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Puerarin(PUE), an isoflavonoid extracted from Pueraria root, has anti‐apoptotic effects. The objective of this research is to examine the impact of PUE on renal apoptosis and inflammation resulting from renal calculi and to elucidate its mechanism. The approach of network pharmacology and molecular docking was employed to discover potential targets and pathways of PUE. An animal model of calcium oxalate crystal deposition by intraperitoneal injection of glyoxylate and a model of COM‐induced human renal tubular epithelial cells (HK2) were used to investigate the pharmacological mechanisms of PUE against apoptosis and inflammation. We used haematoxylin–eosin (H&E) and Periodic Acid‐Schiff staining (PAS) to assess the effect of PUE on crystal deposition and damage. The mechanism of PUE was elucidated and validated using Western blotting, histology and immunohistochemical staining. Network pharmacology findings indicated that the PI3K/AKT pathway plays a crucial role in PUE. We experimentally demonstrate that PUE alleviated COM‐induced changes in apoptotic proteins, increased inflammatory indicators and changes in oxidative stress‐related indicators in HK2 cells by activating the PI3K/AKT pathway, reduced serum creatinine and urea nitrogen levels in mice caused by CaOx, alleviated crystal deposition and damage, and alleviated apoptosis, oxidative stress and inflammation. Puerarin attenuates renal apoptosis and inflammation caused by kidney stones through the PI3K/AKT pathway. [ABSTRACT FROM AUTHOR]

Thiazide and thiazide‐like diuretics (thiazides) belong to the most frequently prescribed drugs worldwide. By virtue of their natriuretic and vasodilating properties, thiazides effectively lower blood pressure and prevent adverse cardiovascular outcomes. In addition, through their unique characteristic of reducing urine calcium, thiazides are also widely employed for the prevention of kidney stone recurrence and reduction of bone fracture risk. Since their introduction into clinical medicine in the early 1960s, thiazides have been recognized for their association with metabolic side effects, particularly impaired glucose tolerance, and new‐onset diabetes mellitus. Numerous hypotheses have been advanced to explain thiazide‐induced glucose intolerance, yet underlying mechanisms remain poorly defined. Regrettably, the lack of understanding and unpredictability of these side effects has prompted numerous physicians to refrain from prescribing these effective, inexpensive, and widely accessible drugs. In this review, we outline the pharmacology and mechanism of action of thiazides, highlight recent advances in the understanding of thiazide‐induced glucose intolerance, and provide an up‐to‐date discussion on the role of thiazides in kidney stone prevention. [ABSTRACT FROM AUTHOR]

Objective: To assess the impact of kidney stone disease (KSD) and its treatment on the health‐related quality of life (HRQOL) of high‐risk stone formers with hyperparathyroidism, renal tubular acidosis, malabsorptive disease, and medullary sponge kidney. Patients and Methods: The Wisconsin Stone Quality of Life questionnaire was used to evaluate HRQOL in 3301 patients with a history of KSD from 16 institutions in North America between 2014 and 2020. Baseline characteristics and medical history were collected from patients, while active KSD was confirmed through radiological imaging. The high‐risk group was compared to the remaining patients (control group) using the Wilcoxon rank‐sum test. Results: Of 1499 patients with active KSD included in the study, the high‐risk group included 120 patients. The high‐risk group had significantly lower HRQOL scores compared to the control group (P < 0.01). In the multivariable analyses, medullary sponge kidney disease and renal tubular acidosis were independent predictors of poorer HRQOL, while alkali therapy was an independent predictor of better HRQOL (all P < 0.01). Conclusions: Among patients with active KSD, high‐risk stone formers had impaired HRQOL with medullary sponge kidney disease and renal tubular acidosis being independent predictors of poorer HRQOL. Clinicians should seek to identify these patients earlier as they would benefit from prompt treatment and prevention. [ABSTRACT FROM AUTHOR]

Peristalsis is a common motion in various biological systems, especially the upper urinary tract, where it plays a pivotal role in conveying urine from the kidneys to the bladder. Using computational fluid dynamics, this study aims to investigate the effect of various peristaltic parameters on the motion of an obstacle through a two‐dimensional ureter. Methodologically, Incompressible Navier–Stokes equations were utilized as the fluid domain's governing equations, and the Dynamic Mesh method (DM) was employed to simulate the peristaltic and obstacle motion. The peristaltic motion was modeled by a sinusoidal contraction wave propagating alongside the ureter at the physiological speed, and the motion of the obstruction through the ureter, which is caused by the fluid forces applied on its surface, was explored using the equation of Newton's second law. Various test cases of different shapes and sizes were supposed as kidney stones to understand the influence of the peristalsis properties on the stone removal process. The results show that the motion of the kidney stone is highly influenced by the gradient pressure force applied to its surface in the fluid domain. Moreover, investigating the effects of the peristaltic physical properties on the obstacle's motion indicates that the stone's motion is dependent on these parameters. Furthermore, this analysis provides insight into the peristaltic motion effects, assisting physicians in developing new medicines to facilitate the kidney stone removal process based on its shape and size. [ABSTRACT FROM AUTHOR]

Objectives: To assess the effects of percutaneous nephrolithotomy (PCNL) vs retrograde intrarenal surgery (RIRS) for the treatment of renal stones in adults. Methods: We performed a comprehensive search of the Cochrane Library, MEDLINE, Embase, three other databases, trials registries, other sources of the grey literature, and conference proceedings up to 23 March 2023. We applied no restrictions on publication language or status. Screening, data extraction, risk‐of‐bias assessment, and certainty of evidence (CoE) rating using the Grading of Recommendations Assessment, Development and Evaluations (GRADE) approach were done in duplicate by two independent reviewers. This co‐publication focuses on the primary outcomes of this review only. Results: We included 42 trials that met the inclusion criteria. Stone‐free rate (SFR): PCNL may improve SFRs (risk ratio [RR] 1.13, 95% confidence interval [CI] 1.08–1.18; I2 = 71%; 39 studies, 4088 participants; low CoE). Major complications: PCNL probably has little to no effect on major complications (RR 0.86, 95% CI 0.59–1.25; I2 = 15%; 34 studies, 3649; participants; moderate CoE) compared to RIRS. Need for secondary interventions: PCNL may reduce the need for secondary interventions (RR 0.31, 95% CI 0.17–0.55; I2 = 61%; 21 studies, 2005 participants; low CoE) compared to RIRS. Conclusion: Despite shortcomings in most studies that lowered our certainty in the estimates of effect to mostly very low or low, we found that PCNL may improve SFRs and reduce the need for secondary interventions while not impacting major complications. Ureteric stricture rates may be similar compared to RIRS. We expect the findings of this review to be helpful for shared decision‐making about management choices for individuals with renal stones. [ABSTRACT FROM AUTHOR]

Objectives: To explore the optimal laser settings and treatment strategies for thulium fibre laser (TFL) lithotripsy, namely, those with the highest treatment efficiency, lowest thermal injury risk, and shortest procedure time. Materials and Methods: An in vitro kidney model was used to assess the efficacy of TFL lithotripsy in the upper calyx. Stone ablation experiments were performed on BegoStone phantoms at different combinations of pulse energy (EP) and frequency (F) to determine the optimal settings. Temperature changes and thermal injury risks were monitored using embedded thermocouples. Experiments were also performed on calcium oxalate monohydrate (COM) stones to validate the optimal settings. Results: High EP/low F settings demonstrated superior treatment efficiency compared to low EP/high F settings using the same power. Specifically, 0.8 J/12 Hz was the optimal setting, resulting in a twofold increase in treatment efficiency, a 39% reduction in energy expenditure per unit of ablated stone mass, a 35% reduction in residual fragments, and a 36% reduction in total procedure time compared to the 0.2 J/50 Hz setting for COM stones. Thermal injury risk assessment indicated that 10 W power settings with high EP/low F combinations remained below the threshold for tissue injury, while higher power settings (>10 W) consistently exceeded the safety threshold. Conclusions: Our findings suggest that high EP/low F settings, such as 0.8 J/12 Hz, are optimal for TFL lithotripsy in the treatment of COM stones. These settings demonstrated significantly improved treatment efficiency with reduced residual fragments compared to conventional settings while keeping the thermal dose below the injury threshold. This study highlights the importance of using the high EP/low F combination with low power settings, which maximizes treatment efficiency and minimizes potential thermal injury. Further studies are warranted to determine the optimal settings for TFL for treating kidney stones with different compositions. [ABSTRACT FROM AUTHOR]

