Risk Of Urinary Stone Formation Research Articles

Intestinal Oxalate Absorption, Enteric Hyperoxaluria, and Risk of Urinary Stone Formation in Patients with Crohn's Disease.

Nephrolithiasis is a common urologic manifestation of Crohn's disease. The purpose of this study was to investigate the clinical characteristics, intestinal oxalate absorption, and risk factors for urinary stone formation in these patients. In total, 27 patients with Crohn's disease and 27 healthy subjects were included in the present study. Anthropometric, clinical, and 24 h urinary parameters were determined, and the [13C2]oxalate absorption test was performed. Among all patients, 18 had undergone ileal resection, 9 of whom had a history of urinary stones. Compared to healthy controls, the urinary excretion values of calcium, magnesium, potassium, sulfate, creatinine, and citrate were significantly lower in patients with Crohn's disease. Intestinal oxalate absorption, the fractional and 24 h urinary oxalate excretion, and the risk of calcium oxalate stone formation were significantly higher in patients with urolithiasis than in patients without urolithiasis or in healthy controls. Regardless of the group, between 83% and 96% of the [13C2]oxalate was detected in the urine within the first 12 h after ingestion. The length of ileum resection correlated significantly with the intestinal absorption and urinary excretion of oxalate. These findings suggest that enteric hyperoxaluria can be attributed to the hyperabsorption of oxalate following extensive ileal resection. Oral supplementation of calcium and magnesium, as well as alkali citrate therapy, should be considered as treatment options for urolithiasis.

Comparison of two software programs used to determine the relative supersaturation of urine ions.

Relative supersaturation (RSS) values for urine crystals are a measure of the risk of urinary stone formation and have been shown to be lowered in foods shown to aid in the management of urolithiasis. In order to calculate RSS in pets, computer programs have been developed to calculate RSS and aid in the understanding of stone formation in veterinary medicine. However, some older programs have not been updated for use in animals, and the specific coefficients used are not publically available. One of the first RSS programs was developed in BASIC computer language and published in 1985 which was called EQUIL2. The EQUIL2 program was updated to a compiled version compatible with a PC platform. However, the formulas could not be read or altered. This study evaluates a new program with known coefficients to the original EQUIL2 program. The RSS values of the two programs were compared through a t-test, calculating the r2 from correlation analysis, Lin's concordance correlation coefficient, and by a Bland-Altman analysis of outputs from the two programs using urine samples from healthy dogs and cats. Our results show that for both magnesium ammonium phosphate (struvite) and calcium oxalate, the RSS values of the original program could be calculated from the new programs RSS values. Although the actual RSS values were different (as might be expected through the use of the updated coefficients and different thermodynamic stability constants in the calculations) the results were highly correlated, finding elevations and reductions in RSS proportionally in the same urine samples. The current work creates a foundation for using the modernized program to calculate RSS and provides a shared method for understanding the risk of struvite and calcium oxalate stone formation.

Dietary weight loss strategies for kidney stone patients

PurposeOverweight has been associated with an increased risk of incident and recurrent kidney stone disease. Weight reduction is the therapeutic consequence to decrease the risk of stone formation. This review examines the effectiveness of different weight loss strategies on weight reduction and cardiometabolic risk profile, with a particular focus on risk factors for urolithiasis.MethodsA selective literature search was performed using PubMed and Cochrane library.ResultsClinical evidence for the potential benefits of dietary weight loss strategies for kidney stone disease is limited. A conventional, energy-restricted diet may significantly induce weight loss and reduce urinary supersaturation of calcium oxalate in overweight individuals with or without a history of stone formation. The current data indicate that an energy-restricted diet with partial meal replacement may additionally decrease the relative supersaturation of uric acid and further improve the cardiometabolic risk profile, and, thus, may be a favourable option for overweight kidney stone patients. Studies on the Mediterranean and DASH diets on the association between weight loss and the risk of urinary stone formation are lacking.ConclusionAn energy-restricted diet with or without meal replacement could be a promising weight loss strategy for overweight kidney stone patients. Further studies are needed to evaluate the impact of different weight loss strategies on urinary risk factors and cardiometabolic risk profile in urolithiasis.

