Background: Kidney stones are composed of approximately 70–80% calcium oxalate. However, the exact mechanism of formation of calcium oxalate kidney stones remains unclear. In this study, we investigated the roles of endoplasmic reticulum stress (ERS), reactive oxygen species (ROS), and the NF-κB signalling pathway in the pathogenesis of oxalate-induced renal tubular epithelial cell injury and its possible molecular mechanisms. Methods: We established a model to evaluate the formation of kidney stones by intraperitoneal injection of glyoxylic acid solution into mice and assessed cell morphology, apoptosis, and the expression levels of ERS, ROS, and NF-κB signalling pathway-related proteins in mouse renal tissues. Next, we treated HK-2 cells with potassium oxalate to construct a renal tubular epithelial cell injury model. We detected the changes in autophagy, apoptosis, and mitochondrial membrane potential and investigated the ultrastructure of the cells by transmission electron microscopy. Western blotting revealed the expression levels of apoptosis and autophagy proteins; mitochondrial structural and functional proteins; and ERS, ROS, and NF-κB (p65) proteins. Lastly, we studied the downregulation of NF-κB activity in HK-2 cells by lentivirus interference and confirmed the interaction between the NF-κB signalling and ERS/ROS pathways. Results: We observed swelling of renal tissues, increased apoptosis of renal tubular epithelial cells, and activation of the ERS, ROS, and NF-κB signalling pathways in the oxalate group. We found that oxalate induced autophagy, apoptosis, and mitochondrial damage in HK-2 cells and activated the ERS/ROS/NF-κB pathways. Interestingly, when the NF-κB signalling pathway was inhibited, the ERS/ROS pathway was also inhibited. Conclusion: Oxalate induces HK-2 cell injury through the interaction between the NF-κB signalling and ERS/ROS pathways.

Background: The morbidity of nephrolithiasis is 2–3 times higher in males than in females, suggesting that androgen plays a key role in nephrolithiasis. The death of renal tubular epithelial cells (TECs) is an important pathophysiological process contributing to the development of nephrolithiasis. Therefore, the aim of this study is to investigate whether androgen directly induces TECs apoptosis and necrosis and its underlying mechanisms in kidney stone formation. Materials and methods: We compared serum testosterone level between male and female healthy volunteers and kidney stone patients. The in vivo nephrolithiasis model was established using glyoxylic acid, and calcium deposits were detected by van Kossa staining. In the in vitro study using mouse TECs (TCMK-1 cells) and human TECs (HK-2 cells), apoptosis, necrosis, and the expression of BH3-only protein Bcl-2-like 19 kDa-interacting protein 3 (BNIP3) were examined incubated with different doses of testosterone using flow cytometry. Levels of apoptosis-related proteins transfected with the BNIP3 siRNA were examined by western blotting. The mitochondrial potential (ΔΨm) was detected by JC-1 staining and flow cytometry. We monitored BNIP3 expression in the testosterone-induced TECs injury model after treatment with hypoxia inducible factor 1α (HIF-1α) and/or hypoxia inducible factor 2α (HIF-2α) inhibitors to determine the upstream protein regulating BNIP3 expression. Additionally, ChIP and luciferase assays were performed to confirm the interaction between HIF-1α and BNIP3. Results: Both male and female patients have significantly higher testosterones compared with healthy volunteers. More calcium deposits in the medulla were detected in male mice compared to female and castrated male mice. Testosterone induced TECs apoptosis and necrosis and increased BNIP3 expression in a dose-dependent manner. Testosterone also increased Bax expression, decreased Bcl-2 expression and induced a loss of ΔΨm. This effect was reversed by BNIP3 knockdown. HIF-1α inhibition significantly decreased BNIP3 expression and protected TECs from testosterone-induced apoptosis and necrosis. HIF-2α inhibition, however, did not influence BNIP3 expression or TECs apoptosis or necrosis. Finally, HIF-1α interacted with the BNIP3 promoter region. Conclusion: Based on these results, testosterone induced renal TECs death by activating the HIF-1α/BNIP3 pathway.

