Urolithiasis

Letter to Editor: Comparison of flexible vacuum-assisted ureteral access sheath versus conventional sheath combined with single-use flexible ureteroscope in the treatment of renal calculi
Haberal HB and Tonyali S
Effect of the plasma metabolites, biomarkers, and inflammatory proteins on urolithiasis: insights from Mendelian randomization and mediation analysis
Huang H, Wen Z, Li H, Wang C, Chen C, Liu Y, Qin J, Cao S and Yang X
Urolithiasis represents a systemic disorder characterized by metabolic circulation issues and ongoing inflammation. The purpose of this research is to explore the relationships of causation among plasma metabolites, biomarkers, inflammatory proteins, and stones within the urinary system. We initially carried out a two-sample Mendelian randomization (MR) analysis to evaluate possible causal connections between 233 plasma metabolites and 35 biomarkers related to urolithiasis. The genetic association study (GWAS) data concerning plasma metabolites were derived from a 2024 publication in Nature, while data for biomarkers were collected from the UK Biobank. To determine causal relationships, we utilized several analytical techniques, including inverse variance weighting (IVW), MR-Egger, weighted median, and weighted mode. Furthermore, we conducted analyses for pleiotropy and heterogeneity to ensure the findings' robustness. A Steiger analysis was used to explore the presence of any reverse causal relationships. Lastly, we conducted mediation analysis to elucidate how inflammatory proteins mediate the associations between plasma metabolites, biomarkers, and stones in the urinary system. Our research demonstrates causal connections between six plasma metabolites and six biomarkers related to upper urinary tract stones. Furthermore, we identified causal associations between ten plasma metabolites and four biomarkers linked to lower urinary tract stones. Most of these metabolites belong to lipid and lipoprotein classes, indicating that changes in blood lipid levels may influence stone formation. Finally, mediation analysis revealed 13 mediating relationships, including the mediating effects of six inflammatory proteins. Our results provide evidence for the causal links among plasma metabolites, biomarkers, and inflammatory proteins associated with urolithiasis. This provides new insights into the potential mechanisms underlying urinary system stone formation, contributing to their prevention, diagnosis, and treatment.
Brown adipose tissue detection using positron emission tomography could help reduce urolithiasis risk
Sugino T, Taguchi K, Yanase T, Unno R, Ando R and Yasui T
Urolithiasis is associated with metabolic syndrome, and reactivation of brown adipose tissue (BAT) may improve metabolic syndrome. In this study, we aimed to evaluate the association of BAT, as detected using positron emission tomography-computed tomography (PET-CT), with urolithiasis in humans. This single center retrospective cohort study involved patients who underwent PET-CT for cancer screening as part of a medical checkup between January 2006 and December 2020. We obtained data on participant demographics, presence of urolithiasis, and metabolic factors (such as obesity, hypertension, diabetes, and hyperlipidemia) from 182 medical records. BAT data and calcification of the abdominal aorta (CAA) rate, determined using abdominal CT, were also recorded. Any association between urolithiasis and other factors was evaluated using logistic regression analysis. Body mass index was higher in participants with BAT than in those without BAT (26.92 vs. 22.86 kg/m, p = 0.001). Participants with BAT had less urolithiasis and a lower CAA rate than those without BAT (10% vs. 37%, p = 0.031 and 50% vs. 79.6%, p = 0.008, respectively). Metabolic factors between the groups were similar (45.0% vs. 48.8%, p = 0.936). Furthermore, BAT and age were associated with a decreased odds ratio (OR) for urolithiasis (OR = 0.186, p = 0.037 and OR = 0.959, p = 0.02, respectively). We demonstrated that high BAT content is associated with a low risk of urolithiasis and CAA. Our findings may contribute to the development of novel preventive methods for urolithiasis.