Effect of nursing guidelines on adherence to healthy lifestyle practices among patients with a small lower ureteric stone

Background: Urinary stone affects about 12% of the world's population and has become a worldwide health problem. Lifestyle practices can contribute to the risk of urinary stone formation; addressing these practices adequately can provide a simple and more cost-effective measure for the prevention of urinary stones and the reduction of its recurrence among urinary stone patients. The current study aimed to evaluate the effect of nursing guidelines on adherence to healthy lifestyle practices among patients with a small lower ureteric stone.Research design: Quasi-experimental design was used to achieve the aim of this study.Sample: A purposive sample of 60 patients was divided into two groups (30 patients in the study group and 30 patients in the control group).Tool (I): includes part one: demographic characteristics of the patients, part two: included present medical history and previous medical history.Tool (II): Adherence of healthy lifestyle practices scale: it was divided into three subscales regarding consumption of restricted foods, consumption of fluids, and healthy usual self-activities.Results: The mean age for the study and control groups are 38.63 and 41.33 years, respectively. More than one-third (36.7%) and 33.3% respectively of the study and control groups have previous histories of urinary tract stones. There are statistically significant differences in mean scores of adherence levels to healthy lifestyle practices between both groups post the nursing guidelines. Only the majority of the study group (93.3%) achieved a satisfactory level following the nursing guidelines.Conclusion: Nursing guidelines have a positive effect on adherence to healthy lifestyle practices to prevent its recurrence.Recommendations: Creation of an educational unit for urinary tract stone patients in the nephrology and urology hospital. Conducting similar studies on a larger probability sample is recommended to achieve generalization of the findings.

Факторы риска нефролитиаза после радикальной цистэктомии с кишечной пластикой мочевого пузыря.

Introduction. Some studies have shown that urolithiasis is much more common in the group of patients who underwent radical cystectomy (RC) with intestinal plastic bladder than the average for the population. The aim of this study included the search of the frequency of urinary stones formation in patients after RC, depending on the type of intestinal plasty of the bladder and the type of urinary diversion, the analysis of risk factors for lithogenesis, the search for metabolic lithogenic disorders in this category of patients, and the assessment of the severity of the identified changes. Materials and methods. The work analyzed the data of 214 patients (169 men and 45 women) who were operated from 2008 to 2021 with a diagnosis of bladder cancer. Patients underwent RC with the formation of a hetero- or orthotopic ileoconduit. We analyzed the indicators of general urine analysis, biochemical blood test, bacteriological analysis of urine for flora, performed both before RC and in the late postoperative period. Also The results of ultrasound of the kidneys, bladder (reservoir), MSCT of the kidneys performed before RC and in the late postoperative period were studied. We selected 37 patients from the general group in random order, who prospectively underwent a biochemical blood test, a biochemical analysis of daily urine, and an assessment of the acid-base composition of venous blood. Statistical analysis was performed by calculating the relative risk, as well as calculating the t-test for independent groups using the computer program Statistica 10.0 (StatSoft USA). Results. Urinary stones of the upper urinary tract after RC, ortho- and heterotopic intestinal plastics of the bladder in the late postoperative period (more than 1 year) were diagnosed in 27 out of 214 patients (12.6%). The relative risk of urolithiasis in patients with pyelectasis before surgery is 3.87 times higher than in patients without changes in pelvicalyceal system at the preoperative stage (p=0.0004). In patients after RC with impaired renal function in stages III-V (GFR 60 ml/min (p=0.005). RC patients with a BMI >30 had a 2.431-fold higher risk of urinary stone formation than those with a BMI 7.0, diagnosed after surgical treatment (p=0.003). The relative risk of developing urolithiasis in patients with urine pH >7.0 detected before surgery is 4.85 (p<0.0001). There was a trend towards an increase in the number of urolithiasis cases in patients who underwent RC with bacteriuria diagnosed after surgery according to urine culture (in patients with identified Enterococcus spp., Enterobacter cloacae, Providencia rettgeri (p<0.05)) compared with patients in of which sterile urine was detected. In patients suffering from urolithiasis after undergoing RC, compared with the control group of patients in the biochemical analysis of blood, there is a statistically significant difference between the level of creatinine (p=0.033), a decrease in the level of GFR from 79.9 to 68.7 (p=0.046). There was a statistically significant increase in the pH level of the urine (p=0.0025), an increase in the level of oxalates in the daily urine (p=0.0035), a decrease in the concentration of uric acid (p= 0.039), calcium (p=0.024) in urolithiasis patients after RCE compared with patients in the control group in biochemical analysis of daily urine. Conclusion. The presence of an expansion of the pelvicalyceal system before surgery, the patient's BMI> 30, urine pH> 7.0 both before and after the operation, a decrease in the patient's GFR <60 ml / min and the presence of bacteriuria in the general analysis of urine after RC are the risk factors for the urolithiasis after RC, intestinal plasty of the bladder.

