Risk Of Urinary Stone Disease Research Articles

VDR gene polymorphism in susceptibility to urolithiasis among the Asian population: A systematic review and meta-analysis

Urolithiasis is one of the most prevalent urinary diseases worldwide. Several studies have reported VDR gene polymorphisms to have a contributing genetic factor in susceptibility to urolithiasis and suggested its possibility of being a good candidate marker for urolithiasis. However, results across numerous studies centred on the relationship between the VDR gene polymorphism and urolithiasis have been inconclusive. To perform a meta-analysis concerning the association between the risk of urolithiasis and VDR gene polymorphismsviz., ApaI, BsmI, FokI, and TaqI among the Asian population. A comprehensive electronic search was conducted to identify published studies that investigates the relationship between four polymorphisms (ApaI, BsmI, FokI and TaqI) in the VDR gene and the risk of urinary stone disease using electronic databases. VDR ApaI and FokI polymorphisms were found to be associated with urolithiasis risk. Results from pooled analysis indicated ApaI aa genotype to be associated with urolithiasis compared to AA or Aa genotypes. In addition, the minor f allele of FokI variant was identified to be the risk allele in susceptibility to urolithiasis while F allele to be protective. Moreover, from the subgroup analysis, the ff genotype of FokI and aa genotype of ApaI were associated with higher risk of urolithiasis among the East Asian but not among the Southwest Asians.

Validation of a LC-MS/MS assay for citric acid, cysteine and oxalic acid determination and its application to explore pre-analytical sample storage

ObjectivesCitrate, oxalate and cystine in 24-h urine are considered to be associated with the incidence and recurrence risk of urinary stone disease (USD). An evaluation of the LC-MS/MS kit for simultaneous quantification of the three analytes was undertaken. Design& Methods: The analytical performance of the kit was investigated based on FDA, EMA and CLSI guidelines. To promote the standardization of sample storage, this kit has been applied to perform systematic pre-analytical stability study of these analytes in urine. ResultsThis method was validated with good linearity with accuracy of 93.1%–104 %. Intra-day and inter-day imprecision were ≤5.55 % and 5.34 %, respectively. Recoveries of citrate, oxalate and cystine added to clinical samples were in the range of 92.0–103 %, 94.8–100 % and 99.0–107 % with CV ≤ 5.52 %. It was recommended that urine preserved with hydrochloric acid could be preferable in consideration of both reliable test results and neglected sample heterogeneity. ConclusionsThis kit is suitable for measurement of citrate, oxalate and cystine for understanding the etiology of urinary stones, and the proper storage of urine samples is crucial for the correctness of the test results.

The relationship between vascular calcifications and urolithiasis in a large, multiethnic patient population.

Several studies have reported associations between vascular calcifications and urinary stone disease (USD). However, results have been inconsistent and the majority of studies did not report on race/ethnicity. We examined the association between vascular calcifications and USD in a large, racially/ethnically diverse patient population. We identified 672 USD cases and 672 controls (i.e., patients without a history of USD) from patients who underwent non-contrast CT imaging at Montefiore Medical Center in Bronx, NewYorkbetween 2004 and 2013. Controls were matched to cases on age, sex and race/ethnicity. The non-contrast CT imaging was used to measure abdominal aortic calcification (AAC) and calculate the AAC severity score. Logistic regression models were used to examine associations of AAC presence and severity score with risks of USD and stone types. Cases and controls had similar AAC prevalence (45.2% vs. 44.8%, p = 0.87), and AAC severity score (median 10 vs. 9.3, p = 0.47). The presence of AAC (OR= 0.98, 95% CI 0.78-1.23; p = 0.86) or AAC severity score were not associated with risk of USD: ORs of 0.96, 0.87, 1.07 and 1.03 for increasing AAC quartiles (p-trend = 0.54). There were also no associations in the stratified analyses by race/ethnicity or by sex. However, when USD patients were stratified by stone type, brushite/apatite stone formers had an inverse association with the lowest quartile of AAC severity score (OR= 0.35, 95% CI 0.11-0.84, p = 0.04) in comparison to patients without AAC. Overall, we found no association between vascular calcifications and risk of urinary stone disease in this large, hospital-based, case-control study.

