Series introduction: drug repurposing for kidney diseases.

Drug repurposing is a promising approach to drug discovery that involves identifying new therapeutic uses for existing drugs. Evaluation of drugs already approved by the US Food and Drug Administration (FDA) for use in humans offers advantages over traditional drug discovery methods, including reduced costs, shorter development timelines, a known safety profile, and a reasonable likelihood of success. Targeted reuse, for instance using known drugs to modify newly discovered disease pathways, has been successful in polycystic kidney disease.1Torres V.E. Chapman A.B. Devuyst O. et al.Tolvaptan in patients with autosomal dominant polycystic kidney disease.N Engl J Med. 2012; 367: 2407-2418Crossref PubMed Scopus (1052) Google Scholar Broad, unbiased screens of thousands of FDA-approved compounds for impact on genetic disease models in vitro and in vivo have also been a successful approach to drug repurposing.2Jardine S. Anderson S. Babcock S. et al.Drug screen identifies leflunomide for treatment of inflammatory bowel disease caused by TTC7A deficiency.Gastroenterology. 2020; 158: 1000-1015Abstract Full Text Full Text PDF PubMed Scopus (23) Google Scholar For example, recent drug repurposing studies have revealed the potential for lasmiditan, a drug currently used to treat migraine headaches, to improve mitochondria dysfunction in acute kidney injury (AKI).3Hurtado K.A. Janda J. Schnellmann R.G. Lasmiditan promotes recovery from acute kidney injury through induction of mitochondrial biogenesis.Am J Physiol Renal Physiol. 2023; 324: F56-F63Crossref Scopus (2) Google Scholar Also, reuse of anti-inflammatory treatments has shown promise in treating diabetic nephropathy.4Rayego-Mateos S. Rodrigues-Diez R.R. Fernandez-Fernandez B. et al.Targeting inflammation to treat diabetic kidney disease: the road to 2030.Kidney Int. 2023; 103: 282-296Abstract Full Text Full Text PDF Scopus (5) Google Scholar Perhaps the biggest, unexpected recent breakthrough in drug discovery has been the success of sodium-glucose cotransporter 2 inhibitors in slowing chronic kidney disease progression,5Heerspink H.J.L. Stefánsson B.V. Correa-Rotter R. et al.Dapagliflozin in patients with chronic kidney disease.N Engl J Med. 2020; 383: 1436-1446Crossref PubMed Scopus (1582) Google Scholar,6Packer M. Anker S.D. Butler J. et al.Cardiovascular and renal outcomes with empagliflozin in heart failure.N Engl J Med. 2020; 383: 1413-1424Crossref PubMed Scopus (1974) Google Scholar which may be seen as a model for future success in drug repurposing. Motivated by the urgent need for new therapies for multiple diseases of the kidney, this Kidney International series of short reviews explores the potential of drug repurposing to impact currently poorly treated kidney conditions, including autosomal dominant polycystic kidney disease, ciliopathy, AKI, podocyte dysfunction, and proximal tubulopathies. All the authors declared no competing interests. Drug repurposing in autosomal dominant polycystic kidney diseaseKidney InternationalVol. 103Issue 5PreviewAutosomal dominant polycystic kidney disease is characterized by progressive kidney cyst formation that leads to kidney failure. Tolvaptan, a vasopressin 2 receptor antagonist, is the only drug approved to treat patients with autosomal dominant polycystic kidney disease who have rapid disease progression. The use of tolvaptan is limited by reduced tolerability from aquaretic effects and potential hepatotoxicity. Thus, the search for more effective drugs to slow down the progression of autosomal dominant polycystic kidney disease is urgent and challenging. Full-Text PDF Open Access