Calcium Nephrolithiasis Research Articles

New pharmacologic approach to patients with idiopathic calcium nephrolithiasis and high uricosuria: Febuxostat vs allopurinol. A pilot study

Objectives: Nephrolithiasis is a disease with a high prevalence in industrialised countries. The most frequent form is calcium nephrolithiasis (80%), leading to the formation of either calcium oxalate (CaOx) or calcium phosphate (CaP) stones. Uric acid nephrolithiasis has a prevalence of about 8% of all stones, although mixed calcium–uric acid stones are frequent. High urinary uric acid excretion is a relevant lithogenic risk factor both for patients with uric acid stones and for patients with calcium stones.

E20 Genomic approach to idiopathic calcium nephrolithiasis: Association with a novel copy-number variant

E20 Genomic approach to idiopathic calcium nephrolithiasis: Association with a novel copy-number variant

E17 Nephrocalcinosis, renal failure and bone disease in patients with Dent's disease (DD) and medullary sponge kidney (MSK): Comparison with patients with recurrent calcium nephrolithiasis (RCN)

E17 Nephrocalcinosis, renal failure and bone disease in patients with Dent's disease (DD) and medullary sponge kidney (MSK): Comparison with patients with recurrent calcium nephrolithiasis (RCN)

Decreased Transcriptional Activity ofCalcium-sensing receptorGene Promoter 1 Is Associated With Calcium Nephrolithiasis

CaSR gene is a candidate for calcium nephrolithiasis. Single-nucleotide polymorphisms (SNPs) encompassing its regulatory region were associated with calcium nephrolithiasis. We tested SNPs in the CaSR gene regulatory region associated with calcium nephrolithiasis and their effects in kidney. One hundred sixty-seven idiopathic calcium stone formers and 214 healthy controls were genotyped for four CaSR gene SNPs identified by bioinformatics analysis as modifying transcription factor binding sites. Strontium excretion after an oral load was tested in 55 stone formers. Transcriptional activity induced by variant alleles at CaSR gene promoters was compared by luciferase reporter gene assay in HEK-293 and HKC-8 cells. CaSR and claudin-14 mRNA levels were measured by real-time PCR in 107 normal kidney medulla samples and compared in patients with different CaSR genotype. Only rs6776158 (A>G), located in the promoter 1, was associated with nephrolithiasis. Its minor G allele was more frequent in stone formers than controls (37.8% vs 26.4%, P = .001). A reduced strontium excretion was observed in GG homozygous stone formers. Luciferase fluorescent activity was lower in cells transfected with the promoter 1 including G allele at rs6776158 than cells transfected with the A allele. CaSR mRNA levels were lower in kidney medulla samples from homozygous carriers for the G allele at rs6776158 than carriers for the A allele. Claudin-14 mRNA levels were also lower in GG homozygous subjects. Minor allele at rs6776158 may predispose to calcium stones by decreasing transcriptional activity of the CaSR gene promoter 1 and CaSR expression in kidney tubules.

Automated Analysis of Urinary Stone Composition Using Raman Spectroscopy: Pilot Study for the Development of a Compact Portable System for Immediate Postoperative Ex Vivo Application

We evaluate a compact portable system for immediate automated postoperative exvivo analysis of urinary stone composition using Raman spectroscopy. Analysis of urinary stone composition provides essential information for the treatment and metaphylaxis of urolithiasis. Currently infrared spectroscopy and x-ray diffraction are used for urinary stone analysis. However, these methods may require complex sample preparation and costly laboratory equipment. In contrast, Raman spectrometers could be a simple and quick strategy for immediate stone analysis. Pure samples of 9 stone components and 159 human urinary calculi were analyzed by Raman spectroscopy using a microscope coupled system at 2 excitation wavelengths. Signal-to-noise ratio, peak positions and the distinctness of the acquired Raman spectra were analyzed and compared. Background fluorescence was removed mathematically. Corrected Raman spectra were used as a reference library for automated classification of native human urinary stones (50). The results were then compared to standard infrared spectroscopy. Signal-to-noise ratio was superior at an excitation wavelength of 532nm. An automated, computer based classifier was capable of matching spectra from patient samples with those of pure stone components. Consecutive analysis of 50 human stones demonstrated 100% sensitivity and specificity compared to infrared spectroscopy (for components with more than 25% of total composition). Our pilot study indicates that Raman spectroscopy is a valid and reliable technique for determining urinary stone composition. Thus, we propose that the development of a compact and portable system based on Raman spectroscopy for immediate, postoperative stone analysis could represent an invaluable tool for the metaphylaxis of urolithiasis.

