Mendelian randomization study of urolithiasis: exploration of risk factors using human blood metabolites.

BACKGROUND: Urolithiasis is a highly prevalent global disease closely associated with metabolic factors; however, the causal relationship between blood metabolites and urolithiasis remains poorly understood. METHOD: In our study, we employed a bi-directional two-sample Mendelian randomization (MR) analysis to investigate the causal associations between urolithiasis and metabolites. The random-effects inverse-variance weighted (IVW) estimation method was utilized as the primary approach, complemented by several other estimators including MR-Egger, weighted median, colocalization and MR-PRESSO. Furthermore, the study included replication and meta-analysis. Finally, we conducted metabolic pathway analysis to elucidate potential metabolic pathways. RESULTS: After conducting multiple tests for correction, glycerol might contribute to the urolithiasis and dehydroisoandrosterone sulfate (DHEA-S) might inhibit this process. Furthermore, several blood metabolites had shown potential associations with a causal relationship. Among the protective metabolites were lipids (dehydroisoandrosterone sulfate and 1-stearoylglycerol (1-monostearin)), amino acids (isobutyrylcarnitine and 2-aminobutyrate), a keto acid (acetoacetate) and a carbohydrate (mannose). The risk metabolites included lipids (1-palmitoylglycerophosphoethanolamine, glycerol and cortisone), a carbohydrate (erythronate), a peptide (pro-hydroxy-pro) and a fatty acid (eicosenoate). In reverse MR analysis, urolithiasis demonstrated a statistically significant causal relationship with butyrylcarnitine, 3-methyl-2-oxobutyrate, scyllo-inositol, leucylleucine and leucylalanine. However, it was worth noting that none of the blood metabolites exhibited statistical significance after multiple corrections. Additionally, we identified one metabolic pathway associated with urolithiasis. CONCLUSION: The results we obtained demonstrate the causal relevance between two metabolites and urolithiasis, as well as identify one metabolic pathway potentially associated with its development. Given the high prevalence of urolithiasis, further investigations are encouraged to elucidate the mechanisms of these metabolites and explore novel therapeutic strategies.

Fructose-Rich Diet Is a Risk Factor for Metabolic Syndrome, Proximal Tubule Injury and Urolithiasis in Rats.

Excessive consumption of fructose (FR) leads to obesity, metabolic syndrome (MS) and insulin resistance, which are known risk factors for kidney stones. The epidemiological study has suggested the association between fructose consumption and urolithiasis, but the precise mechanism is still not well understood. Male Wistar rats were assigned for 8 weeks to three groups with different FR content in diet: RD (n = 5)-regular diet with a FR < 3%; F10 (n = 6)-regular diet with an addition of 10% Fr in drinking water; F60 (n = 5)-60% FR as a solid food. Serum concentration of FR, creatinine (Cr), insulin (Ins), triglycerides (Tg), homocysteine (HCS), uric acid (UA), calcium (Ca), phosphate (Pi), magnesium (Mg) and sodium (Na) were measured. Based on 24 h urine collection the following tests were performed: urine pH, proteinuria (PCR), excretion of N-Acetyl-(D)-Glucosaminidase (NAG), monocyte chemoattractant protein (MCP-1), uric acid (uUAEx), phosphate (uPiEx), calcium (uCaEx), magnesium (uMgEx) and sodium (uNaEx). The creatinine clearance (CrCl) was calculated. Calcium deposits in kidney sections were examined using hematoxylin and eosin (HE) and von Kossa stains. The rats on F10 and F60, as compared to the RD diet, showed a tendency for lower CrCl, higher HCS level and some features of MS as higher Ins and TG levels. Interestingly, F10 (fluid) versus F60 (solid) diet led to higher serum Ins levels. F10 and F60 versus RD demonstrated higher urinary excretion of MCP-1 and NAG which were suggestive for inflammatory injury of the proximal tubule. F10 and F60 as compared to RD showed significantly lower uUAEx, although there were no differences in clearance and fractional excretion of UA. F60 versus RD induced severe phosphaturia (>30×) and natriuria (4×) and mild calciuria. F10 versus RD induced calciuria (3×), phosphaturia (2×) and mild natriuria. Calcium phosphate stones within the tubules and interstitium were found only in rats on FR diet, respectively, in two rats from the F10 group and another two in the F60 group. The rats which developed stones were characterized by significantly higher serum insulin concentration and urinary excretion of calcium and magnesium. A fructose-rich diet may promote development of calcium stones due to proximal tubule injury and metabolic syndrome.

