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Dent disease (DD) is a hereditary renal disorder characterized by low molecular weight (LMW) proteinuria and progressive renal failure. Inactivating mutations of the CLCN5 gene encoding the 2Cl - /H + exchanger ClC-5 have been identified in patients with DD type 1. ClC-5 is essentially expressed in proximal tubules (PT) where it is thought to play a role in maintaining an efficient endocytosis of LMW proteins. However, the exact pathological roles of ClC-5 in progressive dysfunctions observed in DD type 1 are still unclear. To address this issue, we designed a mouse model carrying the most representative type of ClC-5 missense mutations found in DD patients. These mice showed a characteristic DD type 1 phenotype accompanied by altered endo-lysosomal system and autophagy functions. With ageing, KI mice showed increased renal fibrosis, apoptosis and major changes in cell metabolic functions as already suggested in previous DD models. Furthermore, we made the interesting new discovery that the Lipocalin-2-24p3R pathway might be involved in the progression of the disease. These results suggest a crosstalk between the proximal and distal nephron in the pathogenesis mechanisms involved in DD with an initial PT impairment followed by the Lipocalin-2 internalisation and 24p3R overexpression in more distal segments of the nephron. This first animal model of DD carrying a pathogenic mutation of Clcn5 and our findings pave the way aimed at exploring therapeutic strategies to limit the consequences of ClC-5 disruption in patients with DD type 1 developing chronic kidney disease., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objective: To discuss the differences in the effectiveness and security of kidney stones in overweight or obese patients by mini percutaneous nephrolithotomy (MiniPCNL) and retrograde intrarenal surgery (RIRS)., Materials and Methods: We exhaustively searched numerous databases, including PubMed, Embase, Web of Science, Cochrane Library, and CNKI, covering all records from their initiation date until September 2023. This included controlled trials focusing on the use of MiniPCNL and RIRS in the treatment of kidney stones in overweight or obese patients. The gathered data was then analyzed using the Review Manager 5.4 software., Results: 9 studies including 1122 patients were included. Meta-analysis showed that: The MiniPCNL group had higher overall complications, grade I complications, length of hospital stay(LOS), first stone-free rate (SFR), and final SFR in obese patients, with no significant difference between the two groups in terms of operative time(OT), hemoglobin drop, and grade II complication rate. There were more overall complications, grade I complications, final SFR, and LOS with MiniPCNL in patients with stones > 2 cm compared to no significant difference in grade II complications. MiniPCNL performed in the prone position had higher final SFR, less OT, hemoglobin drop, and no statistically significant difference in overall complications or LOS. Sheaths using > 14 F had higher overall complication rates, final SFR, and LOS, and no statistical differences in OT and first SFR between the two modalities. In the MiniPCNL subgroup aged ≤ 50 years, there were higher first SFR, final SFR, and shorter OT, and in the MiniPCNL subgroup aged > 50 years, there were more OT, LOS, and hemoglobin drop, with no statistical difference in overall complications between the two groups., Conclusion: Our study showed that MiniPCNL in obese patients had higher initial SFR and final SFR, fewer procedures, but more postoperative complications, LOS, and grade I complications compared with RIRS. Similar results were seen in patients in the prone position, with stones > 2 cm and age ≤ 50 years., Systematic Review Registration: [ https://www.crd.york.ac.uk/PROSPERO/ ], identifier PROSPERO (CRD42023467284)., (© 2024. The Author(s).)

The incidence and prevalence of genetic diseases associated with chronic kidney disease (CKD) have been increasing over the last decades. To identify the monogenic causes of kidney stone disorders linked to CKD, a comprehensive literature review was conducted to identify monogenic genes causing nephrolithiasis and CKD. Among 41 identifiable monogenic causes of nephrolithiasis the following diseases primary hyperoxaluria familial hypomagnesemia with hypercalciuria and nephrocalcinosis, cystinuria; Dent disease, adenine phosphoribosyltransferase deficiency, Lesch-Nyhan syndrome, and idiopathic Infantile hypercalciuria have been linked to CKD and may progress to end-stage kidney disease (ESKD). Autosomal dominant hypocalcemia and Bartter syndrome (BS) are also hereditary kidney diseases that can cause urolithiasis but are rarely associated with CKD. A few BS type III can be complicated with CKD. A substantial number of kidney stone patients with genetic disorders progress to CKD. Genetic diagnosis should be initiated in all children presenting with kidney stones., (© 2024 Asian Pacific Society of Nephrology.)

Metoclopramide, a prokinetic antiemetic with activity at multiple receptor types, may be a useful treatment for renal colic pain. This review investigated whether metoclopramide is an effective analgesic in the management of adults with renal colic.Eligible studies were randomised, quasi-randomised or case-control trials of metoclopramide for the management renal colic pain. Electronic database searches were performed in November 2022. Screening was performed by two authors independently; disagreement was resolved by discussion or by adjudication by a third author. The Cochrane Collaboration Risk of Bias Tool v2.0 was used to assess bias.Two studies were included, enrolling 279 patients. Heterogeneity of primary outcome measurement and comparators rendered meta-analysis inappropriate; a narrative review is presented. Both studies showed some evidence of analgesic effect. The largest study had a low risk of bias in all assessed domains, whilst the smaller study was at a high risk of bias.There is limited evidence that metoclopramide may be an effective analgesic in the management of renal colic, with the highest quality study demonstrating analgesic properties similar to an intravenous non-steroidal anti-inflammatory medication.Protocol registration Prospero (CRD42022346618)., (© 2024. The Author(s).)

The mitochondrion serves as a critical intracellular organelle, engaging in essential roles in the regulation of energy production, oxidative stress management, calcium homeostasis, and apoptosis. One such disease that has been particularly associated with these functions is kidney stone disease (KSD), specifically calcium oxalate (CaOx). It is underpinned by oxidative stress and tissue inflammation. Recent studies have shed light on the vital involvement of mitochondrial dysfunction, the nucleotide-binding domain and leucine-rich repeat containing protein 3 (NLRP3) inflammasome, endoplasmic reticulum stress and subsequent cell death in CaOx crystal retention and aggregation. These processes are pivotal in the pathogenesis of kidney stone formation. This review focuses on the pivotal roles of mitochondria in renal cell functions and provides an overview of the intricate interconnectedness between mitochondrial dysfunction and NLRP3 inflammasome activation in the context of KSD. It is essential to recognise the utmost significance of gaining a comprehensive understanding of the mechanisms that safeguard mitochondrial function and regulate the NLRP3 inflammasome. Such knowledge carries significant scientific implications and opens up promising avenues for the development of innovative strategies to prevent the formation of kidney stones., (© 2024 BJU International.)

Purpose: Vacuum-assisted mini-percutaneous nephrolithotomy (vmPCNL) is being increasingly adopted due to its faster operating times and lower incidence of postoperative infectious complications (IC), however, studies have been limited by small sample sizes. We hypothesize that vmPCNL is an efficacious treatment for renal stone disease with acceptable stone-free rates (SFR) and low incidence of IC. The objectives of this study were to measure SFR three months after surgery, determine the factors influencing SFR, and determine the rates of postoperative IC after vmPCNL., Materials and Methods: Seven hundred and sixty seven patients underwent vmPCNL for the treatment of renal stones > 20 mm at a single institution. Patients underwent postoperative computed tomography at three months to assess SFR. Postoperative fever and SIRS/Sepsis were recorded for individual patients. Multivariate logistics regression was performed to assess predictors of SFR., Results: The SFR was found to be 73.7% at three months. Stone burden (OR 0.39, 95% CI [0.33-0.46]) and age (OR 1.03, 95% CI [1.01-1.04]) emerged as statistically significant predictors of SFR on multivariate analysis. 5.5% of patients experienced postoperative fever, while 2.9% experienced SIRS/Sepsis., Conclusions: This is the largest continuous cohort of patients to undergo vmPCNL for stone disease and demonstrates that vmPCNL is safe and efficacious, with an SFR of 74% at three months. The incidence of postoperative fever and SIRS/Sepsis is 5.5% and 2.9% respectively. Further randomized studies with large sample sizes are required to ascertain the rates of these complications in comparison to conventional approaches., Competing Interests: None declared., (Copyright® by the International Brazilian Journal of Urology.)

Infantile hypercalcemia type 1 (HCINF1), formerly known as Lightwood syndrome, is a subtype of hypercalcemia caused by loss-of-function biallelic mutations in the vitamin D catabolic enzyme, CYP24A1, which 24-hydroxylates the hormone 1,25-(OH) 2 D 3 . This short review focuses on the main features of the HCINF1 disease; emerging knowledge of the structure and function of the cytochrome P450, CYP24A1 and the location of inactivating mutations; the development of a rapid LC-MS/MS-based laboratory test for defective 24-hydroxylation; and future implications for bioanalytical assay and treatment of all types of vitamin D-related hypercalcemic conditions., (© 2024. The Author(s), under exclusive licence to Italian Society of Endocrinology (SIE).)

