Designing drugs that combat kidney damage

Abstract

Introduction: 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.

Areas covered: 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.

Expert opinion: 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.

Keywords:

• clinical trials
• drug discovery
• kidney damage
• nanomedicine
• nephrology

Declaration of interest

The authors are supported by the Instituto de Salud Carlos III via the following programs: A Ramos, A Sanz and MD Sanchez-Nino are supported by the Miguel Servet program; B Fernandez-Fernandez by the Joan Rodes Program; L Ruiz-Ortega by the Rio Hortega Program; A Ortiz by the Proyectos de Investigational Intensificacion de la Actividad Investigadora and C González-Guerrero by the Redinren program through grants PS09/00447, P113/00047, PI11/02242, PI11/01854, REDINREN/RD06/0016, RD012/0021 FEDER, CAM/CIFRA: S2010/BMD-2378 and FIBROTEAM S010/BMD-232. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Notes

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