Association between blood lipid profile and urolithiasis: A systematic review and meta-analysis of observational studies.

The objective of this study was to pool individual studies regarding the association of blood lipid profiles with urolithiasis to carry out a systematic review and meta-analysis. We searched MEDLINE, PubMed, Embase and Cochrane Library to identify the relevant studies up to November 2017. Studies that met all inclusion criteria were chosen, and a pooled analysis of the odds ratio between urolithiasis and dyslipidemia traits was calculated. A total of 11 observational studies (seven cross-sectional, three cohort, one case-control) with a total of 282 479 participants were examined. The overall pooled analysis of eight studies showed that high triglyceride was associated with increased estimated risk of urolithiasis (odds ratio 1.287, 95% CI 1.073-1.544; P = 0.007). Estimates of the total effect size were consistent in the sensitivity analysis. No evidence of publication bias was detected. The overall pooled analysis of nine studies showed low high-density lipoprotein was weakly associated with increased estimated risk of urolithiasis (odds ratio 1.171, 95% CI 1.010-1.358; P = 0.032). The sensitivity analysis showed conflicting results. No evidence of publication bias was detected. Three studies on the association between any dyslipidemia traits and urolithiasis showed a significant association (odds ratio 1.309, 95% CI 1.202-1.425; P < 0.001). The present meta-analysis showed that patients with higher triglyceride and lower high-density lipoprotein had an increased estimated risk of urolithiasis. A triglyceride-urolithiasis association was found to be more coherent and consistent compared with the high-density lipoprotein-urolithiasis association. Although somewhat contradictory results have been found, the meta-analysis is encouraging for evaluating urolithiasis as a systemic disorder. Further well-designed prospective randomized controlled or cohort studies are necessary to better elucidate the causal association of dyslipidemia and urolithiasis.

[Specific features of the immune status and blebbing of the plasmatic membrane of lymphocytes patients with urolithiasis complicated by the pyelonephritis].

INTRODUCTION: According to the epidemiological studies, prevalence of urolithiasis is nearly 10% worldwide. The course of the disease is often complicated by the development of pyelonephritis, the pathogenesis of which is rather multifactorial. Along with urinary tract obstruction, increasing virulence of microorganisms and immune insufficiency in patients also plays a major role. AIM: To define specific features of immune insufficiency in patients who develop pyelonephritis as a complication of urolithiasis. MATERIALS AND METHODS: A total of 150 patients with urolithiasis complicated by pyelonephritis were prospectively enrolled into our study in order to develop a novel method. All patients were divided into two clinical groups. Group I consisted of 75 patients with urolithiasis complicated by serous pyelonephritis and Group II included 75 patients with urolithiasis complicated by purulent pyelonephritis. In all patients an evaluation of the immune status with a determination of CD3, CD4, CD8, CD16, CD19 level and phagocyte activity of immune system was carried out. The state of lymphocytes plasmatic membrane was evaluated by phase contrast microscopy. RESULTS: It is established that development of pyelonephritis in patients with urolithiasis is accompanied by a lymphopenia, the decrease in relative contents T-helpers, natural killers, as well as a decrease in the immuno-regulatory index and an increase in indicators of terminal and total lymphocytes blebbing. The most pronounced changes were noted in purulent pyelonephritis, where suppressed immune status was confirmed by the high level of lymphocyte with terminal blebbing state.

Sporadic primary hyperparathyroidism and stone disease: a comprehensive metabolic evaluation before and after parathyroidectomy.