Objectives: To understand the implications that the rising upper urinary tract (UUT) stone prevalence in Europe and the increasing burden places on patients and healthcare providers (HCPs), we investigated the evolution of diagnoses and procedures in Germany, France and England over the decade before the coronavirus disease 2019 (COVID‐19) pandemic. Methods: We identified International Classification of Diseases (ICD)‐10 codes related to UUT stones diagnosis and extracted procedure volumes for extracorporeal shockwave lithotripsy (ESWL), ureteroscopy (URS), percutaneous nephrolithotomy and open surgery using national procedure codes from the German Institute for the Hospital Remuneration System, the French Technical Agency of Hospitalisation Information and NHS England Hospital Episode Statistics. We analysed procedures vs hospital diagnoses from 2010 to 2019 and reported results per 100 000 inhabitants. Results: Between 2010 and 2019, ICD‐10 N20 codes for calculus of kidney and ureter increased by 8%, 26% and 15% in Germany, France, and England respectively; whereas procedures increased by 3%, 38% and 18%. Of the patients diagnosed with stones, the percentage that received treatment (of any type) differed between countries. In 2019, in Germany 83% of patients diagnosed with stones received treatment, in France 88%, and in England 56%. These figures were relatively stable over the 10‐year study period. Over the past decade, the dominant procedure shifted from ESWL to URS, and the average length of stay for URS decreased. Day case procedures increased in France and England (by 68% and 23%), no data were available in Germany. Conclusion: This analysis highlights an increase in stone diagnoses and procedures, and a shift of surgical management. This development may be due to clinical advantages and advanced technology. The continued stone prevalence rise affects patients, hospitals, and HCPs. [ABSTRACT FROM AUTHOR]

Background: Ionized calcium concentration ([iCa]) is more sensitive for detecting calcium disturbances than serum total calcium concentration but literature on ionized hypercalcemia in cats is limited. Urolithiasis is a possible adverse consequence of hypercalcemia. Hypothesis/Objectives: To describe clinical details of diagnoses associated with ionized hypercalcemia in cats and association with urolithiasis. Animals: Cats (238) seen between 2009 and 2019 at a referral hospital with [iCa] above the normal reference interval. Methods: Observational cross‐sectional study. Signalment, serum biochemical and imaging findings were reviewed for cats with ionized hypercalcemia considered to be clinically relevant (>1.41 mmol/L). Data were summarized by cause of hypercalcemia (i.e., diagnosis). Results: Diagnoses for the 238 cats with [iCa] >1.41 mmol/L included: acute kidney injury (AKI; 13%), malignancy‐associated (10.1%), idiopathic hypercalcemia (IHC; 10.1%), chronic kidney disease/renal diet‐associated (8.4%), iatrogenic (5.5%), primary hyperparathyroidism (2.1%), vitamin D toxicity (2.1%) and granulomatous disease (1.7%). In 112 cases (47.1%), no cause for ionized hypercalcemia could be determined (n = 95), hypercalcemia was transient (n = 12), or the cat was juvenile (<1 year; n = 5). Urolithiasis was identified in 83.3% of AKI, 72.7% of iatrogenic, 61.1% of CKD/renal diet‐associated and 50% of IHC cases that were imaged (<50% for other diagnoses). Diagnoses with a high proportion of concurrent total hypercalcemia included primary hyperparathyroidism (100%), vitamin D toxicity (100%), malignancy‐associated (71.4%), granulomatous disease (66.7%) and IHC (65.2%). Conclusions and Clinical Importance: Ionized hypercalcemia was most commonly associated with kidney diseases, neoplasia or IHC. The proportion of urolithiasis cases varied by diagnosis. [ABSTRACT FROM AUTHOR]

Background and Aims: Kidney stone disease is a crystal concretion formed usually within the kidneys. The worldwide prevalence of kidney stones could be affected by numerous differences in socioeconomic, and environmental factors. The purpose of this study is to investigate kidney stones among Iranian adults aged between 35 and 70 years and the prevalence and evaluation of socioeconomic inequalities. Methods: In this, a cohort‐based cross‐sectional study was carried out among 20,427 participants of ArNCDs aged 35 and 70 years old. Kidney stone was defined as a dependent (and binary) variable while demographic and socioeconomic factors were considered independent variables. Multivariable logistic regression was used to identify the key socioeconomic factors affecting kidney stone prevalence in Ardabil. Results: The overall prevalence of kidney stones was 17.6 (95% confidence interval [CI]: 16.1–19.2) out of which 21.53% and 14.36% pertained to men and women and 14.18% and 23.17% pertained to the poorest and richest groups, respectively. There was a significant difference in the prevalence of kidney stones between men and women in terms of age, marital status, education level, chronic disease, body mass index, and socioeconomic status (<0.001). The prevalence of kidney stones had a positive correlation with age (1.7, 95% [CI]: 1.42–2.04) and socioeconomic status (1.5, 95% [CI]: 1.34–1.69), where the odds of kidney stones increased significantly by increasing age and socioeconomic status. Moreover, the kidney stone concentration index showed a pro‐rich distribution wherein it was more common among wealthy people (higher socioeconomic status) 0.062 (95% [CI]: 0.051–0.072). Conclusion: The results of this study showed that there is significant inequality in the prevalence of kidney stones, where it was more common among the richest people. In addition, being men and old age are significantly related to kidney stones, so policymakers and physicians should consider these factors. [ABSTRACT FROM AUTHOR]

As small residual fragments are thought to represent a "nidus" of stone re-growth, it is of utmost importance to render patients with infection stones completely stone-free [1]. Case Presentation This case report outlines the treatment regimen in a patient with severe, recurrent, hitherto treatment-refractory struvite stones using a combination of endourological surgery and intraluminal lavage with Renacidin. Case of the month from Lillebaelt hospital, University Hospital of South Denmark, Denmark: Renacidin® - still a useful adjunct to endoscopic surgery for complex renal struvite stone disease Keywords: kidney stone; chemolysis; ureteroscopy; infection stones; renacidin EN kidney stone chemolysis ureteroscopy infection stones renacidin 437 440 4 09/16/22 20221001 NES 221001 Abbreviations ECIRS endoscopic combined intrarenal surgery ICU intensive care unit Introduction Renal infection stones constitute a particular treatment challenge because of the combination of large stone burden and associated UTI with urease-producing bacteria. [Extracted from the article]

Objectives: To evaluate the efficacy of ultrasound‐assisted monitoring during shock wave lithotripsy for kidney and proximal ureteral calculi. Methods: We retrospectively reviewed 535 patients who initially underwent shock wave lithotripsy for renal or proximal ureteral calculi between January 2012 and December 2021. The patients were divided into the X‐ray group (n = 294) and ultrasound plus X‐ray group (n = 241) based on the methods of targeting and monitoring calculi during shock wave lithotripsy. Because of differences in patient backgrounds, 1:1 propensity score‐based matching was performed. The primary endpoint was the stone‐free rate. Results: In the final 1:1 matched cohort, 192 kidney stone cases and 162 proximal ureteral stone cases were analyzed. For patients with kidney calculi, the stone‐free rate of the ultrasound plus X‐ray group was significantly higher than that of the X‐ray group (66.7% vs. 47.9%; P = 0.013). In the multivariate analysis, a large stone area (odds ratio 2.37), lower caliceal stones (odds ratio 3.37), and X‐ray monitoring alone (odds ratio 0.49) were independently associated with shock wave lithotripsy failure. For patients with proximal ureteral stones, there was no significant difference in the stone‐free rate between the ultrasound plus X‐ray group and X‐ray group (71.6% and 58.0%, respectively; P = 0.100). During the multivariate analysis, high computed tomography attenuation (odds ratio 2.31) and large stone area (odds ratio 2.18) were independent factors associated with residual stones after shock wave lithotripsy. Conclusions: Ultrasound‐assisted monitoring may contribute to a higher stone‐free rate for patients with kidney calculi, but not for those with proximal ureteral calculi. [ABSTRACT FROM AUTHOR]

Calcium oxalate (CaC2O4) is the major component of kidney stone. The acidic osteopontin (OPN) protein in human urine can effectively inhibit the growth of CaC2O4 crystals, thereby acting as a potent stone preventer. Previous studies in bulk solution all attest to the importance of binding and recognition of OPN at the CaC2O4 mineral surface, yet molecular level insights into the active interface during CaC2O4 mineralization are still lacking. Here, we probe the structure of the central OPN fragment and its interaction with Ca2+ and CaC2O4 at the water–air interface using surface‐specific non‐linear vibrational spectroscopy. While OPN peptides remain largely disordered in solution, our results reveal that the bidentate binding of Ca2+ ions refold the interfacial peptides into well‐ordered and assembled β‐turn motifs. One critical intermediate directs mineralization by releasing structural freedom of backbone and binding side chains. These insights into the mineral interface are crucial for understanding the pathological development of kidney stones and possibly relevant for calcium oxalate biomineralization in general. [ABSTRACT FROM AUTHOR]