Letter to Editor: Enhancing lithotripsy efficiency in retrograde intrarenal surgery via a flexible kidney-fixed position: findings from a prospective cohort study
Huang S, Liu J, Fu L, Zhu Z, Yuan G and Luo J
A double-blind, randomized, placebo-controlled study to evaluate the efficacy of Oxybutynin Chloride Extended-Release tablets on the double-J stent related symptoms following uncomplicated ureteroscopic lithotripsy
Huang KH, Hsieh TY, Chow PM, Lee YJ, Huang HC, Chiang IN and Yang TK
To evaluate the effects of Oxybutynin Chloride Extended-Release Tablets (Oxbu) on double-J stent-related symptoms following uncomplicated ureterosocpic lithotripsy (URSL). This is a double-blind, randomized, placebo-controlled study with a total of 120 subjects with ureteral calculi receiving double-J stent insertion following URSL. Subjects who meet the inclusion and exclusion criteria will be randomly assigned to Oxbu or placebo group. All patients completed a structured questionnaire assessing the stent-related symptoms one week after operation. The clinical data and stent characteristics were recorded as well. The severity of stent-related symptoms was compared between two groups. The mean age were 58.2 years both in Oxbu group and control group, and the demographic data were all comparable between the two groups. Oxbu group had significant improvement for stent related pain score (-0.47 points, P < 0.01) and quality of life score (-0.17 points, P < 0.01) compared to the control group. The male subgroup showed that Oxbu had less urgency item score (-0.59 points, P < 0.05). The subgroup analysis for female showed that Oxbu had more decrease in the intermittency item score (-0.89 points, P = 0.043) and aged < 50 showed Oxbu had more decrease in Overactive Bladder Symptoms Score total score and urgency item score (-0.8 and - 0.6 points, all P < 0.05). This study showed that Oxbu decreases the severity of double-J stent related pain and the quality of life score for patients received URSL. In the IPSS and OABSS item, the intermittency and urgency are improved in the Oxbu group. In conclusion, Oxbu treatment had beneficial effects to improve the severity of stent related symptoms.
The influence and relationship of dysbiosis in the urinary microbiota on patients with urolithiasis
Lee HY, Lin CY, Juan YS, Wu WJ, Cho SY and Wu DC
Urolithiasis is a disease with high prevalence and recurrence rate. There are various risk factors impacting on stone formation including intestinal micorbiota. This study aims to investigate the relationship between urine microbiota with urolithiasis. We collected mid-stream voided urine samples from urolithiasis patients and control participants and stored them in a freezer at - 80 °C. All enrolled participants were requested to provide information about their clinical characteristics. The procedure included the extraction of the genomic DNA from the urine samples; the amplification by polymerase chain reaction (PCR); PCR product quantification, mixing, and purification; DNA library preparation; and sequencing was performed with quality control (QC) measures. Alpha diversity was indicative of the species complexity within individual urine samples, and beta diversity analysis was used to evaluate the differences among the samples in terms of species complexity. We enrolled 28 urolithiasis patients and 59 control participants who reported no recent antibiotic usage. In the beta diversity analysis, there was a significant difference between the microbiota in the samples of the urolithiasis and control groups according to ANOSIM statistical analysis. (P = 0.004). On comparing the groups, it showed Alcaligenes, Bacteroides, Blautia, Ruminococcaceae_UCG, Cutibacterium, Alistipes, Lachnoclostridium present more significant in control group than urolithiasis patients. In conclusion, our current study shows that dysbiosis of urine microbiota may be related to the development of urolithiasis. Further research targeting specific microbes to identify their role in the development of diseases is necessary and might provide novel diagnostic biomarkers and therapeutic options.
Antiurolithic activity of vanillin in ethylene glycol-induced hyperoxaluric rat model
Khan A, Salim S, Masaud SM, Ahmad A, Akhtar MF and Mandukhail SR
Vanillin, a natural compound derived from vanilla beans, exhibits antioxidant and anti-inflammatory properties, which may contribute to the prevention and treatment of renal stones. Therefore, this study is aimed to investigate the potential antiurolithic effect of vanillin in male hyperoxaluric Wistar rats. Computational molecular docking studies were used to investigate the interaction process and verify vanillin's role in the prevention of kidney stones containing calcium oxalate. Software tools were utilized to analyze the drug ligands' additional molecular characteristics, absorption, distribution, metabolism, and excretion (ADME), and toxicity. Urinary crystals were induced in rats by adding 0.75% ethylene glycol (EG) in drinking water for 3 weeks, along with 1% ammonium chloride (AC) during the initial three days. Molecular docking analysis revealed strong binding interactions of vanillin with Human CTP: Phosphoethanolamine Cytidylyltransferase (PDB ID: 3ELB) at the C5P binding site, with a binding affinity of -7.6 kcal/mol, suggesting a potential molecular basis for its antiurolithic activity. In vivo study showed that vanillin treatment dose dependently (30, 100 and 300 mg/kg body weight) reduced hyperoxaluria, hypercalciuria and crystal counts in kidneys of hyperoxaluric rats. The current results of our study suggest that vanillin possesses potential antiurolithic activity, showing enhanced therapeutic effects in urolithiasis, which could be a safe, effective and non-invasive option in modern medicine for the management of urinary stones.
