Kidney
Generally for NTP studies the right kidney is cross-sectioned while the left kidney is sectioned longitudinally. It is important that both renal papillae and renal pelves are present ( Figure 1 ). This style of sectioning helps to distinguish the kidneys. CPN and most renal toxicants generally affect both kidneys, whereas vascular, inflammatory, or proliferative lesions may affect one or both kidneys.

Figure 2. Demarcated regions of the kidney: cortex, outer stripe of the outer medulla (OSOM), inner stripe of the outer medulla (ISOM), inner medulla, papilla, and renal pelvis.
One of the most heterogeneous tissues in the body, the kidney has a wide variety of cell types. For the most part, renal tubules and/or ducts comprise most of the renal parenchyma and are lined by specialized epithelial cells. Renal interstitial tissue is sparse in the cortex and gradually increases toward the papilla. The distribution of the renal vasculature is uniquely suited to supply more blood to the energy-active cortex.
Each area of the kidney contains defined segments of the nephron, the functional unit of the kidney, and portions of the collecting duct system. It is imperative for pathologists to understand the relationships among the anatomic locations of the various segments of the nephron or collecting duct system since some chemicals have a selective affinity for a particular nephron or duct segment.

Figure 3. Schematic of the anatomic locations of the various nephron and collecting duct segments within the kidney. Image by David Sabio.

Figure 5. Tubule and glomerular basement membranes and proximal convoluted tubule brush borders outlined by PAS staining.
The upper portions of the renal pelves have specialized folds called fornices, which serve to increase the surface area of the pelvis ( Figure 6 ). These folds may collect cellular debris and mineralized concretions as the animal ages. Figure 7 presents a section of the renal papilla, renal pelvis, and renal hilus. The larger vessels of the kidney can be seen in this section adjacent to the renal pelvis. Often islands of hematopoietic tissue may be observed in the hilus in response to increase demand. Accumulations of hematopoiesis should not be confused with inflammatory or neoplastic infiltrates. The renal pelvis is lined by urothelium.

Figure 7. The papilla and surrounding renal pelvis with the adjacent renal hilar area containing the large renal artery and vein. The urothelium-lined opening to the ureter may also be seen.
The kidney undergoes autolysis rapidly, and kidneys from moribund animals or animals dying on test have histologic changes associated with autolysis. Even specimens immersion fixed at the time of sacrifice may contain subtle to large areas of autolysis within the kidney mimicking degeneration and necrosis ( Figure 8 ). Autolysis must be differentiated from lesions such as tubule epithelial vacuolation, degeneration, or acute necrosis. At times this differentiation is difficult even for the seasoned pathologist. Histologic changes associated with autolysis include varying degrees of focal, zonal, or diffuse pale-staining tissue, loss of cytoplasmic and nuclear detail (rarefaction or “ghost-like” cells), retraction of tubule epithelial cells from basement membranes, and tubule vacuolation ( Figure 9 , Figure 10 ). Desquamation of tubule epithelial cells has been reported with autolysis and, therefore, is not always a reliable indicator of tubule cell necrosis.

Figure 9. Consistent histologic features of autolysis are characterized by loss of cytoplasmic and nuclear detail (rarefaction) and retraction of tubule epithelial cells from basement membranes.
Additional artifacts such as mineralization in the outer cortex may be observed and should not be confused with real mineralization ( Figure 11 ).

Figure 11. Artifactual mineralization represented by irregular foci of basophilia in the outer cortex of a male rat.
For more detailed information on the anatomy and physiology of the kidney, see Sands JM, Verlander JW. 2005. Anatomy and physiology of the kidneys. In: Toxicology of the Kidney, 3rd ed (Tarloff JB, Lash LH, eds). CRC Press, Boca Raton, FL, 3-56.
Abstract: http://www.crcnetbase.com/ISBN/9780203646991
References:
Sands JM, Verlander JW. 2005. Anatomy and physiology of the kidneys. In: Toxicology of the Kidney, 3rd ed (Tarloff JB, Lash LH, eds). CRC Press, Boca Raton, FL, 3-56. Abstract: http://www.crcnetbase.com/ISBN/9780203646991
Web page last updated on: October 23, 2014