Tubulointerstitial injury and the progression of chronic kidney disease

Pediatr Nephrol. 2012 Jun;27(6):901-9. doi: 10.1007/s00467-011-1992-9. Epub 2011 Sep 27.


In chronic kidney disease (CKD), once injury from any number of disease processes reaches a threshold, there follows an apparently irreversible course toward decline in kidney function. The tubulointerstitium may play a key role in this common progression pathway. Direct injury, high metabolic demands, or stimuli from various other forms of renal dysfunction activate tubular cells. These, in turn, interact with interstitial tissue elements and inflammatory cells, causing further pathologic changes in the renal parenchyma. The tissue response to these changes thus generates a feed-forward loop of kidney injury and progressive loss of function. This article reviews the mechanisms of this negative cycle mediating CKD.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Cell Communication
  • Chronic Disease
  • Disease Progression
  • Feedback, Physiological
  • Fibrosis
  • Humans
  • Kidney Diseases / metabolism
  • Kidney Diseases / pathology*
  • Kidney Diseases / physiopathology
  • Kidney Tubules / metabolism
  • Kidney Tubules / pathology*
  • Kidney Tubules / physiopathology
  • Nephritis, Interstitial / metabolism
  • Nephritis, Interstitial / pathology*
  • Signal Transduction