Genistein suppresses renal fibrosis in chronic kidney disease through regulation of the CCAR2/SIRT1/p53 signaling axis.

Research on rhubarb's natural components and their potential for treating chronic kidney disease.

Breaking the fibrotic code: Nanotechnology-driven advances in renal fibrosis therapy.

Granzyme B knockdown inhibits NLRP3-mediated pyroptosis and the JAK2/STAT3 signaling in renal fibrosis.

Non-steroidal mineralocorticoid receptor antagonist finerenone ameliorates diabetic nephropathy via suppressing SLC7A11-mediated ferroptosis.

Integrative metabolomics and lipidomics reveal Jian-Pi-Yi-Shen formula improves adenine-induced CKD rats by regulating intrarenal glycolipid metabolism.

Tubular STING drives renal fibrosis via extracellular vesicle-mediated activation of the SMO/GLI-1 pathway.

Zhen-Wu-Tang ameliorates renal fibrosis and tissue stiffness in a murine lupus model, an effect associated with the suppression of fibroblast-to-myofibroblast transition.

BHMT Prevents renal ischemia/reperfusion injury via suppressing ROS-induced apoptosis by targeting NOX4.

Integrated analysis of single-cell and bulk RNA-seq data identifies NR4A1-associated macrophages in immunoglobulin A nephropathy.

Targeted deletion of c-kit in TECs attenuates UUO-induced renal fibrosis through NF-κB pathway inhibition.

This prospective study designed to evaluate the diagnostic capabilities of diffusion kurtosis imaging (DKI) and intravoxel incoherent motion (IVIM) in assessing renal interstitial fibrosis in glomerulonephritis (GN). GN was induced in rats by tail vein injection of puromycin amino nucleoside. Animals were sacrificed at six time points (weeks 2, 4, 6, 10, 14, 16) to capture progressive fibrosis, which was graded T0, T1, and T2 by Masson's trichrome staining. A total of 43 rats included in the final analysis were compared across fibrosis stages, and diagnostic performance was assessed by receiver operating characteristic curve analysis. With increasing fibrosis, MK and FA rose significantly, whereas MD, D, D*, and f declined. Fibrosis categories correlated positively with MK and FA and negatively with MD, D, D*, and f (all P < 0.05). When differentiating T0 from healthy control group and T1 from T0, medullary FA in DKI provided the highest area under the curve (AUC), while medullary D* in IVIM showed the highest AUC. The combination of medullary D* and FA yielded significantly better AUC than individual parameters (P < 0.05). In distinguishing T1 from T2, cortical MK in DKI provided the highest AUC, while medullary D* in IVIM was the most AUC. However, no statistically significant difference was found between the combined and individual parameters (P > 0.05). Mild-to-moderate GN-related fibrosis (T0-T1) was more effectively differentiated using medullary IVIM parameters, whereas advanced fibrosis (T2) was better distinguished by cortical DKI metrics. The combined application of IVIM and DKI provided complementary value for fibrosis staging.

The present study was aimed to investigate whether trimethylamine-N-oxide (TMAO) contributed to kidney aging by activating necroptosis. Male C57BL/6J mice were randomly divided into Control group (3 months old) and Old group (18 months old), compared to 3-month-old controls, 18-month-old male C57BL/6J mice showed significant increases in plasma creatinine (Cre) and blood urea nitrogen (BUN) (P<0.05), enhanced renal fibrosis (P<0.001), elevated plasma TMAO (P<0.01), and upregulation of senescence markers p53, p21, and p16 (P<0.05, P<0.01, and P<0.001, respectively). In order to investigate the effects of TMAO on kidney aging, the mice were intraperitoneally injected with TMAO for one to three months, mice showed time-dependent increases in Cre and BUN (P<0.05, respectively), progressive fibrosis, and gradual upregulation of senescence markers, ZBP1, and phosphorylation of RIPK3 and MLKL (P<0.05, respectively). In addition, three months of DMB treatment (inhibitor for TMAO formation) significantly reduced the plasma Cre and BUN levels (P<0.001 and P<0.05), downregulated the senescence markers expression, and improved kidney fibrosis (P<0.001 or P<0.05, respectively). In conclusion, our studies revealed that TMAO induced kidney aging by activating ZBP1-mediated necroptosis. Moreover, the inhibition of TMAO generation might be a potential treatment for kidney aging. Key words Kidney aging " Trimethylamine-N-oxide " ZBP1 " Necroptosis " DMB.

Chronic kidney disease (CKD) is characterized not only by progressive fibrosis but also by systemic endothelial dysfunction and inflammation. Platelets, traditionally recognized for their role in hemostasis, also serve as key modulators of endothelial activation and immune cell recruitment. Platelet activation is commonly observed in patients with CKD and contributes to the proinflammatory environment. Although platelet-endothelial interactions are well-characterized in cardiovascular disease, their role in renal endothelial dysfunction and inflammation remains poorly understood. To investigate this, we used the unilateral ureteral obstruction (UUO) model in mice, to examine how platelet activation influences endothelial responses and monocyte/macrophage recruitment in the early phase of renal fibrosis development. Platelet depletion reduced the number of infiltrating macrophages in kidney tissue, decreased expression of endothelial activation and inflammation markers, and preserved the peritubular capillary (PTC) integrity. Further in vitro studies using human umbilical vein endothelial cells (HUVECs) showed that activated platelets induced endothelial dysfunction and inflammation, in line with the in vivo findings. To recapitulate the vascular microenvironment, we performed a shear flow-based transmigration assay. Monocyte adhesion and transendothelial migration significantly increased when endothelial cells were pretreated with activated platelets compared to unstimulated controls. Moreover, the presence of platelets on the inflamed endothelium further enhanced monocyte migration, suggesting a synergistic effect in promoting immune cell recruitment. Collectively, our findings highlight that activated platelets contribute to endothelial dysfunction, inflammation, and monocyte infiltration in early kidney injury, suggesting their potential as a therapeutic target to mitigate microvascular injury and preserve renal vascular integrity in kidney disease.