OBJECTIVES: To characterize the stone risk and the impact of parathyroidectomy on the metabolic profile of patients with primary hyperparathyroidism (PHPT) and urolithiasis. PATIENTS AND METHODS: We analysed the prospectively collected charts of patients treated at our stone clinic between January 2001 and January 2016 searching for patients with PHPT and urolithiasis. Imaging evaluation of the kidneys, bones and parathyroid glands was assessed. We analysed the demographic data, serum and urinary variables before and after parathyroidectomy. We used a paired t-test, Fisher's test, Spearman's test and anova in the statistical analysis. RESULTS: A total of 51 patients were included. The mean patient age was 57.1 ± 12.1 years and 82.4% were women. Before parathyroidectomy, mean calcium and parathyroid hormone (PTH) levels were 11.2 ± 1.0 mg/dL and 331 ± 584 pg/dL, respectively. Hypercalcaemia was present in 84.3% of patients. All eight patients with normal calcium levels had elevated PTH levels. Only two patients did not have PTH above the normal range, although both had elevated calcium levels. The most common urinary disorders were low urinary volume (64.7%), hypercalciuria (60.8%), high urinary pH (41.2%) and hypocitraturia (31.4%). After parathyroidectomy, the number of patients with hypercalcaemia (n = 4; 7.8%), elevated PTH (n = 17; 33.3%) and hypophosphataemia (n = 3; 5.9%) significantly decreased (P < 0.001). The number of urinary abnormalities decreased and there was a reduction in urinary calcium (P < 0.001), pH (P = 0.001) and citrate levels (P = 0.003). CONCLUSION: Individuals with PHPT and nephrolithiasis frequently have elevated baseline PTH and calcium levels. Low volume, hypercalciuria, high urinary pH, and hypocitraturia are the most frequent urinary disorders. Parathyroidectomy is effective in normalizing serum calcium and PTH levels, although other urinary metabolic may persist. Patients should be monitored for the need for citrate supplementation.

PREVALENCE AND PREDICTORS OF PRIMARY HYPERPARATHYROIDISM AMONG PATIENTS WITH UROLITHIASIS.

OBJECTIVE: Urolithiasis may be the only presenting manifestation of primary hyperparathyroidism (PHPT), and early detection of PHPT in such patients may prevent future urolithiasis and other PHPT complications. This study was performed to study the prevalence and predictors of PHPT in patients presenting with urolithiasis. METHODS: Consecutive patients presenting with urolithiasis were evaluated for clinical and biochemical manifestations of PHPT with serum and urine calcium (Ca), serum intact parathyroid hormone and 25 (OH) vitamin D. We then compared the clinical and biochemical characteristics of PHPT patients presenting with urolithiasis (group A) and without (group B). RESULTS: During the 3-year study period, 381 patients with urolithiasis were seen with a mean age of 38.5 ± 13.9 years. Nineteen of the 381 (5%) patients had histologically proven PHPT (group A). Four patients in group A (21%) and 8 in group B (2%) had nephrocalcinosis (P<.0001), multiple stones (≥3), calcific pancreatitis, and neuropsychiatric manifestations were more common in group A (P<.0001). Presence of multiple or bilateral stones, and recurrent stone episodes predicted PHPT (odds ratio [OR]: 3.06, confidence interval [CI]: 0.87, 0.7). CONCLUSION: One out of every 20 patients with urolithiasis had PHPT, which is higher than the prevalence of PHPT in general population. The presence of nephrocalcinosis and multiple, bilateral, and recurrent stone disease increased the risk of PHPT among stone formers. ABBREVIATIONS: Ca = calcium; CI = confidence interval; iPTH = intact parathyroid hormone; nPHPT = normocalcemic PHPT; OR = odds ratio; PHPT = primary hyperparathyroidism.

In vitro and ex vivo approach for anti-urolithiatic potential of bioactive fractions of gokhru with simultaneous HPLC analysis of six major metabolites and their exploration in rat plasma.

