[Uric Acid Metabolism, Uric Acid Transporters and Dysuricemia].

Serum urate levels are determined by the balance between uric acid production and uric acid excretion capacity from the kidneys and intestinal tract. Dysuricemia, including hyperuricemia and hypouricemia, develops when the balance shifts towards an increase or a decrease in the uric acid pool. Hyperuricemia is mostly a multifactorial genetic disorder involving several disease susceptibility genes and environmental factors. Hypouricemia, on the other hand, is caused by genetic abnormalities. The main genes involved in dysuricemia are xanthine oxidoreductase, an enzyme that produces uric acid, and the urate transporters urate transporter 1/solute carrier family 22 member 12 (URAT1/SLC22A12), glucose transporter 9/solute carrier family 2 member 9 (GLUT9/SLC2A9) and ATP binding cassette subfamily G member 2 (ABCG2). Deficiency of xanthine oxidoreductase results in xanthinuria, a rare disease with marked hypouricemia. Xanthinuria can be due to a single deficiency of xanthine oxidoreductase or in combination with aldehyde oxidase deficiency as well. The latter is caused by a deficiency in molybdenum cofactor sulfurase, which is responsible for adding sulphur atoms to the molybdenum cofactor required for xanthine oxidoreductase and aldehyde oxidase to exert their action. URAT1/SLC22A12 and GLUT9/SLC2A9 are involved in urate reabsorption and their deficiency leads to renal hypouricemia, a condition that is common in Japanese due to URAT1/SLC22A12 deficiency. On the other hand, ABCG2 is involved in the secretion of urate, and many Japanese have single nucleotide polymorphisms that result in its reduced function, leading to hyperuricemia. In particular, severe dysfunction of ABCG2 leads to hyperuricemia with reduced extrarenal excretion.

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.

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.

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.

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.

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.

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.

24 Hour urine metabolic differences between solitary and multiple stone formers: Results of the Collaboration on Urolithiasis in Pediatrics (CUP) working group.

INTRODUCTION: Specific factors associated with the risk of developing pediatric urinary stone disease remain unclear, especially those that may be associated with recurrent stone disease. OBJECTIVE: We compared the results of 24-h urine collections in children with a solitary stone episode to those with multiple stone episodes to determine if there is a difference that may be associated with multiple stone formation in children. STUDY DESIGN: A multi-institutional retrospective analysis was completed to assess 24-h urinary metabolic profiles in children with urolithiasis aged 2-18 years old. Differences in mean urine collections between the two groups were assessed using chi-square tests to test the associations among gender, stone type, and multiple stone status, as well as multivariate analyses using general linear models. RESULTS: We analyzed 142 solitary stone patients and 136 multiple stone patients from four centers were included. Multiple stone patients were older than solitary stone patients (mean 13.4 ± 3.6 years vs. 12 ± 3.9 years, p = 0.002). Females were more likely to have multiple stones (58% vs. 39%, p = 0.002). BMI was not associated with multiple stones (p = 0.8467). Multiple stone formers had lower urine volumes, although this did not reach statistical significance when compared with solitary stone formation (20.4 mL/kg/day ± 11.5 vs. 22.9 ± 13.0, p = 0.0880). Higher values for super-saturation of calcium oxalate were associated with multiple stone disease in univariate (p = 0.0485) and multivariate analysis (p = 0.0469) (Figure). Centers located in the Southeast of the United States saw a higher proportion of children with multiple stones (Tennessee 62.7%, Virginia 44.4%, Oregon 31.6%, Michigan 27.3%, p < 0.0001). DISCUSSION: In a large multi-institutional retrospective analysis we found that multiple stone disease was associated with higher super-saturations of calcium oxalate. Many urinary parameters changed with patient age, highlighting that the values should be interpreted with respect to patient age. The inability to comment on follow-up because of the nature of our dataset is a limitation of this study. CONCLUSION: Multiple stone disease in children is associated with higher super-saturation calcium oxalate, while lower urinary volume may also be associated with multiple stones; however, further study is required. Early metabolic evaluation may help risk stratify children likely to form multiple stones.

