Chronic kidney disease (CKD) is a progressive disorder that is characterized by the gradual loss of kidney function, often leading to end-stage renal failure. Recent research has highlighted the role of gut dysbiosis and its metabolic byproducts in the pathogenesis of CKD, with a particular focus on short-chain fatty acids (SCFAs). SCFAs, including acetate, propionate, and butyrate, are primarily produced by the fermentation of dietary fibers by the gut microbiota and are known for their systemic anti-inflammatory and immunomodulatory properties. In CKD, gut dysbiosis results in a reduction in SCFA-producing bacteria and an increase in uremic toxin-producing microorganisms, contributing to systemic inflammation, oxidative stress, and renal fibrosis. The depletion of SCFAs has been shown to exacerbate glomerular injury, whereas their presence supports integrity of the glomerular barrier and confers protection against damage. These protective effects are mediated by several mechanisms, including the modulation of immune responses, preservation of epithelial barrier function, and activation of specific receptors, such as G protein-coupled receptor 41 (GPR41), GPR43, and GPR109A. The present review provides a comprehensive overview of current understanding of SCFA-mediated pathways in glomerular protection during CKD progression. It highlights the therapeutic potential of targeting the gut–kidney axis to mitigate CKD progression by examining the complex interplay between gut microbiota and disease development, with a particular focus on strategies to protect the glomerular structure and function.

Lactate has long been acknowledged to be a metabolic waste product, but it has more recently been found as a fuel energy source in mammalian cells. Podocytes are an important component of the glomerular filter, and their role in maintaining the structural integrity of this structure was established. These cells rely on a constant energy supply and reservoir. The utilization of alternative energy substrates to preserve energetic homeostasis is a subject of extensive research, and lactate appears to be one such candidate. Therefore, we investigated the role of lactate as an energy substrate and characterize the lactate transport system in cultured rat podocytes during sufficient and insufficient glucose supplies. The present study, for the first time, demonstrated the presence of lactate transporters in podocytes. Moreover, we observed modified the amount of these transporters in response to limited glucose availability and after l-lactate supplementation. Simultaneously, exposure to l-lactate preserved cell survival during insufficient glucose supply. Interestingly, during glucose deprivation, lactate exposure allowed the steady flow of glycolysis and prevented glycogen reserves depletion. Summarizing, podocytes utilize lactate as an energy substrate and possess a developed system that controls lactate homeostasis, suggesting that it plays an essential role in podocyte metabolism, especially during fluctuations of energy availability.