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

Abstract

We describe and characterize unilateral renal aplasia in a cynomolgus monkey ( Macaca fascicularis) from a chronic toxicology study adding to the limited histopathology reports of congenital renal anomalies in macaques. In the current case, the affected kidney was macroscopically small and characterized microscopically by a thin cortex with an underdeveloped medulla and an absent papilla. The remnant medulla lacked a corticomedullary junction and contained only a few irregular collecting duct-like structures. The cortex had extensive interstitial mature collagen deposition with fibromuscular collar formation around Bowman’s capsules. Due to parenchymal collapse, mature glomeruli were condensed together with occasional atrophic and sclerotic glomeruli. The majority of the cortical tubules were poorly differentiated with only small islands of fully developed cortical tubules present. Histochemical and immunohistochemical stains were utilized to demonstrate key diagnostic features of this congenital defect, to assist with differentiating it from renal dysplasia, and to provide potential mechanistic pathways. Immunostaining (S100, paired box gene 2 [PAX2], aquaporins) of the medulla was compatible with incomplete maturation associated with aplasia, while the immunostaining profile for the cortex (vimentin, calbindin, PAX2-positive cortical tubules, and smooth muscle actin–positive fibromuscular collars) was most compatible with dedifferentiation secondary to degenerative changes.

The Impact of Functional and Structural Maturation of the Kidney on Susceptibility to Drug and Chemical Toxicity in Neonatal Rodents

“…Genes responsible for critical developmental pathways during embryogenesis involved in patterning and morphogenesis can be disrupted by drug or chemical exposure, resulting in renal malformations and kidney aplasia. [12][13][14] Further, the ureteric bud and the metanephric blastema progenitor cells require correct biochemical signaling in the proper sequence for normal morphogenesis and tubule development. 15 Due to their importance in regulating normal nephrogenesis and tubule differentiation, dysregulated proliferation and apoptosis can lead to the various phenotypic malformations of congenital renal disease, depending on timing.…”

“…2 As noted with prenatal human exposure, degenerative lesions in the kidney may also occur in rat or mouse kidneys as a result of neonatal xenobiotic exposure, either as a primary lesion or as a secondary degenerative, cystic, or atrophic process as sequelae to the original malformation. 14 Nephron maturation occurs proximally to distally in an orderly process in which the proximal tubules form initially and distal medullary structures form last during kidney development. 2 Nephrogenesis is completed in humans in utero by gestational week (GW) 36 with a full complement of nephrons in each kidney at birth, 2 while it continues postnatally in rats until at least postnatal day (PND) 11 (Table 1).…”