Abstract: TH-PO303

Outer Stripe of the Outer Medulla in Human and Pig Kidney Is Markedly Reduced or Absent Compared to Rat

Session Information

Category: Acute Kidney Injury

  • 001 AKI: Basic

Authors

  • Pannabecker, Thomas L., University of Arizona, Tucson, Arizona, United States
  • Rosen, Seymour, Beth Israel Deaconess Medical Center, Boston, Massachusetts, United States
Background

In the rat inner and outer stripes of the outer medulla (ISOM, OSOM), there are clear, functionally defined architectural features that lead to physiologically significant nephron and vascular flows. The dynamics of these flows define, in part, our views of basic renal physiology, such as diabetic nephropathy, progression of kidney injury, oxygen delivery and the urine concentrating mechanism. The human and pig medullary architecture differ from the rat in distinct ways, consistent with published observations from the first decade of the 20th century that suggested that the human OSOM, along the corticomedullary axis, has minimal depth.

Methods

We investigated architecture of the human, pig and rat medulla near the corticomedullary junction using tissue embedded in paraffin or resin, followed by sectioning and staining with conventional histochemical (H&E) and immunohistochemical techniques (antibodies for aquaporin1, smooth muscle actin, CD34 and urea transporter UTB and wheat germ lectin). Sections were viewed and photographed using conventional microscopy.

Results

The rat OM has two distinct zones (ISOM, OSOM). The human equivalent of the OM is a single zone whose tubular/vascular structure is largely similar to the rat ISOM. The human basal cortex is almost completely composed of medullary rays, which merge confluently with this single zone (ISOM). The human glomerular efferent arterioles cluster to form the most superficial aspect of the outer medullary vasa recta, which descend, accruing a venous component to form an exclusively arteriolar-venous structure, in contrast to the rat, which also includes thin limbs. The ascending vasa recta bundles of the deeper ISOM become, in the superficial ISOM, composite groupings of venous vasa recta, collecting ducts and thick ascending limbs fusing with medullary rays.

Conclusion

Our studies suggest that in human and pig, the OSOM, as defined by rat medullary architecture, is minimal or absent. Importantly, vascular perfusion of nephron segments in the OM and the deep cortex follows patterns that differ from rat. Re-evaluation of vascular architecture and expected blood flows in human and pig models may provide insights into a number of renal disorders that have resisted advances in treatment and may challenge the use of rat and mouse experimental models that regard outer stripe injury as parallel to human AKI.

Funding

  • NIDDK Support