Retrograde intrarenal lithotripsy in completely bedridden children with severe physical disabilities

Pediatric urolithiasis is often associated with a metabolic disease or with a complication of steroid or antiepileptic agent use. Children who are on long-term bed rest or bedridden are also said to be at risk for urinary stone formation. Here we report two cases of compromised completely bedridden children with renal stones who achieved stone-free status without any complications through detailed intraoperative management. The patient in case 1 is an 8-year-old compromised bedridden boy with epilepsy, chromosomal abnormalities, and ulcerative colitis. In case 2, the patient is a 9-year-old compromised bedridden girl with hypoxic-ischemic encephalopathy and epilepsy. Both children had recurrent urinary tract infections (UTIs), and lithotripsy was planned for multiple renal stones. The patients were expected to be at high risk of developing a postoperative febrile UTI because they are compromised completely bedridden children. A 9.5/11.5-Fr ureteral access sheath was inserted, and lithotripsy was performed. The irrigation flow rate during lithotripsy was frequently adjusted and aspiration of intrarenal saline as necessary so as not to increase intrarenal pressure, with the aim of preventing postoperative febrile UTI. Stone-free status was achieved in both cases, without any intra and postoperative complications. • Long-term bed rest or Bedridden children are at high risk of urinary stone formation. • Bedridden children are high risk of developing febrile urinary tract infections. • Adjustment of irrigation flow rate is essential during retrograde intrarenal lithotripsy.

Approach to Determine Crystalluria Influencing Factors in the Beni Mellal-Khenifra Area in Morocco, by Data Analysis

Urolithiasis presents an ascending prevalence in several countries around the world. The purpose of the present work is to achieve a fast and robust approach to the multiple factors influencing the chemical profile of human crystalluria and therefore in promoting the development of urinary calculi. From February to July 2018, 148 morning urine samples have been collected from 148 patients at the BeniMellal Regional Hospital Center in Morocco. An observation by Polarizing Light Microscopy allowed us to detect the chemical profile of crystalluria.A classification by the Principal Components Analysis (PCA) method has been applied to the individuals that are 148 crystalluria samples and to nine factors that are: ''gender'', ''age'', '' geographical area '', '' water quality'', ''water amount per day '', ''personal and family history'', ''urinary pH'', ''presence of crystals'' and ''chemical profile''. The first results of the principal components analysis (PCA) method shows that there are similarities between crystalluria samples and more or less strong correlations, between some of the nine factors that can influence crystalluria. The frequency of majority constituents in crystalluria is age dependent and oxalic-calcium is the frequent chemical species for both genders. The study of crystalluria would be an excellent laboratory test that brings many benefits for the diagnosis and management of renal pathologies of crystalline origin.One can conclude that urolithiasis is multifactorial, various factors may increase the risk of urinary stone formation.

Dietary Recommendations for Bariatric Patients to Prevent Kidney Stone Formation.

