Understanding the role of zinc ions on struvite nucleation and growth in the context of infection urinary stones.

Taking into account that in recent decades there has been an increase in the incidence of urinary stones, especially in highly developed countries, from a wide range of potentially harmful substances commonly available in such countries, we chose zinc for the research presented in this article, which is classified by some sources as a heavy metal. In this article, we present the results of research on the influence of Zn2+ ion on the nucleation and growth of struvite crystals-the main component of infection urinary stones. The tests were carried out in an artificial urine environment with and without the presence of Proteus mirabilis bacteria. In the latter case, the activity of bacterial urease was simulated chemically, by systematic addition of an aqueous ammonia solution. The obtained results indicate that Zn2+ ions compete with Mg2+ ions, which leads to the gradual replacement of Mg2+ ions in the struvite crystal lattice with Zn2+ ions to some extent. This means co-precipitation of Mg-struvite (MgNH4PO4·6H2O) and Znx-struvite (Mg1-xZnxNH4PO4·6H2O). Speciation analysis of chemical complexes showed that Znx-struvite precipitates at slightly lower pH values than Mg-struvite. This means that Zn2+ ions shift the nucleation point of crystalline solids towards a lower pH. Additionally, the conducted research shows that Zn2+ ions, in the range of tested concentrations, do not have a toxic effect on bacteria; on the contrary, it has a positive effect on cellular metabolism, enabling bacteria to develop better. It means that Zn2+ ions in artificial urine, in vitro, slightly increase the risk of developing infection urinary stones.

Plasma levels and urinary excretion of protein Z in patients with urolithiasis.

OBJECTIVES: Protein Z (PZ) is a γ-carboxyglutamic acid protein present in plasma that is involved in blood coagulation. Detailed analysis of urinary stones from patients with urolithiasis has revealed that PZ is often found in urinary stones composed of calcium oxalate monohydrate. In this study, we compared blood and urinary PZ concentrations between healthy individuals and patients with urolithiasis. METHODS: Plasma and urine were collected from healthy individuals and patients with urolithiasis who provided informed consent. PZ was detected as a urinary stone matrix protein in some of the patients. PZ was quantified by ELISA, creatinine was measured by the enzymatic method, and the total protein concentration was measured by the Bradford method. RESULTS: The plasma PZ level was 2.54 ± 1.02 µg/mL in healthy individuals and that in urolithiasis patients classified by stone history were from 1.16 ± 0.77 to 3.73 ± 1.09 µg/mL, which was not significantly different. The urinary excretion of PZ (PZ/creatinine) was also not different in patients with urolithiasis and in healthy individuals (from 54.1 ± 40.9 to 95.4 ± 69.4 ng/mg vs. 73.3 ± 36.0 ng/mg). A positive correlation was found between the plasma PZ level and creatinine-corrected urinary PZ concentration (r = 0.46). CONCLUSIONS: Both the plasma level and urinary excretion of PZ in urolithiasis patients were not significantly different with normal individuals. PZ detected in urinary stones as a matrix protein is thought to be incorporated into urinary stones regardless of blood and urine levels of PZ.

Correlation between sKL and Nrf2 plasma levels and calcium oxalate urolithiasis.

