Assessment, molecular mechanisms and therapeutic targets for renal functional reserve

Chronic kidney disease (CKD) represents a significant global health challenge. Despite the availability of treatments, there remains a considerable residual risk of disease progression with current therapeutic approaches. Glomerular filtration rate (GFR) can increase due to various physiological and pathological stress responses, and the difference between the maximum GFR and the baseline GFR is termed renal functional reserve (RFR). A decline in RFR has been observed to occur well before CKD is clinically diagnosed. In addition, prolonged pathological stimulation of RFR may promote the development of other metabolic, hemodynamic, inflammatory, and fibrotic processes, which can ultimately drive CKD progression. This review consolidates the current evidence on the molecular mechanisms that underlie the initiation and decline of RFR, a phase that remains largely unaddressed as a primary treatment target but is gaining recognition for its critical role in CKD pathophysiology. Additionally, various methods for the safe and effective assessment of RFR are discussed. Recent clinical trial highlight promising new drug therapies and dietary strategies for the management of subclinical stages of CKD.