Is there a safe no radiation option for endoscopic kidney stone treatment in children? multicenter results of modified retrograde intrarenal surgery without fluoroscopy in pediatric patients
Ozan T, Karakeci A, Yilmaz K, Pirincci N, Osmanlioglu F, Yuvanc E, Yilmaz E and Orhan I
The practice of fluoroscopy during pediatric endoscopic kidney stone procedures requires attention because of radiation concerns that demand new treatment methods. This study aimed to present the multicentric results of single guide wire flexible ureterorenoscopy (URS) and retrograde intrarenal surgery (RIRS) procedures without fluoroscopy and an ureteral access sheath (UAS) in treating kidney stones in pediatric patients. Moreover, we aim to evaluate the efficacy and safety of this procedure to ascertain the feasibility of this radiation-free therapeutic intervention for treating kidney stones in children. A retrospective analysis was done on the data of 105 pediatric patients who underwent retrograde intrarenal surgery (RIRS) treatment in two tertiary healthcare centers without fluoroscopy and UAS between May 2014 and May 2024. Of these 105 patients evaluated, 74 (70.5%) were male and 31 (29.5%) were female. The patients had a mean age of 71 ± 4 (ranging from 6 to 204) months. The mean size of stones was 9.3 ± 5 (ranging from 6 to 20) mm, and the average operation time was 51 (ranging from 31 to 98) minutes. Additionally, in 24 (22.8%) patients, the flexible URS could not proceed through the ureteral orifice. Thus, a double J stent was inserted, and the surgical procedure was repeated one month later without any complications. However, 2 (1.9%) of the patients experienced postoperative fever, and 6 (5.7%) patients had minor complications related to haematuria. Stone-free status was observed in 87 out of 105 patients (82.9%). Despite using a single guide wire without fluoroscopy and UAS in treating kidney stones in pediatric patients, the RIRS procedure is technically effective and safe. It may be considered a viable non-surgical procedure that is effective in safeguarding pediatric patients from the harmful effects of radiation, rendering it a promising alternative for pediatric urolithiasis management.
Preoperative classification of urinary stones based on community detection
Mao D, Liu H, Wang Q, Ma M, Zhang M, Zhao J and Wang X
In the treatment of urinary stones, surgical intervention is crucial. Urinary stones composition and type directly affect surgical planning. However, research on preoperative stone composition analysis is limited. This paper aimed to predict urinary stones types preoperatively using clinical data. Data from 1020 patients, including stone composition, clinical biochemical indicators, and demographic information, were collected. A stone composition graph network was constructed using cosine similarity, with stone composition as nodes and biochemical/demographic data as node features. The Louvain community detection algorithm was utilized to divide the network into distinct communities for the classification of stone types, with the effectiveness of the partitioning evaluated by the Modularity score. Stone types were classified, and their distribution across genders and age groups was described. Clinical feature averages were calculated for each community, and patients were assigned to the most similar community. Six machine learning algorithms (RandomForest, GradientBoosting, SVM, KNN, Logistic Regression, XGBoost) were trained to predict stone types. Model performance was evaluated, and the importance of clinical features for prediction was ranked. Six stone types were identified (Modularity = 0.828), namely common COM (Class I), COM with minor AU (Class II), COM with high UA (Class III), COM containing MAP (Class IV), high CAP-MAP (Class V), and high COM-CAP containing DCPD (Class VI). Among males, Class III and Class I were most prevalent; among females, Class V and Class III were most prevalent (χ = 95.066, P < 0.001). Patients with Class IV stones were significantly older than those with Class I stones (P = 0.038). GradientBoosting showed the best prediction performance, with an Accuracy of 0.837, Precision of 0.840, Recall of 0.8366, F1 Score of 0.8368, and ROC-AUC area of 0.941. Significant clinical features for prediction included urine specific gravity, white blood cells, pH, and crystals. This paper first analyzed stone categories using a community detection algorithm and then predicted types using machine learning, providing a reference for preoperative surgical planning in urinary stones.
