Mechanisms of tubulointerstitial injury in the kidney: final common pathways to end-stage renal failure

Intern Med. 2004 Jan;43(1):9-17. doi: 10.2169/internalmedicine.43.9.


There are many different glomerular disorders, including glomerulonephritis, diabetic nephropathy, and hypertensive nephrosclerosis. However, once glomerular damage reaches a certain threshold, the progression of renal disease is consistent and irreversible. Recent studies emphasized the crucial role of tubulointerstitial injury as a mediator of progression of kidney disease. One common mechanism that leads to renal failure via tubulointerstitial injury is massive proteinuria. Accumulating evidence suggests critical effects of filtered macromolecules on tubular cells, including lysosomal rupture, energy depletion, and tubular injury directly induced by specific components such as complement components. Another common mechanism is chronic hypoxia in the tubulointerstitium. Tubulointerstitial damage results in the loss of peritubular capillaries, impairing blood flow delivery. Interstitial fibrosis also impairs oxygen diffusion and supply to tubular cells. This induces chronic hypoxia in this compartment, rendering a vicious cycle. Development of novel therapeutic approaches against these final common pathways will enable us to target any types of renal disease.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adult
  • Angiotensin-Converting Enzyme Inhibitors / therapeutic use
  • Biopsy, Needle
  • Complement Membrane Attack Complex / metabolism
  • Disease Progression
  • Female
  • Humans
  • Hypoxia / complications
  • Hypoxia / diagnosis
  • Immunohistochemistry
  • Kidney Failure, Chronic / etiology*
  • Kidney Failure, Chronic / physiopathology
  • Kidney Function Tests
  • Kidney Tubules / drug effects
  • Kidney Tubules / pathology
  • Male
  • Middle Aged
  • Nephritis, Interstitial / complications*
  • Nephritis, Interstitial / drug therapy
  • Nephritis, Interstitial / pathology*
  • Prognosis
  • Proteinuria / complications*
  • Proteinuria / diagnosis
  • Risk Factors
  • Severity of Illness Index


  • Angiotensin-Converting Enzyme Inhibitors
  • Complement Membrane Attack Complex