Bariatric surgery (BS) is one of the most common and efficient surgical procedures for sustained weight loss but is associated with long-term complications such as nutritional deficiencies, biliary lithiasis, disturbances in bone and mineral metabolism and an increased risk of nephrolithiasis, attributed to urinary metabolic changes resultant from low urinary volume, hypocitraturia and hyperoxaluria. The underlying mechanisms responsible for hyperoxaluria, the most common among all metabolic disturbances, may comprise increased intestinal oxalate absorption consequent to decreased calcium intake or increased dietary oxalate, changes in the gut microbiota, fat malabsorption and altered intestinal oxalate transport. In the current review, the authors present a mechanistic overview of changes found after BS and propose dietary recommendations to prevent the risk of urinary stone formation, focusing on the role of dietary oxalate, calcium, citrate, potassium, protein, fat, sodium, probiotics, vitamins D, C, B6 and the consumption of fluids.

Estimation of urinary citrate , calcium and PH levels in diabetic patients and the risk of urinary stone formation in correlation with type of disease

Objectives : This study designed to evaluate urinary value of calcium , citrate , and the PH then assess the relation between urinary calcium and citrate with fasting blood sugar and evaluate the risk of renal stones in diabetes patients dependent of their type (type 1 and type 2) . Patients and methods :Fifty four diabetic patients selected with no history of hypertension, no heart disease , and no other disease or smoking. Fasting blood and 24 hour urine samples were collected to evaluate fasting blood sugar, urine calcium, urine citrate , and urine PH. Results: 30 male (55.6 %) and 24 women (44.4%) in a total of 54 patients with diabetes mellitus, aged between 20-65 years. The statistic results of DM type are 25(46.3 %) with type 1 and 29 (53.7 %) with type 2. F.B.S increased (11.79 ± 4.66 mmol/l ) significantly (P 0.05 ) in FBS and urine calcium between DM types except in urine citrate (P < 0.01 ), and urine PH (P < 0.05 ) significantly decreased in type 2. Conclusion: Findings from this study suggest that poor control of diabetes result in increased the risk of urinary stone by causing hypercalciuria, hypocitruturia, and urine acidity . Urine citrate concentration and PH level are more sensitive to the metabolic changes in diabetic patients and correlated with type of disease, their levels in type 2 diabetic patients are significantly lower than type 1, so both types of diabetes have relative risk of prevalent stone disease but type 2 diabetic patients predisposes to calcium Urolithiasis more than type 1.

MP08-16 SURGICAL RISK IN URETERORENOSCOPIC LITHOTORIPSY AMONG BEDRIDDEN ELDERLY PEOPLE: 6492 CASES FROM JAPAN NATIONWIDE DATABASE

INTRODUCTION AND OBJECTIVES:Immobility was a risk of urinary stone formation. In the advanced ageing society, a number of long-term bed-rest patients was increasing. Because a bedridden patient was...

Comparison of metabolic changes for stone risks in 24-hour urine between non- and postmenopausal women.

BackgroundTo explore the differences of 24-hour urine compositions associated with urolithiasis between non- and postmenopausal females.MethodsThe 24-hour urine samples of female participants were collected from May 2013 to July 2014 along with national cross-sectional study of urolithiasis among adults aged ≥18 years in China. The exclusion criteria for the participants were: serum creatinine > 133μmol/L, with urinary tract infection, gout, hyperthyroidism, malignancy, had a history of cancer, kidney stones, enterectomy, had taken thiazide diuretics, allopurinol, vitamin supplement, potassium citrate or calcium supplements during the past two weeks. The compositions associated with urinary stone in 24-hour urine were measured and compared between non-and postmenopausal women.ResultsA total of 603 24-hour urine samples of female participants were analyzed. 354 women with a mean age of 52.5± 14.03 (range 19–84) years met the criteria, including 160 non-menopausal women and 194 postmenopausal women. Compared to the non-menopausal women, postmenopausal women had a lower secretion of citrate (p = 0.043), magnesium (p = 0.001) and creatinine (p = 0.001) in 24h urine. Multivariate linear regression analysis showed that the menopause status was associated with the changes in magnesium (p = 0.003) and creatinine (p = 0.002) secretion, whereas not with the changes in citrate (p = 0.402) secretion.ConclusionsPostmenopausal women have a significant lower secretion of magnesium in their 24-hour urine than non-menopausal ones. We suppose that might be associated with increased risk of urinary stone formation among postmenopausal women.