The role of osteopontin in modulating macrophage phagocytosis of calcium oxalate crystals
Hattori T, Taguchi K, Chaya R, Hamamoto S, Okada A and Yasui T
In inflammation, osteopontin (OPN) acts as both a stone matrix component for calcium oxalate (CaOx) crystal formation and an inflammatory mediator. While previous studies have demonstrated the individual roles of OPN and macrophages (Mφ) in renal CaOx stone formation during inflammation, their interaction remains poorly understood. This study aimed to elucidate the role of OPN in modulating Mφ function during crystal formation, using an ex vivo model. Bone marrow-derived macrophages (BMDM) were isolated from eight-week-old male C57BL/6J wild-type and OPN knockout mice. BMDMs from OPN-positive (BMDM) and OPN-negative (BMDM) mice were co-cultured with fluorescently labeled CaOx monohydrate (COM) crystals for phagocytosis assays and analyzed using the IN Cell Analyzer 6000. We further performed real-time quantitative reverse transcription PCR and RNA sequencing to identify gene expression profiles and clarify the role of OPN in Mφ function. The assay analysis demonstrated that phagocytosis rates were significantly higher in BMDM than in BMDM. Inflammatory markers, such as IL-6, TNF, CD44, were upregulated following COM exposure, and IL-6 expression was significantly lower in BMDM than in BMDM. RNA sequencing revealed that BMDM exhibited a less pro-inflammatory and more anti-inflammatory phenotype (Csf2, Irf5, Itgax, Csf1, Cd163), resembling M2-like Mφs. Further functional analysis indicated that OPN knockdown in Mφs increased the S100 family and CREB signaling, which enhanced the M2-like phenotype shift and phagosome formation. In conclusion, OPN plays a critical role in enhancing pro-inflammatory Mφ function, potentially limiting COM phagocytosis. Modulating OPN expression in circulating Mφs may represent a therapeutic approach for kidney stone disease.
Commentary on:'' ultrasound versus fluoroscopy-guided extracorporeal shockwave lithotripsy in renal calculi: a systematic review and meta-analysis''
Zhang Y, Wang K and Yang L
Access to the upper calyx in supine position: breaking a myth
Van der Jeugt J, Aparicio CM, Martínez SV, Chikhaoui AA, Martín EG and Cepeda M
The feasibility and safety of upper calyx access in supine percutaneous nephrolithotomy (PCNL) remains controversial. We aimed to detail our technique and describe the outcomes in effectivity as well as safety in a large cohort. The authors analyzed patients with renal and proximal ureteral stones who underwent supine PCNL using upper calyx access at Rio Hortega University Hospital Valladolid (Spain) between 2013 and 2023. Patients were placed in the Galdakao-modified supine Valdivia position. Transpapillary percutaneous access to the upper calyx was guided by a combination of ultrasound (US) and fluoroscopy. Stone-free rate (SFR) was assessed by residual fragments < 4 mm assessed by non-contrast CT scan (NCCT) two months postoperatively. The 30-days complications were classified using the PCNL-specific Clavien-Dindo score. One hundred patients were included in the study. Thirty-three (33.3%) were diagnosed with staghorn stones, and 44 (44.4%) with multiple calculi. Upper calyx access was achieved supra-11th rib in 31 (31.9%), supra-12th rib in 64 (66%) and subcostal in 2 (2.1%) cases. Miniaturized PCNL was performed in 64 (64.6%) patients. Median surgical time was 117.5 (100; 150) minutes. There were no intraoperative complications and in 62.1% of the cases, a nephrostomy tube was not necessary. The median hospital stay was 3 (1; 5) days. Twenty-seven postoperative complications occurred, including 8% grade I complications. Grade II complications including the need for blood transfusion and antibiotics occurred in 5% and 9%. Grade III complications were noted in 5%, and no grade IV or V were observed. There were no significant thoracic, liver or spleen complications. The single-procedure SFR was 85%, with only 3 patients requiring a second intervention. US and fluoroscopy guided percutaneous access to the upper calyx in the supine position is feasible and demonstrates a low complication rate alongside a high SFR.
