur secondary to bacterial infection, the metaplasia visible within the present case was considered an excessive reaction to an ascending bacterial pyelonephritis.

JPC Diagnosis:  

Kidney: Pyelonephritis, neutrophilic and lymphohistiocytic, diffuse, marked, with urothelial squamous metaplasia and coccobacilli.

Conference Comment:  

Vitamin A is one of four fat soluble vitamins, along with vitamins D, E and K, and has multiple functions. Vitamin A as retinoic acid functions in morphogenesis during embryonic development, maintenance of epithelial cells, bone growth, reproduction, immunostimulation, and may also have antioxidant effects(3).

Vitamin A deficiency leads to impaired epithelial differentiation through an unknown mechanism, and leads to reduction in mucus-secreting cells, squamous metaplasia of the respiratory and genitourinary epithelium, and hyperkeratosis(4). Hypovitaminosis A also leads to retarded osteoclastic resorption of endosteal bone, and lesions are varied depending on species affected, stage of growth, and severity of the deficiency(7). Vitamin A deficiency also leads to the arrest of spermatogenesis at the spermatid phase in all species, especially in cattle, rats, and chickens, and causes abnormal estrous cycles, congenital anomalies, and fetal resorption. Hypovitaminosis A affects immune function, as vitamin A is thought to stimulate T-cells directly through 14-hydroxyretinol. During infection, synthesis of the negative acute phase protein, retinol-binding protein, is down-regulated, decreasing availability of vitamin A(4).

In dogs, vitamin A deficiency results in hyperkeratosis of sebaceous gland ducts; vitamin A-responsive dermatosis in cocker spaniels is characterized by marked follicular keratosis of the chest and abdomen(2). In male calves, vitamin A deficiency results in stenosis of the optic foramen and atrophy of the optic nerve, leading to blindness. Squamous metaplasia of the parotid gland is a pathognomonic lesion of hypovitaminosis A in cattle(9). In guinea pigs and rats, vitamin A deficiency results in inadequate differentiation and organization of odontoblasts, leading to irregular dentin formation and enamel hypoplasia(5).


1. Beaver DL: Vitamin A deficiency in the germ-free rat. Am J Pathol 38: 335-357, 1961
2. Hargis AM, Ginn PA. The integument. In: McGavin MD, Zachary JF, eds. Pathologic Basis of Veterinary Disease. 4th ed. vol. 1 St. Louis, MO: Elsevier; 2012:1066.
3. Jones TC, Hunt RD, King NW: Nutritional deficiencies. In: Veterinary Pathology, 6th ed, pp. 781-783, Maple Valley Press, Baltimore, MD 1997
4. Meyers RK, McGavin MD, Zachary JF. Cellular adaptations, injury, and death: morphologic, biochemical, and genetic bases. In: McGavin MD, Zachary JF, eds. Pathologic Basis of Veterinary Disease. 4th ed. vol. 1 St. Louis, MO: Elsevier; 2012:29-30.
5. McDowell EM, Shores RL, Spangler EF, Wenk ML, De Luca LM. Anomalous growth of rat incisor teeth during chronic intermittent vitamin A deficiency. J Nutr. 1987 Jul;117(7):1265-74.
6. Munday JS, McKinnon H, Aberdein D, Collett MG, Parton K, Thompson KG: Cystitis, pyelonephritis, and urolithiasis in rats accidentally fed a diet deficient in vitamin A. J Am Assoc Lab Anim Sci 48: 790-794, 2009
7. Thompson K. Bones and joints. In: Maxie MG, ed. Jubb, Kennedy and Palmers Pathology of Domestic Animals. 5th ed. vol. 1 Philadelphia, PA: Saunders Elsevier; 2007:55-56.
8. Weber F: Biochemical mechanisms of vitamin A action. Proc Nutr Soc 42: 31-41, 1983
9. Zachary JF. Nervous system. In: McGavin MD, Zachary JF, eds. Pathologic Basis of Veterinary Disease. 4th ed. vol. 1 St. Louis, MO: Elsevier; 2012:865.

Click the slide to view.

2-1. Kidney

2-2. Kidneys, urinary bladder

2-3. Kidneys, urinary bladder

2-4. Urinary bladder

2-5. Ureter

2-6. Urinary bladder

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