Polycystic and Chronic Kidney Disease in a Young Degu ( degus)

JOAN M. CADILLAC, DVM,1* HOWARD G. RUSH, DVM, DIPLOMATE, ACLAM,1 AND ROBERT E. SIGLER, DVM, PHD, DIPLOMATE, ACVP2

A young adult (approximately 20 months), 125 g, female degu (Octodon degus) was housed with a male degu for approximately 1.2 years as a breeding pair. The female was multiparous and had weaned its third litter 2 weeks earlier. The degu was reported to the veterinary service for bloody vaginal discharge and a hunched, thin appearance of 1 day’s duration. On physical examination, it exhibited cachexia, molting, slight matting of the hair around the eyes, and moderate dehydration. Hematology results included anemia and leukopenia with lymphocytopenia. Biochemical abnormalities included severe azotemia and phosphatemia. Urine specific gravity was 1.016. The condition of this prohibited its continued use in the breeding colony, so it was submitted for necropsy. On gross examination, the left kidney measured 10 × 15 mm, had an irregular surface, and was pale and mildly enlarged, consistent with compensatory hypertrophy. The right kidney was small (5 × 8 mm) and cystic. Both adrenal glands appeared mildly enlarged. Histologically, the left kidney had multiple regions with chronic, diffuse interstitial nephritis, and the right kidney was polycystic. There was mild, focal, cortical nodular hyperplasia in the adrenal glands. In the uterus, there was unilateral, locally extensive necrosis of the endometrium. The clinical chemistry results and histopathology findings are supportive of a diagnosis of renal failure secondary to chronic nephritis and polycystic kidney disease. The etiology of the nephritis is unknown. Polycystic kidney disease can be congenital or hereditary in other .

The degu (Octodon degus) (Fig. 1) is a member of the Rodentia, suborder , and family Octodontidae (1, 2). The degu is a diurnal native to the West Andean slopes of northern and central Chile, inhabiting opens areas near low- lying vegetation or rock formations at elevations up to 1200 m. Degus construct elaborate communal burrows with the main section under rocks or shrubs (1). The degu has proven to be a useful animal model for studies on sleep biology, circadian rhythm, jet lag, neurobiological development, drug tolerance, diabetes development, and cataract formation (3, 4). A breed- ing colony has been maintained at the University of Michigan for approximately 10 years.

Case Report A 20-month-old (average lifespan, 3 to 5 years), 125 g (adult body weight range, 180 to 250 g), breeding female degu was reported to the veterinary staff for a bloody vaginal discharge and a hunched, cachexic appearance. The degu came from a Figure 1. This is a healthy adult male degu (Octodon degus), weighing conventional breeding colony that was monitored for standard approximately 360 g. rodent pathogens. The technical staff avoids inbreeding in the colony by maintaining detailed breeding records. The female Upon physical examination, the degu was in poor body con- degu had been housed with a male degu for approximately 1.2 dition, with slight matting of the hair around the eyes and years and had weaned its third litter 2 weeks earlier. The pair moderate dehydration (approximately 5%). There was a bloody was housed in a polycarbonate solid-bottom rat cage (Allentown vaginal discharge present, as well as symmetrical hair loss on the Caging Equipment, Allentown, N.J.), with corncob bedding (The caudal aspects of the body. The hair loss was attributed to (sea- Andersons, Maumee, Ohio) and was fed a commercial guinea sonal) molting. Thoracic auscultation and abdominal palpation pig chow (Purina LabDiet 5025, PMI International, Brentwood, were unremarkable. The animal was alert but quiet. A presump- Mo.) with ad libitum access to water. The room was maintained tive diagnosis of traumatic breeding was made, and euthanasia on a 12:12-h light:dark cycle, and the average ambient tempera- was elected due to the poor condition of the animal. The degu ture was approximately 22.2°C (72.0°F). The degu was housed was sedated with isoflurane by facemask. Blood was collected in accordance with Animal Welfare Act regulations and the Guide from the right brachiocephalic trunk, and urine was collected for the Care and Use of Laboratory , under a protocol via cystocentesis. The animal then was euthanized with a pento- approved by the University Committee on Use and Care of Ani- barbital solution (1 ml/10 lbs intraperitoneally; Beuthanasia-D, mals. The animal care and use program and facilities are Schering-Plough Animal Health, Kenilworth, N.J.). accredited by AAALAC International. A complete blood count and serum chemistry profile were per- formed (Table 1). The hematology results included normocytic, normochromic anemia and leukopenia with lymphocytopenia. The Unit for Laboratory Animal Medicine, University of Michigan Medical School, 018 ARF, bone marrow appeared normal on histologic exam. Biochemi- 1150 W. Medical Center Drive, Ann Arbor, Michigan 48109-06141; Esperion Therapeu- tics, Inc., 3621 S. State St., 695 KMS Place, Ann Arbor, Michigan 481082 cal abnormalities included severe elevation of blood urea *Corresponding author nitrogen and phosphorus. All other tests were within reference

