Urinary System

Kidney, Renal Tubule - Vacuolation, Cytoplasmic

Narrative

Comment:

Cytoplasmic vacuolation is characterized by the presence of clear vacuoles in renal tubule epithelium in the absence of any morphologic changes associated with degeneration (Figure 1). Cytoplasmic vacuoles are normally present in the outer cortical tubules of male mice in certain strains, but are not typically present in female mice or rats. Abnormal, or pathologic, vacuolation may be seen anywhere along the various tubule segments and collecting ducts. It is more commonly observed in the proximal convoluted tubule epithelium. Vacuolation may be associated with single, larger vesicles (macrovesicular) or may be associated with several smaller vesicles (microvesicular). Osmotically active compounds such as some sugars often result in "osmotic nephrosis," which appears as cytoplasmic vacuolation. Cytoplasmic vacuolation of renal tubule epithelium may also be seen with phospholipidosis-inducing chemicals, cyclodextrins, and other chemicals that induce vacuolation through phagolysosomes. Cytoplasmic vacuolation, in most cases, is reversible. Artifactual vacuolation, related to autolysis or poor fixation, is frequently observed in animals either dying on test or sacrificed in a moribund state. Often it becomes problematic to separate tubule toxicity from artifact.

Recommendations:

Normally, male mice have variable cortical tubule cytoplasmic vacuolation and do not have to be diagnosed (see Kidney - Renal Tubule - Cytoplasmic Alteration ). In male mice, cytoplasmic vacuolation should be diagnosed only when the number and/or size of vacuoles is greater than that of the concurrent controls. Cytoplasmic vacuolation in female mice and male and female rats should be diagnosed whenever present. This diagnosis should be reserved for those cases where the vacuoles are present in the absence of other morphologic features of degeneration. The tubule location and portion of the kidney affected should be described in the pathology narrative. Whenever it is diagnosed, cytoplasmic vacuolation should be graded. Artifactual vacuolation should not be diagnosed.

Related Links:

Kidney - Renal Tubule - Cytoplasmic Alteration

References:

Bendele A, Seely J, Richey C, Sennello G, Shopp G. 1998. Short communication: Renal tubular vacuolation in animals treated with polyethylene-glycol-conjugated proteins. Toxicol Sci 42:152-157.

Abstract: http://www.ncbi.nlm.nih.gov/pubmed/9579027

Johson RC, Dovey-Hartman BJ, Syed J, Leach MW, Frank DW, Sinha DP, Mirro EJ, Little JM, Halliwell WH. 1998. Vacuolation in renal tubular epithelium of Cd-1 mice: An incidental finding. Toxicol Pathol 26:789-792.

Full Text: http://tpx.sagepub.com/content/26/6/789.full.pdf

Khan KNM, Alden CL. 2002. Kidney. In: Handbook of Toxicologic Pathology, 2nd ed (Haschek WG, Rousseaux CG, Wallig MA, eds). Academic Press, San Diego, 255-336.

Abstract: http://www.sciencedirect.com/science/book/9780123302151

Monserrat AJ, Chandler AE. 1975. Effects of repeated injections of sucrose in the kidney: Histologic, cytochemical and functional studies in an animal model. Virchows Arch B 19:77-91.

Abstract: http://www.ncbi.nlm.nih.gov/pubmed/809924

Nonoyama T, Fukuda R. 2008. Drug-induced phospholipidosis - pathological aspects and its prediction. J Toxicol Pathol 21:9-24.

Abstract: https://www.jstage.jst.go.jp/article/tox/21/1/21_1_9/_article

Rees JA, Old SI, Rowlands PC. 1997. An ultrastructural, histochemistry, and light microscopy study of the early development of renal proximal tubular vacuolation after a single administration of the contrast enhancement medium "Iotrolan." Toxicol Pathol 25:158-164.

Abstract: http://www.ncbi.nlm.nih.gov/pubmed/9125774

All Images

Kidney, Renal tubule - Vacuolation, Cytoplasmic in a treated male B6C3F1 mouse from a chronic study. Numerous clear vacuoles are present in the cytoplasm of renal tubule epithelial cells.

Kidney, Renal tubule - Vacuolation, Cytoplasmic in a treated male B6C3F1 mouse from a chronic study (higher magnification of Figure 1). There are variably sized, mostly large vacuoles in the renal tubule epithelial cells.

Authors and Reviewers

Authors 

John Curtis Seely, DVM, DACVP
Senior Pathologist
Experimental Pathology Laboratories, Inc.
Research Triangle Park, NC

Amy Brix, DVM, PhD, DACVP
Senior Pathologist
Experimental Pathology Laboratories, Inc.
Research Triangle Park, NC

Reviewers

Kendall S. Frazier, DVM, PhD, DACVP, DABT
Director, Cellular and Molecular Pathology, Safety Assessment
GlaxoSmithKline
King of Prussia, PA

Gordon C. Hard, BSc, BVSc, PhD, DSc, FRCPath, FRCVS, FAToxSci, DACVP
Expert Consultant
Tairua, New Zealand

Susan A. Elmore, MS, DVM, DACVP, DABT, FIATP
Staff Scientist, NTP Pathologist
NTP Pathology Group
National Toxicology Program
National Institute of Environmental Health Sciences
Research Triangle Park, NC