CONTEXT: Tribulus terrestris L. (Zygophyllaceae) fruits have long been used in traditional systems of medicine for the treatment of various urinary diseases including urolithiasis. OBJECTIVE: To explore the anti-urolithiatic potential of gokhru and to develop an analytical method for quantitative estimation of metabolites for its quality control. MATERIALS AND METHODS: Aqueous extract of gokhru fruit was prepared through maceration followed by decoction to produce a mother extract, which was further used for polarity-based fractionations. In vitro and ex vivo anti-urolithiatic activity of mother extract and fractions at different concentration (100-1000 µg/mL) were carried out using aggregation assay in synthetic urine and in rat plasma, however, nucleation assay for 30 min was done using confocal microscopy. A simultaneous HPLC method has been developed for quantification of diosgenin, catechin, rutin, gallic acid, tannic acid and quercetin in mother extract and in fractions. RESULTS: The extraction resulted in 14.5% of w/w mother extract, however, polarity-based fractionation yielded 2.1, 2.6, 1.5, 1.3 and 6.1% w/w of hexane, toluene, dichloromethane (DCM), n-butanol and water fractions, respectively. In vitro and ex vivo studies showed a significant anti-urolithiatic potential of n-butanol fraction. Further, HPLC analysis revealed significantly (p < 0.01) higher content of quercetin (1.95 ± 0.41% w/w), diosgenin (12.75 ± 0.18% w/w) and tannic acid (9.81 ± 0.47% w/w) in n-butanol fraction as compared to others fractions. DISCUSSION AND CONCLUSION: In vitro and ex vivo studies demonstrated potent anti-urolithiatic activity of n-butanol fraction which can be developed as new phytopharmaceuticals for urolithiasis. HPLC method can be used for quality control and pharmacokinetic studies of gokhru.

[Clinical and biochemical aspects of pathogenesis of urolithiasis].

AIM: To investigate the role of infection in the pathogenesis of urolithiasis using chromatography mass spectrometry analysis. MATERIALS AND METHODS: The study analyzed clinical and laboratory data of 316 urolithiasis patients hospitalized between February 2005 and January 2015. All patients underwent a comprehensive clinical examination, including laboratory tests (hematological and biochemical blood tests, clinical and bacteriological tests of urine) and chromatography mass spectrometry analysis urine and blood. The laboratory testing was carried out both during the patients hospital stay and outpatient follow-up. RESULTS: We analyzed the biological material for the presence of characteristic ions. Urine samples of 316 urolithiasis patients were found to contain activators of "cooperative sensitivity." Moreover, there was a significant increase in the concentration of signaling compounds of the "cooperative sensitivity" of microorganisms in patients with complicated urolithiasis in comparison with the control indices (lactones-0.006 plus/minus 0.0004 mmol/L, normal values less than 0.002, quinolones 0.004 plus/minus 0.0003 mmol/l, normal values - less than 0.002 and furan esters - 0.005 plus/minus 0.0004, normal values less than 0.002). Threshold values of the activators of "cooperative sensitivity" demonstrated the readiness of the microbial community to initiate an inflammatory process. The presence of activators such as lactones, quinolones and furan esters in the samples of urolithiasis patients predisposes to the activation of pathogenic genes in a large group of microorganisms, including gram positive and gram negative species. DISCUSSION: In our opinion, to improve the quality of diagnostic, treatment and preventive measures in patients with different types of stone formation, it is advisable to use chromatography mass spectrometry analysis, which allows determination of priority clinical and laboratory indicators. CONCLUSION: The data on the role of infection in the pathogenesis of urolithiasis obtained by chromatographic methods suggest the possibility of using the indicators of the activators of the "cooperative sensitivity" of microbes in patients with various forms of urolithiasis to assess the disease severity.

Urolithiasis is associated with low serum testosterone levels in men.

