Advances and challenges in kidney fibrosis therapeutics

Abstract

Chronic kidney disease (CKD) is a major global health burden that affects more than 10% of the adult population. Current treatments, including dialysis and transplantation, are costly and not curative. Kidney fibrosis, defined as an abnormal accumulation of extracellular matrix in the kidney parenchyma, is a common outcome in CKD, regardless of disease aetiology, and is a major cause of loss of kidney function and kidney failure. For this reason, research efforts have focused on identifying mediators of kidney fibrosis to inform the development of effective anti-fibrotic treatments. Given the prominent role of the transforming growth factor-β (TGFβ) family in fibrosis, efforts have focused on inhibiting TGFβ signalling. Despite hopes raised by the efficacy of this approach in preclinical models, translation into clinical practice has not met expectations. Antihypertensive and antidiabetic drugs slow the decline in kidney function and could slow fibrosis but, owing to the lack of technologies for in vivo renal imaging, their anti-fibrotic effect cannot be truly assessed at present. The emergence of new drugs targeting pro-fibrotic signalling, or enabling cell repair and cell metabolic reprogramming, combined with better stratification of people with CKD and the arrival of nanotechnologies for kidney-specific drug delivery, open up new perspectives for the treatment of this major public health challenge.