title: Designing drugs that combat kidney damage.
abstract: BACKGROUND
  Kidney disease remains one of the last worldwide frontiers in the field of non-communicable human disease. From 1990 to 2013, chronic kidney disease (CKD) was the top non-communicable cause of death with a greatest increase in global years of life lost while mortality of acute kidney injury (AKI) still hovers around 50%. This reflects the paucity (for CKD) or lack of (for AKI) therapeutic approaches beyond replacing renal function. Understanding what the barriers are and what potential pathways may facilitate the design of new drugs to combat kidney disease is a key public health priority.
  
  
  METHODS
  The authors discuss the hurdles and opportunities for future drug development for kidney disease in light of experience accumulated with drugs that made it to clinical trials.
  
  
  CONCLUSIONS
  Inflammation, cell death and fibrosis are key therapeutic targets to combat kidney damage. While the specific targeting of drugs to kidney cells would be desirable, the technology is only working at the preclinical stage and with mixed success. Nanomedicines hold promise in this respect. Most drugs undergoing clinical trials for kidney disease have been repurposed from other indications. Currently, the chemokine receptor inhibitor CCX140 holds promise for CKD and the p53 inhibitor QPI-1002 for AKI.
authors.affiliation: Instituto de Investigación Sanitaria-Fundación Jiménez Díaz (IIS-FJD), Laboratory of Renal and Vascular Pathology and Diabetes , Av. Reyes Católicos 2, 28040, Madrid , Spain amramos@fjd.es.
authors.forename: Adrián M
authors.initials: AM
authors.lastname: Ramos
authors.forename: Cristian
authors.initials: C
authors.lastname: González-Guerrero
authors.forename: Ana
authors.initials: A
authors.lastname: Sanz
authors.forename: María Dolores
authors.initials: MD
authors.lastname: Sanchez-Niño
authors.forename: Laura
authors.initials: L
authors.lastname: Rodríguez-Osorio
authors.forename: Catalina
authors.initials: C
authors.lastname: Martín-Cleary
authors.forename: Beatriz
authors.initials: B
authors.lastname: Fernández-Fernández
authors.forename: Marta
authors.initials: M
authors.lastname: Ruiz-Ortega
authors.forename: Alberto
authors.initials: A
authors.lastname: Ortiz
mesh_terms: D058186:Acute Kidney Injury / Q000188:drug therapy* / Q000453:epidemiology / Q000473:pathology; D000818:Animals; D016923:Cell Death / Q000187:drug effects; D015195:Drug Design; D058492:Drug Repositioning; D005355:Fibrosis / Q000188:drug therapy; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000473:pathology; D058990:Molecular Targeted Therapy; D050997:Nanomedicine; D051436:Renal Insufficiency, Chronic / Q000188:drug therapy* / Q000453:epidemiology / Q000473:pathology
keywords: clinical trials; drug discovery; kidney damage; nanomedicine; nephrology