OBJECTIVE: To evaluate the relationship among urolithiasis, metabolic syndrome (MetS) and serum testosterone (T) level in men. MATERIAL AND METHODS: 513 men older than 18 years were enrolled in this study: 313 of the subjects had a history of stones (group 1) and 200 had no history of stones (controls, group 2). Early morning T levels were recorded and anthropometric measurements were investigated to evaluate MetS. Analyses were completed using chi-square tests. RESULT: Serum T level was lower in stone forming patients than control subjects and 161 (%51.4) men in group 1 and 92 (%46) men in group 2 were diagnosed with metabolic syndrome. T level was found lower limit (< 285 ng/dl) in the MetS and urolithiasis group (p 0.002, OR 2.71). CONCLUSIONS: We found low testosterone levels in the patients with stone disease and prevalence of the MetS in men with urolithiasis was higher than in men without stone disease. Our findings show that levels of testosterone had no effect on stone formation, but the factors that cause stone formation can have an effect on the level of testosterone.

[PERSISTENCE OF MYCOPLASMA DURING UROLITHIASIS].

AIM: Study the frequency of detection of mycoplasma and ureaplasma in clinical material from urolithiasis patients. MATERIALS AND METHODS: Clinical material samples (blood sera, urine, uroliths) from 31 urolithiasis patients were obtained during operations of urolith-removal. Cultural method, LAR and PCR were used in the study. RESULTS: The study of clinical material from 31 patients by PCR has shown, that in 25 individuals. (80.6%) DNA of mycoplasma and ureaplasma was detected, and mycoplasma DNA was more frequently detected in uroliths and less--in-blood sera. Mycoplasma hominis DNA was detected in clinical material of a significantly largerninmber of patients. 23 cultures were isolated from 8 patients by a cultural method, that were identified by PCR as M. hominis. All the isolates have grown as "mini colonies". Even after multiple passages in agar medium, reversion of "mini-colonies" into colonies with a classic morphology was not obtained. CONCLUSION: A high frequency of detection of mycoplasma and ureaplasma in clinical material of patients with urolithiasis was established. The isolated M. hominis cultures have only grown as "mini-colonies". The phenomenon discovered could give evidence on high variability of mycoplasma and a possibility of existence of previously unknown form of their persistence in human organism.

[THE MODERN PROSPECT FOR CITRATE MIXTURES IN THE TREATMENT OF UROLITHIASIS].

The authors present a review of literature on the use of litholytic citrate medications for conservative management of urolithiasis. Urate urolithiasis is the most common clinical condition encountered by urologists. Citrate agents, in particular Blemaren, not only may be employed in a conservative therapy of uric acid stones, but can also be successfully used in the treatment of the calcium urolithiasis, i.e. mixed composition stones, which is supported by current international urology guidelines.

[THE SEARCH AFTER PROGNOSTIC TESTS OF DEVELOPMENT OF UROLITHIASIS OF PATIENTS WITH VERTEBRO-CEREBROSPINAL TRAUMA].

The article presents analysis of alterations of biochemical indicators in blood serum and day urine of 22 patients in acute and early periods after vertebro-cerebrospinal trauma. Out of total number of patients in 10 (main group) in post-traumatic period urolithiasis developed In 12 patients no signs of urolithiasis were detected These examinedpatients were included into comparative group. The reference group was composed with 20 healthy individuals. The concentration of urea, creatinine, uric acid, calcium and inorganic phosphate in blood serum and day urine were detected In patients of main group statistically significant increasing of levels of urea and creatinine was detected in blood serum relative to patients of comparative group. In examined patients of main group clearance of urea was reliably lower than both values of comparative group (up to 2.55 times; p < 0.05) and indicators of reference group (up to 3.75 times; p < 0.05). In patients of this group, clearance of uric acid also had reliable differences from indicators both in comparative group and reference group. Therefore, in patients in acute and early periods of vertebro- cerebrospinal trauma expressed disorders of biochemical indicators of blood serum and urine that can be referred to predictors of risk of development of urolithiasis in the following. The most informative tests were increasing of concentration of urea in blood serum more than 5.30 mmol/l (ratio of likelihood ofpositive test--4.26) and decreasing of clearance of uric acid and urea.

[The use of NefroDoz in patients with urolithiasis who underwent extracorporeal shock wave lithotripsy].