Objective: To investigate whether the use of statins would alter 24‐h urine biochemistry in male patients with calcium kidney stones. Methods: We prospectively recruited 78 male patients with calcium kidney stones between May 2017 and December 2017, and 30 male controls with matching sex and age, but without kidney stones. All patients were classified into higher‐ and lower‐risk groups of atherosclerotic cardiovascular disease according to the American College of Cardiology/American Heart Association guidelines. Atorvastatin 20 mg per day was prescribed for 12 weeks to the higher risk patients. For kidney stone group, 24‐h urine collections were carried out before and after statin therapy. Results: A total of 78 patients and 30 controls were included. Higher‐risk patients had significantly higher urine uric acid and calcium levels than lower‐risk patients. After atorvastatin treatment for 12 weeks, urine citrate significantly increased (P < 0.001) accompanied with increased urine pH (P < 0.001), whereas urine uric acid significantly decreased after treatment. Although urine oxalate significantly increased after treatment (P = 0.037), we did not find any significant difference in urine calcium, ion activity product of calcium oxalate and ion activity product of calcium phosphate. Conclusion: These findings suggest that atorvastatin administration might increase urinary citrate and decrease urinary uric acid in patients with calcium kidney stones and dyslipidemia. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the utility of kidney injury test (KIT) assay urinary biomarkers to detect kidney stones and quantify stone burden. Patients and Methods: A total of 136 spot urine samples from 98 individuals, with and without kidney stone disease, were processed in a predefined assay to measure six DNA and protein markers in order to generate a risk score for the non‐invasive detection of nephrolithiasis. From this cohort, 56 individuals had spot, non‐timed urine samples collected at the time of radiographically confirmed kidney stones, and 54 demographically matched, healthy controls without kidney stone disease also provided spot, non‐timed urine samples. Sixteen individuals with persistent stone disease had more than one urine sample. Using a proprietary microwell‐based KIT assay, we measured cell‐free DNA (cfDNA), methylated cfDNA, clusterin, creatinine, protein and CXCL10. A KIT stone score was computed across all markers using the prior locked KIT algorithm. The KIT stone score, with a scale of 0 to 100, was then correlated with demographic variables, kidney stone burden, obstructive kidney stone disease, and urine solutes in 24‐h urine collections. Results: The scaled KIT stone score, a composite of all six biomarkers, readily discriminated individuals with current or prior radiographically confirmed kidney stones from healthy controls without kidney stone disease (P < 0.001). In individuals with nephrolithiasis, KIT stone score also correlated with radiologically measured stone size (P = 0.017) and differentiated patients with a clinical radiological diagnosis of obstructive nephrolithiasis associated with upper renal tract dilatation (P = 0.001). Stone burden as assessed by KIT stone score, however, did not correlate with the any of the traditional measures of 24‐h urine solutes or the 24‐h urine supersaturation levels. In patients with persistent stone disease, where multiple urine samples were collected over time and after different interventions, the use of KIT stone score could non‐invasively track stone burden over time through a spot urine, non‐timed urine sample. Conclusions: A random, spot urine‐based assay, KIT stone score, can non‐invasively detect, quantify and monitor current stone burden, and may thus minimize radiographic exposure for kidney stone detection. The KIT stone score assay may also help monitor stone recurrence risk for patients with nephrolithiasis, without the requirement for 24‐h urine collections. [ABSTRACT FROM AUTHOR]

Objective: To estimate the cost of kidney stone disease (KSD) in England. Patients and Methods: We conducted a retrospective cohort study of patients with KSD, referred to a metabolic stone clinic between 1990 and 2007 using electronic records of patients with KSD in a tertiary referral centre, to determine cost using UK National Health Service (NHS) tariff, with subsequent extrapolation to the entire England population. Those with no documentation and <5 years follow‐up were excluded. The outcome measure was calculation of cost (as per 2018 NHS tariff) presented as lower and higher estimates for: per episode; total within the cohort; and estimation of initial, 5‐,10‐ and 15‐year costs for the cohort and total population in England. Linear regression was used to examine for significant predictors of per episode and total cost. Results: A total of 781 patients were included in the study after 1000 records were screened for inclusion, with a mean follow‐up of 19 years. The mean (SD) overall costs per episode were between £1277 (1724) and £2887 (2492). Total initial costs for the cohort were between £950 842 and £2 336 442, rising to between £1.43 million and £3.02 million at 15 years of follow‐up. Estimated cost in 2010 in England alone was between £190 million and £324 million. Conclusion: KSD is a costly disease, comparable to the combined cost of prostate and bladder cancer in UK. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the long‐term outcomes of patients undergoing observation of asymptomatic renal calculi and identify factors associated with stone‐related events. Patients and Methods: Patients with asymptomatic renal calculi electing active surveillance of their stones were retrospectively reviewed. Patients underwent annual ultrasonography and clinical visits with standardised questions regarding the development of symptoms or complications from calculi. Spontaneous stone passage, stone growth, development of stone‐related symptoms, and requirement for intervention during follow‐up were deemed as stone‐related events. Results: Between 2007 and 2017, 293 patients were reviewed to evaluate the natural history of asymptomatic renal calculi. The mean follow‐up was 4.2 years. Overall incidences of spontaneous passage, stone growth, development of stone‐related symptoms, and requirement of intervention were 32.1%, 16.7%, 28.3% and 12.3%, respectively. Stones >5 mm and lower pole stones were significantly less likely to pass spontaneously. Patients with diabetes mellitus (DM), hyperuricaemia or non‐lower calyceal stone were more likely to experience stone growth. Stones >5 mm or non‐lower pole stones were more likely to become symptomatic. Significant predictors of surgical intervention were stone size (>5 mm) and patients' age (>60 years). Primary therapy was extracorporeal shockwave lithotripsy in 33 patients and flexible ureteroscopy in three. Conclusion: The natural history of asymptomatic renal stones rarely requires intervention, although they do have a slightly higher rate of symptomatic events and growth over the intermediate term. In particular, patients with stones >5 mm, DM, hyperuricaemia, or non‐lower calyceal stones are at higher risk of developing stone‐related events, and should therefore be recommended for regular follow‐up. [ABSTRACT FROM AUTHOR]

The differentiated phenotype of renal tubular epithelial cell exerts significant effect on crystal adherence. Peroxisome proliferator‐activated receptor γ (PPARγ) has been shown to be critical for the regulation of cell transdifferentiation in many physiological and pathological conditions; however, little is known about its role in kidney stone formation. In the current study, we found that temporarily high oxalate concentration significantly decreased PPARγ expression, induced Madin Darby Canine Kidney cell dedifferentiation, and prompted subsequent calcium oxalate (CaOx) crystal adhesion in vitro. Furthermore, cell redifferentiation after the removal of the high oxalate concentration, along with a decreasing affinity to crystals, was an endogenic PPARγ‐dependent process. In addition, the PPARγ antagonist GW9662, which can depress total‐PPARγ expression and activity, enhanced cell dedifferentiation induced by high oxalate concentration and inhibited cell redifferentiation after removal of the high oxalate concentration. These effects were partially reversed by the PPARγ agonist 15d‐PGJ2. Similar results were observed in animals that suffered from temporary hyperoxaluria followed by a recovery period. The active crystal‐clearing process occurs through the transphenotypical morphology of renal tubular epithelial cells, reflecting cell transdifferentiation during the recovery period. However, GW9662 delayed cell redifferentiation and increased the secondary temporary crystalluria‐induced crystal retention. This detrimental effect was partially reversed by 15d‐PGJ2. Taken together, our results revealed that endogenic PPARγ activity plays a vital regulatory role in crystal clearance, subsequent crystal adherence, and CaOx stone formation via manipulating the transdifferentiation of renal tubular epithelial cells. The differentiated phenotype of renal tubular epithelial cell exerts significant effect on crystal adherence. Peroxisome proliferator‐activated receptor γ (PPARγ) has been shown to be critical for the regulation of cell transdifferentiation in many physiological and pathological conditions. In the current study, our results revealed that endogenic PPARγ activity plays a vital regulatory role in crystal clearance, subsequent crystal adherence, and calcium oxalate (CaOx) stone formation via manipulating the transdifferentiation of renal tubular epithelial cells. [ABSTRACT FROM AUTHOR]