Volume 42, No. 2 / March 2003 CONTEMPORARY TOPICS © 2003 by the American Association for Laboratory Animal Science 43 Table 1. Biochemical parameters

Reference values Test Results average (range)

Hematology White blood cells, total, × 109/L 3.70 6.23 (2.4–11.36) Neutrophils, × 109/L 2.64 3.37 (1.34–6.32) Lymphocytes, × 109/L 0.86 2.00 (0.27–5.36) Monocytes, × 109/L 0.11 0.77 (0.13–1.87) Eosinophils, × 109/L 0.08 0.06 (0.0–0.34) Basophils, × 109/L 0.00 0.02 (0.0–0.07) Red blood cells, × 1012 g/L 5.55 8.76 (7.07–12.64) Hemoglobin, × 10 g/L 8.6 13.88 (11.20–20.40) Hematocrit, × 10-2 L/L 27.4 39.1 (32.2–55.4) MCV, fL 49.3 44.7 (41.5–52.2) MCH, pg 15.5 15.9 (14–18.5) MCHC, × 10 g/L 31.4 35.5 (33–38.8) RDW, % 18.5 20.5 (17.2–24.6) Platelet count, × 1011/L 204 380 (141–448) MPV, fl 5.8 4.8 (3.6–7.6)

Chemistries Protein, total, g/L 61 (48–83) Figure 3. Photomicrograph of the left kidney (H&E; magnification, ×40). Phosphorus, mmol/L 7.752 (1.4535–3.1977) Note the diffuse interstitial nephritis with multiple regions of mixed in- Urea nitrogen, mmol/L 87.822 (5.712–35.343) Creatinine, µmol/L 79.56 (17.68–61.88) flammatory cell infiltrates, fibrous connective tissue deposition (i.e., scarring, confirmed by trichrome staining), and multifocal dilatation of Urinalysis cortical tubules. Specific gravity 1.016 not determined

MCV, Mean corpuscular volume. MCH, Mean corpuscular hemoglobin. MCHC, Mean corpuscular hemoglobin concentration. RDW, Red cell distribution width. MPV, Mean platelet volume.

Figure 4. Photomicrograph of the right kidney, demonstrating the mul- tiple epithelial-lined cysts (H&E; magnification, ×40). At lower magnification, there was no evidence of a functional, patent renal pelvis (not shown).

Figure 2. At necropsy, the kidneys showed the following gross pathol- cal nodular hyperplasia in both adrenal glands. Microscopically, ogy: enlarged left kidney (large white arrow) and a smaller, fluctuant there was unilateral, locally extensive necrosis of the en- right kidney (small white arrowhead). dometrium. All other examined tissues were within normal limits. ranges (5-7). A very small amount of urine was obtained and Discussion used for the measurement of specific gravity. Degus are nontraditional laboratory animals. Little is known On gross necropsy examination, the left kidney had an irregu- about the naturally occurring diseases and lesions in the spe- lar, granular surface and was pale and mildly enlarged (Fig. 2). cies. This female degu presented with clinical signs, clinical It measured 10 × 15 mm. The right kidney was small and cystic chemistry results, and histopathological findings supportive of and measured 5 × 8 mm (Fig. 2). Enlargement of the left kidney renal failure secondary to chronic nephritis and polycystic kid- was considered a compensatory response (compensatory hyper- ney disease. We assume that the cystic kidney was essentially trophy) due to long-term loss of function in the right kidney. nonfunctional, while the contralateral kidney had marked loss Histologically, the enlarged left kidney had moderate to of functional nephrons (roughly 50% nonfunctional). The patho- marked tubular dilatation with chronic, diffuse interstitial ne- genesis of the nephritis is unknown but is often associated with phritis (Fig. 3). Extensive scarring in this kidney was confirmed polycystic disease. It is possible that the decreased white cell count by positive trichrome staining for collagen (not shown). The right in this animal increased susceptibility for ascending sepsis in the kidney had multiple epithelial-lined cysts with effaced architec- kidney and uterus and subsequent inflammation and necrosis ture and no evidence of remaining functional nephrons or a in these tissues. functional renal pelvis (Fig. 4). Murphy et al. reviewed the types of lesions that spontaneously Both adrenal glands appeared mildly enlarged. The left adre- occur in degus (2). In that report, abnormalities affecting the nal gland measured 4 × 7 mm, and the right adrenal gland urinary system were infrequent and mild in all but one case. One measured 3 × 6 mm. Histologic exam showed mild, focal, corti- degu had severe lesions in both kidneys. The lesions were char-

