Kidney stone disease is a lifestyle-related disease prevalent in developed countries; however, effective medical treatment for the disease is not yet well established. As cellular damage in renal tubular cells (RTCs) is responsible for the disease, here, we focused on the role of macroautophagy/autophagy in RTCs. We found that autophagic activity was significantly decreased in mouse RTCs exposed to calcium oxalate (CaOx) monohydrate crystals and in the kidneys of GFP-conjugated MAP1LC3B (microtubule- associated protein 1 light chain 3 beta) transgenic mice with CaOx nephrocalcinosis induced by glyoxylate. This caused accumulation of damaged intracellular organelles, such as mitochondria and lysosomes, the normal functioning of which is mediated by functional autophagy. An impairment of autophagy was also observed in the mucosa with plaques of CaOx kidney stone formers. We determined that the decrease in autophagy was caused by an upregulation of MTOR (mechanistic target of rapamycin kinase), which consequently resulted in the suppression of the upstream autophagy regulator TFEB (transcription factor EB). Furthermore, we showed that an MTOR inhibitor could recover a decrease in autophagy and alleviate crystal-cell interactions and the formation of crystals associated with increased inflammatory responses. Taken together, we conclude that autophagy compromised by MTOR deregulation is a fundamental feature in the pathology of kidney stone formation, and propose that chemical inhibition of MTOR could be a prospective strategy for disease suppression. Abbreviations: ACTB: actin, beta; CaOx: calcium oxalate; CKD: chronic kidney disease; COM: calcium oxalate monohydrate; LGALS3/galectin-3: lectin, galactose binding, soluble 3; GFP: green fluorescent protein; GOX: glyoxylate; HE: hematoxylin and eosin; MAPLC3B: microtubule- associated protein 1 light chain 3 beta; MTOR: mechanistic target of rapamycin kinase; NAC: N-acetyl-L-cysteine; ROS: reactive oxygen species; RTC: renal tubular cell; SQSTM1/p62: sequestosome 1; TFEB: transcription factor EB; TEM: transmission electron microscopy; tfLC3: tandem fluorescent-tagged LC3; 3-MA: 3-methyladenine.

We investigated the renoprotective ability of healthy people against kidney stone formation. To clarify intratubular crystal kinetics and processing in human kidneys, we performed a quantitative and morphological observation of nephrectomized renal parenchyma tissues. Clinical data and pathological samples from 60 patients who underwent radical nephrectomy for renal cancer were collected from June 2004 to June 2010. The patients were retrospectively classified as stone formers (SFs; n = 30, kidney stones detected by preoperative computed tomography) and non-stone formers (NSFs; n = 30, no kidney stone history). The morphology of parenchymal intratubular crystals and kidney stone-related gene and protein expression levels were examined in noncancerous renal sections from both groups. SFs had a higher smoking rate (P = 0.0097); lower red blood cell, hemoglobin, and hematocrit values; and higher urinary red blood cell, white blood cell, and bacterial counts than NSFs. Scanning electron microscopy revealed calcium-containing crystal deposits and crystal attachment to the renal tubular lumen in both groups. Both groups demonstrated crystal transmigration from the tubular lumen to the interstitium. The crystal diffusion analysis indicated a significantly higher crystal existing ratio in the medulla and papilla of SFs and a significantly higher number of papillary crystal deposits in SFs than NSFs. The expression analysis indicated relatively high osteopontin and CD68, low superoxide dismutase, and significantly lower Tamm–Horsfall protein expression levels in SFs. Multivariate logistic regression analysis involving the above factors found the presence of renal papillary crystals as a significant independent factor related to SFs (odds ratio 5.55, 95% confidence interval 1.08–37.18, P = 0.0395). Regardless of stone formation, intratubular crystals in the renal parenchyma seem to transmigrate to the interstitium. SFs may have reduced ability to eliminate renal parenchymal crystals, particularly those in the papilla region, than NSFs with associated gene expression profiles.

Objectives: To evaluate the feasibility of robot-assisted fluoroscopy-guided (RAG) puncture and to compare RAG puncture, utilizing a novel robot system for percutaneous renal access, with ultrasound-guided (USG) puncture. Materials and Methods: We conducted a benchtop study with a renal phantom model using the automated needle targeting with an X-ray system. Seventeen urologists participated in this study and performed RAG and USG phantom punctures. The number of needle punctures, device setup time, and fluoroscopic exposure duration were recorded for the analyses. Results: The single puncture success rates of the RAG and USG punctures were 100% and 70.6%, respectively ( p = 0.021). The median needle puncture time of RAG puncture was 24% shorter than that of USG puncture (35.0 vs 46.0 seconds; p < 0.001), and the median device setup time of RAG puncture was a minute longer than that of USG puncture (93.0 vs 30.5 seconds; p < 0.001). The median duration of fluoroscopic exposure of RAG puncture was longer than that of USG puncture (38.0 vs 6.5 seconds; p < 0.001). The surgeon's self-assessment results demonstrated that the participating urologists found RAG puncture to be safer and have better visibility than USG puncture; they were also more satisfied with RAG puncture. Subanalysis revealed that, in the RAG group, the attending surgeons had shorter total procedural time than the residents ( p = 0.045). Conclusion: RAG puncture showed comparable results and accuracy rates with USG puncture for renal access.