Between 1% and 15% of people are globally affected by kidney stones, and this disease has become more common since the 1970s. Therefore, this study aims to investigate the effects of gastrin‐releasing peptide receptor (GRPR) gene silencing via the PI3K/Akt signaling pathway on the development of the epithelial–mesenchymal transition (EMT) and formation of a calcium oxalate crystal in renal tubular epithelial cells (TECs) of kidney stones. A total of 70 clean and healthy C57BL/6J mice were assigned into the normal (n = 10) and kidney stones groups (n = 60). The underlying regulatory mechanisms of GRPR were analyzed in concert with the treatment of shGRPR‐1, LY294002, and shGRPR‐1 + LY294002 in TECs isolated from mice with kidney stones. A series of experiments were conducted for the measurement of urinary oxalate and urinary calcium, the renal calcium salt deposition, the positive rate of GRPR, the expressions of renal TECs related genes and calcium oxalate regulation related genes, and the growth of calcium crystals induced by cells. After treatment of shGRPR‐1 and shGRPR‐1 + LY294002, levels of urinary oxalate and urinary calcium in the serum, as well as positive rate of GRPR, became relatively low, levels of E‐cadherin enhanced, whereas levels of Akt, PI3K, GRPR, extents of PI3K and Akt phosphorylation, α‐SMA, Vimentin and FSP‐1, OPN, MCP‐1, and CD44 decreased and a number of crystals reduced. Taken together, we conclude that GRPR gene silencing suppresses the development of the EMT and formation of the calcium oxalate crystal in renal TECs of kidney stones through the inactivation of the PI3K/Akt signaling pathway. Gastrin‐releasing peptide receptor gene silencing suppresses the development of the epithelial–mesenchymal transition (EMT) and formation of a calcium oxalate crystal in renal tubular epithelial cells (TECs) of kidney stones through the inactivation of the PI3K/Akt signaling pathway. [ABSTRACT FROM AUTHOR]

Asymptomatic urolithiasis is common and of mixed composition in patients with β-thalassaemia major. Twenty-seven subjects were imaged using dual-energy computer tomography to determine the presence and composition of urolithiasis. The prevalence of urolithiasis was 59% and affected patients generally had multiple stones, often with more than one component: struvite (33%), calcium oxalate (31%) and cystine (22%). Hypercalciuria was present in 78% of subjects and calcium-containing urolithiasis was associated with reduced femoral neck Z scores. [ABSTRACT FROM AUTHOR]

This population-based retrospective cohort study sought to determine if anorexia nervosa (AN) is associated with a higher risk of urolithiasis. Nine thousand three hundred two females with AN were compared to 92 959 randomly selected age-matched and practice-matched females. Cox regression was used to estimate the hazard ratio (HR) for urolithiasis and evaluate effect modification by age. Twenty-three participants with AN (0.25%) developed urolithiasis compared with 154 unexposed participants (0.17%) over a median of 4 years of observation. The risk of urolithiasis varied significantly with age (interaction p = 0.02). AN was associated with a more than threefold higher risk of urolithiasis in females ≤25 years of age (HR 3.49, 95% CI: 1.56-7.81; p = 0.002), but not in females over 25 years (HR 1.18, 95% CI: 0.69-2.02; p = 0.54). The distribution of diagnosis codes for urolithiasis differed between groups ( p = 0.04), with a higher proportion of codes for uric acid urolithiasis in the AN (16.2%) versus unexposed group (5.0%). Copyright © 2017 John Wiley & Sons, Ltd and Eating Disorders Association. [ABSTRACT FROM AUTHOR]

Objective To evaluate the protective effects of selenium with vitamins A, C and E (selenium ACE, i.e. antioxidants), verapamil (calcium channel blocker), and losartan (angiotensin receptor blocker) against extracorporeal shockwave lithotripsy ( ESWL)-induced renal injury. Patients and Methods A randomised controlled trial was conducted between August 2012 and February 2015. Inclusion criteria were adult patients with a single renal stone (<2 cm) suitable for ESWL. Patients with diabetes, hypertension, congenital renal anomalies, moderate or marked hydronephrosis, or preoperative albuminuria (>300 mg/L) were excluded. ESWL was performed using the electromagnetic DoLiS lithotripter. Eligible patients were randomised into one of four groups using sealed closed envelopes: Group1, control; Group 2, selenium ACE; Group 3, losartan; and Group 4, verapamil. Albuminuria and urinary neutrophil gelatinase-associated lipocalin ( uNGAL) were estimated after 2-4 h and 1 week after ESWL. The primary outcome was differences between albuminuria and uNGAL. Dynamic contrast-enhanced magnetic resonance imaging was performed before ESWL, and at 2-4 h and 1 week after ESWL to compare changes in renal perfusion. Results Of 329 patients assessed for eligibility, the final analysis comprised 160 patients (40 in each group). Losartan was the only medication that showed significantly lower levels of albuminuria after 1 week ( P < 0.001). For perfusion changes, there was a statistically significant decrease in the renal perfusion in patients with obstructed kidneys in comparison to before ESWL ( P = 0.003). These significant changes were present in the control or antioxidant group, whilst in the losartan and verapamil groups renal perfusion was not significantly decreased. Conclusions Losartan was found to protect the kidney against ESWL-induced renal injury by significantly decreasing post- ESWL albuminuria. Verapamil and losartan maintained renal perfusion in patients with post- ESWL renal obstruction. [ABSTRACT FROM AUTHOR]

Objectives To evaluate the effect of potassium-sodium citrate on the development of computed tomography-detected renal microcalculi into symptomatic stones in calcium stone-forming patients. Methods Patients (aged 20-80 years) with history of calcium component stones who visited Nagoya City Hospital, Nagoya, Aichi, Japan, between April 2009 and June 2014 were included. They were retrospectively divided into those who did not receive potassium-sodium citrate (non-citrate group, n = 157) and those who did (citrate group, n = 60). For patients in both groups, we evaluated blood and urine biochemistry and sediment, number of computed tomography-detected microcalculi, number of asymptomatic microcalculi disappearances, and pain events. Observations were made at study initiation and 12 months later. Results The citrate group showed a significantly increased urine pH ( P < 0.001) and daily citrate excretion ( P < 0.001) over the study period. The non-citrate group showed increased numbers of microcalculi at study completion ( P = 0.002); over the same period, the number of microcalculi in the citrate group decreased significantly ( P = 0.03). Additionally, multivariable analysis showed more asymptomatic microcalculi disappearances (odds ratio 2.84, 95% confidence interval 1.49-5.39) and fewer pain events (odds ratio 0.37, 95% confidence interval 0.16-0.72) in the citrate group than in the non-citrate group. A sex-adjusted analysis showed more asymptomatic microcalculi disappearances (odds ratio 3.96, 95% confidence interval 1.57-10.02) and fewer pain events (odds ratio 0.22, 95% confidence interval 0.07-0.70) in women than in men after citrate treatment. Conclusions Potassium-sodium citrate prevents the development of renal microcalculi into symptomatic stones in calcium stone-forming individuals. [ABSTRACT FROM AUTHOR]

Pathogenic mechanisms of kidney stone disease remained unclear. This study investigated its initial cellular/molecular mechanisms when calcium oxalate monohydrate (COM) crystal adhered to renal tubular cells. Transmission electron microscopy revealed decreased length and density of microvilli, whereas Western blot analysis showed that whole‐cell ezrin (a microvillus‐stabilizing protein), not β‐actin, was decreased in COM‐treated cells. Immuno fluorescence staining, followed by laser‐scanning confocal microscopy and subcellular fractionations, revealed decreases in both ezrin and F‐/β‐actin at apical membrane. Cytoskeletal extraction by Triton X‐100 showed reduced cytoskeleton‐associated ezrin, consistent with colocalization data of ezrin/F‐actin. Thr567‐phosphorylated ezrin and RhoA increased in COM‐treated cells. A protein oxidation blot assay showed an increase in oxidized proteins in COM‐treated cells that could be prevented by epigallocatechin‐3‐gallate (EGCG), which also preserved the whole‐cell ezrin level, stabilized apical membrane ezrin/F‐actin colocalization, and maintained microvillar structure in COM‐treated and H2O2‐treated cells. Our data clearly demonstrated the reduction of ezrin and actin expression at the apical membrane of COM‐treated cells, most likely because of oxidative stress, which could be prevented by EGCG. These findings provide a novel approach to better understanding of the pathogenesis of kidney stone disease in its initial phase and offer potential preventive strategy against microvillar injury induced by COM crystals in patients with kidney stones.—Fong‐ngern, K., Vinaiphat, A., Thongboonkerd, V. Microvillar injury in renal tubular epithelial cells induced by calcium oxalate crystal and the protective role of epigallocatechin‐3‐gallate. FASEB J. 31, 120–131 (2017) www.fasebj.org [ABSTRACT FROM AUTHOR]