44 CONTEMPORARY TOPICS © 2003 by the American Association for Laboratory Animal Science Volume 42, No. 2 / March 2003 acterized by the presence of sclerotic glomeruli, dilated tubules Acknowledgments containing proteinaceous casts, focal hyperplasia of ductal epi- We thank Anna Colvig, B.A., for her assistance during the post-mortem thelium, and focal interstitial lymphocytic infiltrates (2). Chronic examination. We also thank Kay-Ann Schuck, B.S, M.T. (ASCP), for per- nephrosis has been reported as a spontaneous lesion in mul- forming the hematology and biochemical assays. We thank Elizabeth tiple degus of unspecified ages (2). In addition, lymphocytic Horn for her assistance with the photographs. This work was supported infiltrates have been described as spontaneous lesions in the kid- in part by NIH/NCRR T32 RR07008. neys of degus. By comparison, chronic nephrosis or nephropathy has been described in aged rats, guinea pigs, and other rodents References (8). However, the present case demonstrates a higher degree of 1. Nowak, R. M. 1999. Rodentia; family Octodontidae: octodonts, p. inflammation than is common in rats. Furthermore, the case we 1681-1682. In Walker’s of the world, 6th ed., vol. II. The describe occurs in a young adult. Consequently, advanced-age John Hopkins University Press, Baltimore. lesions, if they exist in the degu, do not apply in this case. Histol- 2. Murphy, J. C., T. P. Corwell, K. M. Hewes, et al. 1980. Spontane- ogy suggests that this degu had complete loss of function in the ous lesions in the degu, p. 437-444. In R. J. Montali and G. Migaki cystic kidney and marked loss of functional nephrons in the con- (ed.), The comparative pathology of zoo animals. Smithsonian In- tralateral kidney, resulting in renal failure. stitution Press, Washington, D.C. Chronic renal failure (CRF) is characterized by irreversible 3. Geol, N., M. M. Governale, T. J. Jechura, et al. 2000. Effects of renal dysfunction that tends to deteriorate progressively over a intergeniculate leaflet lesions on circadian rhythms in Octodon degus. Brain Res. 877(2):306-313. period of months to years. CRF may be congenital, familial, or 4. Donnelly, T. M. and F. W. Quimby. 2002. XVI. Degu or trumpet- acquired in origin (9, 10). Congenital and familial causes of CRF tailed rats: Octodon, p. 284-286. In J. G. Fox, L. C. Anderson, F. M. are often suspected on the basis of breed and family history, Loew, and F. W. Quimby (ed.), Laboratory animal medicine, 2nd early onset of renal disease or failure, or radiographic and ed. Academic Press, San Diego, Calif. ultrasonographic findings (e.g., polycystic kidney disease) (10). 5. Rush, H. G. 2001. Personal communication. Acquired CRF may result from any disease process that injures 6. Murphy, J. C, S. M. Niemi, K. M. Hewes, et al. 1978. Hematologic renal glomeruli, tubules, interstitium, and/or vasculature and and serum protein reference values of the Octodon degus. Am. J. causes sufficient irreversible loss of functional nephrons to re- Vet. Res. 39(4):713-715. 7. C. A. Johnson-Delaney. 1996. Special rodents: degu, p. 27-32. In C. sult in primary renal failure (9, 10). Anemia was present in this A. Johnson-Delaney and L. R. Harrison (ed.), Exotic companion animal and considered secondary to the CRF. Often in CRF, medicine handbook for veterinarians. Wingers Publishing, Inc., hematocrit and red blood cell counts drop due to inadequate Lake Worth, Fla. formation of erythropoietin, as well as variable increase in 8. Montgomery, C. A. and J. C. Seely. 