Klotho alleviates oxidative stress and mitochondrial dysfunction through the Nrf2/HO-1 pathway, thereby reducing renal senescence induced by calcium oxalate crystals
Xu Y, You J, Yao J, Hou B, Wang W and Hao Z
Klotho is an antiaging protein that is primarily secreted by the kidneys. This study aimed to explore the protective effects of Klotho against calcium oxalate (CaOx) crystal-induced renal aging and the underlying mechanisms involved. We established a mouse model of CaOx crystal deposition via the intraperitoneal injection of glyoxylate (Gly) and constructed an in vitro model by stimulating HK2 cells with calcium oxalate monohydrate (COM). Renal aging levels were assessed through β-galactosidase (SA-β-gal) staining and the detection of senescence-associated markers. By overexpressing Klotho both in vitro and in vivo, we examined oxidative stress, mitochondrial function, and renal aging levels. We then evaluated the role of Nrf2/HO-1 signalling pathway-mediated oxidative stress in CaOx crystal-induced renal aging by applying the oxidative stress scavenger N-acetylcysteine (NAC) and overexpressing or inhibiting Nrf2 in HK2 cells. We subsequently overexpressed Klotho while inhibiting Nrf2 to confirm that Klotho exerts its protective effects through the Nrf2/HO-1 pathway. Finally, we measured the methylation levels of the Klotho promoter and assessed the degree of renal aging induced by CaOx crystals after the inhibition of Klotho DNA methylation. We found that the overexpression of Klotho alleviated CaOx crystal-induced oxidative stress and mitochondrial dysfunction, thereby reducing renal aging. NAC mitigated CaOx crystal-induced renal aging. The overexpression of Nrf2 alleviated CaOx crystal-induced oxidative stress and mitochondrial dysfunction, thus reducing renal aging, whereas the knockdown of Nrf2 exacerbated CaOx crystal-induced oxidative stress and mitochondrial dysfunction, leading to more severe renal aging. The combination of Klotho overexpression and Nrf2 knockdown reversed the protective effects of Klotho. CaOx crystals induced an increase in the DNA methylation levels of Klotho in the kidneys, and the inhibition of DNA methylation alleviated CaOx-induced renal aging. This study revealed that Klotho plays a crucial role in calcium oxalate crystal-induced kidney senescence by influencing kidney oxidative stress and mitochondrial function through the Nrf2/HO-1 pathway.
Neutrophils as mediators of the association between lipid accumulation product and kidney stones, but not for recurrent kidney stones in US adults
Gao S, He J, Liu H, Fan L and Tian R
Kidney stones (KS) are prevalent and often recur, with obesity, metabolic disorders, and inflammation significantly impacting their pathophysiology. The traditional body mass index (BMI) has limitations, as it cannot effectively differentiate between fat and lean body mass or provide information about fat distribution. In contrast, the lipid accumulation product (LAP), which combines waist circumference and triglyceride levels, serves as a crucial indicator of visceral fat. This study examines the relationship between LAP and KS, including recurrent kidney stones (RKS), using data from the National Health and Nutrition Examination Survey (NHANES). It also investigates whether neutrophils mediate the connection between LAP and KS/RKS, comparing the predictive accuracy of LAP and BMI. Data from 2007 to 2014 covered 9910 KS participants and 880 RKS participants. Weighted logistic regression assessed the LAP-KS/RKS relationship, while mediation analysis explored the role of neutrophils. Receiver Operating Characteristic (ROC) curves evaluated the predictive capabilities of LAP and BMI. Results showed LAP was significantly associated with KS (OR = 1.629; 95% CI 1.296-2.047) and RKS (OR = 1.561; 95% CI 1.145-2.128). Neutrophils partially mediated the LAP-KS relationship (7.6%, p = 0.018), with no effect found for RKS. Moreover, LAP outperformed BMI in diagnostic accuracy. These findings suggest that LAP is an effective marker for assessing KS and RKS, aiding in the early identification of potential patients to reduce the incidence and recurrence of kidney stones.
Commentary on "ureteral access sheath or percutaneous nephrostomy during flexible ureteroscopy: which is better?"