Chronic kidney disease (CKD) is characterized by renal fibrosis as its core pathological feature, and lipid metabolism disorders are a key driver of disease progression. However, the specific pathological significance of elevated lactate levels in patients with CKD remains unclear. This study aimed to verify the hypothesis that lactate exacerbates renal fibrosis by inhibiting the PPARα/FAO pathway. A total of 15 healthy controls and 75 CKD patients were enrolled. Serum lactate levels were measured, and their correlations with Scr, BUN, eGFR, and lipid metabolism parameters (triglycerides [TG], total cholesterol [TCH]) were analyzed. Meanwhile, unilateral ureteral obstruction (UUO) mouse models and transforming growth factor-β1 (TGF-β1)-induced human proximal tubular epithelial cells (HK-2 cells) were used to validate the regulatory role of lactate in renal fibrosis. Results showed that serum lactate levels in CKD patients significantly increased with disease stage progression, and were positively correlated with Scr, BUN, TG, and TCH (p < 0.05), while negatively correlated with eGFR (p < 0.0001). RNA sequencing and Western blot confirmed that UUO mouse kidney tissues exhibited lactate accumulation, downregulation of the PPARα/FAO pathway, lipid accumulation, and aggravated renal fibrosis. Exogenous lactate supplementation exacerbated TGF-β1-induced fibrosis and lipid disorders in HK-2 cells, whereas inhibition of lactate production by oxamic acid sodium significantly reversed these pathological effects. In conclusion, lactate disrupts renal lipid homeostasis and exacerbates renal fibrosis by inhibiting the PPARα/FAO pathway. This study provides an important theoretical basis for elucidating the pathological mechanism of CKD and developing novel therapeutic targets.

Phosphocreatine attenuates diabetes-exacerbated kidney fibrosis via TGF-β/Smad and PI3K/Akt pathways in a dual rat model.

Nephropathy 1 Formula (N1F) mitigates cisplatin-induced acute kidney injury by inhibiting TAK1-dependent NF-κB signaling.

Ketone bodies have traditionally been recognized as glucose-sparing energy sources, with hepatic ketogenesis and peripheral ketolysis serving pivotal functions in maintaining energy homeostasis during fasting. Although they are commonly seen as harmful due to their link with ketoacidosis, recent studies emphasize their roles in organ protection. This has sparked interest in their possible use as a treatment for chronic kidney disease (CKD). In this study, we examined both exogenous and endogenous ketone body supplementation in adenine-induced kidney injury in mice. Supplementation with the ketone body precursor 1,3-butanediol significantly improved adenine-induced renal fibrosis, inflammation, and apoptotic cell death. However, genetically deleting 3-hydroxy-3-methylglutaryl-CoA synthase 2 (HMGCS2), the key enzyme for ketogenesis, in the liver, kidney, or entire body, and removing Succinyl-CoA:3-ketoacid-CoA Transferase 1 (OXCT1), the enzyme for ketolysis, in the kidney alone, did not affect the severity of adenine-induced kidney damage. In contrast, the protective effects of 1,3-butanediol were partially diminished in mice with kidney-specific OXCT1 deficiency, indicating that OXCT1-mediated ketolysis is at least partly necessary for the renal protection afforded by exogenous ketone body supplementation. These findings suggest that supplementing with exogenous ketone bodies, rather than relying on endogenous hepatic or renal ketone production, protects the kidneys in adenine-induced kidney injury in mice, implying that local ketolysis within the kidney plays a mechanistic role in this protection. Our results highlight the therapeutic potential of exogenous ketone body administration in CKD and offer insights into how renal ketone metabolism helps protect against kidney injury.

This narrative review aims to elucidate the significance of the synergistic effects of linagliptin and resveratrol and also explores their individual mechanisms of action in diabetic complications such as nephropathy. A systematic literature analysis examined the synergistic potential of resveratrol and linagliptin in diabetic nephropathy. A critical review of their antioxidant, anti-inflammatory, and anti-fibrotic mechanisms was conducted. Various studies revealed that linagliptin improves renal outcomes through both incretin-dependent and independent pathways, reducing oxidative stress, inflammation, and AGE-RAGE axis activation. It also exhibits the capacity to reduce albuminuria and renal fibrosis in diabetic animal models. Resveratrol similarly demonstrates substantial renoprotective benefits through activation of the AMPK/Nrf2 pathway, mitigating oxidative stress and downregulating inflammatory markers such as tumor necrosis factor-alpha and interleukin-1 beta. The synergistic use of linagliptin and resveratrol may provide greater benefits than their individual effects, including improved glycaemic control, reduced renal oxidative stress, and decreased inflammatory and fibrotic markers, thereby offering superior protection against diabetic nephropathy.

QingShen granules activates mitophagy to suppress renal tubular epithelial-mesenchymal transition via the miR-23b-5p/Nrf2/PINK1 axis.