Background/Objectives: Immuno-oncology plus tyrosine kinase inhibitor (IO+TKI) combination therapy is an essential first-line therapy for advanced renal cell carcinoma (RCC). However, reports of its efficacy and safety as late-line therapy are lacking. This study aimed to examine the efficacy and safety of IO+TKI combination therapy as a late-line therapy for patients with RCC. Methods: We retrospectively examined 17 patients with RCC who received IO+TKI combination therapy as a second-line therapy or beyond (pembrolizumab plus axitinib, n = 10; avelumab plus axitinib, n = 5; nivolumab plus cabozantinib, n = 2). Results: The overall response and disease control rates of IO+TKI combination therapy were 29.4% and 64.7%, respectively. The median overall survival was not attained. Progression-free survival was 552 days, and 94.1% of patients (n = 16) experienced adverse effects (AEs) of any grade; moreover, 41.2% of patients (n = 7) experienced grade ≥ 3 immuno-related AEs. Conclusions: IO+TKI combination therapy may be a late-line therapy option for RCC.

Background/Objectives: Predicting kidney stone recurrence after active stone treatment remains challenging due to its multifactorial nature. Artificial intelligence, particularly machine learning, provides new methods for identifying hidden patterns in high-dimensional clinical data. We conducted a study applying machine learning to identify key predictors of recurrence following endoscopic combined intrarenal surgery (ECIRS) in patients with calcium stones. Methods: This retrospective cohort analysis included 72 patients with calcium stones who underwent ECIRS between June 2019 and May 2022 and achieved a complete stone-free status on postoperative CT. Patients were followed for two years, with recurrence assessed through protocolized imaging. We collected 235 variables, including clinical data, 24 h urine collections, stone composition, imaging features, and perioperative findings. Several machine learning models were developed, and SHapley Additive exPlanations (SHAP) analysis identified features associated with recurrence. Results: Within two years, 29 of 72 patients (40.3%) experienced recurrence. The TabNet model demonstrated the highest predictive accuracy (AUC = 0.89), outperforming traditional machine learning algorithms. SHAP analysis identified urinary oxalate ≥ 25.4 mg/day and hemoglobin (Hb) drop ≥ 0.3 g/dL at 3 months postoperatively as independent predictors, even within normal limits. A simplified TabNet-based model using three key features (oxalate, urine volume, and 3-month ΔHb) maintained a strong performance (AUC = 0.75), supporting its clinical utility. Conclusions: Machine learning enabled the accurate prediction of kidney stone recurrence after ECIRS. The inclusion of 24 h urine data significantly improved the performance. Even patients with “normal” oxalate levels showed increased risk, suggesting current clinical thresholds may require re-evaluation.

In the dynamic field of urology, percutaneous nephrolithotomy is the gold standard procedure for treating large kidney stones and has greatly benefitted from technological advancements that improve its safety and efficacy. This review highlights significant innovations in percutaneous nephrolithotomy including integrated navigation systems, robotics, artificial intelligence, and suction access sheaths, each collectively providing greater precision and improved patient outcomes. Three‐dimensional navigation systems offer unparalleled anatomical insights, facilitate more accurate targeting, and reduce intraoperative complications, as evidenced by studies demonstrating higher success rates and shorter operation times. Robotic advancements can further refine percutaneous nephrolithotomy by offering superior control and accuracy. Emerging technologies such as the automated needle targeting with X‐ray and MONARCH platforms show the potential to reduce radiation exposure and improve procedural efficiency. Additionally, artificial intelligence in percutaneous nephrolithotomy is a novel tool for preoperative planning and outcome prediction, which can enhance decision‐making and potentially lead to customized treatment strategies. Suction access sheaths represent another important innovation that facilitates stone removal and reduces the risk of postoperative complications. Integration of these technologies can improve how urologists perform percutaneous nephrolithotomy, and it highlights the benefit of ongoing research and development in the evolving field of kidney stone surgery. Through a comprehensive analysis of peer‐reviewed studies, this manuscript delves into the advancements of the last 5 years, underscoring the transformative impact of these innovations on percutaneous nephrolithotomy and setting the stage for future developments in this critical field of urology.