Xu H, Zhang S and Song Y
Rutin ameliorates calcium oxalate crystal-induced kidney injury through anti-oxidative stress and modulation of intestinal flora
Zhang H, Yang H, Du S, Ren J, Qiao G and Ren J
Kidney stones are a common urological disease. Although there are many ways to treat them, their high recurrence rate remains unresolved. Research has demonstrated that Lysimachia christinae Hance influences kidney stone development; however, the exact mechanism remains unclear. In this experiment, we investigated the protective effect of Lysimachia christinae Hance extract, rutin, on renal injury and its mechanism of action in a mouse model of glyoxalate-induced renal calculi. A kidney stone model was established in Balb/c mice by continuous intraperitoneal injection of glyoxalate (80 mg/kg) for 6 days. Simultaneous gavage of 30, and 60 mg/kg of rutin was administered for 6 days. Samples were collected for determination of index coefficients. Mouse kidney tissue was collected for RNA-seq, and segments of mouse colon were analyzed with 16 S RNA sequencing. We found that rutin significantly reduced renal calcium oxalate deposition and renal tissue injury in the glyoxylate-induced kidney stone model of mice. Rutin also significantly inhibited calcium oxalate deposition-induced apoptosis. In addition, rutin attenuates oxidative stress damage and inhibits the expression of signaling pathways associated with inflammation. 16 S RNA sequencing revealed that rutin regulated intestinal flora composition, significantly increasing the relative abundance of short-chain fatty acid-producing flora and promoting short-chain fatty acid production. In summary, rutin ameliorated renal tubular damage and apoptosis caused by renal stone deposition and reduced oxidative stress. It also regulates the intestinal flora, increases the enrichment of intestinal probiotics, and promotes the production of short-chain fatty acids, thereby inhibiting the formation of kidney stones.
Understanding the clinical genetics of kidney stone disease using the Natera Renasight panel
Baca AL, Patel RD, Labagnara K, Green B, Zhu M, Gupta K, Edelblute B, Asencio AA, Sharma D, Chen W, Raskolnikov D, Donnelly J, Watts KL and Small AC
We aimed to characterize the underlying genetics of kidney stone disease (KSD) in an urban and diverse population using the Natera Renasight genetic panel. This was a single-center prospective study of high-risk KSD patients, defined as recurrent stone formers or those with a family history with KSD. Buccal saliva DNA samples were collected with the commercially available Natera Renasight genetic panel and were analyzed using next-generation sequencing. The panel assesses 385 kidney disease related genes, including 45 linked to KSD. One hundred eleven high-risk KSD patients were enrolled. The majority were female (56%) with a median age of 50 (IQR 39.5-59.5), compromising a diverse ethnic background with 62% Hispanic, 23% White and 11% Black. Patients had median 3 (IQR 2-5) lifetime stone episodes, and 41% had family history of KSD. Genetic analysis was possible for 105 patients (95%). Eight (8%) had positive tests with only one patient found to have a pathogenic mutation associated with KSD (SLC7A9, cystinuria). The other 7 positive tests included amyloidosis (TTR, N = 3), Alport syndrome (COL4A3, N = 2), polycystic kidney disease (PKD1, N = 1), and susceptibility to ESRD (APOL1, N = 1). Patients with positive tests were more likely to have chronic kidney disease (38% vs 5%, p < 0.01), gout (13% vs 1%, p = 0.02) and carbonate apatite stones (38% vs 7%, p < 0.01). Our study sheds light on genetic factors of KSD in a diverse patient population. The results suggest that KSD is unlikely monogenetic in nature, but is more likely due to a complex interplay of polygenetic and environmental influences. Genetic testing may be most useful in KSD patients with chronic kidney disease.
OxDc-A0: an oral gastro-tolerant oxalate decarboxylase for treating secondary hyperoxaluria
Liu HF, Li CY, Liu YH, Yao Q, Li QS and Yu LJ
Secondary hyperoxaluria is an acquired oxalate metabolic disorder characterized by increased urinary oxalate excretion. Reducing exogenous oxalate absorption through enzyme therapy represents a promising therapeutic strategy. However, the extremely acidic pH and protease-rich environment of the upper gastrointestinal tract pose major obstacles for the oral administration of protein therapeutics. OxDc-A0, a novel gastro-tolerant recombinant oxalate decarboxylase, can degrade oxalate in the stomach, thereby limiting the oxalate pool in the gastrointestinal tract and reducing oxalate absorption and urinary excretion. This study aimed to investigate the pharmacodynamics, pharmacokinetics, and safety profile of OxDc-A0 to assess its drug likeliness. The pharmacodynamics were evaluated in vitro and in hyperoxaluria beagle dog model induced by a high-oxalate diet. OxDc-A0 exhibited excellent gastric tolerance and significant efficacy in reducing urinary oxalate excretion in the dog model with hyperoxaluria. The safety of OxDc-A0 was evaluated in Sprague-Dawley rats, beagle dogs, and golden hamsters according to the guidelines for preclinical safety studies. No adverse effects were observed on the central nervous, cardiovascular, or respiratory system in rats or dogs treated orally with OxDc-A0 up to 37,500 U/kg. Pharmacokinetic studies showed that OxDc-A0 is non-systemically absorbed and is mainly distributed in the gastrointestinal tract. Toxicological studies showed that OxDc-A0 has excellent tolerance, with a NOAEL of 37,500 U/kg/day in both rats and dogs. The maximum tolerated dose was ≥ 105,000 U/kg in rats and ≥ 87,000 U/kg in dogs. Overall, OxDc-A0 shows great potential as a new drug candidate for treating secondary hyperoxaluria.