Identification of new urinary risk markers for urinary stones using a logistic model and multinomial logit model.

Risk assessment for urinary stones has been mainly based on urinary biochemistry. We attempted to identify the risk factors for urinary stones by statistically analyzing urinary biochemical and inflammation-related factors. Male participants (age, 20-79years) who visited Nagoya City University Hospital were divided into three groups: a control group (n = 48) with no history of stones and two stone groups with calcium oxalate stone experience (first-time group, n = 22; recurring group, n = 40). Using 25-µL spot urine samples, we determined the concentrations of 18 candidate urinary proteins, using multiplex analysis on a MagPix® system. In univariate logistic regression models classifying the control and first-time groups, interleukin (IL)-1a and IL-4 were independent factors, with significantly high areas under the receiver operating characteristic curve (1.00 and 0.87, respectively, P < 0.01 for both). The multivariate models with IL-4 and granulocyte-macrophage colony-stimulating factor (GM-CSF) showed higher areas under the receiver operating characteristic curve (0.93) compared to that for the univariate model with IL-4. In the classification of control, first-time, and recurrence groups, accuracy was the highest for the multinomial logit model with IL-4, GM-CSF, IL-1b, IL-10, and urinary magnesium (concordance rate 82.6%). IL-4, IL-1a, GM-CSF, IL-1b, and IL-10 were identified as urinary inflammation-related factors that could accurately distinguish control individuals from patients with urinary stones. Thus, the combined analysis of urinary biochemical data could provide an index that more clearly evaluates the risk of urinary stone formation.

Dietary risk factors for urolithiasis in Korea: A case-control pilot study.

PurposeDietary factors are one of the main causes of urolithiasis. However, little research has evaluated dietary factors related to urolithiasis in Korea. We investigated the various dietary risk factors for urinary stone formation in Korean people.Materials and MethodsWe conducted a prospective case-control pilot study. A total of 27 patients newly diagnosed with urolithiasis and 20 applicants without urolithiasis were designated as the patients and the control group, respectively. A face-to-face survey was carried out using a food-frequency questionnaire. After adjustment for physical activity level and total energy intake, multivariate logistic regression models were applied to search for risk factors for urolithiasis.ResultsThere were no significant differences between the two groups in gender, age, body mass index, family history, or total energy intake. The physical activity level of the control group was significantly higher than that of the patients (p=0.012). The results of the multivariate logistic regression model demonstrated that intake of carbohydrate (odds ratio [OR], 1.055; 95% confidence interval [CI], 1.012–1.099), protein (OR, 1.101; 95% CI, 1.001–1.211), and cereals (OR, 1.012; 95% CI, 1.002–1.023) could increase the risk for urolithiasis.ConclusionsA higher intake of carbohydrate, protein, and cereal may increase the risk of urinary stone formation among Korean people.

Influence of weight status on 24-hour urine composition in adults without urolithiasis: A nationwide study based on a Chinese Han population.