OBJECTIVE: To investigate the relationship between plasma levels of sKL and Nrf2 and calcium oxalate calculi. METHODS: The clinical data of 135 patients with calcium oxalate calculi treated in the Department of Urology of the second affiliated Hospital of Xinjiang Medical University from February 2019 to December 2022, and 125 healthy persons who underwent physical examination in the same period were collected and divided into healthy group and stone group. The levels of sKL and Nrf2 were measured by ELISA. Correlation test was used to analyze the risk factors of calcium oxalate stones, logistic regression analysis was used to analyze the risk factors of calcium oxalate stones, and ROC curve was used to evaluate the sensitivity and specificity of sKL and Nrf2 in predicting urinary calculi. RESULTS: Compared with the healthy group, the plasma sKL level in the stone group decreased (111.53 ± 27.89 vs 130.68 ± 32.51), while the plasma Nrf2 level increased (300.74 ± 114.31 vs 246.74 ± 108.22). There was no significant difference in the distribution of age and sex between the healthy group and the stone group, but there were significant differences in plasma levels of WBC, NEUT, CRP, BUN, BUA, SCr, BMI, and eating habits. The results of correlation test showed that the level of plasma Nrf2 was positively correlated with SCr (r = 0.181, P < 0.05) and NEUT (r = 0.144 P < 0.05). Plasma sKL was not significantly correlated with Nrf2 (r = 0.047, P > 0.05), WBC (r = 0.108, P > 0.05), CRP (r = - 0.022, P > 0.05), BUN (r = - 0.115, P > 0.05), BUA (r = - 0.139, P > 0.05), SCr (r = 0.049, P > 0.05), and NEUT (r = 0.027, P > 0.05). Plasma Nrf2 was not significantly correlated with WBC (r = 0.097, P > 0.05), CRP (r = 0.045, P > 0.05), BUN (r = 0.122, P > 0.05), and BUA (r = 0.122, P > 0.05); (r = 0.078, P > 0.05) had no significant correlation. Logistic regression showed that elevated plasma sKL (OR 0.978, 95% CI 0.969 ~ 0.988, P < 0.05) was a protective factor for the occurrence of calcium oxalate stones, BMI (OR 1.122, 95% CI 1.045 ~ 1.206, P < 0.05), dietary habit score (OR 1.571, 95% CI 1.221 ~ 2.020, P < 0.05), and WBC (OR 1.551, 95% CI 1.423 ~ 1.424, P < 0.05). Increased NEUT (OR 1.539, 95% CI 1.391 ~ 1.395, P < 0.05) and CRP (OR 1.118, 95% CI: 1.066 ~ 1.098, P < 0.05) are risk factors for the occurrence of calcium oxalate stones. CONCLUSION: Plasma sKL level decreased and Nrf2 level increased in patients with calcium oxalate calculi. Plasma sKL may play an antioxidant role in the pathogenesis of calcium oxalate stones through Nrf2 antioxidant pathway.

Metabolomic changes in cats with renal disease and calcium oxalate uroliths.

INTRODUCTION: There is a significant incidence of cats with renal disease (RD) and calcium oxalate (CaOx) kidney uroliths in domesticated cats. Foods which aid in the management of these diseases may be enhanced through understanding the underlying metabolomic changes. OBJECTIVE: Assess the metabolomic profile with a view to identifying metabolomic targets which could aid in the management of renal disease and CaOx uroliths. METHOD: This is a retrospective investigation of 42 cats: 19 healthy kidney controls, 11 with RD, and 12 that formed CaOx nephroliths. Cats were evaluated as adults (2 through 7 years) and at the end of life for plasma metabolomics, body composition, and markers of renal dysfunction. Kidney sections were assessed by Pizzolato stain at the end of life for detection of CaOx crystals. CaOx stone presence was also assessed by analysis of stones removed from the kidney at the end of life. RESULTS: There were 791 metabolites identified with 91 having significant (p < 0.05, q < 0.1) changes between groups. Many changes in metabolite concentrations could be explained by the loss of renal function being most acute in the cats with RD while the cats with CaOx stones were intermediate between control and RD (e.g., urea, creatinine, pseudouridine, dimethylarginines). However, the concentrations of some metabolites differentiated RD from CaOx stone forming cats. These were either increased in the RD cats (e.g., cystathionine, dodecanedioate, 3-(3-amino-3-carboxypropyl) uridine, 5-methyl-2'-deoxycytidine) or comparatively increased in the CaOx stone forming cats (phenylpyruvate, 4-hydroxyphenylpyruvate, alpha-ketobutyrate, retinal). CONCLUSIONS: The metabolomic changes show specific metabolites which respond generally to both renal diseases while the metabolomic profile still differentiates cats with RD and cats with CaOx uroliths.

Subcutaneous Adipose Tissue Accumulation Is an Independent Risk Factor of Urinary Stone in Young People.

