High serum levels of free fatty acids (FFAs) could contribute to obesity-induced nephropathy. CD36, a class B scavenger receptor, is a major receptor mediating FFA uptake in renal proximal tubular cells. Empagliflozin, a new anti-diabetic agent, is a specific inhibitor of sodium-glucose co-transporter 2 channels presented on renal proximal tubular cells and inhibits glucose reabsorption. In addition, empagliflozin has shown renoprotective effects. However, the mechanism through which empagliflozin regulates CD36 expression and attenuates FFA-induced lipotoxicity remains unclear. Herein, we aimed to elucidate the crosstalk between empagliflozin and CD36 in FFA-induced renal injury. C57BL/6 mice fed a high-fat diet (HFD) and palmitic acid-treated HK-2 renal tubular cells were used for in vivo and in vitro assessments. Empagliflozin attenuated HFD-induced body weight gain, insulin resistance, and inflammation in mice. In HFD-fed mice, CD36 was upregulated in the tubular area of the kidney, whereas empagliflozin attenuated CD36 expression. Furthermore, empagliflozin downregulated the expression of peroxisome proliferator-activated receptor (PPAR)-γ. Treatment with a PPARγ inhibitor (GW9662) did not further decrease PPARγ expression, whereas a PPARγ antagonist reversed this effect; this suggested that empagliflozin may, at least partly, decrease CD36 by modulating PPARγ. In conclusion, empagliflozin can ameliorate FFA-induced renal tubular injury via the PPARγ/CD36 pathway.

Background: Thrombospondin-1 (TSP-1) is a matricellular protein involved in kidney fibrosis, potentially influencing the progression of proteinuria. However, its potential as a predictive biomarker for proteinuria events in children with chronic kidney disease (CKD), particularly across different etiological subgroups, such as congenital anomalies of the kidney and urinary tract (CAKUT) and non-CAKUT, has not been fully explored. Methods: In this prospective study of 60 children with CKD, we assessed baseline plasma TSP-1 and tracked proteinuria events over one year. Participants were stratified into CAKUT and non-CAKUT groups. Results: In total, 5 of 60 participants had proteinuria events. Plasma TSP-1 was significantly lower in patients with events (21.18 vs. 36.28 μg/mL, p = 0.0364). In multivariable analysis, TSP-1 lost significance overall but remained predictive in the non-CAKUT subgroup (AUC = 0.79, p = 0.064; OR = 0.93, p = 0.028). Conclusions: Plasma TSP-1 may serve as an etiology-specific biomarker for proteinuria events in pediatric CKD, particularly among non-CAKUT patients, and warrants further investigation for personalized risk assessment.

Background: Uremic pruritus is a distressing and common symptom in patients with end-stage renal disease. The development of uremic pruritus involves a multifactorial pathogenesis, including systemic inflammation, dysregulated immune responses, and altered opioid receptor activity. Omega-3 polyunsaturated fatty acids have been reported to mitigate uremic pruritus symptoms. Among omega-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have been reported as potential candidates for alleviating uremic pruritus due to their anti-inflammatory properties. Methods: A meta-analysis of seven randomized controlled trials was conducted to evaluate the efficacy of omega-3 supplementation in alleviating uremic pruritus among patients affected with end-stage renal disease. Effect sizes were calculated using Hedges’ g with a random-effects model. Heterogeneity, sensitivity, and meta-regression analyses were performed to explore influencing factors. Results: A total of 266 participants were included for analysis. Omega-3 supplementation significantly reduced pruritus severity compared with placebo. Sensitivity analyses were conducted to exclude a single large trial contributing to the results. Meta-regression indicated that higher EPA, DHA, and total omega-3 dosages, and longer treatment duration, were associated with reduced severity of the uremic pruritus than the placebo. No serious adverse events were reported. Conclusions: Omega-3 fatty acid supplementation significantly alleviates uremic pruritus in patients with ESRD. These findings support the use of omega-3 fatty acids as a safe and effective adjunct therapy. Further large-scale, long-term trials are warranted to verify these results and assess the long-term effects and safety of omega-3 fatty acids in attenuating uremic pruritus.