Purpose: Multiple factors are thought to give rise to common, recurrent kidney stone disease, but for monogenic stone disorders a firm diagnosis is possible through genetic testing. The autosomal recessive primary hyperoxalurias (PH) are rare forms of monogenic kidney stone disease. All 3 types of PH are caused by inborn errors of glyoxylate metabolism in the liver, leading to hepatic oxalate overproduction and excessive renal urinary oxalate excretion. These conditions are characterized by kidney stones, nephrocalcinosis, progressive chronic kidney disease, and kidney failure. Systemic oxalosis, the extra-renal deposition of oxalate resulting in severe morbidity and mortality, occurs in chronic kidney disease when oxalate clearance by the kidneys declines. Novel small interfering RNA-based therapeutics targeting the liver to reduce urinary oxalate excretion have been approved, introducing precision medicine to treat primary hyperoxaluria type 1. The goal of this narrative review is to address the benefits and practicalities of genetic testing for suspected monogenic kidney stone disease and the critical roles of a multidisciplinary team., Materials and Methods: We collated our procedures, education, training, and workflows to help other clinicians integrate genetic assessment into their diagnostic routines., Results: In our experience, increased access to genetic testing facilitates early detection of PH and other monogenic causes of kidney stone disease so that individualized care can be instituted promptly., Conclusions: Alongside biochemical assessments, more widespread genetic testing may ensure more timely diagnoses so that patients with suspected monogenic kidney stone disease gain access to an expanded range of services and enrollment in clinical trials and registries.

The primary hyperoxalurias (PH 1, 2, and 3) are rare autosomal recessive disorders of glyoxylate metabolism resulting in hepatic overproduction of oxalate. Clinical presentations that should prompt consideration of PH include kidney stones, nephrocalcinosis, and kidney failure of unknown etiology, especially with echogenic kidneys on ultrasound. PH1 is the most common and severe of the primary hyperoxalurias with a high incidence of kidney failure as early as infancy. Until the recent availability of a novel RNA interference (RNAi) agent, PH care was largely supportive of eventual need for kidney/liver transplantation in PH1 and PH2. Together with the Oxalosis and Hyperoxaluria Foundation, the authors developed a diagnostic algorithm for PH1 and in this report outline best clinical practices related to its early diagnosis, supportive treatment, and long-term management, including the use of the novel RNAi. PH1-focused approaches to dialysis and kidney/liver transplantation for PH patients with progression to chronic kidney disease/kidney failure and systemic oxalosis are suggested. Therapeutic advances for this devastating disease heighten the importance of early diagnosis and informed treatment., (© 2024. The Author(s), under exclusive licence to International Pediatric Nephrology Association.)

Tumor lysis syndrome (TLS) is a life-threatening metabolic disorder caused by massive tumor lysis. Allopurinol, a xanthine oxidase inhibitor, is initiated during chemotherapy to prevent hyperuricemia and subsequent acute kidney injury (AKI). We report two cases of xanthine nephrolithiasis during TLS in newly diagnosed hematologic malignancy patients receiving prophylactic allopurinol. Allopurinol use likely promoted xanthine crystallization, stone formation, and AKI., (© 2024. The Author(s), under exclusive licence to International Pediatric Nephrology Association.)

Background: With the dramatic rise of telemedicine in the post coronavirus disease 2019 (COVID-19) pandemic, our objective was to develop a totally virtual multidisciplinary kidney stone clinic and assess patient satisfaction of this format., Methods: The virtual multidisciplinary stone clinic began July 2021 and continued monthly. Prior to the beginning of each clinic, providers from the urology, nephrology, and dietitian teams meet virtually to discuss the patients. Patients would then log into WebEx virtual platform and providers would subsequently log into the patient's virtual room, to review radiology, laboratory results, and dietary logs then provide counseling. Patients were then sent a survey via electronic mail regarding their experience. A 5-point Likert scale was used for responses ranging from strongly disagree to strongly agree. Scores were averaged to rank results., Results: A total of 122 patients were sent surveys, and a total of 31 surveys were completed. Sixty-one percent of patients strongly agree and 13% agree that they felt comfortable using the virtual platform. When asked if they prefer using the virtual platform for their visit, 70% of patients agreed or strongly agreed and only 16% of patients disagreed or strongly disagreed. In regards to potential advantages of a virtual visit, the Likert scores were averaged and ranked from most to least important with improved timeliness (3.7) and ease of scheduling into day (3.6) the highest rated advantages. Most patients did not find any concerns using the virtual platform, however the ability to see the provider in-person and connecting personally was of highest concern with an average Likert score of 2.3. Overall, 83% of patients agreed or strongly agreed that the multidisciplinary stone clinic satisfied their kidney stone related questions regarding treatment and prevention., Conclusions: A virtual multidisciplinary kidney stone clinic can be implemented with high patient satisfaction scores and help overcome the limitations of physical clinic space and provider schedule coordination. There are few disadvantages to using the platform., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tau.amegroups.com/article/view/10.21037/tau-24-248/coif). I.M. reports consulting fees from Sonomotion (reimbursement for DSMB work) and Cambria (advisory board). The other authors have no conflicts of interest to declare., (2024 AME Publishing Company. All rights reserved.)

Purpose: Uric acid stones (UAS) can be treated non-invasively by oral chemolysis. However, it is crucial to identify individuals who are most likely to benefit from this approach, specifically, patients with pure UAS. The aim of this study was to develop a nomogram that can differentiate between pure and mixed UAS., Methods: A retrospective analysis of demographic, clinical and stone composition data of patients with a predominant UAS composition (≥ 50%) treated between 2014 and 2022., Results: A total of 135 patients were included in the analysis, 37.8% had mixed UAS (50-90% UA) and 62.2% had pure UAS (≥ 95% UA). The mean stone density and the percentage of radiopaque stones in the pure UAS group were significantly lower than those in the mixed UAS group (450 Hounsfield Units [HU] vs. 600 HU, and 24% vs. 58%, respectively). A stepwise multivariate logistic regression revealed that lower stone density, bigger size, decreased stone opacity and older age are predictive variables for pure UAS. Accordingly, a nomogram was generated with a receiver operating characteristic (ROC) curve that showed an area under the curve (AUC) of 0.78. A patient with a total score of 156 has a probability of > 95% for pure UAS., Conclusion: Imaging and demographic data can be used to identify patients with pure UAS. The nomogram may be useful for counseling patients regarding oral chemolysis. Future validation of the nomogram with a different data set is required to assess its efficacy., (© 2024. The Author(s).)

Objectives: To evaluate and compare the performance of ChatGPT™ (Open AI ® ) and Bing AI™ (Microsoft ® ) for responding to kidney stone treatment-related questions in accordance with the American Urological Association (AUA) guidelines and assess factors such as appropriateness, emphasis on consulting healthcare providers, references, and adherence to guidelines by each chatbot., Methods: We developed 20 kidney stone evaluation and treatment-related questions based on the AUA Surgical Management of Stones guideline. Questions were asked to ChatGPT and Bing AI chatbots. We compared their responses utilizing the brief DISCERN tool as well as response appropriateness., Results: ChatGPT significantly outperformed Bing AI for questions 1-3, which evaluate clarity, achievement, and relevance of responses (12.77 ± 1.71 vs. 10.17 ± 3.27; p < 0.01). In contrast, Bing AI always incorporated references, whereas ChatGPT never did. Consequently, the results for questions 4-6, which evaluated the quality of sources, were consistently favored Bing AI over ChatGPT (10.8 vs. 4.28; p < 0.01). Notably, neither chatbot offered guidance against guidelines for pre-operative testing. However, recommendations against guidelines were notable for specific scenarios: 30.5% for the treatment of adults with ureteral stones, 52.5% for adults with renal stones, and 20.5% for all patient treatment., Conclusions: ChatGPT significantly outperformed Bing AI in terms of providing responses with clear aim, achieving such aim, and relevant and appropriate responses based on AUA surgical stone management guidelines. However, Bing AI provides references, allowing information quality assessment. Additional studies are needed to further evaluate these chatbots and their potential use by clinicians and patients for urologic healthcare-related questions., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: To compare neonatal outcomes following URS, stent, or PCN in pregnant women presenting with suspected renal colic., Methods: Women undergoing a procedure for suspected renal colic during pregnancy at a large multi-center institution between 2008 and 2022 were retrospectively reviewed and categorized by initial intervention. Neonatal outcomes were recorded and linked to maternal and obstetric data. Groups were compared by a Kruskal-Wallis, ANOVA, or Fisher's Exact test, followed by pairwise post-hoc testing as appropriate (α = 0.05). Multivariate analyses were also conducted., Results: 95 patients were analyzed, of whom 32 were managed with PCN, 47 with stent, and 16 with URS. Maternal baseline characteristics were similar between groups, except for lower gravidity and parity in the stent group. Rates of premature delivery did not differ, but gestational age at delivery was lower in the PCN group versus the stent and URS groups (p = 0.006 and p = 0.025, respectively). Neonatal Intensive Care Unit (NICU) admission rates were higher in the PCN group versus the stent and URS groups (p = 0.006 and 0.036, respectively). Respiratory distress syndrome significantly differed between groups (p = 0.041). Neonatal birth weight, Apgar scores, and other complications did not significantly differ., Conclusion: This study demonstrated higher rates of NICU admissions and lower gestational age at delivery for neonates born to mothers managed with PCN compared to stent and URS. Larger multi-institutional studies are warranted to further explore these associations., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Smita De reports a relationship with Boston Scientific Corporation that includes: consulting or advisory. Sri Sivalingam reports a relationship with Fortec medical that includes: consulting or advisory and travel reimbursement. Sri Sivalingam reports a relationship with BD Urology that includes: consulting or advisory and travel reimbursement. Sri Sivalingam reports a relationship with Karl Storz Endoscopy America Inc that includes: consulting or advisory and travel reimbursement. Sri Sivalingam reports a relationship with Cook Medical Inc that includes: consulting or advisory and travel reimbursement. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