Background: Urinary stones usually start at a young age and tend to recur. Therefore, preventing stone occurrence and recurrence in young people is crucial. We aimed to investigate the association between subcutaneous adipose tissue, visceral adipose tissue, and stone episodes in young people. Methods: We retrospectively studied patients aged below 40 years with kidney or ureteral stones. Data on demographic and metabolic characteristics, urolithiasis history, subcutaneous fat area (SFA), and visceral fat area (VFA) were collected. We evaluated the association between SFA or VFA and the occurrence or recurrence of stone episodes using binary logistic regression and Poisson regression analyses. Results: In total, 120 patients were included. Abdominal obesity, overweight or obesity, dyslipidemia, metabolic syndrome, SFA, and VFA increased with the number of stone episodes (all p < 0.05). The increase in SFA was independently associated with episode occurrence (p = 0.015). Patients with an SFA > 97 cm2 had a higher risk of episode occurrence. SFA and VFA accumulation were independently associated with episode recurrence (all p < 0.05), and SFA had a stronger association than VFA did. Conclusions: In young people, SFA accumulation is an independent and early risk factor for the occurrence and recurrence of stone episodes. Subcutaneous fat could be a convenient and effective indicator to assess the risk of stone episodes before the development of metabolic disorders.

Xanthine Oxidoreductase Inhibitors Suppress the Onset of Exercise-Induced AKI in High HPRT Activity Urat1-Uox Double Knockout Mice.

BACKGROUND: Hereditary renal hypouricemia type 1 (RHUC1) is caused by URAT1/SLC22A12 dysfunction, resulting in urolithiasis and exercise-induced AKI (EIAKI). However, because there is no useful experimental RHUC1 animal model, the precise pathophysiologic mechanisms underlying EIAKI have yet to be elucidated. We established a high HPRT activity Urat1-Uox double knockout (DKO) mouse as a novel RHUC1 animal model for investigating the cause of EIAKI and the potential therapeutic effect of xanthine oxidoreductase inhibitors (XOIs). METHODS: The novel Urat1-Uox DKO mice were used in a forced swimming test as loading exercise to explore the onset mechanism of EIAKI and evaluate related purine metabolism and renal injury parameters. RESULTS: Urat1-Uox DKO mice had uricosuric effects and elevated levels of plasma creatinine and BUN as renal injury markers, and decreased creatinine clearance observed in a forced swimming test. In addition, Urat1-Uox DKO mice had increased NLRP3 inflammasome activity and downregulated levels of Na+-K+-ATPase protein in the kidney, as Western blot analysis showed. Finally, we demonstrated that topiroxostat and allopurinol, XOIs, improved renal injury and functional parameters of EIAKI. CONCLUSIONS: Urat1-Uox DKO mice are a useful experimental animal model for human RHUC1. The pathogenic mechanism of EIAKI was found to be due to increased levels of IL-1ß via NLRP3 inflammasome signaling and Na+-K+-ATPase dysfunction associated with excessive urinary urate excretion. In addition, XOIs appear to be a promising therapeutic agent for the treatment of EIAKI.

Effect of magnesium ammonium phosphate on the expression of adhesion molecules in sheep renal tubular epithelial cells.

Adhesion molecules play an important role in urinary calculus formation. The expressions of adhesion molecules in renal tubular has been reported in some animals. However, the role of adhesion molecules in the process of sheep urinary calculus formation is still unclear. The magnesium ammonium phosphate (MAP) is the main component of sheep urinary calculus. In this paper, the sheep renal tubular epithelial cells (RTECs) were isolated and treated with MAP, the expressions of osteopontin (OPN), intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and apoptosis-related indicators caspase-3, Bcl-2 and Bax in RTECs were observed, the viability of RTECs was detected by Cell Counting Kit-8 (CCK-8). The levels of superoxide dismutase (SOD) and malondialdehyde (MDA), and the expressions of inflammatory factors Interleukin-6 (IL-6), Interleukin-1 (IL-1), Interleukin-17 (IL-17) and tumor necrosis factor-α (TNF-α) were measured by enzyme-linked immunosorbent (ELISA). The histopathological observation of kidney in urolithiasis sheep was made. The results showed that MAP could reduce the viability and SOD activity, enhance the activity of MDA significantly and promote the expressions of IL-1, IL-6, IL-17 and TNF-α of RTECs. By western blot and qPCR methods, the expressions of ICAM-1, VCAM-1 and OPN increased in 48 h. In addition, the expression of caspase-3 increased significantly and the ratio of Bcl-2/Bax reduced with exposure to MAP. The renal tissue structure was seriously damaged, the RTECs in urolithiasis sheep were degenerative and necrotic.

1,3,5,6-tetrahydroxyxanthone promotes diuresis, renal protection and antiurolithic properties in normotensive and hypertensive rats.