Calcium renal lithiasis and bone mineral density. Importance of bone metabolism in urinary lithiasis

ContextCalcium nephrolithiasis is a multifactorial disease; in its pathophysiology is involved various minerals and metabolic factors that may be altered, including bone and phosphorus–calcium metabolism. ObjectiveTo establish the scientific evidence and demonstrate the relationship between calcium nephrolithiasis and bone mineral density loss, through the use of bone turnover markers, serum and urinary metabolites. Evidence acquisitionWe performed a PubMed literature review using different MeSH Terms like “Nephrolithiasis” “Bone mineral density”, “Urinary stones”, “Calcium”, “Bone resorption” and “Bone formation”, with different combinations. We only selected articles with abstracts in English or Spanish and discarded clinical cases and articles with inappropriate statistical study. A total of 40 articles were selected. Evidence synthesisIn different studies reviewed, it has been observed that patients with hypercalciuria have a higher bone mineral density loss with respect to normocalciuric. Among patients with calcium stones (normocalciuric or hypercalciuric), there is loss of bone mineral density, being more evident in patients with stones and hypercalciuria. This mineral density loss is marked and important in patients with recurrent calcium stones. Increased markers like fasting calcium/creatinine and β-CrossLaps are determinant of nephrolithiasis and mineral density loss in these patients. ConclusionWe recommend performing markers of bone turnover and fasting calcium/creatinine in patients with recurrent calcium stones by the significant presence of bone mineral density loss, with a level of evidence III.

English

Abstract IntroductionThe genetics underlying the idiopath-ic hypercalciuria leading to calcium-containing renal stones remains elus-ive. The discovery of rare monogenic tubulopathies, often leading to hype-rcalciuria, has increased our underst-anding of tubular physiology and pat-ho-physiology. However, insights int-o idiopathic calcium stone formation have not been gained from these dis-orders. The aim of this study is to ex-amine CYP24A1 mutations in cohorts of patients with calcium nephrolithi-asis.Materials and MethodsWe examined two cohorts of stone-forming patients for mutations in CYP24A1, which encodes the vitamin D24-hydroxylase enzyme. The first cohort had a biochemical phenotype of suppressed parathyroid hormone and high normal serum calcium, whilst the second cohort had a hypercalciuria phenotype. We did not identify bi-allelic sequence variants in CYP24A1 in our cohorts.ResultsIn cohort 1, we identified 9 known s-equence variants. In cohort 2 we ide-ntified 7 known sequence variants.ConclusionCYP24A1 mutations remain a rare cause of calcium nephrolithiasis and hypercalciuria.

Nutrition in calcium nephrolithiasis

Idiopathic calcium nephrolithiasis is a multifactorial disease with a complex pathogenesis due to genetic and environmental factors. The importance of social and health effects of nephrolithiasis is further highlighted by the strong tendency to relapse of the disease. Long-term prospective studies show a peak of disease recurrence within 2–3 years since onset, 40-50% of patients have a recurrence after 5 years and more than 50-60% after 10 years. International nutritional studies demonstrated that nutritional habits are relevant in therapy and prevention approaches of nephrolithiasis. Water, right intake of calcium, low intake of sodium, high levels of urinary citrate are certainly important for the primary and secondary prevention of nephrolithiasis.In this review is discussed how the correction of nutritional mistakes can reduce the incidence of recurrent nephrolithiasis.