Ramadan Fasting and Kidney Stones: A Systematic Review.

Ramadan fasting in Muslims may contain several hours of abstaining from food and drinking in any kind. This can potentially increase the risk of urinary stone disease. Current literature on possible effects of Ramadan fasting on urolithiasis is rather limited. Having the gap in scientific background, we decided to evaluate the available comparative information in this systematic review. We included all studies comparing fasting and non-fasting conditions, studies evaluating stone formation and clinical manifestations of kidney stone disease. All the English studies published from January 1980 to the end of 2019 were included. The exclusion criteria were as followed: fasting out of Ramadan, non-comparative studies, animal studies, patients with bladder stones, and studies evaluating conditions that are only indirectly related to the stone formation or clinical manifestations of it. Applying the Joanna Briggs Institute (JBI) methodology for systematic review showed the quality of included studies was not high. Only five studies remained after exclusion. Meta-analysis was not applicable due to the diversity in methods and evaluated population. Main trend of the included studies is toward showing no difference between fasting and non-fasting conditions in terms of renal stone formation. However, generalization of the findings to greater populations should be applied carefully considering the heterogeneity of results and quality of studies.

Assessment of the impact of geogenic and climatic factors on global risk of urinary stone disease

Urinary Stone Disease (USD) or urolithiasis has plagued humans for centuries, and its prevalence has increased over the past few decades. Although USD pathology could vary significantly among individuals, previous qualitative assessments using limited survey data demonstrated that the prevalence of USD might exhibit a distinctive geographical distribution (the so-called “stone belt”), without any knowledge about the characteristics and contribution factors of the belt. Here, we argue that the spatial distribution of USD can at least partly be explained by geogenic and climatic factors, as it correlates with the ambient geo-environmental conditions modulated by lithology/mineralogy, water quality and climate. Using a Bayesian risk model, we assessed the global risk of USD based on updated big data of four key geogenic factors: phosphorite mines (inventory >1600 points), carbonate rocks (at the scale of 1:40 million), Ca2+/Mg2+ molar ratio of river water (1.27 million samples distributed over 17,000 sampling locations), and mean air temperature (0.5o × 0.5° resolution) representing the climate. We quantitatively identified possible contributions of the factors to USD and delineated the regions with the high USD risk which stretched from southern North America, via the Mediterranean region, northeastern Africa, southern China to Australia, and roughly coincide with the world's major areas of carbonate outcropping. Under current climate conditions, the areas with the probabilities for the USD prevalence of ≥50% and ≥30% covered 3.7% and 20% of the Earth's land surface, respectively. By the end of the 21st century, such total areas could rise to 4.4% and 25% as a result of global warming. Since the USD data used in this study were quite heterogeneous, the prediction results needed further calibration with additional high-quality prevalence data in the future.

Twenty-Four Hour Urine Testing and Prescriptions for Urinary Stone Disease-Related Medications in Veterans.

Current guidelines recommend 24-hour urine testing in the evaluation and treatment of persons with high-risk urinary stone disease. However, how much clinicians use information from 24-hour urine testing to guide secondary prevention strategies is unknown. We sought to determine the degree to which clinicians initiate or continue stone disease-related medications in response to 24-hour urine testing. We examined a national cohort of 130,489 patients with incident urinary stone disease in the Veterans Health Administration between 2007 and 2013 to determine whether prescription patterns for thiazide diuretics, alkali therapy, and allopurinol changed in response to 24-hour urine testing. Stone formers who completed 24-hour urine testing (n=17,303; 13%) were significantly more likely to be prescribed thiazide diuretics, alkali therapy, and allopurinol compared with those who did not complete a 24-hour urine test (n=113,186; 87%). Prescription of thiazide diuretics increased in patients with hypercalciuria (9% absolute increase if urine calcium 201-400 mg/d; 21% absolute increase if urine calcium >400 mg/d, P<0.001). Prescription of alkali therapy increased in patients with hypocitraturia (24% absolute increase if urine citrate 201-400 mg/d; 34% absolute increase if urine citrate ≤200 mg/d, P<0.001). Prescription of allopurinol increased in patients with hyperuricosuria (18% absolute increase if urine uric acid >800 mg/d, P<0.001). Patients who had visited both a urologist and a nephrologist within 6 months of 24-hour urine testing were more likely to have been prescribed stone-related medications than patients who visited one, the other, or neither. Clinicians adjust their treatment regimens in response to 24-hour urine testing by increasing the prescription of medications thought to reduce risk for urinary stone disease. Most patients who might benefit from targeted medications remain untreated.