OBJECTIVES: This study investigated the prolonged diuretic and renal effects of 1,3,5,6- tetrahydroxyxanthone (THX) in rats. METHODS: Normotensive (NTR) and hypertensive rats (SHR) received orally the treatment with THX, hydrochlorothiazide or vehicle (VEH). Urine volume, urinary, plasma and kidney parameters were evaluated daily or at the end of 7 days of the experiment. KEY FINDINGS: The urinary volume of both NTR and SHR were significantly augmented with the THX treatment, an effect associated with increased levels of urinary Na+ and K+, besides a Ca2+-sparing effect. As well, THX decreased the quantity of monohydrate crystals in urines from NTR and SHR when compared with VEH-group. Regarding the renal analyses, the glutathione levels and the activities of superoxide dismutase, glutathione S-transferase and myeloperoxidase in kidney homogenates of the SHR group were decreased. In contrast, the generation of lipid hydroperoxides (LOOH) and catalase activity was significantly increased. THX reduced the content of LOOH and increased nitrite levels in kidney homogenates obtained from SHR. Additionally, THX also augmented the levels of nitrite in the plasma from the SHR group. CONCLUSIONS: Therefore, THX can be highlighted as a natural diuretic agent with renal protective properties and antiurolithic action.

Transplantation of a kidney with a heterozygous mutation in the SLC22A12 (URAT1) gene causing renal hypouricemia: a case report.

BACKGROUND: Renal hypouricemia (RHUC) is a genetic disorder caused by mutations in the SLC22A12 gene, which encodes the major uric acid (UA) transporter, URAT1. The clinical course of related, living donor-derived RHUC in patients undergoing kidney transplantation is poorly understood. Here, we report a case of kidney transplantation from a living relative who had an SLC22A12 mutation. After the transplantation, the recipient's fractional excretion of UA (FEUA) decreased, and chimeric tubular epithelium was observed. CASE PRESENTATION: A 40-year-old man underwent kidney transplantation. His sister was the kidney donor. Three weeks after the transplantation, he had low serum-UA, 148.7 µmol/L, and elevated FEUA, 20.8% (normal: < 10%). The patient's sister had low serum-UA (101.1 µmol/L) and high FEUA (15.8%) before transplant. Suspecting RHUC, we performed next-generation sequencing on a gene panel containing RHUC-associated genes. A heterozygous missense mutation in the SLC22A12 gene was detected in the donor, but not in the recipient. The recipient's serum-UA level increased from 148.7 µmol/L to 231.9 µmol/L 3 months after transplantation and was 226.0 µmol/L 1 year after transplantation. His FEUA decreased from 20.8 to 11.7% 3 months after transplantation and was 12.4% 1 year after transplantation. Fluorescence in situ hybridization of allograft biopsies performed 3 months and 1 year after transplantation showed the presence of Y chromosomes in the tubular epithelial cells, suggesting the recipient's elevated serum-UA levels were owing to a chimeric tubular epithelium. CONCLUSIONS: We reported on a kidney transplant recipient that developed RHUC owing to his donor possessing a heterozygous mutation in the SLC22A12 (URAT1) gene. Despite this mutation, the clinical course was not problematic. Thus, the presence of donor-recipient chimerism in the tubular epithelium might positively affect the clinical course, at least in the short-term.

Dietary risk factors for urinary stones in children.

PURPOSE OF REVIEW: As the incidence of urinary stone disease in children is increasing, identifying dietary risk factors becomes vitally important, especially in the context of targeting interventions to reduce risk for stone formation. Indiscriminant dietary restrictions are not appropriate for paediatric patients. RECENT FINDINGS: Although large, prospective studies are still needed to better quantify dietary risk factors for paediatric stone formers, a number of smaller studies provide data to identify common risk factors to help prevent stone formation, while minimizing inappropriate dietary restrictions. SUMMARY: Interpretation of 24-h urine samples to identify individualized dietary risk factors is crucial for implementing a strategy for prevention of further urinary stone formation in children. Clinicians should avoid generalized dietary restrictions in stone-forming children uninformed by laboratory data.

Diagnostic accuracy of dual-energy computed tomography (DECT) to differentiate uric acid from non-uric acid calculi: systematic review and meta-analysis.

