The osteoprotegerin/tumor necrosis factor related apoptosis-inducing ligand axis in the kidney

Curr Opin Nephrol Hypertens. 2014 Jan;23(1):69-74. doi: 10.1097/01.mnh.0000437611.42417.7a.


Purpose of review: Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is a cytokine belonging to the TNF superfamily. TRAIL may modulate cell survival and proliferation through interaction with two different receptors, TRAIL-R1 and TRAIL-R2. The actions of TRAIL are regulated by three decoy receptors, TRAIL-R3, TRAIL-R4 and osteoprotegerin (OPG). There is evidence that both TRAIL and OPG are expressed by renal cells. The OPG/TRAIL axis has been recently linked to the pathogenesis of renal damage and, in particular, diabetic nephropathy.

Recent findings: In patients with kidney diseases, serum TRAIL and OPG levels are increased in parallel and are significantly associated with each other. In diabetic nephropathy, the renal expression of TRAIL and OPG is elevated, and in tubular cells proinflammatory cytokines enhance TRAIL expression. Additionally, a high-glucose microenvironment sensitizes tubular cells to apoptosis induced by TRAIL, whereas OPG counteracts the actions of TRAIL in cultured cells.

Summary: It seems that the expression and levels of TRAIL and OPG at serum and kidney levels are crucial for the pathogenesis of kidney diseases, and in particular diabetic nephropathy. Although further studies are necessary to clarify the exact role of the OPG/TRAIL axis in the kidney, this system seems to hold promise to provide therapeutic approaches for the management of renal damage.

Video abstract available: See the Video Supplementary Digital Content 1 (

Publication types

  • Review
  • Video-Audio Media

MeSH terms

  • Animals
  • Apoptosis
  • Diabetic Nephropathies / metabolism*
  • Diabetic Nephropathies / pathology
  • Humans
  • Kidney / metabolism*
  • Kidney / pathology
  • Osteoprotegerin / metabolism*
  • Renal Insufficiency, Chronic / metabolism*
  • Renal Insufficiency, Chronic / pathology
  • Signal Transduction*
  • TNF-Related Apoptosis-Inducing Ligand / metabolism*


  • Osteoprotegerin
  • TNF-Related Apoptosis-Inducing Ligand