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.

Chronic kidney disease (CKD) is characterized by the progressive loss of renal function; moreover, CKD progression commonly leads to multiple comorbidities, including neurological dysfunction and immune disorders. CKD-triggered neuroinflammation significantly contributes to cognitive impairment. This study aimed to investigate the contribution of uremic toxins to cognitive impairment. Serum creatinine, blood urea nitrogen (BUN), indoxyl sulfate (IS), and p-cresol sulfate (PCS) levels were measured using an enzyme-linked immunosorbent assay and high-performance liquid chromatography. The creatinine, BUN, IS, and PCS levels were increased from 4 weeks after 5/6-nephrectomy in mice, which suggested that 5/6-nephrectomy could yield a CKD animal model. Further, CKD mice showed significantly increased brain and serum indoxyl sulfate levels. Immunohistochemistry analysis revealed hippocampal inflammation and NLRP3-inflammasomes in astrocytes. Further, the Y-maze and Morris water maze tests revealed learning and memory defects in CKD mice. AST-120, which is also an IS absorbent, effectively reduced serum and hippocampal IS levels as well as reversed the cognitive impairment in CKD mice. Additionally, NLRP3-knockout mice that underwent 5/6-nephrectomy showed no change in cognitive function. These findings suggested that IS is an important uremic toxin that induces NLRP3 inflammasome-mediated not only in microglia, but it also occurred in astrocytic inflammation, which subsequently causes cognitive impairment.

A correlation between impaired bone metabolism, chronic kidney disease, and cardiovascular diseases (CVD) has been suggested. This study aimed to compare the effects of denosumab and alendronate, two anti-resorptive agents, on cardiovascular and renal outcomes in osteoporotic patients. Propensity score-matched cohort study comparing denosumab to alendronate users between January 2005 and December 2017 was conducted from a large medical organization in Taiwan. Risks of CVD development and renal function decline were estimated using Cox proportional hazard regression. A total 2523 patients were recruited in each group. No significant difference in cardiovascular events was found between the two groups over a 5-year study period. Stratified analysis results showed that denosumab was likely to exert protective effects against composite CVD in patients with medication possession rate ≥60% (adjusted hazard ratio (AHR), 0.74; p = 0.0493) and myocardial infraction (AHR, 0.42; p = 0.0415). Denosumab was associated with increased risk of renal function decline in male patients (AHR, 1.78; p = 0.0132), patients with renal insufficiency (AHR, 1.5; p = 0.0132), and patients with acute kidney injury during the study period (AHR, 1.53; p = 0.0154). Conclusively, denosumab may exert cardiovascular benefits in patients with good adherence but may have renal disadvantages in certain conditions and thus must be used with caution.

Mitochondria are important organelles responsible for energy production, redox homeostasis, oncogenic signaling, cell death, and apoptosis. Deregulated mitochondrial metabolism and biogenesis are often observed during cancer development and progression. Reports have described the crucial roles of mitochondria in urothelial carcinoma (UC), which is a major global health challenge. This review focuses on research advances in the role of mitochondria in UC. Here, we discuss the pathogenic roles of mitochondria in UC and update the mitochondria-targeted therapies. We aim to offer a better understanding of the mitochondria-modulated pathogenesis of UC and hope that this review will allow the development of novel mitochondria-targeted therapies.

Both osteoporosis and kidney diseases are common and intercorrelate to increase morbidity and mortality in elderly women. This study aimed to compare adverse kidney outcome between women initiated with denosumab and a matched group of raloxifene initiators using propensity score matching methods in a large healthcare delivery system in Taiwan. The risks of adverse kidney outcomes were estimated using Cox proportional hazard regression and the change in kidney function over time was analyzed using the linear mixed model. A total of 9444 (4722 in each group) women were identified who matched the inclusion criteria between January 2003 and December, 2018. Denosumab use was significantly associated with higher risk of eGFR decline ≥ 30% from baseline than raloxifene use (aHR: 1.26; 95% CI: 1.16–1.36, p < 0.0001). The mean change in eGFR over time was 1.24 mL/min/1.73 m² per year in the denosumab group and 0.45 mL/min/1.73 m² per year in the raloxifene group (p = 0.0004). However, the risks of acute kidney injury (10.53%) and chronic dialysis (0.66%) in this study cohort were not significantly different for the two anti-osteoporosis treatments. Close monitoring of the residual kidney function and treatment effect is needed in those with denosumab.

Background: Anti-thymocyte globulin (ATG) as induction therapy in renal transplantation is facing the dilemma of reducing the incidence of acute rejection (AR) and delayed graft function (DGF) or increasing risks of infection and malignancy. The purpose of this study was to delineate the safety and efficiency of the optimal ATG dosage.Methods: We retrospectively evaluated 91 deceased donor kidney transplant recipients (KTRs) in our institution between March 2011 and January 2019. The patients were classified into three groups based on induction therapy: (1) Group 1: modest-dose ATG (three mg/kg) intraoperatively (N= 21); (2) Group 2: low-dose ATG (1–1.5 mg/kg) intraoperatively (N= 23); (3) Group 3: basiliximab 20 mg both on day 0 and 4 (N= 47). In Groups 1 and 2, all patients received a daily low-dose program (1–1.5 mg/kg each day) with target dosage of six mg/kg. Induction therapy was combined with standard immunosuppressive regimen consisting of calcineurin inhibitors, mycophenolate/the mammalian target of rapamycin inhibitors and corticosteroids.Results: There was no significant difference in patient characteristics among groups. The outcomes of infection rate, biopsy-proven acute rejection, post-transplant diabetes mellitus, graft survival, and patient survival were similar among groups. Compared to the daily low-dose ATG regimen, the intraoperative modest-dose regimen did not cause more dose interruption and hence was more likely to reach the target ATG dosage. The intraoperative modest-dose regimen also seemed to reduce the rate of DGF.Discussion: In recent years, a trend of using a “lower” dose of ATG has seemed to emerge. Our results suggest intraoperative modest-dose ATG followed by daily low-dose ATG regimen was safe and effective in cadaveric renal transplantations for preventing DGF, AR, and graft loss.