We performed a systematic review and meta-analysis to evaluate the benefits and harms of pharmacotherapies for patients with calcium oxalate stones and abnormal urine chemistry. This article is a modified and detailed version of the commentary on Clinical Question 10 described in the Japanese Clinical Practice Guidelines for the Management of Urinary Stones, Third Edition. PubMed and Ichushi Web were searched through August 2020 for articles on pharmacotherapies for calcium oxalate stones (thiazides, citrate preparations, uric acid production inhibitors, and magnesium preparations). Two reviewers independently selected randomized controlled trials reporting reduction of stone recurrence and adverse drug reactions as outcomes and performed data extraction and quality assessment. Meta-analyses with random effects models and rating of the strength of evidence were performed. Pharmacotherapies were shown to significantly reduce stone recurrence (risk ratio 0.47, 95% confidence interval 0.35-0.63). Meanwhile, the pharmacotherapies increased adverse drug reactions leading to study dropout (risk ratio 2.51, 95% confidence interval 1.09-5.75) and adverse drug reactions/adverse events (risk ratio 1.95, 95% confidence interval 1.07-3.56). The reported adverse drug reactions were, however, mainly minor and did not frequently require discontinuation of medication (2%-16%). The strengths of evidence for both outcomes were rated as moderate, because the risk of bias, indirectness, inconsistency, imprecision, and publication bias were all serious except for one item. The overall strength of evidence across outcomes was therefore determined to be moderate. These results support the conditional recommendation to initiate pharmacotherapies for patients with calcium oxalate stones and abnormal urine chemistry., (© 2024 The Japanese Urological Association.)

Objective: To investigate the outcomes of ureteroscopy and lasertripsy in lower pole renal stones <2 cm when treated in situ compared to displacement to the upper pole., Patients and Methods: Using the Medical Literature Analysis and Retrieval System Online (MEDLINE)/PubMed, the Excerpta Medica dataBASE (EMBASE), Cumulative Index to Nursing and Allied Health Literature (CINAHL), the Cochrane Library, and Clinicaltrials.gov we identified adult population, English language, studies published until March 2023 comparing surgical outcomes and stone-free rates (SFRs) in relation to lower pole stones <2 cm managed in situ vs those displaced (International Prospective Register of Systematic Reviews [PROSPERO] identifier: CRD42023432750). Analysis was performed using R with the 'meta' package. Bias analysis was performed using the Cochrane Risk of Bias 2 tool for randomised trials and the Newcastle-Ottawa scale for observational studies. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach was used to ascertain the certainty of evidence., Results: A total of five studies were included, comprising two retrospective cohort studies, three randomised trials, with a total of 408 patients. Meta-analysis demonstrated SFRs are significantly higher in those patients undergoing displacement vs those managed in situ (risk ratio 1.21, 95% confidence interval [CI] 1.10-1.34, P < 0.001). There was no significant difference in complication rates. Operative time was significantly longer in the displacement group (mean difference 5.62 min, 95% CI 0.40-10.83 min; P = 0.03). Overall risk of bias was moderate. Certainty of evidence was moderate for stone-free status, and very low for all other outcomes., Conclusions: This systematic review and meta-analysis demonstrates that for lower pole stones <2 cm displacement strategies have significantly higher SFRs than treatment in situ, with no significant difference in complications. There is significantly increased operative time in the displaced group, but an additional 6 min is unlikely to be clinically significant., (© 2024 The Author(s). BJU International published by John Wiley & Sons Ltd on behalf of BJU International.)

With the improvement of people's living standards,the incidence of nephrolithiasis is increasing year by year.Nephrolithiasis poses a serious threat to the patients due to the unclear etiology,complicated composition of stones,and high recurrence rate after surgery.As the research on the pathogenesis and pathophysiology of nephrolithiasis keeps deepening in recent years,researchers have made achievements in the drug treatment,which has become a hot topic for urologists.This paper reviews the advances in the research on the possible formation mechanism and drug-induced litholysis and prevention for nephrolithiasis,aiming to provide theoretical references for subsequent clinical research.

Background: The recurrent nature and socioeconomic burden of nephrolithiasis demand effective treatments. Delineating the crosstalk between inflammatory processes and the endogenous oxalate metabolism pathway, which underpins nephrolithiasis pathogenesis, is essential for advancing treatment strategies., Purpose: We aim to screen therapeutic Chinese herbal remedies and their bioactive constituents for kidney stone treatment using a fruit fly model, followed by efficacy and mechanism validation in a rodent nephrolithiasis model as well as in vitro human cell culture model., Study Design and Methods: We developed a fruit fly model to screen for efficient traditional Chinese medicine herbs and their active compounds for kidney stone treatment. Candidate active compounds from efficient herbs were separated and identified by solid-phase chromatography coupled with LC-MS analysis. Fruit fly genetic tools were employed to manipulate the expression of related genes to explore the therapeutic mechanisms of the Lycii Cortex and kukoamine A (KuA). To confirm the therapeutic effects and mechanisms of KuA for mammalian nephrolithiasis, mouse model of glyoxylate-induced kidney stone and human renal tubular cells were used. The therapeutic role of kukoamine A in nephrolithiasis was evaluated by assessing tubular injury, crystal deposition, and adhesion. The level of expression and phosphorylation in cells and mice was assessed using RT-qPCR and western blot., Results: Our findings indicate that Lycii Cortex potently inhibits calcium oxalate stone formation via activation of the JNK/Upd3/JAK/STAT signaling cascade, resulting in diminished endogenous oxalate synthesis by downregulating D-amino acid oxidase (DAO) gene expression, predominantly in fruit fly Malpighian tube stellate cells. KuA was identified as the principal bioactive constituent mediating these effects. Both mouse models and human cell assays confirmed KuA's efficacy in preventing calcium oxalate nephrolithiasis in mammals, through hepatic JAK/STAT3 pathway activation and upregulation of IL-6, culminating in reduced urinary crystal deposition., Conclusion: Our research underscores the potential of kukoamine A as a lead compound in treating nephrolithiasis and reveals the interplay between the IL-6/JAK/STAT3 inflammatory pathway and endogenous oxalate metabolism in nephrolithiasis pathogenesis. Additionally, it highlights the utility of the fruit fly model as a powerful tool for deciphering the therapeutic mechanisms of traditional Chinese herbs., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests. One patent application related to this work has been filed: ZL2023111623344, the use of kukoamine A in the treatment of kidney stones (Y. Wang, Y.J., Z.G., X.T., and Y.M. et al.)., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

Urolithiasis (UL) is increasingly prevalent due to rising cardiorenometabolic diseases, posing significant management challenges despite advances in urological techniques. Sodium-glucose cotransporter-2 (SGLT2) inhibitors, primarily used for type 2 diabetes mellitus, chronic kidney disease, and heart failure, have emerged as a potential novel approach for UL treatment. These inhibitors may help reduce the risk of urolithiasis, particularly in patients with diabetes, by improving glycemic control and altering urinary chemistry, which are crucial factors in stone formation. However, the changes in urinary composition induced by SGLT2 inhibitors might also increase the risk of uric acid stone formation. This review evaluates the potential of SGLT2 inhibitors in managing UL, highlighting both the benefits and the risks. While these inhibitors show promise in reducing new and recurrent urinary stones in patients with diabetes, data on their effects in patients without diabetes who form stones are limited. Current human evidence largely comes from post hoc analyses of randomized controlled trials (RCTs) and large-scale database studies, with only one study providing detailed stone composition data. Experimental studies in animal models and cell lines have focused on calcium oxalate (CaOx) stones, showing that SGLT2 inhibitors specifically target CaOx stone formation and related renal inflammation. Although primarily studied for CaOx stones, their potential impact on other calcium-containing stones, such as calcium phosphate, remains promising. Further research is needed to explore their therapeutic potential and optimize treatment strategies.

