Perirenal fat (PRF), the adipose tissue that encases the kidneys, has long been considered a passive energy reservoir and mechanical buffer. However, emerging evidence has identified PRF as a biologically active visceral fat depot that secretes adipocytokines, inflammatory mediators, and other bioactive molecules, and thereby contributes to the pathogenesis and progression of several systemic diseases. PRF is associated with renal cell carcinoma, cardiovascular disease, chronic kidney disease, obesity, and metabolic syndrome. In renal cell carcinoma, PRF thickness correlates positively with tumor stage and negatively with prognosis. In cardiovascular and renal disorders, PRF accumulation is linked to elevated blood pressure and impaired renal function. Furthermore, PRF promotes a pro‐inflammatory microenvironment that exacerbates chronic kidney disease and metabolic abnormalities. These findings underscore the clinical relevance of PRF, both as a diagnostic and prognostic marker and a potential target for therapeutic intervention. This review provides a comprehensive overview of the roles of PRF in disease development and progression and emphasizes its emerging significance in clinical practice.

The biological significance of sodium–glucose cotransporter 2 (SGLT2) in clear cell renal cell carcinoma (ccRCC) has yet to be elucidated. In this study, we aimed to determine the role of SGLT2 in ccRCC tumor progression. The human ccRCC line KMRC-1, which contains a von Hippel–Lindau (VHL) gene mutation, was used to assess the effects of the SGLT2 inhibitor (SGLT2i) dapagliflozin on proliferation and migration in media containing different glucose concentrations (25, 12.5, or 5 mM). Dapagliflozin significantly reduced cell proliferation and migration in 25 mM glucose medium. Similarly, SGLT2 knockdown involving short hairpin RNA lentiviral transfection significantly decreased cell viability, migration, and colony formation compared with the control subline in 25 mM glucose medium. Moreover, tumor progression was inhibited in the media with low glucose concentrations. Remarkably, 2 µM dapagliflozin inhibited the progression of ccRCC at concentrations as low as 5 mM (normoglycemic model) glucose medium as well as 25 mM (severe glycemia model) glucose medium. In addition, dapagliflozin treatment significantly enhanced the apoptosis of ccRCC cells. Our findings demonstrate that SGLT2 impacts the progression of ccRCC with the VHL mutation. In light of the above findings, SGLT2is, which exert the dual effects of SGLT2 blockade and glycemic control, may represent a novel therapeutic agent, particularly in patients with ccRCC who suffer from concurrent diabetes mellitus. To the best of our knowledge, this is the first preclinical study demonstrating the impact of SGLT2 inhibition on the progression of ccRCC with the VHL mutation.

The kidney is enveloped by perirenal fat, which secretes various hormones and cytokines, known as adipokines. Adipokines have been demonstrated to influence the development and progression of tumors, including renal cell carcinoma (RCC). Visfatin, an adipokine secreted by the adipose tissue, has been implicated in RCC, but its precise role remains unclear. In this study, we investigated the expression of visfatin in perirenal fat from patients with RCC and its correlation with the RCC malignant phenotype, and we examined the role of visfatin in RCC cell lines in vitro. This study included adipose tissue samples from 57 Japanese patients with clear cell RCC who underwent partial or radical nephrectomy. We examined the mRNA expression level of visfatin using real-time PCR. In vitro MTT assay and western blot were performed using human RCC cell lines. The mRNA expression of visfatin in peri-tumor versus peri-normal fat was higher in Fuhrman grade ≥2 cases compared with Fuhrman grade 1 cases. Furthermore, the addition of visfatin to RCC cell lines promoted cell proliferation, which was accompanied by increased protein expression of HIF1α, p-Akt, and p-ERK. Conversely, the addition of FK866, a visfatin inhibitor, suppressed cell proliferation and reduced these proteins. Our findings suggest that visfatin from peri-tumor adipose tissue influences the malignancy of RCC and plays a role in promoting the growth of RCC. This indicates a potential mechanism by which adipose tissue contributes to the progression of RCC, providing a possible target for therapeutic intervention.