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

Abstract

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.

Correlations of serum biochemistry profile with ultrasonic histogram of liver, gallbladder, and kidneys and morphometry of rescued long‐tailed macaques (Macaca fascicularis)

“…Creatinine was higher in males compared to females similar to previous studies 2,7,8 . The observed sex‐related difference in creatinine could be due to relatively higher muscle mass in males as previously described 7 .…”

“…2,7,8 The observed sex-related difference in creatinine could be due to relatively higher muscle mass in males as previously described. 7 Creatine values for both sexes in this study was higher compared to previous reports. 2,6,8,14 but comparable to the baseline values reported earlier.…”

“…Serum biochemistry values for laboratory‐kept long‐tailed macaques originated from Mauritius, 1 China, 2 and Cambodia 3 were previously reported. Sex‐related differences were observed on serum biochemistry values of healthy male and female macaques in previous studies 4‐8 …”

Identification and classification of interstitial cells in the mouse renal pelvis

“…Similar to the mouse, the cynomolgus monkey ( Macaca fascicularis ) possesses a unicalyceal renal system (Chamanza et al . 2019) but has much closer genetic similarities to humans (Gibbs et al . 2007).…”

Congenital Unilateral Renal Aplasia in a Cynomolgus Monkey (Macaca fascicularis) With Investigation Into Potential Pathogenesis

“…16 and in a baboon (Papio anubis) utilized in a toxicity study, but the latter monkey had unilateral absence of renal tissue and ureter which was more consistent with renal agenesis. 23 Other spontaneous congenital anomalies have been reported in cynomolgus (Macaca fascicularis) and/or rhesus (Macaca mulatta) macaques but at a low frequency: a few cases of spontaneous renal dysplasia, 22,24,25 several cases of spontaneous congenital polycystic kidney disease, 17,[26][27][28] and single cases of hypoplasia, double ureter, renal ectasia, and unilateral cystic kidney. 22,29 Spontaneous renal dysplasia has been reported relatively frequently in many species 8,11,14,30,31,32,33,34,[35][36][37]38,39,[40][41][42]43,44 and is known to be familial/inherited in some species.…”