A previous study reported that lamin A/C (LMNA) expression was increased in renal tubular cells adhered with calcium oxalate monohydrate (COM) crystals; however, its functional significance in kidney stone disease remained unknown. In the present study, increased levels of LMNA and its partner, nesprin-1 (SYNE1), in Madin-Darby canine kidney cells upon COM crystal adhesion were confirmed by Western blotting and immunofluorescence staining. LMNA was then knocked down by small interfering RNA. Immunofluorescence staining confirmed the efficiency of small interfering RNA of LMNA (si-LMNA), which also reduced expression of its partner, SYNE1. Scratch assay and total cell count revealed defects in tissue repair and cell proliferation, respectively, whereas cell death quantitation showed no cytotoxicity in si-LMNA-transfected cells. Crystal-binding assay highlighted the role of LMNA in crystal adhesion, whereas protein network analysis revealed interactions between LMNA and potential COM crystal receptors. Their associations were confirmed by reduced levels of these proteins, including vimentin, tubulin, enolase, S100, and annexin A2, in si-LMNA-transfected cells. These data have demonstrated for the first time, to our knowledge, that LMNA in renal tubular cells is important for tissue repair, cell proliferation, and COM crystal adhesion and is associated with potential COM crystal receptors. Therefore, LMNA may serve as a potential target for prevention of kidney stone disease and its recurrence. [ABSTRACT FROM AUTHOR]

Kidney stone disease is endemic. Extracorporeal shockwave lithotripsy was the first major technological breakthrough where focused shockwaves were used to fragment stones in the kidney or ureter. The shockwaves induced the formation of cavitation bubbles, whose collapse released energy at the stone, and the energy fragmented the kidney stones into pieces small enough to be passed spontaneously. Can the concept of microbubbles be used without the bulky machine? The logical progression was to manufacture these powerful microbubbles ex vivo and inject these bubbles directly into the collecting system. An external source can be used to induce cavitation once the microbubbles are at their target; the key is targeting these microbubbles to specifically bind to kidney stones. Two important observations have been established: (i) bisphosphonates attach to hydroxyapatite crystals with high affinity; and (ii) there is substantial hydroxyapatite in most kidney stones. The microbubbles can be equipped with bisphosphonate tags to specifically target kidney stones. These bubbles will preferentially bind to the stone and not surrounding tissue, reducing collateral damage. Ultrasound or another suitable form of energy is then applied causing the microbubbles to induce cavitation and fragment the stones. This can be used as an adjunct to ureteroscopy or percutaneous lithotripsy to aid in fragmentation. Randall's plaques, which also contain hydroxyapatite crystals, can also be targeted to pre-emptively destroy these stone precursors. Additionally, targeted microbubbles can aid in kidney stone diagnostics by virtue of being used as an adjunct to traditional imaging methods, especially useful in high-risk patient populations. This novel application of targeted microbubble technology not only represents the next frontier in minimally invasive stone surgery, but a platform technology for other areas of medicine. [ABSTRACT FROM AUTHOR]

We recently reported that occupational exposure to trimethyltin (TMT) is a risk factor for developing kidney stones. To further examine the association between TMT exposure and the formation of kidney stones, we conducted a 180-day animal study and exposed the randomly grouped Sprague-Dawley (SD) rats to TMT in the drinking water at doses of 0, 8.2, 32.8 and 131.3 µg kg-1 day-1. Transient behavioral changes were observed in the high-dose group during the first 2 weeks of exposure. TMT exposure led to a significant dose-dependent inhibition of renal H+/K+-ATPase and an increase in urinary pH. In comparison to no kidney stones being identified in the control and the lowest dose group, 1 rat in the 32.8 µg kg-1 day-1 dose group and 3 out of 9 rats in the 131.3 µg kg-1 day-1 dose group were found to have stones in the kidney/urinary tract. Pathological analysis showed that more wide spread calcium disposition was observed in kidneys of rats with TMT exposure compared with the rats in the control group. However, X-ray diffraction (XRD) analysis found that the kidney stones were mainly composed of struvite with the formula: NH4MgPO4 6H2O, while calcium-containing components were also detected. Together, this study further demonstrates through animal studies that chronic exposure to a relatively low level of TMT induces nephrotoxicity and increases the risk for developing kidney stones. Copyright © 2014 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Objectives To investigate the effect of weight loss intervention on the urinary stone risk parameters in a rat model of metabolic syndrome. Methods In a prevention study, 4-week-old male Otsuka Long-Evans Tokushima 'Fatty' rats were randomly assigned to three groups: control, food-restricted and food-restricted + exercise-trained groups. In a treatment study, 24-week-old male Otsuka Long-Evans Tokushima 'Fatty' rats that had already developed type 2 diabetes were randomly assigned to the same three groups. Blood and 24-h urine chemistry were measured after 16 weeks. Results In both studies, food-restricted and food-restricted + exercise-trained rats showed significantly higher urinary pH and higher excretion of urinary citrate than control rats. In the prevention study, ion-activity products of calcium oxalate in the food-restricted and food-restricted + exercise-trained groups were significantly lower than that of control rats. In the treatment study, ion-activity products of calcium oxalate index in food-restricted + exercise-trained rats was significantly lower than that of control rats. Conclusions Weight loss intervention seems to reduce the risk of uric acid stone formation by improving low urine pH and calcium oxalate stone formation by increasing urinary citrate excretion. The present study provides the first theoretical evidence to support weight loss intervention programs for nephrolithiasis patients with metabolic syndrome. [ABSTRACT FROM AUTHOR]

Objective To investigate factors predicting spontaneous clearance of residual renal fragments after flexible ureteroscopy. Methods Among 546 patients who underwent lithotripsy with flexible ureteroscopy, 81 had residual renal fragments, as determined by kidney-ureter-bladder films on postoperative day 1. The final outcome was determined at 3 months after the last flexible ureteroscopy session using non-contrast computed tomography. Patient characteristics and preoperative factors were analyzed using the unpaired t-test and χ2-test. Correlations between the possible predictive factors and the spontaneous clearance of residual renal fragments after flexible ureteroscopy were analyzed using a multivariate logistic regression model with backward selection. Results Non-contrast computed tomography at postoperative month 3 showed that 33 cases (40.7%) had spontaneous clearance of residual renal fragments, whereas 48 (59.3%) showed non-clearance. Significant differences were found between these cases in terms of stone number, stone location, presence of lower pole calculi and preoperative stent placement. Multivariate assessment showed that stone number ( P = 0.004), presence of lower pole calculi ( P = 0.021) and presence of hydronephrosis ( P = 0.024) were independent predictors of the spontaneous clearance of residual renal fragments after flexible ureteroscopy. Conclusions Stone number, presence of lower pole calculi and presence of hydronephrosis are independent predictive factors of the spontaneous clearance of residual renal fragments after flexible ureteroscopy. [ABSTRACT FROM AUTHOR]

Objective To develop and internally validate a preoperative nomogram for predicting stone-free status ( SF) after flexible ureteroscopy ( fURS) for renal stones, as there is a need to predict the outcome of fURS for the treatment of renal stone disease. Patients and Methods We retrospectively analysed 310 fURS procedures for renal stone removal performed between December 2009 and April 2013. Final outcome of fURS was determined by computed tomography 3 months after the last fURS session. Assessed preoperative factors included stone volume and number, age, sex, presence of hydronephrosis and lower pole calculi, and ureteric stent placement. Multivariate logistic regression analysis with backward selection was used to model the relationship between preoperative factors and SF after fURS. Bootstrapping was used to internally validate the nomogram. Results Five independent predictors of SF after fURS were identified: stone volume ( P < 0.001), presence of lower pole calculi ( P = 0.001), operator with experience of >50 fURS ( P = 0.026), stone number ( P = 0.075), and presence of hydronephrosis ( P = 0.047). We developed a nomogram to predict SF after fURS using these five preoperative characteristics. Total nomogram score (maximum 25) was derived from summing individual scores of each predictive variable; a high total score was predictive of successful fURS outcome, whereas a low total score was predictive of unsuccessful outcome. The area under the receiver operating characteristics for nomogram predictions was 0.87. Conclusion The nomogram can be used to reliably predict SF based on patient characteristics after fURS treatment of renal stone disease. [ABSTRACT FROM AUTHOR]