BACKGROUND: Uric acid stone diagnosis is presently done primarily with in vitro analysis of stones. In vivo diagnosis with dual-energy CT (DECT) would allow earlier initiation of therapy with urine alkalinization and avoid surgical intervention. OBJECTIVE: To evaluate if DECT, using stone analysis as reference standard, is sufficiently accurate to replace stone analysis for diagnosis of uric acid stones. METHODS: Original studies in patients with urolithiasis examined with DECT with stone analysis as the reference standard were eligible for inclusion. MEDLINE (1946-2018), Embase (1947-2018), CENTRAL (August 2018), and multiple urology and radiology conferences were searched. QUADAS-2 was used to assess risk of bias and applicability. Meta-analyses were performed using a bivariate random-effects model. RESULTS: A total of 21 studies (1105 patients, 1442 stones) were included. Fourteen studies containing 662 patients (944 stones) were analyzed in the uric acid dominant target condition (majority of stone composition uric acid): mean sensitivity was 0.88 (95% CI 0.79-0.93) and specificity 0.98 (95% CI 0.96-0.99). Thirteen studies (674 patients, 760 stones) were analyzed in the uric acid-containing target condition (< majority of stone composition uric acid): mean sensitivity was 0.82 (95% CI 0.73-0.89) and specificity 0.97 (95% CI 0.94-0.98). Meta-regression showed no significant variability in test accuracy. Two studies had one or more domains at high risk of bias and there were no concerns regarding applicability. CONCLUSION: DECT is an accurate replacement test for diagnosis of uric acid calculi in vivo, such that stone analysis could be replaced in the diagnostic pathway. This would enable earlier initiation of urine alkalinization. KEY POINTS: • DECT for uric acid dominant stones has sensitivity of 0.88 (95% CI 0.79-0.93) and specificity of 0.98 (95% CI 0.96-0.99); uric acid-containing stones had mean sensitivity of 0.82 (95% CI 0.73-0.89) and specificity of 0.97 (95% CI 0.94-0.98). • Meta-regression did not identify any variables (study design, reference standard, dual-energy CT type, dose, risk of bias) that influenced test accuracy. • Only 2 of the 21 included studies had 1 or more domain considered to be at high risk of bias with the majority of domains considered at low risk of bias; there were no concerns regarding applicability in any of the included studies.

The Impact of Glycosylation of Osteopontin on Urinary Stone Formation.

Osteopontin (OPN) is a matrix glycoprotein of urinary calculi. This study aims to identify the role of aberrant glycosylation of OPN in urolithiasis. We retrospectively measured urinary glycosylated OPN normalized by urinary full-length-OPN levels in 110 urolithiasis patients and 157 healthy volunteers and 21 patients were prospectively longitudinal follow-up during stone treatment. The urinary full-length-OPN levels were measured using enzyme-linked immunosorbent assay and glycosylated OPN was measured using a lectin array and lectin blotting. The assays were evaluated using the area under the receiver operating characteristics curve to discriminate stone forming urolithiasis patients. In the retrospective cohort, urinary Gal3C-S lectin reactive- (Gal3C-S-) OPN/full-length-OPN, was significantly higher in the stone forming urolithiasis patients than in the healthy volunteers (p < 0.0001), with good discrimination (AUC, 0.953), 90% sensitivity, and 92% specificity. The Lycopersicon esculentum lectin analysis of urinary full-length-OPN showed that urinary full-length-OPN in stone forming urolithiasis patients had a polyLacNAc structure that was not observed in healthy volunteers. In the prospective longitudinal follow-up study, 92.8% of the stone-free urolithiasis group had Gal3C-S-OPN/full-length-OPN levels below the cutoff value after ureteroscopic lithotripsy (URS), whereas 71.4% of the residual-stone urolithiasis group did not show decreased levels after URS. Therefore, Gal3C-S-OPN/full-length-OPN levels could be used as a urolithiasis biomarker.

Idiopathic renal hypouricemia: A case report and literature review.