Antibiotic Use and Risk of Incident Kidney Stones in Female Nurses

The intestinal microbiome may affect urinary stone disease by modulating the amount of oxalate absorbed from the intestine and subsequently excreted in urine. This study sought to explore the association between antibiotics, which alter the intestinal microbiota, and risk for urinary stone disease. Prospective cohort study. 5,010 women in the Nurses' Health Study (NHS) I and II who had collected 24-hour urine samples. Use of antibiotics during the age range of 40 to 49 (NHS II), 40 to 59 (NHS I), and 20 to 39 years (both cohorts). Incident symptomatic urinary stone disease; urine composition. Cause-specific hazards regression adjusted for age, body mass index, comorbid conditions, thiazide use, and dietary factors. Follow-up was censored at the time of asymptomatic kidney stones, cancer, or death. Cumulative use of antibiotics for a total of 2 or more months during the age range of 40 to 49 years (NHS II) and 40 to 59 years (NHS II) was associated with significantly higher risk for developing incident stones compared with no use (pooled HR, 1.48; 95% CI, 1.12-1.96). Similar results were found for the period of 20 to 39 years (pooled HR, 1.36; 95% CI, 1.00-1.84). Results were unchanged after excluding participants who reported urinary tract infection with their stone event or as the most common reason for antibiotic use. Urine composition was generally similar across antibiotic groups except for marginally lower urine pH and citrate values among those taking antibiotics for 2 or more months. Observational design; lack of information for type of antibiotic used; relatively large span of time between antibiotic use and urine collection. Use of antibiotics for more than 2 months in early adulthood and middle age is associated with higher risk for urinary stone disease in later life.

Redefining the Stone Belt: Precipitation Is Associated with Increased Risk of Urinary Stone Disease.

The American Southeast has been labeled the "Stone Belt" due to its relatively high burden of urinary stone disease, presumed to be related to its higher temperatures. However, other regions with high temperatures (e.g., the Southwest) do not have the same disease prevalence as the southeast. We seek to explore the association of stone disease to other climate-associated factors beyond temperature, including precipitation and temperature variation. We identified all patients who underwent a surgical procedure for urinary stone disease from the California Office of Statewide Health Planning and Development (OSHPD) databases (2010-2012). Climate data obtained from the National Oceanic and Atmospheric Administration (NOAA) were compared to population adjusted county operative stone burden, controlling for patient and county demographic data as potential confounders. A total of 63,994 unique patients underwent stone procedures in California between 2010 and 2012. Multivariate modeling revealed that higher precipitation (0.019 average increase in surgeries per 1000 persons per inch, p < 0.01) and higher mean temperature (0.029 average increase in surgeries per 1000 persons per degree, p < 0.01) were both independently associated with an increased operative stone disease burden. Controlling for county-level patient factors did not change these observed effects. In the state of California, higher precipitation and higher mean temperature are associated with increased rates of stone surgery. Our results appear to agree with the larger trends seen throughout the United States where the areas of highest stone prevalence have warm wet climates and not warm arid climates.

Obesity and metabolic stone disease.

In this article, we aim to review the data regarding associations between obesity and nephrolithiasis to assist with workup and treatment of these intersecting disorders. As obesity has a multifactorial influence on the risk for urinary stone disease, the complicated mechanisms will be discussed to improve diagnosis and management. Obesity and metabolic syndrome interact with nephrolithiasis risk factors to produce a myriad of bodily responses that induce stone formation. For this reason, many societies recommend prompt metabolic workup to evaluate the precise causes of stone formation. Data have shown that dietary and directed medical therapies can produce an excellent therapeutic response in this patient population, although the response may be blunted compared with nonobese patients. Given the increasing number of obese and overweight patients, the urologist should be familiar with the pathophysiology, workup, and treatment of metabolic stone disease in this population, which are outlined here.