Prospective evaluation of efficacy, safety, cumulative laser energy, and stone-free rates in the post-market SOLTIVE SuperPulsed laser system registry: insights from team of worldwide endourological researchers' (T.O.W.E.R.) research consortium
Chew BH, Wong VKF, Humphreys MR, Molina W, Knudsen B, Gupta M, Baldwin DD, Kronenberg P, Osther P and Traxer O
The Thulium fiber laser (TFL) is a relatively new tool for endoscopic laser lithotripsy. The Endourological Society's T.O.W.E.R. registry sought to evaluate the stone-free rate (SFR) at 3 months following URS. A subset of the study sought to determine the association between cumulative TFL energy and SFRs. 423 patients with planned ureteroscopic lithotripsy using TFL (SOLTIVE, Gyrus ACMI, Inc. d/b/a Olympus Surgical Technologies America) were prospectively enrolled between December 2020 and May 2023 at nine international sites. Baseline clinical characteristics and SFR data for kidney and ureteral stones were separately analyzed according to quartile cumulative TFL energy ranges. Median patient age was 58.0 (IQR: 44-67) years and maximal stone diameters were 9.9 (IQR: 7-12.9) mm and 7.4 (IQR 6.1-9.4) mm for kidney and ureteral stones, respectively. Overall SFR (no fragments) for renal and ureteral stones were 73.0% and 85.7% at 3-months. Cumulative energy levels were divided into quartiles and lower SFRs were observed with the highest quartile for kidney stones (p = 0.001), but not in ureteral stones. This correlated with kidney stone size as larger stones required more energy. The rate of adverse events related to the procedure was 1.9% (8/423). Higher stone burdens had lower stone free rates and required more cumulative laser energy. The TFL is effective in endoscopic lithotripsy. This post-marketing survey demonstrates that TFL is a safe and effective tool for endoscopic laser lithotripsy.
Recommendations for optimizing Urolithiasis treatment protocols: insights into MPCNL and FURL efficacy and safety
Jiang B and Xiao J
Efficacy of methylene blue-assisted tract visualization in ultrasound-guided percutaneous nephrolithotomy: a salvage technique for failed renal access
Hassani AH, Kamran H and Haghpanah A
We propose using methylene blue with ultrasound-guided percutaneous nephrolithotomy (US-PCNL) as a salvage method when ultrasonography access is challenging, to prevent the necessity of creating a new tract or access failure. We retrospectively evaluated adult patients who underwent US-PCNL over two years by a single surgeon. Patients were divided into two groups based on methylene blue usage. In cases with challenging renal access, diluted methylene blue was injected via the ureteral catheter, and the nephroscope was used to locate the parenchymal defect by visualizing the blue area. Among 120 patients, 34 (28.3%) required methylene blue for renal access. Recurrent stones (70.6% vs. 47.7%; p-value: 0.023) and previous PCNL (41.2% vs. 18.6%; p-value: 0.010) were more common in these patients. All achieved successful access with a single tract. Although access time (median: 235 vs. 160 s; p-value: < 0.001) and operative duration (median: 90 vs. 85 min; p-value: 0.023) were statistically longer when methylene blue was used, the differences were not clinically significant. Analgesic use, hospital stay, hemoglobin drop, and creatinine rise were similar between groups. Stone-free rates after the first session were 50.0% with methylene blue and 57.0% without it (p-value: 0.489). Residual stone rates requiring ancillary procedures were higher when methylene blue was needed (20.6% vs. 9.4%), but the difference was not statistically significant (p-value: 0.126). Complication rates were similar between the groups. Methylene blue injection into the ureteral catheter is a safe and effective procedure for US-PCNL, reducing access failure and the need for new tracts.