Antifibrotic Agents for the Management of CKD: A Review

Kidney fibrosis is a hallmark of chronic kidney disease (CKD) and a potential therapeutic target. However, there are conceptual and practical challenges to directly targeting kidney fibrosis. Whether fibrosis is mainly a cause or a consequence of CKD progression has been disputed. It is unclear whether specifically targeting fibrosis is feasible in clinical practice because most drugs that decrease fibrosis in preclinical models target additional and often multiple pathogenic pathways (eg, renin-angiotensin-aldosterone system blockade). Moreover, tools to assess whole-kidney fibrosis in routine clinical practice are lacking. Pirfenidone, a drug used for idiopathic pulmonary fibrosis, is undergoing a phase 2 trial for kidney fibrosis. Other drugs in use or being tested for idiopathic pulmonary fibrosis (eg, nintedanib, PRM-151, epigallocatechin gallate) are also potential candidates to treat kidney fibrosis. Novel therapeutic approaches may include antagomirs (eg, lademirsen) or drugs targeting interleukin 11 or NKD2 (WNT signaling pathway inhibitor). Reversing the dysfunctional tubular cell metabolism that leads to kidney fibrosis offers additional therapeutic opportunities. However, any future drug targeting fibrosis of the kidneys should demonstrate added benefit to a standard of care that combines renin-angiotensin system with mineralocorticoid receptor (eg, finerenone) blockade or with sodium/glucose cotransporter 2 inhibitors.