Idiopathic renal hypouricemia is a rare hereditary condition. Type 2 renal hyperuricemia (RHUC2) is caused by a mutation in the SLC2A9 gene, which encodes a high­capacity glucose and urate transporter, glucose transporter (GLUT)9. RHUC2 predisposes to exercise­induced acute renal failure (EIARF) and nephrolithiasis, which is caused by a defect in renal tubular urate transport and is characterized by increased clearance of renal uric acid. In the present study a case of a 35­year­old Chinese man with EIARF is reported. The patient had isolated renal hypouricemia, with a serum uric acid level of 21 µmol/l and a fractional excretion of uric acid of 200%. The mutational analysis revealed a homozygous mutation (c.857G>A in exon 8) in the SLC2A9 gene. The patient's family members carried the same mutation, but were heterozygous and clinically asymptomatic. In conclusion, to the best of our knowledge, this is the first report of a RHUC2 patient with a GLUT9 mutation, p.W286X, which may be a pathogenic mutation of RHUC2. Further investigation into the functional role of GLUT9 in this novel SLC2A9 mutation is required.

Ureteral Stone Mimicking Abnormal Sacral Uptake on 99mTc MDP Bone Scintigraphy: The Usefulness of SPECT/CT.

Bone tracer uptake related to ureteral stones has been reported several times before. We present a right ureteral stone mimicking abnormal focal sacral uptake on planar scan in a patient with rectal cancer. This case highlights the necessity of performing SPECT/CT to ascertain the origin of abnormal focal sacral uptake on planar scan, especially in patients with a history of kidney stones.

Determination of urinary stone composition using biochemical analysis of fluid samples taken during ureterorenoscopic laser lithotripsy.

PURPOSE: The present study aims to biochemically analyze the fluid samples containing stone dust taken during the perioperative period to determine the role of fluid in the prediction of stones in patients treated with ureterorenoscopic procedures. Our secondary aim is to investigate the role of both fluid analysis and stone analysis in predicting the results of the metabolic analysis. METHODS: Comparative analyses were performed using fluid samples containing stone dust from 93 patients. Biochemical analysis of fluid containing stone dust was conducted; stone fragments were examined at a separate location using X-ray diffractometry(XRD). Metabolic analysis was performed to patients who provided stone-free status 1 month later. The results of chemical analysis were compared with the results of the XRD analysis. RESULTS: Patients' stone type was determined with high accuracy using biochemical analysis. Differences were noted in ten patients following biochemical analysis and XRD analysis. Biochemical analysis predicted metabolic disorders in more patients than XRD analysis, particularly for those patients with multiple stone compositions. However, no significant differences between the results of biochemical and XRD analysis methods were found (κ = 0.27; p = 0.002). Moreover, biochemical analysis results revealed metabolic disorders in five patients; these findings were missed by XRD analysis. CONCLUSION: Biochemical analysis of fluid taken perioperatively during ureterorenoscopic laser lithotripsy to treat urinary system stone disease was found to determine stone composition with high accuracy. Biochemical analysis of fluid samples taken during the perioperative period is, thus, an easy, reliable and cost-effective test to assess stone composition in patients undergoing ureterorenoscopic procedures.

Metabolic evaluation: who, when and how often.

PURPOSE OF REVIEW: To summarize recommendations of the guidelines of the American Urological Association and European Association of Urology, and our opinion on which urinary tract stone disease patients should be metabolically evaluated at which moment and how often. RECENT FINDINGS: A standard metabolic evaluation should be performed in all stone formers to prevent recurrent disease. This includes a medical and lifestyle history, physical examination, basic urine and blood analysis, radiological examination and stone analysis. The latter should already be performed during surgery, especially when only a couple of fragments are sent for analysis. Supplementary, performing a 24-h urine analysis should be supported in all patients to understand the lithogenic process that will guide the according follow-up. When risk factors are found, an extended individualized metabolic evaluation should be performed to exclude underlying metabolic diseases and to start stone-specific recurrence prevention. SUMMARY: Urologists should be trained in perioperative stone characterization, because it contains information of urinary environment at the times of stone formation and growth. The extensiveness and frequency of metabolic work-up and follow-up of stone formers should be tailored to the type of stone, severity of the disease, patient's comorbidities and medications.