Background Chronic kidney disease (CKD) is a prevalent global health issue characterized by progressive renal dysfunction and fibrosis, often leading to end-stage renal failure. Renal fibrosis, a hallmark of CKD, is driven by complex immune responses, including macrophage polarization and inflammatory signaling pathways. Progranulin (PGRN), a glycoprotein involved in inflammation and tissue repair, has emerged as a key regulator in various fibrotic diseases. However, the precise role of PGRN in macrophage polarization and renal fibrosis in CKD remains unclear and warrants further investigation. Methods Renal tissue samples from CKD patients and unilateral ureteral obstruction (UUO)-induced mice were analyzed using immunohistochemistry, immunofluorescence, Western blotting, and qRT-PCR to assess fibrosis, macrophage infiltration, and key markers of autophagy and inflammation. Recombinant PGRN (rPGRN) was administered in vivo to assess its effects on renal fibrosis, macrophage polarization, and autophagic flux. To evaluate the role of PGRN, PGRN knockout (PGRN^−/−) mice were also utilized. The effects of PGRN on autophagic flux and mitochondrial dynamics were studied using mCherry-GFP-LC3 dual-labeling, and macrophage polarization was analyzed by flow cytometry and cytokine profiling. Results PGRN expression is significantly elevated in CKD patients and UUO mice and is associated with increased macrophage infiltration and renal fibrosis. rPGRN administration in vivo aggravated fibrosis and promoted M2 macrophage polarization. In contrast, PGRN^−/− mice showed reduced renal fibrosis, significantly reduced collagen deposition, and reduced expression of pro-fibrotic cytokines. In addition, the mitochondrial function of PGRN^−/− renal fibrosis mice was improved, the mtDNA content of mouse kidney tissue was increased, the results of electron microscopy showed that the mitochondrial structure was relatively normal, the mitochondrial biogenesis related genes PGC1α, TOMM20 and Fis1 were up-regulated, and the levels of MFN2 and Drp1 were significantly reduced. In addition, autophagy related gene LC3 was decreased and P62 protein level was increased in PGRN^−/− model mice. Mechanically, PGRN interacts with autophagy related proteins ATG5 and ATG12 to regulate autophagy flux through the PI3K-Akt signaling pathway and promote the polarization of M2 macrophages. Conclusion PGRN plays a critical role in driving renal fibrosis by regulating macrophage polarization, autophagy, and mitochondrial dynamics. Our findings suggest that PGRN exacerbates CKD progression by promoting M2 macrophage polarization and disrupting autophagic processes, highlighting PGRN as a potential therapeutic target for the treatment of CKD and renal fibrosis.

Introduction: To investigate the ablation efficiency of super-pulse thulium fiber laser (SPTFL) with different laser settings and fiber usage. Materials and Methods: SPTFL machine was attached with different fibers. Artificial stones were fixed in water, whereas laser fiber was driven on a platform for ablation. Pulse energy, frequency, fiber-moving speed, fiber-to-stone distance, and fiber size were adjusted in each trial. The cross-sectional area of craters on the lateral stone surface was measured for comparison of ablation rate, combined with fiber-moving speed. Results: There was a trend that the ablation rate increased as pulse energy or frequency increased. When pulse energy was set as 0.2 J and frequency was increased from 50 to 150 Hz, the cross-sectional area of the crater was enlarged from 0.21 to 0.37 mm ² ( p < 0.05); when the frequency was set as 100 Hz and pulse energy was increased from 0.1 to 0.3 J, the crater was enlarged from 0.10 to 0.45 mm ² ( p < 0.05). Furthermore, energy demonstrated greater impact on ablation rate and the crater was enlarged from 0.20 mm ² in the 0.1 J × 300 Hz group to 0.44 mm ² in the 0.3 J × 100 Hz group ( p < 0.05). Then fiber was set at different moving speeds with the same laser setting; the ablation rate of 3 mm/second group was 3.64 times higher than 0.5 mm/second group ( p < 0.05). Ablation diminished as fiber-to-stone distance grew. A 200 μm fiber produced thinner and deeper fissure than 272 and 550 μm fibers, and the ablation rate was the highest for the 200 μm fiber. Conclusion: Pulse energy is a more important factor in influencing ablation efficiency compared with frequency. Closer fiber-to-stone distance, faster fiber movement, and smaller fiber size increase ablation efficiency.