Urinary stone disease in pediatric and adult metabolic bone clinic patients.

calcium (48%), vitamin D (40%), bisphosphonates (48%). The majority (75%) were non-ambulatory. Most frequent lithogenic medications: Topiramate (42%) and corticosteroids (27%). This is one of the first studies to consider metabolic bone patients as high risk for urinary stone disease. We found a higher rate of kidney stones in pediatric metabolic bone patients compared to data available for the general pediatric kidney stone population. The most common risk factor for bone and stone disease was nonambulatory status. Males were more frequently affected than females; this is the reverse of general adolescent kidney stone population. The predominance of cerebral palsy and seizure patients can be attributed to their frequency of non-ambulatory status and lithogenic medications such as Topiramate.

Significant differences in struvite and cystine stone frequency seen among Chinese nephrolithiasis patients living in North America compared to those living in China.

BackgroundInterracial disparities in nephrolithiasis prevalence have been reported, but the interplay between genetics and the environment for urinary stone disease risk factors is poorly understood. To examine how environment may alter genetic predisposition for stone formation, we established the International Chinese Consortium on Nephrolithiasis (ICCON) as a multi-institutional collaboration to examine patterns of nephrolithiasis presentation between Chinese patients living in different countries.MethodsChinese patients undergoing percutaneous nephrolithotomy (PCNL) at six participating institutions in China and North America over 4 years were reviewed retrospectively. Patient demographics and clinical data were compared between Chinese patients living in China and North America.ResultsA total of 806 patients were included, encompassing 721 Chinese patients living in China and 85 living in North America. Nephrolithiasis patients living in China were more likely to be male (67% vs. 56%, P=0.02), present at a younger age (48.6±15.0 vs. 55.0±13.0 years, P<0.01), and have a lower BMI (24.6±4.0 vs. 25.9±5.7, P=0.04) but were less likely to form struvite stones (5.5% vs. 14.1%, P<0.01). No cystine stone patients were seen in North American Chinese patients, whereas 1.8% of nephrolithiasis patients living in China presented with cystine stones. Similar rates of calcium-based and uric acid calculi as well as urinary pH were seen among both groups.ConclusionsSignificant differences exist between Chinese nephrolithiasis patients living in China compared to those living in North America, highlighting the importance of environmental factors in addition to genetics in modulating risk for urinary stone disease.

Moderately increased risk of urinary stone disease in patients with biopsy‐verified coeliac disease

Urinary stone disease is a mal-absorptive disorder that is a significant health problem because of its high prevalence and incidence. However, there are few population-based studies on the risk of urinary stone disease in patients with coeliac disease (CD). To examine the risk of urinary stone disease in CD. Population-based cohort study. Using small intestinal biopsy report data from 1969 to 2008 obtained from all Swedish pathology departments (n=28), we identified 28735 patients with CD (equal to Marsh 3: villous atrophy). Patients were then matched for gender, age, county and calendar year to 142177 reference individuals from the Swedish general population. We used Cox regression to estimate hazard ratios (HRs) for future urinary stone disease and conditional logistic regression to calculate odds ratios (ORs) for urinary stone disease before diagnosis of CD. Individuals with urinary stone disease were identified through the Swedish National Patient Register that contains data on inpatient care, outpatient care and day surgery. During follow-up, 314 individuals with CD and 1142 reference individuals developed urinary stone disease. This corresponded to a 27% increased risk of urinary stone disease in CD [95% confidence interval (CI)=1.12-1.44]. CD patients had an absolute risk of urinary stone disease of 107/100000 person-years (excess risk of 23/100000). Risk estimates were similar in men and women, and did not differ according to age at CD diagnosis. Conditional logistic regression found that patients with CD were at a slightly increased risk also of prior urinary stone disease (OR=1.19; 95% CI=1.06-1.33). In this study, coeliac disease was associated with a moderately increased risk of urinary stone disease both before and after coeliac disease diagnosis.