ObjectivesThis study sought to explore the influence of different body weight statuses on 24-hour urine compositions in adults without urolithiasis based on a nationwide study of a Chinese Han population.Material and methodsTwenty-four-hour urine samples from 584 Chinese Han adults without urolithiasis in six cities were analyzed. The participants were divided into four body weight status types according to their body mass indices (BMIs) according to WHO guidelines. The baseline characteristics and 24-hour urine compositions of the standard weight group were compared with those of the underweight, overweight and obese groups. The influences of different body weight statuses on the 24-hour urine compositions were explored using univariate and multivariate logistic regressions.ResultsThe numbers of participants in the underweight, standard weight, overweight and obese status groups were 24, 376, 149 and 35, respectively. The overweight and obese groups suffered significantly higher risks of hypertension and diabetes mellitus than the standard weight group. In the univariate analyses, compared with the standard weight group, the overweight group had significantly higher levels of urine citrate (mean difference [MD] = 0.51 mmol, 95% confidence interval [CI]: 0.15–0.87, P = 0.001), potassium (MD = 6.63 mmol, 95% CI: 1.13–12.14, P = 0.01) and magnesium (MD = 0.38 mmol, 95% CI: 0.08–0.69, P = 0.014). Significant increases in urine citrate (MD = 0.85 mmol, 95% CI: 0.01–1.68, P = 0.046), magnesium (MD = 0.69 mmol, 95% CI: 0.13–1.25, P = 0.016) and phosphate (MD = 2.28 mmol, 95% CI: 0.03–4.54, P = 0.047) were found in the obese group. No significant differences were detected between the standard weight and underweight groups. In the multivariate logistic regression analyses, we only observed significantly higher levels of urine potassium (odds ratio [OR] = 1.02, 95% CI: 1.00–1.04, P = 0.03) in the overweight group and phosphate (OR = 1.32, 95% CI: 1.05–1.66, P = 0.018) in the obese group when compared with the standard weight group.ConclusionsNonstone-forming adults with overweight or obese statuses were at higher risks of hypertension and diabetes mellitus. Obese nonstone-formers might have a greater risk of urinary stone formation due to increased urinary phosphate excretion. Additionally, underweight status had no influence on 24-hour urine composition.

Prediction and preclinical diagnosis of the risk of urinary stone formation using biophysical technologies

The study involved 836 patients with various forms of urolithiasis, all the patients were undergone by the method of dynamic light scattering particle size of the Tamm-Horsfall protein (THP) in the urine. It was found that the average particle size of the THP urolithiasis patients amounted 1115.95 ± 46.5 nm, whereas only 138.4 ± 7.7 nm in the control group. We think that in patients with urolithiasis change in the electrical properties of the surface THP molecules leads to their agglutination and formation megamolecule complexes which can be the centers of crystallization of oxalate stone formation and one of the factors of the urolithiasis.

Can the manipulation of urinary pH by beverages assist with the prevention of stone recurrence?

The formation of various types of stones in the urinary tract is strongly influenced by urinary pH. An acidic urinary pH promotes the crystallization of uric acid and cystine, respectively. Moreover, changes in systemic acid-base homeostasis alter urinary excretion of citrate, an important inhibitor of calcium oxalate stone formation. The effect of beverages on urinary pH and citrate excretion is mainly determined by the presence of bicarbonate and citrate. The bicarbonate content of mineral water can replace alkalization therapy with potassium citrate and contribute to urine inhibitory power by increasing urinary pH and citrate excretion. Citrus juices are rich sources of citrate. Oral citrate is absorbed in the intestine and nearly completely metabolized to bicarbonate, providing an alkali load, which in turn increases urinary pH and citrate excretion. However, data from observational and interventional studies on the effect of different types of citrus juices on the risk of urinary stone formation are conflicting. In conclusion, favourable changes in urinary pH and citrate excretion can be attained by various beverages. However, the long-term efficacy of certain beverages for the recurrence prevention of different types of stones has yet to be determined.

Dietary treatment of urinary risk factors for renal stone formation. A review of CLU Working Group.

Dietary treatment of urinary risk factors for renal stone formation. A review of CLU Working Group.

