Normal Anatomy, Histology, and Spontaneous Pathology of the Kidney, and Selected Renal Biomarker Reference Ranges in the Cynomolgus Monkey.

To further our understanding of the nonhuman primate kidney anatomy, histology, and incidences of spontaneous pathology, we retrospectively examined kidneys from a total of 505 control Cynomolgus monkeys (Macaca fascicularis; 264 male and 241 females) aged 2 to 6 years, from toxicity studies. Kidney weights, urinalysis, and kidney-related clinical biochemistry parameters were also evaluated. Although the functional anatomy of the monkey kidney is relatively similar to that of other laboratory animals and humans, a few differences and species-specific peculiarities exist. Unlike humans, the macaque kidney is unipapillate, with a relatively underdeveloped papilla, scarce long loops of Henle, and a near-equivalent cortical to medullary ratio. The most common spontaneous microscopic findings were interstitial infiltrates or interstitial nephritis and other tubular lesions, but several forms of glomerulopathy that may be interpreted as drug-induced were occasionally observed. Common incidental findings of little pathological significance included: papillary mineralization, epithelial pigment, multinucleate cells, cuboidal metaplasia of the Bowman's capsule, and urothelial inclusions. Kidney weights, and some clinical chemistry parameters, showed age- and sex-related variations. Taken together, these data will aid the toxicologic pathologist to better evaluate the nonhuman primate kidney and assess the species' suitability as a model for identifying and characterizing drug-induced injury.

Findings in Historical Control Harlan RCCHan™: WIST Rats from 104-week Oral Gavage Studies.

Vehicle control Harlan RCCHan™:WIST rats were examined to provide control data for subsequent studies. The rats (180 male and 180 female) were dosed daily via oral gavage with reverse osmosis water for up to 104 weeks. At necropsy, body weights and macroscopic findings were recorded and tissues were collected for histopathology. The mean body weight at terminal sacrifice was 687 g for males and 466 g for females. The overall survival rate was 62% for males and 59% for females. The most common cause of death for males and females found dead or examined following unscheduled euthanasia was pituitary neoplasia with an incidence of 13.9% for males and 18.9% for females. Macroscopic and neoplastic and nonneoplastic microscopic findings are presented by body system.

Fetal omphalocele in a common bottlenose dolphin (Tursiops truncatus).

A routine pregnancy ultrasound examination of a 30-yr-old, multiparous, common bottlenose dolphin, Tursiops truncatus, detected an approximately 16-wk (gestational age) fetus with an omphalocele, an abdominal wall defect at the base of the umbilical cord. Throughout the pregnancy, ultrasound allowed for identification of the omphalocele contents, which included a portion of the liver and intestinal loops. The maximum diameter of the omphalocele was 11.4 cm at an estimated 51-wk gestation. Color Doppler was utilized to study the blood flow within the omphalocele as well as diagnose an associated anomaly of the umbilical cord, which contained three vessels instead of four. Gross necropsy and histopathology confirmed the ultrasound diagnoses. This is the first report of an omphalocele in a T. truncatus fetus, and the first report of a fetal and umbilical cord anomaly diagnosed with ultrasound in a cetacean.

Findings in Historical Control Harlan RCCHanTM: WIST Rats from 4-, 13-, 26-Week Studies.

Vehicle control Harlan RCCHan™: WIST rats were examined to provide control data for subsequent studies. Sixty male and 60 female rats were sacrificed after 4, 13, and 26 weeks (360 animals total) of daily oral gavage dosing with reverse osmosis water. At necropsy, body weights, organ weights, and macroscopic findings were recorded, and tissues were collected for histopathology. Mean terminal body and organ weight data demonstrated expected age-related trends. Macroscopic findings occurred sporadically, generally at singular or at very low incidence, and with no observable age-related trend. The most frequent observation was discoloration of the stomach mucosa. Neoplastic microscopic findings were uncommon (one endometrial stromal polyp; one hepatocellular adenoma; one C-cell adenoma; and one sarcoma, NOS). The most common and/or notable nonneoplastic microscopic findings included basophilic tubules and mononuclear cell infiltration in the kidney, macrophage infiltration in pulmonary alveoli, and mononuclear infiltration in the liver of males and females, and myocardial degeneration/necrosis and mononuclear cell infiltration in the heart of males. Female reproductive tracts were staged to establish a representative baseline distribution. Diestrus, proestrus, estrus, and metestrus were diagnosed 45.8%, 11.9%, 30.5%, and 11.9%, respectively, at 4 weeks and 27.6%, 13.8%, 50.0%, and 8.6%, respectively, at 13 weeks.