Urat1-Uox double knockout mice are experimental animal models of renal hypouricemia and exercise-induced acute kidney injury.

Renal hypouricemia (RHUC) is a hereditary disease characterized by a low level of plasma urate but with normal urinary urate excretion. RHUC type 1 is caused by mutations of the urate transporter URAT1 gene (SLC22A12). However, the plasma urate levels of URAT1 knockout mice are no different from those of wild-type mice. In the present study, a double knockout mouse, in which the URAT1 and uricase (Uox) genes were deleted (Urat1-Uox-DKO), were used as an experimental animal model of RHUC type 1 to investigate RHUC and excise-induced acute kidney injury (EIAKI). Mice were given a variable content of allopurinol for one week followed by HPLC measurement of urate and creatinine concentrations in spot urine and blood from the tail. The urinary excretion of urate in Urat1-Uox-DKO mice was approximately 25 times higher than those of humans. With allopurinol, the plasma urate levels of Urat1-Uox-DKO mice were lower than those of Uox-KO mice. There were no differences in the urinary urate excretions between Urat1-Uox-DKO and Uox-KO mice administered with 9 mg allopurinol /100 g feed. In the absence of allopurinol, plasma creatinine levels of some Urat1-Uox-DKO mice were higher than those of Uox-KO mice. Consequently, hypouricemia and normouricosuria may indicate that the Urat1-Uox-DKO mouse administered with allopurinol may represent a suitable animal model of RHUC type 1. Urat1-Uox-DKO mice without allopurinol exhibited acute kidney injury, thus providing additional benefit as a potential animal model for EIAKI. Finally, our data indicate that allopurinol appears to provide prophylactic effects for EIAKI.

High (18)F-FDG uptake in urinary calculi on PET/CT: An unrecognized non-malignant accumulation.

AIM: To assess the high (18)F-fluorodeoxyglucose ((18)F-FDG) uptake in urinary calculi on positron-emission tomography/computed tomography (PET/CT). METHODS: In this study, (18)F-FDG PET/CT examinations were retrospectively reviewed from November 2013 to February 2016 in a single center, and patients with high (18)F-FDG uptake in urinary calculi were identified. The following data were collected from each patient, including age, sex, primary disease, method to verify the urinary calculus, and imaging characteristics of the calculus. RESULTS: A total of 2758 PET/CT studies (2567 patients) were reviewed, and 52 patients with urinary calculi were identified, in which 6 (11.5%, 6/52) patients (5 males, 1 female, age 34-73 years, median age 60.5 years) demonstrated high (18)F-FDG uptake in the urinary calculi. Among the 6 patients, 3 patients had bladder calculi, 2 patients had renal calculi, and 1 patient had both bladder and renal calculi. The size of the urinary calculi varied from sandy to 19mm on CT. The maximal Hounsfield units of the calculi ranged from 153 to 1078. The SUVmax of the calculi on the routine PET/CT scan ranged from 11.7 to 143.0. Delayed PET/CT scans were performed on 4 patients, which showed the calculi SUVmax increasing in 2 patients, while decreasing in the other 2 patients. One patient with bladder calculus underwent a follow-up PET/CT, which showed enlargement of the calculus as well as the increased SUVmax. CONCLUSION: This study shows an uncommon high (18)F-FDG uptake in urinary calculi. Recognition of this non-malignant accumulation in urinary calculi is essential for correct interpretation of PET/CT findings.

Urinary stone composition in Oman: with high incidence of cystinuria.