Background/Objectives : Damage to renal tubular cells (RTCs) represents a critical pathological manifestation in calcium oxalate (CaOx) stone disease, but the underlying mechanism remains elusive. Energy metabolism reprogramming is a vital influencer of RTC survival, and SMYD2 is a histone methylation transferase that has been extensively implicated in various metabolic disorders. Hence, this research aimed to identify whether SMYD2 induces the reprogramming of energy metabolism in RTCs exposed to CaOx nephrolithiasis. Methods : Kidney samples were obtained from patients who underwent laparoscopic nephrectomy for non-functioning kidneys caused by nephrolithiasis. The glyoxylate-induced CaOx stone mice model was established and treated with AZ505. The SMYD2-knockout HK-2 cell line was constructed. Histological changes were evaluated by HE, VK, Tunel, Masson stainings. The molecular mechanism was explored through co-immunoprecipitation and western blotting. Results : The results found that SMYD2 upregulation led to energy reprogramming to glycolysis in human kidney tissue samples and in mice with CaOx nephrolithiasis. We also identified the substantial involvement of glycolysis in the induction of apoptosis, inflammation, and epithelial-mesenchymal transition (EMT) in HK-2 cells caused by calcium oxalate monohydrate (COM). In vivo and in vitro results demonstrated that SMYD2 inhibition reduces glycolysis, kidney injury, and fibrosis. Mechanistically, SMYD2 was found to promote metabolic reprogramming of RTCs toward glycolysis by activating the AKT/mTOR pathway via methylated PTEN, which mediates CaOx-induced renal injury and fibrosis. Conclusions : Our findings reveal an epigenetic regulatory role of SMYD2 in metabolic reprogramming in CaOx nephrolithiasis and associated kidney injury, suggesting that targeting SMYD2 and glycolysis may represent a potential therapeutic strategy for CaOx-induced kidney injury and fibrosis.

Background/Objectives: Nephrolithiasis (kidney stones) is a frequently occurring urologic condition resulting in significant patient morbidity and healthcare costs. Despite the higher prevalence of metabolic risk factors for nephrolithiasis among Black women, there have been few epidemiologic studies of kidney stones focusing on this group. Methods: We describe demographic and health characteristics, diagnostics, and metabolic profiles of US Black women with self-reported kidney stones. The women were participants in the Black Women's Health Study (BWHS), a large prospective cohort of US Black women (median age 38 years) begun in 1995. Results: Among the 2750 BWHS participants who completed an online supplemental questionnaire assessing urologic health, 201 women reported nephrolithiasis. Of this number, 62% had completed ≥ 16 years of education, and 82% reported access to health care. Overall, 39% reported experiencing ≥ 2 stones in their lifetime, and 29% required surgery to treat the condition. Thirty-two percent reported having completed a metabolic evaluation, while 70% had undergone a CT scan to diagnose nephrolithiasis. The frequency of metabolic evaluation increased with the number of metabolic components reported: 3% (0 components) to 43% (3-4 components). Conclusions: Our findings are consistent with reports of lower rates of metabolic evaluation among Black patients despite their having multiple risk factors for nephrolithiasis. Further study is needed to identify the barriers and facilitators of metabolic and diagnostic workup of nephrolithiasis in Black women.

Ethnopharmacological Relevance: Traditional herbal remedies have been used for treating nephrolithiasis, but the relevant scientific evidence is limited. Zaleya pentandra (L.) C. Jeffrey is traditionally used for the prevention of kidney stones in various cultures. However, its efficacy has not been scientifically studied., Aim of the Study: This study aimed to investigate the antiurolithic activity of Zaleya pentandra, and validate its traditional used for preventing kidney stones., Materials and Methods: The crude ethanolic extract of Z. pentandra (Zp.Crd) was evaluated through in vitro and in vivo studies. In vitro experiments assessed its impact on crystal count and morphology in metastable calcium oxalate solutions. In vivo studies involved diuretic and ethylene glycol-induced calcium oxalate crystal formation in male Wistar rats., Results: Zp.Crd transforms calcium oxalate crystals from harmful calcium oxalate monohydrate (COM) to calcium oxalate dihydrate (COD). In vivo, Zp.Crd exhibited dose-dependent (30-300 mg/kg) diuretic activity in rats by significantly increasing urinary sodium (Na + ) and potassium (K + ) excretion, similar to the standard diuretic hydrochlorothiazide (HCT). In the urolithiasis model, Zp.Crd exhibited dose-dependent antiurolithic effects by reducing kidney crystals and significantly altering lithogenic factors induced by ethylene glycol, including crystalluria, oxaluria, calcium, creatinine, and urea, in the urine and serum of treated rats. Zp.Crd also exhibited antioxidant effects, effectively combating oxidative lithogenic stress in rats., Conclusion: Zp.Crd has been shown to demonstrate antiurolithic activity against CaOx stones through CaOx crystal inhibition, diuretic activity, antioxidant properties, hypocalciuric effects, and hypercitrauric actions. The findings underscore Zp.Crd's potential as a viable alternative or supplemental therapy to current urolithiasis treatments, paving the door for further clinical trials and its inclusion into modern medical practices., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

An older wild female chimpanzee (Pan troglodytes) was found dead with a large calcium oxalate stone in the renal pelvis. Histopathological changes included glomerulosclerosis, interstitial nephritis and fibrosis, focal mineralization, and medial hypertrophy. Urinary albumin-creatinine-ratio showed increased values from 15 months before death. Causes of the kidney disease remain unconfirmed., (© 2024 The Author(s). Journal of Medical Primatology published by John Wiley & Sons Ltd.)

Kidney stone disease (KSD) is a major public health concern associated with high morbidity and recurrence, places a significant burden on the health care system worldwide. Calcium oxalate (CaOx) alone or a mixture of CaOx and calcium phosphate stones accounting for more than 80 % of cases. However, beyond surgical removal, the prevention and reduction of recurrence of CaOx kidney stones have always been a challenge. Given that macrophages are traditional innate immune cells that play critical roles in the clearance of pathogens and the maintenance of tissue homeostasis, which have gained more and more interests in nephrolithiasis. Several studies recently clearly demonstrated that M2-macrophage could reduce the renal calcium oxalate (CaOx) crystal acumination, and provide premise insights and therapeutic options for KSD by modulating the macrophage phenotypes. However, the mechanism of macrophage-polarization regulation and that effects on kidney stone prevention and treatments are far from clear. Here, we comprehensively reviewed the literatures related to cytokines, epigenetic modifications and metabolic reprograming of macrophage in CaOx kidney stone disease, aimed to provide better understandings on macrophage polarization regulation as well as its potential clinical applications in CaOx kidney stone disease treatments and prevention., Competing Interests: Declaration of Competing Interest The authors declare that the results as reported in this manuscript are original and have not been published previously or accepted for publication elsewhere, and also not under consideration for publication elsewhere. All authors have seen and approved its publication. We also declare that there is no financial conflict of interest in this work., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Objective: To compare the efficacy and postoperative infection rate of super mini percutaneous nephrolithotomy (SMP) and flexible ureteroscopic lithotripsy (FURL) in patients with diabetic nephrolithiasis and to explore the risk factors associated with postoperative infection following these two procedures. Methods: The medical history and surgery details of 252 patients with diabetic nephrolithiasis who underwent lithotripsy in our hospital between January 2018 and May 2023, including 144 SMP and 108 FURL, were reviewed and compared. Perioperative outcomes were compared between the two groups. Logistic regression was performed to identify the significant risk factors for infection after each procedure. Results: SMP achieved a higher stone-free rate (SFR) on postoperative day 1 and postoperative day 30 compared with FURL ( p < 0.05). The mean operative time was shorter in SMP ( p < 0.01). FURL was associated with less hemoglobin drop ( p < 0.01) and shorter length of stay ( p < 0.01). The incident rate of systemic inflammatory response syndrome (SIRS) was higher after SMP (p = 0.019), while the incident rate of urinary tract infection (UTI) was higher after FURL ( p = 0.021). Overall postoperative infection and sepsis rates were similar between the two procedures. Logistic regression analysis revealed that gender odds ratio [OR]: 0.225, 95% confidence interval [CI]: 0.079-0.639), HbA1c (OR: 3.516, 95% CI: 1.841-6.716), and operation time (OR: 1.037, 95% CI: 1.008-1.066) were independent risk factors for infection after FURL, while operation time (OR: 1.063, 95% CI: 1.022-1.106) and HbA1c (OR: 7.443, 95% CI: 2.956-18.742) significantly predicted SMP-associated infections. Conclusion: In diabetic patients, SMP demonstrated higher SFR and shorter operation time, whereas FURL was associated with less bleeding and shorter hospitalization. SMP had a higher incident rate of SIRS and FURL had a higher incident rate of UTI. Elevated HbA1c and prolonged operative duration increased infection risk after both procedures, while female gender was an additional risk factor for FURL-related infections.