Fragmentación dirigida a discontinuidades preferentes: un nuevo concepto en endolitotricia con láser Holmium:YAG / Fragmentation targeted at preferred discontinuities: A new concept in endolithotripsy with Holmium laser:YAG

Introducción: En la actualidad existen 3 modalidades técnicas de endolitotricia con láser Holmium:YAG (Ho:YAG) consideradas básicas (fragmentación, pulverización, "pop-corn"). Presentamos la técnica de fragmentación dirigida por discontinuidades preferentes (FDDP), un nuevo concepto de endolitotricia con láser Ho:YAG. Material y métodos: La técnica de FDDP se basa en la aplicación selectiva (dirigida a un punto concreto preseleccionado) de la energía sobre una zona visualmente proclive a la formación de una línea de fractura o discontinuidad preferente (condicionada por la anisotropía de la urolitiasis). El régimen energético (setting) idóneo consiste en un elevado rango de energía de trabajo (2-3J) con un muy bajo rango de frecuencia (5-8 Hz) y pulso de amplitud corta. Entre enero del 2015 y febrero del 2017 se ha realizado la técnica de FDDP en 37 procedimientos (7 NLP, 16 RIRS, 12 URS, 2 cistolitotomía), con un láser Ho:YAG (Lumenis Pulse 120H(R), Tel-Aviv, Israel). Potencia máxima empleada: 24 W (3 J/8Hz) con fibras de 365 y 273 mi. (URS, RIRS), y 32 W (4 J/8Hz) con fibras de 550 mi. (NLP, cistolitotomía). Resultados: Con técnica de FDDP se obtuvo en todos los casos una mejora estratégica para continuar la endolitotricia o extraer fragmentos. No se registraron complicaciones derivadas de la aplicación de esta modalidad. Conclusiones: La FDDP puede ser considerada como una opción complementaria en combinación con las modalidades básicas de fragmentación y pulverización. En nuestra experiencia, significa un avance para optimizar el rendimiento de la endolitotricia con láser Ho:YAG

Introduction: There are currently 3holmium laser, YAG (Ho:YAG) endolithotripsy procedures that are considered basic (fragmentation, pulverisation, "pop-corn" technique). We present the technique of fragmentation targeted at preferred discontinuities (FTPD), a new concept of endolithotripsy by Ho:YAG laser. Material and methods: The FTPD technique is based on the selective application of energy (targeting a specific preselected point) to an area that is visually prone to the formation of a fracture line or preferred discontinuity (conditioned by the anisotropy of the urolithiasis). The ideal energy regimen (setting) is a high range of working energy (2-3J) with a very low frequency range (5-8Hz) and short pulse width. Between January 2015 to February 2017, the FTPD technique was used in 37 procedures (7 NLP, 16 RIRS, 12 URS, 2 cystolithotomies), with a Ho:YAG laser (Lumenis Pulse 120H (R), Tel-Aviv, Israel). Maximum power used: 24W (3J/8Hz) with fibres of 365 mi. and 273 mi. (URS, RIRS), and 32W (4J/8Hz) with fibres of 550 mi. (NLP, cystolithotomy). Results: Strategic improvement was achieved in all cases using the TFPD technique to continue the endolithotripsy or remove fragments. No complications were recorded after the use of this method. Conclusions: FTPD can be considered a complementary option in combination with the basic methods of fragmentation and pulverisation. In our experience, it constitutes significant progress in optimising the performance of Ho:YAG laser endolithotripsy

Urinary tract stones in cystic fibrosis.

Urinary tract stones are a common problem in a general population but increasingly so in cystic fibrosis (CF) patients as survival improves. Mechanisms of stone formation are discussed, particularly those unique to CF patients. Modalities of treatment and the decision making process in this choice is outlined as well as possible future preventative strategies.

Renal hypouricemia caused by novel compound heterozygous mutations in the SLC22A12 gene: a case report with literature review.

BACKGROUND: Renal hypouricemia (RHUC) is a heterogeneous genetic disorder that is characterized by decreased serum uric acid concentration and increased fractional excretion of uric acid. Previous reports have revealed many functional mutations in two urate transporter genes, SLC22A12 and/or SLC2A9, to be the causative genetic factors of this disorder. However, there are still unresolved patients, suggesting the existence of other causal genes or new mutations. Here, we report an RHUC patient with novel compound heterozygous mutations in the SLC22A12 gene. CASE PRESENTATION: A 27-year-old female presenting with recurrent hypouricemia during routine checkups was referred to our hospital. After obtaining the patient's consent, both the patient and her healthy parents were analyzed using whole-exome sequencing (WES) and Sanger sequencing to discover and validate causal mutations, respectively. The prioritization protocol of WES screened out two mutations of c.269G > A/p.R90H and c.1289_1290insGG/p.M430fsX466, which are both located in the SLC22A12 gene, in the patient. Sanger sequencing further confirmed that the patient's heterozygous c.269G > A/p.R90H mutation, which has been reported previously, derived from her mother, and the heterozygous c.1289_1290insGG/p.M430fsX466 mutation, which was found for the first time, derived from her father. p.R90H, which is highly conserved among different species, may decrease the stability of this domain and was considered to be almost damaging in silicon analysis. p.M430fsX466 lacks the last three transmembrane domains, including the tripeptide motif (S/T)XΦ (X = any amino acid and Φ = hydrophobic residue), at the C-terminal, which interact with scaffolding protein PDZK1 and thus will possibly lead to weak functioning of urate transport through the disruption of the "transporter complex" that is formed by URAT1 and PDZK1. CONCLUSIONS: We report a Chinese patient with RHUC, which was caused by compound heterozygous mutations of the SLC22A12 gene, using WES and Sanger sequencing for the first time. Mutation-induced structural instability or malfunction of the urate transporter complex may be the main mechanisms for this hereditary disorder.