The article presents the results of the multicenter clinical comparative open-label trial in three parallel groups, which was aimed to the evaluation of the efficacy and safety ofbiologically active food supplement NefroDoz after extracorporeal shock wave lithotripsy (ESWL) in patients with urolithiasis. NefroDoz was prescribed for the lithokinetic purpose. The study involved 114 patients from different regions of the Russian Federation aged from 18 to 75 years (mean age 45.56 +/- 12.49 years) with a diagnosis of urolithiasis who underwent ESWL. Patients were divided into 3 groups according to the type oftreatment. Evaluation of the effectiveness was performed using data from a blood test, urine analysis, and biochemical blood assay, ultrasound and KUB X-ray. The results showed that NefroDoz has diuretic, anti-inflammatory, and lithokinetic effects, and is effective and safe drug for the patients with urolithiasis who underwent ESWL.

[Potential biochemical factors for the development of urolithiasis in patients with spinal cord injuries].

A comparative analysis of biochemical parameters of blood serum and daily urine in patients with urolithiasis developed after spinal cord injury (study group--35 patients) and patients without development of the disease (comparison group--20 patients) was performed. It was found that patients after spinal cord injury have developed productive azotemia, which led to the disruption of renal excretory function (accumulation of urea and creatinine in blood, and lowering their clearance). Against this background, there is violation of excretion of uric acid, magnesium, decreased sensitivity of the renal tubules to aldosterone (in patients with nephrolithiasis K/Na ratio in urine was lower). As a result, patients have decreased reabsorption of sodium and water retention, increased urine osmolality; against the background of electrolyte imbalance in urine, this leads to the formation of stones. In patients with spinal cord injuries, main trigger mechanism of formation of urinary stones was excessive posttraumatic azotemia. The high concentration of the products of protein-nitrogen catabolism in the serum of patients in the acute and early periods of spinal cord injury may be unfavorable criterion determining the significant risk of developing of kidney stones.

Validation of a reference interval for symmetric dimethylarginine in healthy goats and its comparison to values in goats with obstructive urolithiasis.

BACKGROUND: Symmetric dimethylarginine (SDMA), a sensitive biomarker for detecting renal injury, has not been characterized in goats. Obstructive urolithiasis (OU) is the most common urinary tract disease in male small ruminants. HYPOTHESIS/OBJECTIVE: Establish an SDMA reference interval (RI) in healthy adult goats and describe SDMA concentrations in goats with OU. We hypothesize that the SDMA RI in healthy adult goats will be similar to that of other adult veterinary species and that SDMA can be utilized to assess the renal function of goats experiencing OU. ANIMALS: Fifty-five healthy adult male and female goats from a university herd were enrolled for SDMA RI development. Twenty male and female goats from a university herd were enrolled for validation of the SDMA RI established. Thirteen male goats diagnosed with OU were enrolled. METHODS: Clinical trial. Serum samples for all animals enrolled were collected and analyzed for SDMA using an immunoassay (IDEXX Laboratories, Inc); goats with OU had additional blood work analyzed (PCV, total solids, and serum biochemistry). Symmetric dimethylarginine and other values in goats with OU were analyzed and compared at specific time points. RESULTS: The SDMA RI for healthy, adult goats is 8.03 µg/dL (90% CI 4.81-11.04) to 25.93 µg/dL (90% CI 22.88-28.97). There was no correlation identified between serum creatinine and SDMA in goats with OU. CONCLUSIONS AND CLINICAL IMPORTANCE: The SDMA RI for adult goats is higher than in other adult large animal species. Use of SDMA in goats with OU is not useful in assessing their renal function.

Pediatric primary urolithiasis: 12-year experience at a Midwestern Children's Hospital.