Background: Percutaneous nephrolithotomy (PCNL) is widely regarded as the first-line treatment for upper urinary tract stones larger than 2 cm, as recommended by major urological associations. However, a growing body of research highlights the safety and effectiveness of retrograde intrarenal surgery (RIRS) for managing stones of this size in the upper urinary tract, especially with the advent of suction-assisted techniques in RIRS. This study aims to systematically evaluate the safety and efficacy of negative pressure aspiration-assisted RIRS (NPAA-RIRS) in comparison to traditional PCNL. Method: Eligible studies were found by searching the PubMed, Embase, Web of Science and the CNKI databases for relevant reports published until July 2024. Outcome measures included initial and final stone-free rate (SFR), secondary operation, operation time, hemoglobin level reduction, blood transfusion, interventional embolization, postoperative hospital stay, complications. The assessment of publication bias was conducted using a funnel plot. Ten studies from nine articles were included, involving 1259 patients. Results: NPAA-RIRS group showed lower hemoglobin level reduction (WMD = −1.31, 95% CI [−1.64, −0.99], P < 0.001), less blood transfusion (RR = 0.15, 95% CI [0.05, 0.50], P = 0.002), shorter postoperative hospital stay (WMD: −1.93, 95% CI [−2.54, −1.32], P < 0.001), lower Clavien-Dindo I–II complication rate (RR: 0.51, 95% CI [0.38, 0.67], P < 0.001), and lower overall complication rate (RR = 0.52, 95% CI [0.40, 0.68], P < 0.001) compared to the PCNL group. The PCNL group had shorter operation time (WMD = 0.68, 95% CI [0.22, 1.13], P = 0.003), higher initial SFR (RR = 0.87, 95% CI [0.83, 0.92], P < 0.001), and lower rate of secondary operation (RR = 2.51, 95% CI [1.52, 4.12], P < 0.001) compared to the NPAA-RIRS group. There were no statistically significant differences between the two groups in interventional embolization (RR = 0.28, 95% CI [0.06, 1.33], P = 0.11), final SFR (RR = 0.98, 95% CI [0.94, 1.01], P = 0.740), and Clavien-Dindo III–IV complication rate (RR: 0.65, 95% CI [0.28, 1.51], P = 0.316). Conclusion: For upper urinary tract stones larger than 2 cm, both NPAA-RIRS and PCNL are equally safe and effective, achieving comparable final SFR. NPAA-RIRS offers advantages in terms of reduced complications, whereas PCNL shows benefits in shorter operation times and a lower likelihood of requiring secondary procedures. Clinicians can therefore select the most suitable approach based on individual patient circumstances.

Background: Nephrolithiasis seriously affects people’s health with increasing prevalence and high recurrence rates. However, there is still a lack of effective interventions for the clinical prevention of kidney stones. Hyperoxaluria-induced renal tubular epithelial cell (TEC) injury is a known key factor in kidney stone formation. Thus, developing new drugs to inhibit the hyperoxaluria-induced TEC injury may be the best way. Methods: We synthesized the Se@SiO₂ nanocomposites as described in Zhu’s study. The size and morphology of the Se@SiO₂ nanocomposites were captured by transmission electron microscopy. Cell viability was measured by a Cell Counting Kit-8 (CCK-8) assay. The mice were randomly divided into the following four groups: (I) the control group (n=6); (II) the Se@SiO₂ group (n=6); (III) the glyoxylic acid monohydrate (GAM) group; and (IV) the GAM + Se@SiO₂ group (n=6). The concentration of Se in the mice was quantified using inductively coupled plasma atomic emission spectroscopy. Results: The CCK-8 assays showed that Se@SiO₂ nanocomposites had almost no obvious cytotoxicity on the Transformed C3H Mouse Kidney-1 (TCMK-1) cell. The mice kidney Se concentration levels in the Se@SiO₂ groups (Se@SiO₂ 6.905±0.074 mg/kg; GAM + Se@SiO₂ 7.673±2.85 mg/kg) (n=6) were significantly higher than those in the control group (Control 0.727±0.072 mg/kg; GAM 0.747±0.074 mg/kg) (n=6). The Se@SiO₂ nanocomposites reduced kidney injury, calcium oxalate crystal deposition, and the osteoblastic-associated proteins in the hyperoxaluria mice models. Conclusions: Se@SiO₂ nanocomposites appear to protect renal TECs from hyperoxaluria by reducing reactive oxygen species production, suggesting the potential role of preventing kidney stone formation and recurrence.