Introduction: The thulium fiber laser (TFL) generates a focused beam, which can be transmitted to laser fibers with small core diameters and may facilitate in situ lower-pole lithotripsy. This study compares lithotripsy performance of the 150 and 200 µm TFL in a lower pole benchtop kidney model. Materials and Methods: Using a 3D model printed from an actual kidney, in situ laser lithotripsy was performed on 1 cm lower-pole BegoStones (calcium oxalate monohydrate consistency) using four different settings (all 20W) and two fiber sizes (150 and 200 µm). Procedure time, laser time, total pulse energy, and fiber stripping were compared between the two fibers using an ANOVA or independent t-test . Results: The 150 µm fiber at 0.2 J × 100 Hz had the shortest lasing and procedure time (17.3 and 18.5 minutes) and lowest total pulse energy (20.75 kJ) compared with other study arms ( p < 0.001). Overall procedure time, lasing time, and total pulse energy were significantly different between the 8 settings ( p < 0.001 for all). At higher frequency (100 and 200 Hz), lasing time was significantly faster compared with 20 and 50 Hz (19.9 vs 27.3 minutes; p < 0.001). Furthermore, the average total procedure time was shorter with 150 µm compared with 200 µm regardless of settings (23.2 vs 29.8 minutes; p < 0.001). Conclusion: The 150 µm fiber results in shorter procedure and lasing time at lower total energy levels during lower-pole in situ lithotripsy. Overall, the fastest setting was 0.2 J and 100 Hz with the 150 µm fiber. Smaller laser fibers can potentially allow more efficient in situ laser lithotripsy with better irrigation and visibility at higher deflection angles.

Background and Objectives: Urolithiasis, commonly known as kidney stones, is a condition significantly impacted by dietary habits. The objective of this study is to evaluate the impact of a tailored dietary plan on the crystalluria and biological parameters of patients with different types of kidney stones over a 3-month period., Methods and Study Design: We conducted a prospective study of 3 months. The study involved patients with recurrent nephrolithiasis. Alongside the medical consultation, a comprehensive dietary survey was performed to assess the patients' nutritional habits. Urinary parameters, including volume, calcium, oxalate, uric acid, and power of hydrogen (pH), were evaluated both before and after the dietary intervention., Results: 69 patients were involved. There were 17 patients diagnosed with cystine lithiasis, 33 with oxalocalcic lithiasis and 19 with uric lithiasis. After 3 months, only 32 patients revisited for follow-up. There were significant changes ( p  = 0.002 and 0.04) in urine crystalluria for cystinic and uric lithiasis. For the urinary oxalate variation, there was a significant decrease from T1 (before dietary intervention) to T2 (after dietary intervention), with levels dropping from 0.289 ± 0.10 umol/l to 0.215 ± 0.079 umol/l ( p  = 0.02).Regarding urinary calcium (calciuria), there was a trend toward a decrease from T1 to T2, although the change was not statistically significant, with levels decreasing from 2.42 ± 1.68 umol/l to 2.14 ± 1.62 umol/l ( p  = 0.1)., Conclusions: Our research underscores the favorable effects of a tailored and well-balanced diet on both the crystalluria and biological parameters of individuals with recurrent lithiasis., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Endoscopic and biopsy findings have identified two distinct phenotypes among individuals with calcium oxalate (CaOx) kidney stones. The first type has normal renal papillae but shows interstitial mineral deposition, known as Randall's plaque. The other phenotype presents with collecting duct plugging and a higher incidence of loss of papilla tissue mass. With Randall's plaque, renal papilla injury involves the loss of small patches of calcified tissue (Randall's plaque detaching with the stone), which likely results in damage to only a few nephrons. In contrast, collecting duct mineral plugs are very large, causing obstruction to tubular flow. Since each terminal collecting duct drains thousands of nephrons, ductal plugs could lead to the degeneration of many nephrons and a significant loss of renal glomeruli. New visualization techniques for immune cells in papillary biopsies have revealed that the Randall's plaque phenotype is marked by the accumulation of macrophages around the plaque regions. In contrast, preliminary data on the plugging phenotype shows collecting duct damage with mineral plugs and increased T-lymphocytes throughout the papilla. These regions also show tubulitis, i.e., T-cell infiltration into nearby collecting duct epithelium. This suggests that while some CaOx stone formers may have some papillary inflammation but with minimal damage to nephrons, others suffer from obstruction to flow for many nephrons that may also include destructive inflammation in the renal tissue. We propose that CaOx stone formers with the plugging phenotype will have a higher long-term risk for loss of renal function., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: In this study, we aimed to evaluate and compare the expression profiles of CLDN gene family members responsible for the mechanism of stone formation in patients with recurrent calcium oxalate stones and in a control group without a history of renal stones., Methods: Nineteen patients with recurrent calcium oxalate renal calculi who underwent percutaneous nephrolithotomy and 21 control patients without renal calculi who underwent surgery for other reasons were included in the study. The urinary calcium, oxalate, and citrate levels of the patients included in the study, as well as those in the control group, were within normal ranges. They did not have proteinuria in their urine. The biochemical parameters were also within normal limits. Biopsy samples taken from the intact renal cortex parenchymal tissue were consistent. Total RNA was isolated from biopsy samples and expression profiles of target genes ( Claudin 1-4, 7, 8, 10, 14, 16, 18, 19 ) were determined by real-time polymerase chain reaction (PCR)., Results: It was determined that CLDN1 gene expression in patients with recurrent calcium oxalate kidney stones was approximately four times higher than in the control group; this difference was statistically significant (p<0.050). CLDN1 expression was also strongly positively correlated with CLDN4 (r=0.642), CLDN7 (r=0.753) and CLDN14 (r=0.651) Conclusions: We thought that CLDN1 overexpression might play a role in the pathogenesis of recurrent calcium oxalate stone formation. CLDN1 together with CLDN2 , CLDN4 , CLDN7 , and CLDN14 are also probably responsible for this pathogenesis., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Pamukkale University Institutional Review Board issued approval No: 2019/20. This study was conducted in compliance with the Declaration of Helsinki. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: This work was supported by the Scientific and Investigational Projects Reserve of the University of Pamukkale (Project No.: 2020TPF009). Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Uysal et al.)

Cat calcium oxalate monohydrate kidney stone matrix proteome showed great similarity to human calcium oxalate monohydrate stone matrix proteome, but inference of mechanistic similarity was limited by the absence of cat urine proteomic data. In this study, urine proteome distributions were measured by the same methods in 7 healthy cats for comparison to both the published human urine and cat calcium oxalate stone matrix proteomes to assess for similar enrichment patterns in both species. Furthermore, proteomic distributions were determined in cat struvite stone matrix to test for similarity to calcium oxalate monohydrate stone matrix and urine proteomes. Cat urine proteins demonstrated a similar distribution of abundance as a function of isoelectric points or net charge to human urine samples, and consequently the similarly altered patterns of protein distributions seen in calcium oxalate monohydrate stone matrix seen from both cat and human stones likely derives from the same preferential adsorption mechanism. Furthermore, the fact that protein abundance patterns seen in cat struvite stone matrix samples differ from both urine and calcium oxalate monohydrate stone matrix proteomes in systematic ways suggests that a combination of protein-protein and protein crystal interactions underly the formation of the crystal aggregates that comprise stones., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Variants in SLC34A1 and SLC34A2 genes, which encode co-transporters NaPi2a and NaPi2c, respectively, can lead to hypophosphatemia due to renal phosphate loss. This condition results in hypercalcitriolemia and hypercalciuria, leading to formation of kidney stones and nephrocalcinosis. Phenotype is highly variable. Management includes hyperhydration, dietary modifications, and/or phosphate supplementation. Thiazides and azoles may be used, but randomized studies are needed to confirm their clinical efficacy., Methods: We conducted a retrospective study in the pediatric nephrology unit at Grenoble University Hospital from January 2010 to December 2023. The study aimed to describe clinical and biological symptoms of patients with confirmed SLC34A1 and SLC34A3 gene variants and their outcomes., Results: A total of 11 patients (9 females) from 6 different families had variants in the SLC34A1 (5 patients) and SLC34A3 (6 patients) genes. Median age at diagnosis was 72 [1-108] months. Average follow-up duration was 8.1 ± 4.5 years. Presenting symptom was nephrocalcinosis (4 cases), followed by renal colic (3 cases). At diagnosis, 90% of patients had hypercalciuria and 45% had hypercalcitriolemia. Management included hyperhydration and dietary advice. All patients showed favorable outcomes with normal growth and school attendance. One patient with an SLC34A3 variant showed regression of nephrocalcinosis. Kidney function remained normal., Conclusion: Clinical and biological manifestations of SLC34 gene variants are highly variable, even among siblings; therefore, management must be personalized. Hygienic and dietary measures (such as hyperhydration, a low sodium diet, and age-appropriate calcium intake) result in favorable outcomes in most cases. Use of azoles (e.g., fluconazole) appears to be a promising therapeutic option., (© 2024. The Author(s), under exclusive licence to International Pediatric Nephrology Association.)