PURPOSE: Due to environmental and social changes (and possibly obesity) as new risk factors for stone formation in adults and changes in imaging techniques, we assessed whether etiologies of primary pediatric urolithiasis have changed, and if relationships exist between the condition and obesity or imaging technique. MATERIALS AND METHODS: All pediatric patients with documented primary urolithiasis who underwent serum and 24-hour urine analyses between 1999 and 2010 were evaluated. Age at diagnosis, gender, body mass index and imaging technique were recorded. RESULTS: Of the 222 patients (48% male) all had normal serum creatinine, electrolytes and minerals. Primary pediatric urolithiasis was diagnosed by ultrasound in 73% of cases and computerized tomography in 27%. Mean ± SD annual incidence of urolithiasis per 1,000 clinic visits increased from 2.4 ± 1.5 in the first half of the study period to 6.2 ± 2.1 in the second half (p <0.005). Mean ± SD age at diagnosis was 11.8 ± 3.8 years and body mass index was 21.7 ± 5.7 (rate of overweight 15%). A total of 140 patients had urine output less than 1.0 ml/kg per hour, with this being the only abnormality in 54. Hypercalciuria was observed in 46% of patients, hypocitraturia in 10% and high calcium-to-citrate ratio in 51%. Mild absorptive hyperoxaluria was noted in 3 patients and hyperuricosuria in 11, with all 14 exhibiting at least 1 additional abnormality. Cystinuria was present in 1 patient. No etiology was identified in 20 patients (9.0%). CONCLUSIONS: Oliguria and hypercalciuria continue to be the most common etiologies of pediatric primary urolithiasis, followed by hypocitraturia. The recent increase in stone incidence is unlikely due to increased use of computerized tomography. Incidence of obesity was not higher than in the general population. Hyperoxaluria and cystinuria are rare, and thus might not be indicated in the initial analysis.

OPN gene polymorphism (Ala250) and lower serum OPN levels are associated with urolithiasis.

Osteopontin (OPN) is one of the urinary proteins with an important role in stone formation. Recently, OPN Ala250 (rs1126616) polymorphism and other single nucleotide polymorphisms (SNPs) have been studied to define their role in urolithiasis. This study was conducted to examine the impact of OPN Ala250 polymorphism on the risk of stone formation and their association with serum OPN levels. OPN Ala250 polymorphism was investigated in 127 urolithiasis patients and 92 healthy controls. Stones were analyzed for their chemical composition by using X-Ray diffraction method. Genomic DNA was isolated from peripheral blood leucocytes. The study groups were genotyped by PCR-RFLP and serum OPN levels were measured by ELISA. There was a significant difference between urolithiasis patients and controls concerning genotype and allele frequencies of OPN Ala250 (p < 0.05). Separate analysis by BMI greater or less than 25 kg/m(2) showed that the presence of one mutant T-allele was more frequent in patients with higher BMI than patients with BMI less than 25 kg/m(2) (p < 0.05). Serum OPN concentrations were two-fold higher in the control group compared to urolithiasis patients (p < 0.05). But the mean serum levels did not show any significant difference between OPN Ala250 genotypes in both groups. Moreover, we found an association between higher BMI and stone formation. Our findings suggest that OPN Ala250 polymorphism is associated with the correlation between weight gain and urolithiasis. However, the correlation between urolithiasis and obesity needs to be further studied in larger cohorts.

Preliminary investigation on ultra high diluted B. vulgaris in experimental urolithiasis.

PURPOSE: The study focuses on the anti-urolithiasis potential of ultra-diluted homeopathic potency of Berberis vulgaris (B. vulgaris) root bark, commonly used in homeopathic system to treat renal calculi. METHODOLOGY: B. vulgaris root bark (200c, 20 µl/100 g body weight/day, p.o, for 28 days) was tested in an animal model of urolithiasis. Urolithiasis was induced in male Wistar rats by adding 0.75% ethylene glycol (EG) to drinking water. Urine and serum samples were analyzed for calcium, magnesium, phosphorus, uric acid and creatinine. Enzymic makers of renal damage (alkaline phosphatase, lactate dehydrogenase, leucine aminopeptidase and γ-glutamyl transpeptidase) were assessed in kidney and urine. Renal tissues were analyzed for oxalate content. RESULTS: Administration of EG to rats increased the levels of the stone-forming constituents calcium, phosphorus and uric acid, in urine. Levels were normalized by B. vulgaris treatment. The decrease in the urolithiasis inhibitor magnesium in urine was prevented by treatment with B. vulgaris. Serum creatinine levels were largely normalized by B. vulgaris treatment. Hyperoxaluria induced renal damage was evident from the decreased activities of tissue marker enzymes and an apparent escalation in their activity in the urine in control animals; this was prevented by B. vulgaris treatment. CONCLUSION: Homeopathic B. vulgaris root bark has strong anti-urolithiasis potential at ultra-diluted dose.

