Renal fibrosis

Renal fibrosis is the final common pathological process of nearly all progressive chronic kidney diseases (CKD), characterized by the excessive accumulation of extracellular matrix (ECM) components like collagen and fibronectin within the kidney parenchyma [7, 17]. This accumulation leads to the destruction of normal renal architecture, including glomerulosclerosis and tubulointerstitial fibrosis, which eventually causes irreversible loss of organ function and progression to end-stage renal disease [3, 13, 20]. The fibrotic process is driven by sustained tissue injury that activates a complex signaling network, most notably the transforming growth factor-beta (TGF-beta)/SMAD pathway, which triggers the activation of myofibroblasts and epithelial-mesenchymal transition (EMT) [1, 18, 21]. While renal fibrosis is a pathological state rather than a single molecular target, it is a primary therapeutic focus for preventing renal failure [4, 11]. Current clinical interventions primarily utilize drugs that target the renin-angiotensin-aldosterone system (RAAS), such as Losartan and Enalapril, or mineralocorticoid receptor antagonists like Finerenone, to reduce the pro-fibrotic and pro-inflammatory environment [7, 11, 13]. Novel strategies under investigation include the use of anti-fibrotic agents like Pirfenidone and Nintedanib, which more directly interfere with ECM production and tyrosine kinase signaling pathways [1, 6, 11]. Monitoring the progression of fibrosis and the efficacy of these treatments typically involves biomarkers such as estimated glomerular filtration rate (eGFR), albuminuria, and emerging markers like KIM-1 and PIIINP [12, 15, 19].

Other names

Kidney fibrosisTubulointerstitial fibrosisRenal scarringGlomerulosclerosisRenal interstitial fibrosis

Therapeutic strategies target the drivers of the fibrotic process, including the inhibition of the renin-angiotensin-aldosterone system (RAAS), antagonism of mineralocorticoid receptors, and the attenuation of pro-fibrotic signaling pathways such as TGF-beta/SMAD and JAK-STAT to reduce extracellular matrix accumulation.