Cuantificación del riesgo de formación de cálculos cálcicos en la orina correspondiente a 2 momentos del día en un grupo de niños estudiados para descartar prelitiasis / Quantification of the risk of urinary calcium stone formation in the urine collected at 2 times of the day in a group of children studied to rule out prelithiasis

ANTECEDENTES: En la urolitiasis inte:rvienen diversos factores genéticos y ambientales. Las 2 anomalías metabólicas más frecuentes son el incremento en la eliminación urinaria de calcio y la reducción en la de citrato. El cociente calculado entre las concentraciones de ambas sustancias es un buen marcador de riesgo de formación de cálculos cálcicos. OBJETIVOS: Determinar si el riesgo litógeno en la orina de un mismo paciente cambia a lo largo del día. MÉTODOS: Se estudiaron 56 niños (23 V, 33 M) para comprobar si eran portadores de prelitiasis. Se determinaron las concentraciones de calcio, citrato y creatinina en 2 muestras de orina recogidas, una, antes de cenar, y la otra, por la mañana, al levantarse. Se anotó si tenían cálculos ecográficos y si existían antecedentes de urolitiasis en los familiares de primer y/o segundo grado. RESULTADOS: En 25 pacientes (44,6%) la ecografía renal fue positiva para litiasis (cálculos [n = 9] y microcálculos [n = 16]). En 40 de las 56 familias (71,4%) existían antecedentes de urolitiasis. El porcentaje mayor de valores anormales de la concentración urinaria de calcio (28,6%) y del cociente calcio/citrato (69,6%) correspondió a la primera orina del día. Este último parámetro fue el único entre los estudiados que se relacionó con los antecedentes familiares de urolitiasis. No se comprobaron diferencias en los parámetros urinarios al comparar a los pacientes con presencia o ausencia de litiasis renal ecográfica. CONCLUSIONES: Las concentraciones urinarias de calcio y del cociente calcio/citrato se modifican a lo largo del día. Las orinas formadas durante la noche son más litógenas

BACKGROUND: Various genetic and environmental factors are involved in urolithiasis. The 2 most common metabolic abnormalities are the increase in urinary calcium and low urinary citrate excretion. The ratio calculated between the concentrations of both substances is a good risk marker for the formation of calcium stones. OBJECTIVES: To determine whether the risk of urinary calcium stone formation changes throughout the day in the same patient. METHODS: We studied 56 children (23 V, 33 M) to check if they had prelithiasis. Calcium, citrate, and creatinine concentrations were determined in two urine samples collected one before dinner and the other in the morning. It was collected if they had ultrasound stones and if there was a history of urolithiasis in first and/or second degree relatives. RESULTS: In 25 patients (44.6%), renal ultrasound was positive for lithiasis (stones [n = 9] and microlithiasis [n = 16]). Forty of the 56 families (71.4%) had a history of urolithiasis. The percentage of abnormal urinary calcium (28.6%) concentrations and an abnormal calcium/citrate ratio (69.6%) was higher in the first urine of the day. The calcium/citrate ratio was the only studied parameter that was related to a family history of urolithiasis. There were no differences in urinary parameters between patients with and without ultrasound-confirmed kidney stones. CONCLUSIONS: Urinary concentrations of calcium and the calcium/citrate ratio vary throughout the day. Urine produced at night has a higher risk of urinary calcium stone formation