Objective: We investigated if socioeconomic and demographic factors predict post-surgical follow-up in pediatric stone patients., Materials and Methods: All patients having kidney stone surgery at a single academic pediatric hospital over a 5 year period (2016-2020) were identified through the use of CPT® codes specific to ureteroscopy, shock wave lithotripsy, and percutaneous nephrolithotomy. Electronic charts were reviewed for patient demographics, stone characteristics, and characteristics of intervention. Unique patients with a scheduled post-operative follow-up office visit following a first time stone surgery were included in the patient cohort (Figure 1). Primary outcome was attendance of a scheduled provider visit within 6 months after surgery. Secondary outcomes included completion of scheduled post-operative imaging and 24-h urine study. Univariable analysis was performed., Results: 195 pediatric patients, a median age of 15.4 years (IQR: 11.34, 17.14) at surgery, were identified. The majority were non-Hispanic white (86.2%) and female (62.1%). Most had undergone ureteroscopy alone (85.6%). Of the 195 patients, 146 (74.9%) attended a post-operative office visit. Indicators of lower socioeconomic status, such as having public insurance and being from a single-parent home, were associated with not attending a scheduled follow-up visit (p < 0.01 and p = 0.02, respectively). Patients with a pre-operative urology clinic visit were more likely to follow-up with a clinic visit (p = 0.02), while those with a larger total stone burden treated were more likely to undergo ordered imaging (p < 0.01)., Discussion: We found that indicators of lower socioeconomic status, such as having public insurance status and being in a single-parent household, were associated with lower pediatric follow-up compliance after kidney stone surgery, while patients seen in the urology clinic preoperatively were more likely to attend follow-up., Conclusion: Identifying factors that may predict non-compliance could be used to help at-risk patient populations., Competing Interests: Conflicts of interest None., (Copyright © 2024 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.)

Dent disease type 1 is a rare X-linked recessive inherited renal disorder affecting mainly young males, generally leading to end-stage renal failure and for which there is no cure. It is caused by inactivating mutations in the gene encoding ClC-5, a 2Cl - /H + exchanger found on endosomes in the renal proximal tubule. This transporter participates in reabsorbing all filtered plasma proteins, which justifies why proteinuria is commonly observed when ClC-5 is defective. In the context of Dent disease type 1, a proximal tubule dedifferentiation was shown to be accompanied by a dysfunctional cell metabolism. However, the exact mechanisms linking such alterations to chronic kidney disease are still unclear. In this review, we gather knowledge from several Dent disease type 1 models to summarize the current hypotheses generated to understand the progression of this disorder. We also highlight some urinary biomarkers for Dent disease type 1 suggested in different studies.

Dietary factors may be implicated in the formation of kidney stones and should be closely monitored. To achieve this aim, patients are routinely assessed by means of generic dietary recall, a tool widely used by authors in a range of extensive patient populations to record food intake; the findings obtained, however, may be skewed due to dietary variations and underestimation of the effect of food additives. Fifty Frequent Kidney Stone Formers (FKSFs, mean age: 54.3 ± 13.9 years) with normal kidney function, absence of comorbidities, and reliable compliance were selected from a total of 68 patients' resident in Sardinia, an Italian island where genetic admixtures have been relatively rare for generations. The study, conducted from 1 January 2020 to 31 December 2023, was aimed at assessing nutritional values based on the meticulous recording of food quantities, quality, and potential modifications related to food preparation. Patients were selected during an initial clinical check-up and all efforts made to ensure they were capable of reliably recording all food and drinks consumed. A seven-day food diary was provided in which food and drink intake and their impact on 24 h urine output was recorded. The following parameters were measured in both foods and urine output: citrates, oxalates, calcium, phosphorous, uric acid, proteins and nitrogen compounds, magnesium, sulfates, potassium, carbohydrates, free fatty acids. Study outcomes established the presence of hypocitraturia, hyperoxaluria, hypercalciuria, and moderately high levels of nitrogen compounds. Univariate analysis followed by multivariate analysis for further confirmation were performed and the following observations made. Citrate intake correlated with citraturia but did not promote oxaluria; calcium intake promoted onset of sulfaturia, azoturia, and ammoniuria, whilst magnesium correlated with magnesiuria but not with oxaluria, calciuria, phosphaturia, and azoturia; sulfate intake elicited onset of azoturia but not kaliuresis; potassium intake promoted oxaluria and protein intake resulted in onset of ammoniuria and azoturia. (A) The chemical composition of urine based on dietary intake is hard to predict without taking into account the presence of dietary and urinary interferents; (B) the geographic isolation of patients studied underlines the importance of epigenetics in maintaining a traditional dietary heritage. (C) Moreover, the widespread use of food additives should consistently be taken into account to ensure a correct diagnosis of FKSF and set up a valid treatment plan.

Background and Objectives : Retrograde intrarenal surgery (RIRS) is a minimally invasive technique for nephrolithiasis. RIRS is performed via a monitor screen displaying a magnified surgical site. Respiration can affect the stability of the surgical view during RIRS because the kidneys are close to the diaphragm. The purpose of this trial is to compare the effect of anesthesia type on the stability of the surgical view during RIRS between spinal anesthesia and general anesthesia. Materials and Methods : Patients were allocated to the general anesthesia group or spinal anesthesia group. During surgery, movement of the surgical field displayed on the monitor screen was graded by the first assistant on a 10-grade numeric rating scale (0-10). Next, it was also graded by the main surgeon. After surgery, we evaluated the discomfort with the anesthesia method for all patients. Results : Thirty-four patients were allocated to the general anesthesia group and 32 patients to the spinal anesthesia group. The average values of the two surgeons for surgical field oscillation grade showed vision on the monitor screen was more stable in the general anesthesia group than the spinal anesthesia group (3.3 ± 1.6 vs. 5.0 ± 1.6, p < 0.001). The degrees of the inconvenience of the surgery did not differ between the groups (0.7 ± 1.8 vs. 1.6 ± 2.6, p = 0.114), even though more patients reported inconvenience with a grade of 3 or more in the spinal anesthesia group (8.8% vs. 28.1%, p = 0.042). Conclusions : In terms of the visualization of the surgical site, general anesthesia might provide a more stable surgical view during RIRS compared to spinal anesthesia without increasing inconvenience induced by the type of anesthesia.

Endoscopic and biopsy findings have identified two distinct phenotypes among individuals with calcium oxalate (CaOx) kidney stones. One phenotype exhibits normal renal papillae but shows interstitial mineral deposition, known as Randall's plaque. The other phenotype presents with collecting duct plugging and a higher incidence of loss of papilla tissue mass. With Randall's plaque, renal papilla injury involves the loss of small patches of calcified tissue (Randall's plaque detaching with the stone), which likely results in damage to only a few nephrons. In contrast, collecting duct mineral plugs are very large, causing obstruction to tubular flow. Since each terminal collecting duct drains thousands of nephrons, ductal plugs could lead to the degeneration of many nephrons and a significant loss of renal glomeruli. New visualization techniques for immune cells in papillary biopsies have revealed that the Randall's plaque phenotype is marked by the accumulation of macrophages around the plaque regions. In contrast, preliminary data on the plugging phenotype shows collecting duct damage with mineral plugs, increased T-lymphocytes throughout the papilla, and tubulitis, characterized by T-cell infiltration into nearby collecting duct epithelium. This suggests that while some CaOx stone formers may have some papillary inflammation but with minimal damage to nephrons, others suffer from obstruction to flow for many nephrons that may also include destructive inflammation in the renal tissue. We propose that the long-term risks for loss of renal function will be greater for CaOx stone formers with the plugging phenotype.

Nephroureterectomy is currently the criterion-standard treatment for high-grade upper tract urothelial carcinoma (UTUC). Current guidelines and expert opinions propose some exceptions to this approach based on patient characteristics, disease status, and function of the contralateral kidney. We present a rare case of a patient with horseshoe kidney, bilateral large nephrolithiasis, high-grade UTUC in one moiety, and relative parenchymal thinning of the contralateral side. The patient was treated with a percutaneous, minimally invasive, nephron sparing approach. The patient also had intracollecting system instillations of gemcitabine and docetaxel. Minimally invasive percutaneous resection of high-grade UTUC is a safe procedure in select cases. Current guidelines may not apply to all patients; unique scenarios with UTUC may require personalized decision-making and treatment at specialized centers., Competing Interests: No conflict of interest has been declared by the authors., (Copyright © 2022 The Authors. Published by Wolters Kluwer Health, Inc.)

