TY - JOUR
T1 - Treatment of Renal Fibrosis—Turning Challenges into Opportunities
AU - Klinkhammer, Barbara M.
AU - Goldschmeding, Roel
AU - Floege, Jürgen
AU - Boor, Peter
N1 - Funding Information:
This work was supported by grants from the German Research Foundation (Deutsche Forschungsgemeinschaft) SFB/TRR 57 P25 (to PB and JF), by the German Federal Ministry of Education and Research (BMBF 01GM1518A to PB), and by the Interdisciplinary Center for Clinical Research (IZKF) within the Faculty of Medicine at the RWTH Aachen University to BK and PB (09/15) and PB and JF (K7-3). Roel Goldschmeding has received research support from FibroGen Inc., San Francisco, CA. Barbara Klinkhammer, Jürgen Floege and Peter Boor do not declare any conflicts of interest.
Publisher Copyright:
© 2016 National Kidney Foundation, Inc.
PY - 2017/3/1
Y1 - 2017/3/1
N2 - 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.
AB - 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.
KW - Antifibrotic therapy
KW - Biomarker
KW - Chronic kidney disease
KW - Growth factors
KW - Kidney imaging
UR - https://www.scopus.com/pages/publications/85014812273
U2 - 10.1053/j.ackd.2016.11.002
DO - 10.1053/j.ackd.2016.11.002
M3 - Review article
AN - SCOPUS:85014812273
SN - 1548-5595
VL - 24
SP - 117
EP - 129
JO - Advances in Chronic Kidney Disease
JF - Advances in Chronic Kidney Disease
IS - 2
ER -