Objectives To determine whether stone burden correlates with the degree of chronic kidney disease in kidney stone formers. Methods A total of 97 extracorporeal shockwave lithotripsy candidates aged 18 years and older were included. Size, number and location of the kidney stones, along with cumulative stone size, defined as the sum of diameters of all stones) were determined. Estimated glomerular filtration rate was determined using the Chronic Kidney Disease Epidemiology Collaboration cystatin C/creatinine equation, and chronic kidney disease was defined as estimated glomerular filtration rate <60 mL/min/1.73 m2. Results In individuals with cumulative stone size <20 mm, estimated glomerular filtration rate significantly decreased when moving from the first (estimated glomerular filtration rate 75.5 ± 17.8 mL/min/1.73 m2) to the fourth (estimated glomerular filtration rate 56.4 ± 20.44 mL/min/1.73 m2) quartile ( P = 0.004). When patients with a cumulative stone size ≥20 mm were included, the observed association was rendered non-significant. In individuals with a cumulative stone size <20 mm, each 1-mm increase in cumulative stone size was associated with a 20% increased risk of having chronic kidney disease. The relationship persisted even after adjustment for age, sex, body mass index, C-reactive protein, fasting plasma glucose, thyroid stimulating hormone, presence of microalbuminuria, history of renal calculi, history of extracorporeal shockwave lithotripsy, number and location of the stones (odds ratio 1.24, 95% confidence interval 1.02-1.52). The same was not observed for individuals with a cumulative stone size ≥20 mm. Conclusions In kidney stone formers with a cumulative stone size up to 20 mm, estimated glomerular filtration rate linearly declines with increasing cumulative stone size. Additionally, cumulative stone size is an independent predictor of chronic kidney disease in this group of patients. [ABSTRACT FROM AUTHOR]

Purpose: Renal calculi are common extracolonic incidental findings on computed tomographic colonography (CTC). This work aims to develop a fully automated computer-aided diagnosis system to accurately detect renal calculi on CTC images. Methods: The authors developed a total variation (TV) flow method to reduce image noise within the kidneys while maintaining the characteristic appearance of renal calculi. Maximally stable extremal region (MSER) features were then calculated to robustly identify calculi candidates. Finally, the authors computed texture and shape features that were imported to support vector machines for calculus classification. The method was validated on a dataset of 192 patients and compared to a baseline approach that detects calculi by thresholding. The authors also compared their method with the detection approaches using anisotropic diffusion and nonsmoothing. Results: At a false positive rate of 8 per patient, the sensitivities of the new method and the baseline thresholding approach were 69% and 35% (p < 1e - 3) on all calculi from 1 to 433 mm³ in the testing dataset. The sensitivities of the detection methods using anisotropic diffusion and nonsmoothing were 36% and 0%, respectively. The sensitivity of the new method increased to 90% if only larger and more clinically relevant calculi were considered. Conclusions: Experimental results demonstrated that TV-flow and MSER features are efficient means to robustly and accurately detect renal calculi on low-dose, high noise CTC images. Thus, the proposed method can potentially improve diagnosis. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 40-year-old woman with history of chronic migraine and later developed kidney stone. Topics discussed include the complications caused by the kidney stone formation from the use of topiramate (TPM) and zonisamide (ZNS) in treating migraine and idiopathic intracranial hypertension (IIH), the risk of acetazolamide (ATZ) combined with TPM, and the stone formation's pathophysiology.

Patients with asymptomatic kidney stones have a high rate of progression to becoming symptomatic kidney stones when followed for several years. Small kidney stones are often found incidentally on imaging when evaluating patients for kidney donation, and there is a concern that after nephrectomy, the donor may become symptomatic and incur damage to the remaining kidney. We reviewed kidney donors at our institution with asymptomatic stones and surveyed them several years after donation to see if the stones became clinically active. [ABSTRACT FROM AUTHOR]

Objective To examine the risk of diabetes mellitus within a 5-year period among patients with nephrolithiasis undergoing percutaneous nephrolithotomy . Methods A total of 304 patients who underwent percutaneous nephrolithotomy were included in the study cohort. A total of 3040 patients with nephrolithiasis who did not undergo percutaneous nephrolithotomy were used as a comparison cohort. All participants included in the present study were individually tracked for a 5-year period in order to identify those who developed diabetes mellitus during this timeframe. Results The incidence rate of diabetes mellitus was 3.03 per 100 person-years in participants who underwent percutaneous nephrolithotomy and 1.65 per 100 person-years in participants who did not undergo percutaneous nephrolithotomy. After adjusting for the participants' monthly income, geographic location, urbanization level, hypertension, hyperlipidemia and alcohol abuse/alcohol dependence syndrome, the hazard ratio of receiving a first diagnosis of diabetes mellitus during the 5-year follow-up period was 1.96 (95% confidence interval 1.40-2.77) for participants who underwent percutaneous nephrolithotomy. Furthermore, compared with extracorporeal shock wave lithotripsy or endoscopic intervention, participants who underwent percutaneous nephrolithotomy had a significantly increased hazard of developing diabetes mellitus (adjusted hazard ratio 1.79 for a percutaneous nephrolithotomy vs extracorporeal shockwave lithotripsy, and adjusted hazard ratio 1.71 for a percutaneous nephrolithotomy vs an endoscopic intervention). Conclusions The present results suggest an association between patients with nephrolithiasis who undergo a percutaneous nephrolithotomy and a subsequent diabetes mellitus diagnosis. [ABSTRACT FROM AUTHOR]

The enamel-renal syndrome of amelogenesis imperfecta (AI) and nephrocalcinosis, and the amelogenesis imperfecta-gingival fibromatosis syndrome have both been associated with mutations in FAM20A. We report on two unrelated Thai patients with three novel and one previously reported mutations in FAM20A with findings suggesting both disorders, including hypoplastic AI, gingival fibromatosis, unerupted teeth, aggressive periodontitis, and nephrocalcinosis/nephrolithiasis. Additional findings consisted of a supernumerary premolar, localized aggressive periodontitis, thin alveolar bone, vitamin D deficiency-associated hyperparathyroidism, and heterotopic calcification in other tissues, including lungs, dental pulp, gingiva, dental follicles, and periodontal tissues, and early cessation of limited menstruation. Greater promotory activity of urine on calcium oxalate crystal growth compared to controls may help to explain the pathogenesis, and suggest that FAM20A mutations can contribute to nephrocalcinosis/nephrolithiasis. Our findings expand the phenotypic spectrum of FAM20A mutations. Since both of our patients and a large number of previously reported cases had all the important features of both syndromes, including AI, renal anomalies, and gingival fibromatosis, we are convinced that these two disorders actually are the same entity. The name of enamel-renal-gingival syndrome is suggested. © 2013 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Study Type - Prognosis (cohort series) Level of Evidence 2b What's known on the subject? and What does the study add? Epidemiologic studies have shown that warmer climates are associated with increased incidence of nephrolithiasis. Many hypothesize that this is due to dehydration and lower urine volumes. The current study of stone formers reports that greater temperatures are associated with significant increases in urine calcium which may shed light on the mechanism underlying the increased stone incidence associated with increased ambient temperature. OBJECTIVE To understand the effects of temperature, humidity and season of year on 24-h urine composition in patients with nephrolithiasis., PATIENTS AND METHOD A retrospective review was performed of patients evaluated at four metabolic stone clinics., Multivariate linear regression models examined the relationship between mean temperature, average humidity, season of year and 24-h urine composition., Multivariate models adjusted for known risk factors for stone disease., Mean temperature and average humidity data were obtained from http://www.weatherunderground.com based on patient-provided addresses., RESULTS A total of 599 patients were included in the study, comprising 239 women and 360 men with a mean age of 53.6 years ( sd 15.0)., Mean temperature was 16.9 °C ( sd 4.8, range −21.1 to 38.3 °C) and average humidity was 58.1% ( sd 23.5, range 11-100%)., On multivariate linear regression, increasing temperature was associated with increasing urine calcium (β= 11.3, 95% CI 2.2-20.0), super-saturation of calcium oxalate (β= 0.6, 95% CI 0.2-0.9), super-saturation of calcium phosphate (β= 0.14, 95% CI 0.03-0.2), and decreasing urine sodium (β=−5.2, 95% CI −10.3 to −0.1)., As seasons become warmer (i.e. from winter to autumn to spring to summer), changes were increased urine volume (β= 0.09, 95% CI 0.01-0.2) and decreased super-saturation of calcium phosphate (β=−0.2, 95% CI −0.3 to −0.03)., There were no associations between quintile of humidity and any 24-h urine constituents., CONCLUSIONS Increasing temperature may increase stone risk by increasing urine excretion of calcium, and the super-saturation of calcium oxalate and calcium phosphate., These findings were independent of humidity and of season of year., This appears to be related to a physiological impact of temperature itself, rather than to geographic location. [ABSTRACT FROM AUTHOR]