Determination of components in traditional Chinese medicines associated with promoting or inhibiting urinary stone formation

ObjectiveTo measure oxalate, calcium, and sodium contents of traditional Chinese medicines (TCMs) that are commonly used to prevent and dissolve urinary stones to exclude the possibility that long-term use of such medicines promotes stone formation. The second objective was to measure citrate, potassium, and magnesium contents in the same medicines to provide possible clues about the mechanisms of prevention and dissolution of urinary stones by TCMs. MethodsTen of the most commonly-used TCMs for preventing and dissolving urinary stones were chosen and subjected to ion chromatography (IC) to measure water-soluble and total oxalate and citrate contents. Inductively coupled plasma atomic emission spectrometry (ICP-AES) was used to measure calcium, potassium, magnesium, and sodium contents in a water extract and in digestion liquid. ResultsAverage contents of water-soluble oxalate, calcium, and sodium in the water extract were 41.92, 84.32, and 22.82 mg/100 g, respectively, far below the normal dietary intake of adults in China. The average contents of citrate and magnesium in water extracts were 268.99 and 66.65 mg/100 g, respectively, below the recommended intake for adults. These ion contents are therefore insufficient to inhibit the formation of urinary stones. The average content of potassium in the water extract was 867.71 mg/100 g, which was relatively abundant, so taking the prescription used in this experimental protocol can increase the body's potassium content to some extent. ConclusionsLong-term use of TCMs would not increase the risk of urinary stone formation. The potassium content in TCMs is high, which is one possible reason for the prevention of urinary stones by TCMs.

Synergistic mutations in SLC3A1 and SLC7A9 leading to heterogeneous cystinuria phenotypes: pitfalls in the diagnostic workup

Cystinuria is an inherited disorder of a renal tubular amino acid transporter and leads to increased cystine excretion with the risk of urinary stone formation. Phenotypical classification is based on urinary amino acid concentration as type I (silent), type non-I (hyper-excretors), mixed or untyped. Genotypic classification is based on mutations in SLC3A1 (type A) or SLC7A9 (type B). We present six family members with a complex phenotypic profile based on mutations in both genes. The index patient presents a known homozygous mutation (p.T189M) in SLC3A1 and a homozygous mutation (c.225C > T) in SLC7A9. Based on a bioinformatics analysis and published findings, we considered p.T189M to be pathogenic and initially classified c.225C > T as a silent variant. However, segregation analysis detected homozygosity for p.T189M also in non-affected individuals, whereas homozygous c.225C > T segregated with the phenotype. RNA studies confirmed c.225C > T to cause aberrant splicing. Based on our findings, we conclude that c.225C > T in SLC7A9 determines the clinical phenotype in this family, whereas additional SLC3A1 mutations aggravate the phenotype in heterozygotes for c.225C > T in SLC7A9 without resulting in cystinuria in the homozygous state. Our results underline the need for careful biochemical characterization of family members of an index case of cystinuria. Genetic analysis of both cystinuria genes may be necessary due to the synergistic effects of mutations in two genes.

An association between urinary cadmium and urinary stone disease in persons living in cadmium-contaminated villages in northwestern Thailand: A population study

Excessive urinary calcium excretion is the major risk of urinary stone formation. Very few population studies have been performed to determine the relationship between environmental cadmium exposure and urinary stone disease. This population-based study examined an association between urinary cadmium excretion, a good biomarker of long-term cadmium exposure, and prevalence of urinary stones in persons aged 15 years and older, who lived in the 12 cadmium-contaminated villages in the Mae Sot District, Tak Province, northwestern Thailand. A total of 6748 persons were interviewed and screened for urinary cadmium and urinary stone disease in 2009. To test a correlation between urinary excretion of cadmium and calcium, we measured urinary calcium content in 1492 persons, who lived in 3 villages randomly selected from the 12 contaminated villages. The rate of urinary stones significantly increased from 4.3% among persons in the lowest quartile of urinary cadmium to 11.3% in the highest quartile. An increase in stone prevalence with increasing urinary cadmium levels was similarly observed in both genders. Multiple logistic regression analysis revealed a positive association between urinary cadmium levels and stone prevalence, after adjusting for other co-variables. The urinary calcium excretion significantly increased with increasing urinary cadmium levels in both genders, after adjusting for other co-variables. Elevated calciuria induced by cadmium might increase the risk of urinary stone formation in this environmentally exposed population.