Design and optimization strategies for the development of new drugs that treat chronic kidney disease

ABSTRACTIntroduction: Chronic kidney disease (CKD) is characterized by increased risks of progression to end-stage kidney disease requiring dialysis and cardiovascular mortality, predicted to be among the five top causes of death by 2040. Only the design and optimization of novel strategies to develop new drugs to treat CKD will contain this trend. Current therapy for CKD includes nonspecific therapy targeting proteinuria and/or hypertension and cause-specific therapies for diabetic kidney disease, autosomal dominant polycystic kidney disease, glomerulonephritides, Fabry nephropathy, hemolytic uremic syndrome and others.Areas covered: Herein, the authors review the literature on new drugs under development for CKD as well as novel design and development strategies.Expert opinion: New therapies for CKD have become a healthcare priority. Emerging therapies undergoing clinical trials are testing expanded renin-angiotensin system blockade with double angiotensin receptor/endothelin receptor blockers, SGLT2 inhibition, and targeting inflammation, the immune response, fibrosis and the Nrf2 transcription factor. Emerging therapeutic targets include cell senescence, complement activation, Klotho expression preservation and microbiota. Novel approaches include novel model systems that can be personalized (e.g. organoids), unbiased systems biology-based identification of new therapeutic targets, drug databases that speed up drug identification and repurposing, nanomedicines that improve drug delivery and RNA targeting to expand the number of targetable proteins.