Background/aims: The association between inflammatory bowel disease (IBD) and gallstone and renal stone formation has been established. However, few studies have investigated this association in patients with intestinal Behçet's disease (BD). We aimed to examine the prevalence of gallstones and renal stones in patients with intestinal BD and identify potential risk factors., Methods: We analyzed gallstone and renal stone occurrences in 553 patients diagnosed with intestinal BD who had undergone cross-sectional imaging examinations between March 2005 and April 2021 at the IBD Center, Severance Hospital, Seoul, South Korea. Logistic regression models were used to identify risk factors for gallstone and renal stone formation., Results: Of 553 patients over a mean 12.1-year duration, 141 (25.4%) patients had gallstones and 35 (6.3%) had renal stones. In multivariate logistic regression analysis, disease duration > 19 years (OR 2.91, 95% CI 1.56-5.44, 0.002). No significant correlation 0.001), prior intestinal BD-related surgery (OR 2.29, 95% CI 1.42-3.68, p < 0.001), and disease activity index for intestinal BD scores ≥ 75 (OR 2.23, 95% CI 1.12-4.45, p = 0.022) were associated with increased gallstone occurrence. A positive correlation was observed between renal stones, disease duration > 19 years (OR 5.61, 95% CI 1.98-15.90, p = 0.001) and frequent hospitalization (> 3 times) (OR 3.29, 95% CI 1.52-7.13, p = 0.002). No significant correlation was observed between gallstone and renal stone occurrence., Conclusion: These findings contribute to greater understanding concerning gallstone and renal stone prevalence and associated risk factors in patients with intestinal BD.

Purpose: In previous studies, magnesium (Mg) was found to be lower in cases with more severe primary hyperparathyroidism (PHPT) and higher calcium (Ca) levels. This study evaluated the relationship between serum Mg and serum Ca and phosphorus (P) levels in PHPT and their utility in determining the presence of osteoporosis and nephrolithiasis., Methods: Patients who were followed up with PHPT between March 2019 and March 2023 were analyzed retrospectively. Biochemical data, renal ultrasonography results, dual-energy x-ray absorptiometry (DEXA) reports, and technetium 99 m sestamibi parathyroid scintigraphy reports were obtained. MgxP, Mg/P, Ca/P, and corrected Ca (cCa)/P values were calculated. The relationships between biochemical parameters and clinical outcomes were evaluated statistically., Results: A total of 543 patients were included in the study. Patients with nephrolithiasis had higher cCa/Mg or Ca/Mg than those without nephrolithiasis. Additionally, ROC analysis revealed that cCa/Mg greater than 5.24 could identify the presence of nephrolithiasis with a sensitivity of 73.3% and a specificity of 73%. No statistically significant correlation existed between the results of the Mg/P, MgxP, cCa/Mg, Ca/Mg values, and DEXA-bone mineral densitometry(BMD)., Conclusion: Ca/Mg and cCa/Mg ratios in particular seem more valuable in determining the presence of nephrolithiasis than the currently used 24-h urine Ca measurement. Compared to urinary Ca measurements, they are cheaper, more practical, and more accessible., (© 2024. The Author(s), under exclusive licence to Hellenic Endocrine Society.)

Introduction: Financial toxicity has been described in stone formers; however, little is understood regarding its causes and how it may relate to stone surgery. We therefore aimed to longitudinally describe markers of financial strain in stone formers from the preoperative to postoperative time points., Methods: A prospective cohort study was conducted from January 2022 to April 2023. Patients were enrolled in the waiting area prior to undergoing elective ureteroscopy or percutaneous nephrolithotomy. Participants completed The Commonwealth Fund's Biennial Health Insurance Survey at this time point and at 30 days postoperatively. Items were preselected from the survey to capture markers of financial strain due to health care costs., Results: One hundred nine participants were enrolled. White (70%), college-educated (62%), and privately insured (72%) patients comprised the majority of participants. Despite these traditionally protective sociodemographic features, 42% of patients reported some marker of financial strain at the preoperative time point. Patients with Medicaid reported even higher financial stress (67%). Furthermore, 46% of patients did not know their deductible amount. Response rate was low at 30 days postoperatively (35%) but suggested some patients were experiencing new financial strains., Conclusions: This paper shows that a significant proportion of stone patients are already displaying markers of financial strain from health care bills even prior to surgery as well as poor understanding of the costs they may incur. This makes them vulnerable to experiencing financial toxicity postoperatively and emphasizes the importance of understanding all contributing factors when developing future strategies to intervene in financial toxicity.

Purpose: The screening test to suspect infantile hypercalcemia-1 (HCINF1) is the measure of 25(OH)D 3 /24,25(OH) 2 D 3 ratio at mass spectroscopy (MS). When the ratio is > 80, the gold standard for the diagnosis is genetic analysis. Given its limited availability, MS may not represent a screening test and most cases of HCINF1 remain undiagnosed. Aim of the study is to identify cut-offs of serum calcium and PTH useful to suspect patients with HCINF1., Methods: We compared the levels of total serum calcium and PTH of 6 patients with HCINF1 harboring biallelic CYP24A1 pathogenic variants with 3 different control groups: (1) 12 subjects wild type for CYP24A1; (2) 12 subjects matched for age and sex; (3) 12 subjects matched for vitamin D levels. We validated the cut-offs, testing the number of adult patients affected by HCINF1 reported in the literature that could be identified using these cut-offs., Results: A serum calcium level > 9.6 mg/dL showed the highest sensitivity (100%) and specificity (91%) in the comparison between homozygous and wild-type subjects. A serum PTH index < 0.315 showed the highest sensitivity (100%) and specificity (83.3%). A serum calcium level > 9.6 mg/dL was able to identify all adult HCINF1 patients whereas a PTH ratio < 0.315 identified 89.8% of the cases. Superimposable results were obtained using the other control groups., Conclusion: Patients with serum calcium levels higher than 9.6 mg/dL and a PTH index lower than 0.315 are likely to be affected by HCINF1. Their diagnosis may be confirmed using MS and genetic analysis., (© 2024. The Author(s), under exclusive licence to Italian Society of Endocrinology (SIE).)

Objective: To analyze the association between the triglyceride-glucose (TyG) index and the risk of nephrolithiasis across various demographic and clinical subgroups, aiming to enhance early diagnosis and treatment of nephrolithiasis and promote personalized care in diverse populations., Methods: This cross-sectional study analyzed the medical records of 84 968 adults, stratified into three categories (low, middle, high) according to their TyG index scores. To evaluate the association between the TyG index and nephrolithiasis risk, multivariable Logistic regression models were employed, adjusting for potential confounders. Additionally, piecewise linear regression models were used to investigate the non-linear dynamics of the TyG index's relationship with nephrolithiasis risk. Subgroup analyses were performed to explore variations in the effects of the TyG index across different demographic and clinical populations., Results: Increasing TyG index was associated with a higher risk of nephrolithiasis, rising from 4.36% in the low group to 8.96% in the high group ( P < 0.001). In adjusted models, males in the middle and high TyG index categories demonstrated significantly elevated risks of nephrolithiasis, with odds ratios of 1.18 (95% CI : 1.07-1.31, P =0.002) and 1.29 (95% CI : 1.15-1.45, P < 0.001), respectively. Conversely, in females, the association was not statistically significant post-adjustment ( OR =0.98, 95% CI : 0.82-1.16, P =0.778). Among males, for each unit increment in the TyG index below the critical threshold of 8.98, there was a notable 40% escalation in the risk of developing nephrolithiasis ( OR =1.40, 95% CI : 1.24-1.58, P < 0.001). Surpassing this threshold, the TyG index no longer conferred a significant increase in risk ( OR =0.91, 95% CI : 0.78-1.06, P =0.24). Subgroup analyses indicated that this association remained stable regardless of age, BMI, or hypertension status., Conclusion: The TyG index is positively associated with the risk of nephrolithiasis in males, demonstrating a nonlinear dose-response relationship that becomes especially pronounced at certain index levels. This biomarker could potentially serve as a valuable clinical tool for identifying males who are at a high risk of developing nephrolithiasis, thereby enabling targeted preventive strategies. Further research is urgently needed to explore the underlying mechanisms and to verify the applicability of these results across different populations.

