Treatment of Renal Fibrosis-Turning Challenges into Opportunities

Adv Chronic Kidney Dis. 2017 Mar;24(2):117-129. doi: 10.1053/j.ackd.2016.11.002.

Abstract

Current treatment modalities are not effective in halting the progression of most CKD. Renal fibrosis is a pathological process common to all CKD and thereby represents an excellent treatment target. A large number of molecular pathways involved in renal fibrosis were identified in preclinical studies, some of them being similar among different organs and some with available drugs in various phases of clinical testing. Yet only few clinical trials with antifibrotic drugs are being conducted in CKD patients. Here we review those clinical trials, focusing on agents with direct antifibrotic effects, with particular focus on pirfenidone and neutralizing antibodies directed against profibrotic growth factors and cell connection proteins. We discuss the potential reasons for the poor translation in treatment of renal fibrosis and propose possible approaches and future developments to improve it, eg, patient selection and companion diagnostics, specific and sensitive biomarkers as novel end points for clinical trials, and drug-targeting and theranostics.

Keywords: Antifibrotic therapy; Biomarker; Chronic kidney disease; Growth factors; Kidney imaging.

Publication types

  • Review

MeSH terms

  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use
  • Antibodies, Monoclonal / therapeutic use
  • Antibodies, Monoclonal, Humanized
  • Antibodies, Neutralizing / therapeutic use
  • Biomarkers
  • Connective Tissue Growth Factor / antagonists & inhibitors
  • Connective Tissue Growth Factor / immunology
  • Elasticity Imaging Techniques
  • Endpoint Determination
  • Extracellular Matrix
  • Fibrosis
  • Galectin 3 / antagonists & inhibitors
  • Humans
  • Kidney / diagnostic imaging
  • Kidney / pathology*
  • Magnetic Resonance Imaging
  • Polysaccharides / therapeutic use
  • Pyridones / therapeutic use
  • Renal Insufficiency, Chronic / drug therapy*
  • Renal Insufficiency, Chronic / etiology
  • Renal Insufficiency, Chronic / pathology*
  • Transforming Growth Factor beta / antagonists & inhibitors
  • Transforming Growth Factor beta / immunology

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Antibodies, Neutralizing
  • Biomarkers
  • GCS-100
  • Galectin 3
  • Polysaccharides
  • Pyridones
  • Transforming Growth Factor beta
  • Connective Tissue Growth Factor
  • pirfenidone
  • pamrevlumab