The increased risk of urinary stone disease in betel quid chewers

The chewing of betel quid is a common practice in many countries of the world, particularly in Southeast Asia. The quid consists of a preparation of areca nut, betel leaf and calcium hydroxide "lime" paste ("chuna"). For the first time, we present a study that links its use to urinary stone disease. Eight patients (seven male and one female) who presented to our Stone Unit with recurrent urinary stones were included in the study. All were from the Indian subcontinent and were found to regularly chew betel. The patients underwent metabolic screening including blood, random urine and 24-h urine tests, quantitative chemical analysis of their calculi (where possible) and each completed a 7-day Diet Diary on his/her free, home diet. The study demonstrated a high incidence of hypercalciuria, a tendency to pass an alkaline urine and low urinary citrate excretion among the patients. Together these urinary risk factors increase the probability of developing both calcium phosphate-containing and calcium oxalate-containing stones. In support of this hypothesis, the patients were found to form stones consisting mainly of calcium phosphate but mixed with calcium oxalate. It is concluded that the use of calcium hydroxide "chuna" in the betel quid is the major contributor to the cause of urinary stones in its users. Moreover, the development of urinary lithiasis in such patients may be a precursor to milk-alkali syndrome in those individuals whose chewing habit is more extensive than in the patients in this study and who do not seek to decrease their habit over the long term.

Urinary stone disease in diabetes mellitus.

Diabetes mellitus (DM) and urinary stone disease (USD) are common diseases in the community. The prevalence of USD has not previously been studied in DM patients. We evaluated 286 diabetics and 111 age-matched controls by means of direct urinary system X-ray, ultrasonography and/or intravenous pyelography. We also examined the history, risk factors and clinical aspects of USD in DM patients. The prevalence of USD (21% vs 8%; p < 0.05) and the rate of recurrence (2.1 +/- 2.2 vs 1.3 +/- 0.5 stones/case; p < 0.05) were higher in the diabetics compared to the controls. Family history and male gender were significant risk factors for the development of USD in the DM patients. Increased daily total fluid consumption was not preventive for USD in the DM patients, and the type of fluid consumed did not have an impact on the risk of USD. Alcohol consumption was a significant risk factor for the development USD in the DM patients (odds ratio 3.68; 95% confidence interval 1.29-10.45; p < 0.05). Crystaluria (10% vs 1%; p < 0.05) and positive urine culture (8% vs 1%; p < 0.05) were also more prominent in the diabetics compared to the controls. The results of this study suggest that DM is a risk factor for the development USD.

An evaluation of four methods for the detection of heterozygous cystinuria

Heterozygotes for cystinuria (types II and III) may be detected on the basis of slight to moderate elevations in urinary cystine, lysine and sometimes arginine. This seems to be a common genetic trait, and there are indications of an increased risk of urinary stone disease. In order to test the sensitivity and reliability of the procedures normally used for screening and diagnosis of heterozygous cystinuria, we studied 32 heterozygotes previously diagnosed by ion-exchange chromatography of urinary amino acids, and 23 healthy individuals. A random urine sample from each subject was analysed using the cyanide-nitroprusside test, thin-layer amino acid chromatography, colorimetric estimations of cystine and lysine, and ion-exchange amino acid chromatography. Thin-layer chromatography provided the highest sensitivity. Thus the frequency of heterozygotes calculated in previous studies, based on screening by the cyanidenitroprusside test, may be under-estimated. The colorimetric estimations of cystine and lysine provided low sensitivity as screening tests and, compared with the ion-exchange chromatography, were unreliable diagnostic methods.

Prevalence of Urinary Stone Disease in Vegetarians

A study was carried out to determine the effect of a low animal protein diet, such as taken by vegetarians, on the risk of urinary stone disease. A nation-wide survey of vegetarians in the UK showed that the prevalence of urinary stone formation is 40-60% of that predicted for a group of individuals taken from the general population and matched for age, sex and social class with the vegetarians. The findings support the hypothesis that a diet low in animal protein reduces the risk of urinary stone formation.