Purpose of Review: The impact of nephrolithiasis on skeletal growth and bone health across the life span of kidney stone formers is reviewed., Main Findings: Bone disease is an early event among kidney stone formers (SF), with distinct phenotypes according to each age, sex, menopausal status, dietary, hormonal and genetic factors. Nephrolithiasis-associated bone disorder is characterized by reduced bone mineral density (BMD) and histologically discloses low bone formation, high bone resorption and abnormal mineralization. Although hypercalciuria has been presumed to be pathogenic for bone loss in SF, the association of BMD with urinary calcium is not uniform in all studies. Hypocitraturia, metabolic disturbances, cytokines and receptors, growth factors and acid-base status may all influence skeletal outcomes. The potential link of bone disease with vascular calcification and cardiovascular disease among SF is discussed. The unique vulnerability of the younger skeleton to the effects of nephrolithiasis on attainment of peak bone mass and strength is highlighted and the association of bone loss with kidney stone formation early in life indicate the opportunity for intervention to reduce the risk of future bone fractures., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: Urolithiasis, the formation of kidney stones, is a common and severe condition. Despite advances in understanding its pathophysiology, affordable treatment options are needed worldwide. Hence, the interest is in herbal medicines as alternative or supplementary therapy for urinary stone disease. This review explores the use of plant extracts and phytochemicals in preventing and treating urolithiasis., Methods: Following PRISMA standards, we systematically reviewed the literature on PubMed/Medline, focusing on herbal items evaluated in in vivo models, in vitro studies, and clinical trials related to nephrolithiasis/urolithiasis. We searched English language publications from January 2021 to December 2023. Studies assessing plant extracts and phytochemicals' therapeutic potential in urolithiasis were included. Data extracted included study design, stone type, plant type, part of plant used, solvent type, main findings, and study references., Results: A total of 64 studies were included. Most studies used ethylene glycol to induce hyperoxaluria and nephrolithiasis in rat models. Various extraction methods were used to extract bioactive compounds from different plant parts. Several plants and phytochemicals, including Alhagi maurorum, Aerva lanata, Dolichos biflorus, Cucumis melo, and quercetin, demonstrated potential effectiveness in reducing stone formation, size, and number., Conclusions: Natural substances offer an alternative or supplementary approach to current treatments, potentially reducing pain and improving the quality of life for urolithiasis patients. However, further research is needed to clarify their mechanisms of action and optimize their therapeutic use. The potential of plant-based therapies in treating urolithiasis is promising, and ongoing research is expected to lead to treatment advancements benefiting patients globally., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Purpose of Review: Kidney stone disease (KSD) is a common and potentially life-threatening condition, and half of patients experience a repeat kidney stone episode within 5-10 years. Despite the ~50% estimate heritability of KSD, international guidelines have not kept up with the pace of discovery of genetic causes of KSD. The European Association of Urology guidelines lists 7 genetic causes of KSD as 'high risk'., Recent Findings: There are currently 46 known monogenic (single gene) causes of kidney stone disease, with evidence of association in a further 23 genes. There is also evidence for polygenic risk of developing KSD. Evidence is lacking for recurrent disease, and only one genome wide association study has investigated this phenomenon, identifying two associated genes (SLC34A1 and TRPV5). However, in the absence of other evidence, patients with genetic predisposition to KSD should be treated as 'high risk'. Further studies are needed to characterize both monogenic and polygenic associations with recurrent disease, to allow for appropriate risk stratification. Durability of test result must be balanced against cost. This would enable retrospective analysis if no genetic cause was found initially. We recommend genetic testing using a gene panel for all children, adults < 25 years, and older patients who have factors associated with high risk disease within the context of a wider metabolic evaluation. Those with a genetic predisposition should be managed via a multi-disciplinary team approach including urologists, radiologists, nephrologists, clinical geneticists and chemical pathologists. This will enable appropriate follow-up, counselling and potentially prophylaxis., (© 2024. The Author(s).)

Calyceal rupture, defined as the extravasation of urine from the renal calyces into the perinephric or paranephric spaces, typically results from increased intrapelvic pressure due to urinary tract obstruction. This condition can lead to the formation of a perinephric urinoma and severe complications, such as infection, abscess formation, and impaired renal function. Timely diagnosis and management are crucial to prevent these adverse outcomes. Calyceal rupture often results from urolithiasis, with other causes including strictures, tumors, and congenital abnormalities. The rupture occurs when intrapelvic pressure exceeds the tensile strength of the calyceal walls, leading to urine leakage and potential inflammation or sepsis. Calyceal ruptures are quite rare, with their exact incidence not well-documented due to the infrequency of the condition and potential underreporting. Although relatively uncommon, the condition is more prevalent in individuals with recurrent nephrolithiasis and other predisposing factors. Timely recognition and intervention, guided by imaging studies such as non-contrast CT scans, are essential. Conservative management with medical therapy is effective in many cases, but surgical intervention may be necessary for larger stones or complications. This report presents the case of a 36-year-old female with calyceal rupture secondary to nephrolithiasis, presenting with severe flank pain. Upon initial presentation, the patient underwent a thorough workup, including imaging studies, appropriate medical management, and continuous monitoring. She was stabilized, her pain was effectively managed, and she was discharged with a scheduled outpatient follow-up. This case highlights the importance of early diagnosis, comprehensive management, and vigilant monitoring in preventing complications and promoting favorable outcomes., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Cruz et al.)

Background: Molecular mechanisms of kidney stone formation remain unknown in most patients. Previous studies have shown a high heritability of nephrolithiasis, but data on the prevalence and characteristics of genetic disease in unselected adults with nephrolithiasis are lacking. This study was conducted to fill this important knowledge gap., Methods: We performed whole exome sequencing in 787 participants in the Bern Kidney Stone Registry, an unselected cohort of adults with one or more past kidney stone episodes [kidney stone formers (KSFs)] and 114 non-kidney stone formers (NKSFs). An exome-based panel of 34 established nephrolithiasis genes was analysed and variants assessed according to American College of Medical Genetics and Genomics criteria. Pathogenic (P) or likely pathogenic (LP) variants were considered diagnostic., Results: The mean age of KSFs was 47 ± 15 years and 18% were first-time KSFs. A Mendelian kidney stone disease was present in 2.9% (23/787) of KSFs. The most common genetic diagnoses were cystinuria (SLC3A1, SLC7A9; n = 13), vitamin D-24 hydroxylase deficiency (CYP24A1; n = 5) and primary hyperoxaluria (AGXT, GRHPR, HOGA1; n = 3). Of the KSFs, 8.1% (64/787) were monoallelic for LP/P variants predisposing to nephrolithiasis, most frequently in SLC34A1/A3 or SLC9A3R1 (n = 37), CLDN16 (n = 8) and CYP24A1 (n = 8). KSFs with Mendelian disease had a lower age at the first stone event (30 ± 14 versus 36 ± 14 years; P = .003), were more likely to have cystine stones (23.4% versus 1.4%) and less likely to have calcium oxalate monohydrates stones (31.9% versus 52.5%) compared with KSFs without a genetic diagnosis. The phenotype of KSFs with variants predisposing to nephrolithiasis was subtle and showed significant overlap with KSFs without diagnostic variants. In NKSFs, no Mendelian disease was detected and LP/P variants were significantly less prevalent compared with KSFs (1.8% versus 8.1%)., Conclusion: Mendelian disease is uncommon in unselected adult KSFs, yet variants predisposing to nephrolithiasis are significantly enriched in adult KSFs., (© The Author(s) 2024. Published by Oxford University Press on behalf of the ERA.)

Dysregulation of renal tubular epithelial cell (RTEC) apoptosis is one of the critical steps underlying the occurrence and development of nephrolithiasis. Although N6-methyladenosine (m 6 A) modification has been extensively studied and associated with various pathologic processes, research on its specific role in RTEC injury and apoptosis remains limited. In this study, we found that overexpression of ALKBH5 reduced the level of m 6 A modification in RTEC cells and notably promoted RTEC apoptosis. Further mechanism studies revealed that ALKBH5 mainly  decreased the m 6 A level on the mRNA of  Mucin 1 (MUC1) gene in RTECs. Moreover, ALKBH5  impaired the stability of MUC1 mRNA in RTECs, leading to  attenuated expression of MUC1. Finally, we determined that the ALKBH5-MUC1 axis primarily facilitated RTEC apoptosis by regulating the PI3K/Akt signaling pathway. This study revealed the critical role of the ALKBH5-MUC1-PI3K/Akt regulatory system in RTEC apoptosis and provided new therapeutic targets for treating nephrolithiasis., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The research on the mechanism of nephrolithiasis formation is of great importance due to the fact that the high incidence and recurrence rate of nephrolithiasis bring considerable economic burdens to patients and society. As an important component in the nephrolithiasis formation process, the immune-inflammatory process has been gradually valued by researchers in recent years. In this study, articles related to the immune-inflammatory process of nephrolithiasis published since 2000 were retrieved based on the Web of Science (WoS) database. Eventually, a total of 370 articles were selected for subsequent analyses. Besides, VOSviewer, CiteSpace, and Bibliometrix were employed to quantitatively analyze and visualize the data. The number of articles related to the immune-inflammatory process of nephrolithiasis has increased rapidly in the last five years. From the country level, most articles were contributed by China (n = 140) and the United States (n = 99) contributed the most documents. From the institution level, University of Florida (n = 36) and Nagoya City University (n = 21) had the most articles. From the journal level, Journal of Urology and Urolithiasis published the most articles in this field. Keywords mainly included inflammation, oxidative stress, calcium oxalate, osteopontin, and hyperoxaluria, which represented the research directions in this field. The most productive author was Khan SR (n = 33), whose articles obtained the highest number of citations (2086 times). These efforts may help researchers understand the current progress and status of research on the immune-inflammatory process of nephrolithiasis and identify future research hotspots and directions., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier Ltd.)