1990. Kidney, p. 127-153. In G. hemolysis (11). The finding of anemia in a severely azotemic A. Boorman, S. L. Eustis, M. R. Elwell, C. A. Montgomery, Jr., and animal in poor condition would point to renal failure as a pos- W. F. MacKenzie (ed.), Pathology of the Fischer rat. Academic Press, sible primary disease. San Diego, Calif. Polycystic kidney disease (PKD) is a disorder in which large 9. Adams, L. G. and C. A. Osborne. 1997. Renal failure, chronic, p. 1018-1019. In L. P. Tilley and F. W. K. Smith, Jr., The 5-minute veteri- portions of normally differentiated renal parenchyma are dis- nary consult: canine and feline. Williams and Wilkins, Baltimore. placed by multiple cysts. Renal cysts develop in preexisting 10. Polzin, D. J., C. A. Osborne, F. Jacob, et al. 2000. Chronic renal nephrons and collecting ducts. Affected individuals may be as- failure, p. 1634-1662. In S. J. Ettinger and E. C. Feldman (ed.), ymptomatic or show evidence of rapidly progressing renal failure, Textbook of veterinary internal medicine, 5th ed. W. B. Saunders depending on the presence of remaining functional nephrons Co., Philadelphia. as cystic nephrons are essentially nonfunctional. It is hypoth- 11. Contran, R. S., V. Kumar, and T. Collins. 1999. Red cells and bleed- esized that cysts develop as a result of an abnormality of cell ing disorders, p. 633. In R. S. Contran, V. Kumar, and T. Collins differentiation associated with sustained cellular proliferation (ed.), Robbins pathologic basis of disease, 6th ed. W. B. Saunders Co., Philadelphia. of lining cells. PKD is thought to be congenital, and some con- 12. Murcia, N. S., W. E. Sweeney, Jr., and E. D. Avner. 1999. New in- tributing genes have been identified in the mouse (12). The sights into the molecular pathophysiology of polycystic kidney disease has been well described in Cairn terriers and longhaired disease. Kidney Int. 55:1187-1197. cats (13, 14). PKD also has been documented in other nontradi- 13. DiBartola, S. P. 2000. Familial renal disease in dogs and cats, p. 1698- tional laboratory animals including the woodchuck (15), striped 1703. In S. J. Ettinger and E. C. Feldman (ed.), Textbook of veterinary skunk, and Mongolian gerbil (16). In man, the disease is geneti- internal medicine, 5th ed. W. B. Saunders Co., Philadelphia. cally heterogenous, caused by mutations of three separate genes. 14. Lulich, J. P. and C. A. Osborne. 1997. Polycystic kidney disease, p. The pattern of inheritance can be autosomal dominant or re- 964. In L. P. Tilley and F. W. K. Smith, Jr., The 5-minute veterinary consult: canine and feline. Williams and Wilkins, Baltimore. cessive (17). The adrenal nodular hyperplasia was an incidental 15. Young, R. A. and W. S. Webster. 1985. Tumors and polycystic renal finding in this animal. disease in two captive woodchucks (Marmota monax). Lab. Anim. This is the first report of a multiparous female degu with bilat- Sci. 35(5):493-496. eral renal dysfunction involving nephritis and polycystic kidney 16. Ryan, C. P. 1981. Polycystic disease of the kidneys in a striped skunk disease. Over the past 11 years, 68 degus from the colony have and Mongolian gerbil. Vet. Med. Small Anim. Clin. 76(9):1351-1354. been necropsied. There have been 13 cases of kidney disease, 17. Contran, R. S., V. Kumar, and T. Collins. 1999. The kidney, p. 973. including nephrosis, pyelonephritis, glomerulonephritis, and In R. S. Contran, V. Kumar, and T. Collins (ed.), Robbins patho- renal failure. logic basis of disease, 6th ed. W. B. Saunders Co., Philadelphia.

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