It has been reported that kidney stones are linked to metabolic syndrome (MetS), which is characterized by insulin resistance. The aim of the present study was to examine the association of insulin resistance, insulin and adiponectin with kidney stones in a Japanese population. From February 2007 to March 2008, 1036 (529 men and 507 women) apparently healthy Japanese subjects, aged 35-79 years, were analyzed. Weight, height, waist circumference and blood pressure were measured. Overnight fasting blood was collected to measure insulin and adiponectin levels. Homeostasis model assessment of insulin resistance (HOMA-IR) was calculated to assess insulin resistance. Logistic regression analysis was used to estimate the odds ratio (OR) and 95% confidence intervals for a self-reported history of kidney stones across tertiles of HOMA-IR, insulin and adiponectin. Of the participants, 84 men (15.6%) and 35 women (6.9%) had a history of kidney stones. Age, body mass index, waist circumference, systolic and diastolic blood pressures, HOMA-IR and insulin were significantly higher in women with than in women without kidney stones. There was no difference in adiponectin level between subjects with and without a history of kidney stones in either sex. Furthermore, a significant positive trend was observed in the age-adjusted OR for a history of kidney stones across insulin tertiles ( P-value for trend = 0.04) in women. For Japanese women, HOMA-IR and insulin are associated with a history of kidney stones. The findings suggest that MetS components could increase the risk of kidney stones through subclinical hyperinsulinemia and insulin resistance. [ABSTRACT FROM AUTHOR]

OBJECTIVE To present our experience with 454 patients who had tubeless percutaneous nephrolithotomy (TPCNL) over last 3 years. PATIENTS AND METHODS From September 2004 to August 2007, all patients aged >14 years and undergoing PCNL were considered for TPCNL. Exclusion criteria were the presence of pyonephrosis, matrix calculi, significant bleeding or residual stone burden and need for three of more percutaneous accesses. These patients had a nephrostomy tube placed after PCNL (control group). The remaining patients undergoing TPCNL (study group) had antegrade ureteric stenting. Demographic and perioperative data were compared retrospectively. RESULTS Of 840 patients who had PCNL during the study period, 454 had TPCNL. The two groups had comparable demographic data except for a smaller stone burden (322.8 vs 832.2 mm2) and fewer staghorn calculi (94 vs 154) in patients undergoing TPCNL ( P < 0.001). The mean number of tracts per renal unit and operative duration were statistically higher in patients undergoing standard PCNL (1.5 vs 1.1, and 68.8 vs 52.2 min, respectively). The decrease in haemoglobin, complication and stone-free rates were comparable. TPCNL was associated with less postoperative pain, analgesia requirement and earlier discharge ( P < 0.001). CONCLUSIONS TPCNL can be used with a favourable outcome and no increase in complications in selected patients, with the potential advantages of decreased postoperative pain, analgesia requirement and hospital stay. Its application can be extended to patients with a solitary kidney, previous ipsilateral open surgery, raised serum creatinine level, in the presence of three renal accesses or supracostal access, and in patients undergoing bilateral synchronous PCNL or contralateral endourological stone treatment. [ABSTRACT FROM AUTHOR]

OBJECTIVE To define incidence of renal matrix calculi in patients undergoing percutaneous nephrolithotomy (PCNL), and describe its clinical, laboratory and radiological features; we also studied the efficacy of PCNL in managing this rare entity. PATIENTS AND METHODS We retrospectively reviewed the records of 1368 PCNLs performed from April 2003 to March 2008, and identified 17 patients (mean age 44.3 years; 11 women and six men) having matrix calculi. The patients’ clinical, laboratory and radiological features were studied, and the perioperative outcome and follow-up data analysed. RESULTS Flank pain was commonest mode of presentation (15) followed by recurrent urinary tract infection (five). Pyuria was present in 14 patients and urine culture showed significant growth in 10. A plain X-ray showed a small radio-opaque calculus (10 renal units) and faint laminated calcification (four). Intravenous urography showed a filling defect and non-visualized system in nine and five patients, respectively. Non-contrast computed tomography and magnetic resonance urography diagnosed calculi in two and one patient, respectively, on haemodialysis. PCNL was abandoned initially in four patients due to pyonephrosis. The mean hospital stay was 3.4 days and decrease in haemoglobin was 0.89 g/dL. One patient developed sepsis. Of 11 stones analysed, two were composed entirely of proteins and the remaining nine had crystalline components. At a mean follow-up of 12.6 months, no patients had recurrence of stone. CONCLUSIONS Matrix calculi occurred in 1.24% of patients undergoing PCNL. Although considered radiolucent, plain X-ray showed a small radio-opaque calculi or faint laminated calcifications in 10 of 17 patients. PCNL rendered patients stone-free with minimum morbidity. [ABSTRACT FROM AUTHOR]

OBJECTIVES To investigate the intrarenal mRNA expression of monocyte chemoattractant protein-1 (MCP-1) and interleukin-6 (IL-6) in patients with nephrolithiasis, and to evaluate whether their expression is associated with renal function, as oxidative stress and inflammation are involved in the pathogenesis of nephrolithiasis. PATIENTS, SUBJECTS AND METHODS Renal biopsies from near the stone, and blood and 24-h urine specimens were collected from 29 patients with nephrolithiasis. Control renal tissues were taken from non-cancerous and cancerous portions of nephrectomy from six patients with renal cancers, and control 24-h urine samples were obtained from 30 healthy subjects. Corrected creatinine clearance, urinary N-acetyl-β-glucosaminidase activity and 8-hydroxy-deoxyguanosine (8-OHdG) were determined. The mRNA expressions of MCP-1 and IL-6 in the tissues were measured by real time reverse transcription-polymerase chain reaction. RESULTS Patients with nephrolithiasis had significantly greater renal tubular damage and oxidative stress than the healthy controls. Intrarenal mRNA expressions of MCP-1 and IL-6 in stone-adjacent renal tissues were significantly lower than in cancerous renal tissues, but not statistically different from that in non-cancerous renal tissues. In stone-adjacent renal tissues, the mRNA level of MCP-1 was significantly higher than that of IL-6, but their expressions were significantly correlated with each other. Histological examination showed that the number of infiltrated leukocytes corresponded well with the intrarenal mRNA levels of MCP-1 and IL-6. Patients with nephrolithiasis and compromised renal function had significantly higher intrarenal mRNA levels of MCP-1 and IL-6 than those with preserved renal function. Also, the mRNA levels in patients with severe renal tubular damage were significantly greater than in those with less renal tubular damage. There was no association between intrarenal mRNA expression and urinary 8-OHdG. CONCLUSION Nephrolithiasis was associated with low-grade intrarenal inflammation. A greater intrarenal mRNA expression of MCP-1 and IL-6 was associated with enhanced renal impairment. Thus, expression of MCP-1 and IL-6, at least in part, contributed to the progression of nephrolithiasis. [ABSTRACT FROM AUTHOR]

Abstract Background: The kidney eliminates the major fraction of plasma oxalate. It is well known that oxalate is freely filtered by glomeruli and secreted by the proximal tubules. However, the renal handling of oxalate in distal nephrons, which is considered as playing an important role in stone formation, remains obscure. Methods: At 15–180 min after intravenous injection of 14 C-oxalate to rats, the intrarenal localization of radioactivity was quantitatively measured by the radioluminographic method using a bioimaging analyzer. Tissue radioactivity was compared with plasma, and urinary radioactivities were measured by a liquid scintillation counter. The control study was conducted with 14 C-inulin. Results: The radioactivity of 14 C-oxalate in the papilla was 10 times greater than in the cortex and eight times greater than in the medulla 180 min after injection when almost no radioactivity was present in the urine. In contrast, the radioactivity of 14 C-inulin was nine times less in the papilla than in the cortex at the same time. Conclusion: Oxalate remains in the renal papilla for an extended period. This accumulation of oxalate may be attributed to calcium oxalate crystal fixation along the deep nephron which is considered to be the first step of stone formation. [ABSTRACT FROM AUTHOR]