Urinary stones are a common problem in Oman and their composition is unknown. The aim of this study is to analyze the components of urinary stones of Omani patients and use the obtained data for future studies of etiology, treatment, and prevention. Urinary stones of 255 consecutive patients were collected at the Sultan Qaboos University Hospital. Stones were analyzed by Fourier transform infrared spectrophotometer. The biochemical, metabolic, and radiological data relating to the patients and stones were collected. The mean age was 41 years, with M:F ratio of 3.7:1. The common comorbidities associated with stone formation were hypertension; diabetes, benign prostate hyperplasia; urinary tract infection; obesity; and atrophic kidney. The common presentation was renal colic and flank pain (96%). Stones were surgically retrieved in 70% of patients. Mean stone size was 9 ± 0.5 mm (range 1.3-80). Stone formers had a BMI ≥ 25 in 56% (P = 0.006) and positive family history of stones in 3.8%. The most common stones in Oman were as follows: Calcium Oxalates 45% (114/255); Mixed calcium phosphates & calcium oxalates 22% (55/255); Uric Acid 16% (40/255); and Cystine 4% (10/255). The most common urinary stones in Oman are Calcium Oxalates. Overweight is an important risk factor associated with stone formation. The hereditary Cystine stones are three times more common in Oman than what is reported in the literature that needs further genetic studies.

In vitro studies of epithelium-associated crystallization caused by uropathogens during urinary calculi development.

Infectious urinary stones account for about 10% of all urinary stones. In 50% of cases urolithiasis is a recurrent illness, which can lead to the loss of a kidney if not properly treated. One of the reasons for recurrence of the disease may be the ability of bacteria to invade urothelial cells, persist in the host cells and serve as potential reservoirs for infection. Various uropathogens are associated with the formation of bacteria-induced urinary stones but Proteus mirabilis is the most commonly isolated (70%). An in vitro model was used in this study to analyze intracellular growth and crystallization in the presence of P. mirabilis, Klebsiella pneumoniae and Escherichia coli. Human ureter (Hu 609) and bladder (HCV 29) epithelial cell lines were infected with bacteria and incubated (3-72 h) in the presence of synthetic urine and amikacin to prevent extracellular bacterial growth. During the incubation the number of bacteria (CFU/ml) inside epithelial cells and the intensity of crystallization were established. Crystallization was determined as an amount of a calcium radioisotope. The chosen strains of uropathogens were able to invade both types of epithelial cells but the Hu 609 cells were invaded to a higher extent. However, crystallization occurred only in the presence of P. mirabilis strains which were invasive and urease-positive. The highest intensity of cell-associated crystallization was observed when the number of bacteria within the urothelium remained stable during the time of incubation. These results show that P. mirabilis has an ability to form crystals inside the host cells. Under these conditions bacteria are protected from antibiotic killing, which leads to persistent and recurrent infections. We also suspect that this phenomenon may be an important stage of kidney stones formation.

Bilateral urinary calculi with discordant stone composition.

OBJECTIVES: To describe a cohort of bilateral stone formers with significantly different compositions between renal units. METHODS: Patients treated for bilateral nephrolithiasis over a 4-year period (2007-2010) were identified. Stones were categorized by dominant (≥50%) mineralogical component. Patients with significant compositional differences between renal units (discordant stone formers) were compared to patients with a similar stone type in each kidney. RESULTS: Fifteen of the 59 bilateral stone formers (25.4%) were discordant stone formers with significant differences in stone composition between renal units. Forty-four of the 59 patients (74.6%) had the same stone composition on each side. Thirty percent of discordant stones had calcium phosphate as the dominant stone component. Discordant stone formers were younger, had better renal function, and tended to have a larger stone burden (p < 0.05). CONCLUSIONS: A significant minority of bilateral stone formers form a different type of stone in each kidney. Local or micro-environmental etiologies may explain this phenomenon and may also account for failure of preventive therapy in some patients.

[Hormonal and metabolic disorders as systemic factor for the formation of urinary calculi].