Serum fetuin-A and recurrent urolithiasis in young adults.

OBJECTIVE: Recurrence of urolithiasis is frequent. There are no reliable markers able to indicate recurrent stone former patients. Fetuin-A inhibits hydroxyapatite crystals formation and expansion. This study aims at evaluating whether serum fetuin-A may predict recurrent urolithiasis in young adults. MATERIALS AND METHODS: This is a multicentre study. Young adults patients with recurrent urolithiasis attending 3 urology clinics were enrolled from July 2011 to December 2012. Inclusion criteria were: age 18-40 years, presence of more than one kidney stone. Exclusion criteria were: diabetes mellitus, metabolic disorders, obesity, hypertension, cardiovascular disease, infection diseases. Controls were participants without history of urolithiasis and currently undetected stones. Routine biochemistry, serum concentration of oxalate, fetuin-A, and parathyroid hormone (PTH) were assessed; 24/h urinary excretion of creatinine, uric acid, calcium, sodium, phosphorus, potassium, magnesium, glucose, oxalate, amylase, and protein was measured. Kidney ultrasonography and plain X-ray examination was performed. RESULTS: The total cohort was represented by 120 young adults participants (90 patients, and 30 controls). Clinical characteristics were not different between patients and controls. No significant differences were found in serum concentrations as well as in 24/h urinary excretion of recorded variables. No significant difference was found in serum concentration of fetuin-A (median 35.1 ± 18.62 SD Vs 35.12 ± 14.12, µg/ml; p = 0,908). CONCLUSIONS: The data of present study do not substantiate the hypothesis that serum fetuin-A may be a reliable predictor of recurrent urolithiasis in young adults.

[Clinical and laboratory parameters in patients with urolithiasis in the presence and absence of primary hyperparathyroidism].

The clinical and laboratory findings in 78 patients with various forms of urolithiasis depending on the presence of primary hyperparathyroidism (PHPT) were analyzed. PHPT was diagnosed in 17 patients. Group "without PHPT" and group "with PHPT" differed significantly in terms of parathyroid hormone (PTH) level, serum calcium, phosphorus, chloride, alkaline phosphatase, calciuria and kaliuria. In patients with staghorn calculi, PHPT was diagnosed in 12.5%, and staghorn calculi in the presence of PHPT were identified in 17.7% of cases. Hypercalciuria in the group "with PHPT" was detected in 82.4% of patients (all 3 patients with staghorn calculi), and in the group "without PHPT"--in 18% of patients (2 of 21 patients with staghorn calculi). Hyperoxaluria was observed in 42.3% of patients "without PHPT" and in 35.3% of patients "with PHPT", in 36.8% of patients with simple stones and in 57.2%--with staghorn calculi. In 39% of patients "without PHPT", secondary hyperparathyroidism (SHPT) was diagnosed. SHPT prevalence was 28% in patients with staghorn calculi, and 45% in patients with simple stones. In 87.5% of patients with hypomagnesemia, staghorn calculi were observed. Significant relationship between magnesium and triglycerides (r(s) = -0.296; P = 0.041), and magnesium and high-density lipoproteins (r(s) = 0.339; P = 0.032) in all patients with urolithiasis were revealed. Thus, the study found no association between staghorn nephrolithiasis and PHPT. Elevated PTH levels usually indicate SHPT rather than PHPT. In hypocalcemia, there was more strong association between PTH and calcium, in normocalcaemia--between PTH and magnesium.