Objective To fractionate renal-stone matrix proteins, identify the presence of oxalate-binding protein and assess its effect in a calcium oxalate (CaOx) crystal growth system. Materials and methods Proteins were isolated from the matrix of kidney stones containing CaOx as the major constituent, using EDTA as a demineralizing agent. The solubilized proteins were subjected to cellulose-column chromatography by eluting with increasing sodium chloride concentrations in Tris-HCl buffer. Three protein fraction peaks were eluted, i.e. fraction I in buffer, fraction II in 0.05 mol/L NaCl in buffer and fraction III in 0.3 mol/L NaCl in buffer. The protein fractions were tested for their effects on CaOx crystal growth. Results All three fractions had maximum CaOx binding activity at pH 7.4 but fraction II also had activity at pH 4.5. Fraction I promoted in vitro CaOx crystal growth, while fractions II and III were inhibitory. When fraction I was further separated on a Sephadex G-200 column, two protein fractions (Ia and Ib) were obtained. Fraction Ia protein had high and fraction Ib low CaOx-binding activity. Fraction Ia had a molecular weight of 48 kDa on gel electrophoresis and Western blotting. The 48 kDa protein did not cross-react with crystal matrix protein antibody, band-3 protein antibody, or albumin. The protein promoted CaOx crystal growth, with an optimum temperature of 37 °C and pH 6.5. The inhibitory effect of citrate on crystal growth was significantly lower in the presence of the 48 kDa protein. The protein promoted nucleation and aggregation of CaOx crystals in the in vitro crystallization system at pH 6.5, whereas fraction Ib (29 kDa) inhibited both nucleation and aggregation. Using the 48 kDa antibody, the yield of the protein from the stone matrix was 32% by EDTA extraction and only 3% with other methods. The protein was also detected in the nucleus and mitochondria, and in other matrix fractions of calcium phosphate and uric acid stones.... [ABSTRACT FROM AUTHOR]

Objective To determine if the incidence of lower-pole nephrolithiasis is increasing. Methods A previously published meta-analysis of trends in the location of stones in the kidney, using data from 1984 to 1992, determined the percentage of lower pole stones in 26 722 kidney stones treated by extracorporeal shockwave lithotripsy (ESWL). We performed prospective studies on all patients treated by ESWL for a single renal stone (not manipulated from the ureter) in two organizations; at Lithotripters Inc., 47 303 stones were treated with ESWL by 1000 urologists in private practice from 1989 to 1995. At the Midwest Urologic Stone Unit, 9357 stones were treated with ESWL by 200 urologists in private practice from 1987 to 1995. The distribution of stones in both samples was compared with that reported earlier. Results The meta-analysis for stone location trends from the previously published article suggested that the percentage of kidney stones in the lower pole at ESWL increased erratically from 1984 to 1989 but was then stable for 3 years. The Lithotripters Inc. sample showed an essentially constant incidence from 28% in 1990 to 30% in 1995, and the Midwest Urologic Stone Unit sample showed an essentially constant incidence from 35% in 1988 to 36% in 1995. Conclusion The incidence of lower pole nephrolithiasis has remained stable from 1990. [ABSTRACT FROM AUTHOR]

Introduction: Ureteroscopy has dramatically changed the management of ureteral calculi. RIRS provided significantly higher stone-free rate (86.5% vs 67.7%) and lower retreatment rate compared with ESWL (60% vs 8%). Analysis showed that stone size, location, composition, number, renal malformations, and lower pole infundibulopelvic angle had significant influence on the stone-free rate (86%) after RIRS. Material and method: This is a case report study of n = 1. Result: A 48-year-old woman who was admitted into our hospital with bilateral flank pain and fever. Physical examination showed bilateral costovertebral angle tenderness. She was previously treated by ESWL for bilateral kidney stones in 2011 and semi-rigid URS for left ureteral stone in 2013. A non-contrast CT urography was performed, which showed right lower calyceal stones (11.4 × 10.7 mm; 7.4 × 6.6 mm), right distal ureteral stone (18.5 × 5.5 mm), left lower calyceal stones (21.4 × 13.1 mm; 6.6 × 6 mm), left ureterovesico junction stone (3.3 × 1.9 mm). We performed bilateral semi-rigid URS to clean ureteral stones, combine with bilateral RIRS through a ureteral access sheath to disintegrate lower calyceal stones using Ho: YAG wasintroduced the fragments were removed using nitinol tip-less basket. No prior stenting was performed in this patient during the initial assessment of the left pelviocalyces, the lower calyx containing the stone could not be identified. On a more detail inspection, a membrane was found to be covering the lower calyx orifice (Fig. 1), Ho: YAG fulguration was done on this membrane which then revealed already fragmented stones in the minor calyx (Figs 2,3). Conclusion: RIRS could be performed successfully without prior stenting in already dilated ureters due distal ureteral stone obstruction and RIRS could also manage anatomical anomaly which has caused failure of stone clearance during previous ESWL treatment. [ABSTRACT FROM AUTHOR]

Introduction: Staghorn stone disease is still a present challenge in an ever developing urology specialty. Open surgery or percutaneous nephrolithotomy (PCNL) are the standard treatment modalities to treat this particular stone. To undergo these procedures safely a patient needs to have a good cardiac tolerance. Major technological progress has been achieved for retrograde intrarenal surgery [(flexible URS)], with improved deflection mechanisms, better durability, and recently, digital optical systems. Shockwave lithotripsy and RIRS are available treatment modalities for renal calculi. However ESWL and flexible ureterorenoscopy (f-URS) may be preserved specifically to manage smaller and simpler stones. Material and method: This is case report study of n = 1. Result: A 46-year-old man was admitted into our hospital with bilateral flank pains and dyspnea. His serum creatinine at admission was 4.8 mg/dL and uric acid 12.8 mg/dl. A-non contrast CT urography was performed, the result showed right kidney stone (26.1 mm × 15.2 mm) and left kidney stone (36.0 mm × 41.5 mm). his comorbidities included gouty arthritis and congestive heart failure with ejection fraction 20%. His cardiac tolerance to undergo open surgery is classified as high risk. Th us other procedures with less morbidity and quick completion allowance should be considered. Two sessions of ESWL were performed bilaterally without significant disintegration of his stones. Th en bilateral kidney stones disintegration using Holium YAG laser through semirigid URS and JJ stent insertions were performed and followed by bilateral f-URS procedure showed significant disintegration and reduction of his bilateral stone sizes. Two more session of ESWL were performed and a post treatment non contrast CT urography showed that his right kidney has been cleared of stone fragments while residual stone fragments were visible in his right kidney. The whole procedures were performed in a period of 18 months due patient's poor compliance to treatment schedules and uric acid management, his serum uric acid ranged between 9.1-13.4. Conclusion: Multi modalities, multiple sessions of ESWL, URS, and F-URS, can be utilized safely and effectively in this patient with severe cardiac comorbidity, while invasive surgery is considered high risk and ESWL alone could not disintegrate his stones. However patient's compliance is the limiting factor of the success of his treatment. [ABSTRACT FROM AUTHOR]

Objectives To determine if levels of inter-α-trypsin inhibitor (IαTI)-trimer differ in normal individuals based on age, gender or hormonal status, as the regulation of calcium oxalate (CaOx) crystallization inhibitors, e.g. by sex steroids, could be a mechanism contributing to the differences in CaOx urolithiasis between the sexes. Subjects and methods Voided urine samples were collected from normal males and females. In Experiment 1 samples were grouped by gender and age, i.e. paediatric (PED) ≤ 10 years, male (M) 21, female (F) 14; young adult (YGAD) 20–30 years, M 23, F 18; adults (AD), 35–50 year, M 25, F 13; adults aged ≥ 60 years (> 60), M 24, F 16 (totals, M 93, F 61). In Experiment 2 samples were grouped by gender, age and hormonal status, i.e. PED, M 24, F 17; AD, M 24, F 22; > 60 and not on hormonal therapy, M 23, F 30; M > 60 and on androgen deprivation therapy (ANDEP) 18; and F > 60 on oestrogen supplementation, F+EST, 18 (total M 89, F 85). Levels of urinary IαTI-trimer were determined by immunoblotting and enhanced chemiluminescence, and relative densities of the bands determined. Results In both experiments the relative levels of IαTI-trimer were 2–7 times higher in M-PED than in all other groups of males ( P ≤ 0.007). Among adult males, IαTI-trimer levels were similar in all groups, including ANDEP ( P ≥ 0.9). There were no differences in the relative levels of IαTI-trimer among any of the groups of females, regardless of age or hormonal status ( P ≥ 0.7). Conclusions In males a decrease in IαTI-trimer was associated with the onset of adulthood and entry into the ‘stone-forming years’. Females did not show this decrease, and neither sex showed an increase in IαTI-trimer in the > 60 group, when the incidence of CaOx urolithiasis is supposedly declining. While changes in urinary... [ABSTRACT FROM AUTHOR]