Tubular cross talk in acute kidney injury: a story of sense and sensibility

Am J Physiol Renal Physiol. 2015 Jun 15;308(12):F1317-23. doi: 10.1152/ajprenal.00030.2015. Epub 2015 Apr 15.


The mammalian kidney is an organ composed of numerous functional units or nephrons. Beyond the filtering glomerulus of each nephron, various tubular segments with distinct populations of epithelial cells sequentially span the kidney from cortex to medulla. The highly organized folding of the tubules results in a spatial distribution that allows intimate contact between various tubular subsegments. This unique arrangement can promote a newly recognized type of horizontal epithelial-to-epithelial cross talk. In this review, we discuss the importance of this tubular cross talk in shaping the response of the kidney to acute injury in a sense and sensibility model. We propose that injury-resistant tubules such as S1 proximal segments and thick ascending limbs (TAL) can act as "sensors" and thus modulate the responsiveness or "sensibility" of the S2-S3 proximal segments to injury. We also discuss new findings that highlight the importance of tubular cross talk in regulating homeostasis and inflammation not only in the kidney, but also systemically.

Keywords: Tamm-Horsfall protein; acute kidney injury; sepsis; tubular cross talk; uromodulin.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Acute Kidney Injury / metabolism*
  • Acute Kidney Injury / pathology*
  • Animals
  • Epithelial Cells / metabolism
  • Epithelial Cells / pathology*
  • Humans
  • Kidney Tubules, Proximal / metabolism
  • Kidney Tubules, Proximal / pathology*
  • Loop of Henle / metabolism
  • Loop of Henle / pathology*
  • Nephrons / metabolism
  • Nephrons / pathology*
  • Uromodulin / metabolism


  • Uromodulin