Targeting the progression of chronic kidney disease

Abstract

Chronic kidney disease (CKD) is a devastating condition that is reaching epidemic levels owing to the increasing incidences of diabetes mellitus, hypertension and obesity as well as ageing of the global population. Regardless of the underlying aetiology, CKD is slowly progressive and leads to irreversible nephron loss, end-stage renal disease and/or premature death. Factors that contribute to CKD progression include parenchymal cell loss, chronic inflammation, fibrosis and the reduced regenerative capacity of the kidney. Current therapies have limited effectiveness and only delay disease progression, underscoring the need to develop novel therapeutic approaches to either stop or reverse progression. Preclinical studies have identified several approaches that reduce fibrosis in experimental models, including targeting cytokines, transcription factors, developmental and signalling pathways and epigenetic modulators, particularly non-coding RNAs. Some of these nephroprotective strategies are now being tested in clinical trials. Lessons learned from TGFβ1 blockade underscore the need for a holistic approach to CKD therapy as approaches that target a single pathogenic process may result in unexpected negative effects on simultaneously occurring processes. Additional promising approaches include preventing tubular cell injury and anti-fibrotic strategies targeting activated myofibroblasts, the main collagen producing cells.