In patients suffering from urolithiasis, metabolic diagnostics often reveals abnormalities contributing to the formation of stones: hypocitraturia, hyper- and hypocalcemia, hypercalciuria, hypomagnesemia/hypomagnesuria, hyperoxalaturia, etc. Before surgery, complex biochemical examination of blood and 24-hourcollection urine in 82 patients with urolithiasis was performed. The analysis of the main laboratory parameters of carbohydrate, lipid, calcium and phosphorus and purine metabolism found the prevalence of violations of calcium and phosphorus metabolism in these patients. Dyslipidemia was diagnosed in 31 (37.8%) patients. There was a significant positive correlation between serum total cholesterol and serum total calcium (rs = 0.3315, P = 0.0103). Low serum calcium levels were associated with hyperoxalaturia (rs = -0.4270, P = 0.0295). There was a significant effect of natriuria on urinary excretion of oxalate (rs = 0.6107, P = 0.0001), Mg (rs = 0.4156, P = 0.0096) and K (rs = 0.5234, P = 0.00005). The study shows the role of magnesium in the prevention of recurrence and manifestation of urolithiasis. The combination of two or more types of hormonal and metabolic disorders increases the incidence of recurrent stones. Timely correction of hormonal-metabolic status allows to reduce the risk of stone formation, and hospitalization attributable to the complications associated.

Escherichia coli infection induces mucosal damage and expression of proteins promoting urinary stone formation.

The effect of urinary tract infection (UTI) on mucosal damage and production of proteins promoting urinary stone formation has not been elucidated. Osteopontin production, with associated mucosal damage due to UTI, may allow easier crystal retention and nucleation resulting in stone formation. The aim of this study is to demonstrate that expression of osteopontin (OPN), OPN mRNA, TLR-4, JNK, TNFR-1, iNOS, HMGB-1, and apoptosis process is higher than normal at renal tubular cells due to urinary tract infection by Escherichia coli. Adult male New Zealand strain rabbits were used. Thirty New Zealand strain rabbits were divided into three groups. The first group acted as controls, the second group underwent ligation of right ureter, and the third group underwent ligation of right ureter and injection of Escherichia coli 105/ml proximal to ligation. Nephrectomy and histological examination were performed after 5 days. All groups were HE stained to examine mucosal damage, specific monoclonal antibodies for TLR-4, JNK, mRNA OPN, OPN, TNFR-1, iNOS and HMGB-1. Apoptotic nuclei were demonstrated using TUNEL method. Statistical calculations were performed using ANOVA test, with p < 0.05 considered significant. The findings confirmed the hypothesis that infection of urinary tract by Escherichia coli demonstrated higher expression of OPN, OPN mRNA, TLR-4, JNK, TNFR-1, iNOS, HMGB-1, apoptosis process and mucosal damage than normal. Infection of urinary tract by Escherichia coli caused higher than normal expression of promoter protein osteopontin and mucosal damage at renal tubular cells. These suggest that urinary infection may promote stone formation by mucosal damage and elevate promoter protein osteopontin at tubulus cell, allowing easier crystal retention and nucleation.

Association between body mass index, lipid profiles, and types of urinary stones.

OBJECTIVE: The purpose of this study was to determine the differences in body mass index (BMI), levels of cholesterol, and levels of triglycerides (TGs) among urolithiasis patients with different stone compositions. MATERIALS AND METHODS: Forty-nine patients who had a diagnosis of nephrolithiasis and had undergone open surgery or percutaneous surgery were included, and patients without urolithiasis were randomly selected as controls. Urinary stones were collected and analyzed using infrared spectroscopy. Data relating to patient's age, BMI at diagnosis, serum total cholesterol (TC), high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol (LDL-C) were collected. The stone groups including calcium oxalate monohydrate-calcium oxalate dihydrate (COM-COD), COM, and uric acid were compared with one another and with the control group. In addition, the stone formers group (COM-COD, COM, uric acid, calcium phosphate, and mixed-type stones) was compared to the control group. RESULTS: BMI, TC, and TG levels were significantly higher in stone formers compared with the control group; this association of BMI and TC with stone formation was more prominent in uric acid and COM-COD stone formers, but there was no such prominence for COM stones. LDL-C levels in COM-COD stone formers were significantly higher when compared with COM stone formers. CONCLUSION: Elevated BMI, hypercholesterolemia, and hyperlipidemia, which are leading components of metabolic syndrome, may be associated with different types of urinary stone formation.