The changing profile of patients with calcium nephrolithiasis and the ascendancy of overweight and obesity: a comparison of two patient series observed 25 years apart

Epidemiological data indicate an increasing incidence and prevalence of nephrolithiasis (NL) worldwide in the last few decades. The aim of this study was to compare the clinical and biochemical profiles of recurrent stone formers referred to a Kidney Stone Centre from March 1983 to June 1986 with the one featured by patients seen 25 years later in the same geographical area, Campania, southern Italy. Idiopathic calcium stone formers made up the large majority of the patient population in both series. Those examined in 2008-11 showed higher age at the onset of NL, higher prevalence of overweight/obesity and higher urinary excretion of oxalate and phosphate compared with those seen in 1983-86. The differences in the urinary biochemical variables remained significant upon accounting for age, gender, creatinine clearance and body mass index (BMI), and were not observed in patients with primary hyperparathyroidism enrolled in the same periods. A greater prevalence of uric acid stone formers was also observed in the 2008-11 population. The massive epidemics of overweight/obesity and the substantial modifications of dietary habits over the last few decades in most Western countries may be the factors underlying the changing clinical and biochemical profiles of patients with recurrent NL.

Calcium renal lithiasis: metabolic diagnosis and medical treatment

Calcium renal lithiasis is a frequent condition that affects the worldwide population and has a high recurrence rate. Different metabolic changes may trigger the onset of calcium stone disorders, such as hypercalciuria, hyperoxaluria, hyperuricosuria, hypocitraturia and others. There are also other very prevalent disorders that are associated with calcium calculi, such as arterial hypertension, obesity and loss of bone mineral density. A correct diagnosis needs to be obtained through examining the serum and urinary parameters of mineral metabolism in order to carry out adequate prevention and treatment of this condition. Once the metabolic diagnosis is known, it is possible to establish dietary and pharmacological treatment that may enable monitoring of the disease and prevent recurrence of stone formation. Some advances in treating this pathological condition have been made, and these include use of sodium alendronate in patients with calcium renal lithiasis and osteopenia/osteoporosis, or use of a combination of a thiazide with a bisphosphonate. In summary, calcium renal lithiasis often requires multidrug treatment with strict control and follow-up of patients.

Litiasis renal cálcica y densidad mineral ósea. Importancia del metabolismo óseo en la litiasis urinaria

ContextCalcium Nephrolithiasis is a multifactorial disease; in its pathophysiology is involved various minerals and metabolic factors that may be altered, including bone and phosphor-calcium metabolism. ObjectiveTo establish the scientific evidence and demonstrate the relationship between calcium nephrolithiasis and bone mineral density loss, through the use of bone turnover markers, serum and urinary metabolites. Evidence acquisitionWe performed a PubMed literature review using different MeSH Terms like «Nephrolithiasis» «Bone mineral density»,«Urinary stones», «Calcium», «Bone resorption» and «Bone formation», with different combinations. We only selected articles with abstracts in English or Spanish and discarded clinical cases and articles with inappropriate statistical study. A total of 40 articles were selected. Evidence synthesisIn different studies reviewed have been observed that patients with hypercalciuria have a higher bone mineral density loss with respect to normocalciuric. Among patients with calcium stones (normocalciuric or hypercalciuric), there is loss of bone mineral density, being more evident in patients with stones and hypercalciuria. This mineral density loss is marked and important in patients with recurrent calcium stones. Increased markers like fasting calcium/creatinine and β-CrossLaps are determinant of nephrolithiasis and mineral density loss in these patients. ConclusionWe recommend perform markers of bone turnover and fasting calcium/creatinine in patients with recurrent calcium stones by the significant presence of bone mineral density loss, with a level of evidence III.

Familial clustering of medullary sponge kidney is autosomal dominant with reduced penetrance and variable expressivity

Medullary sponge kidney (MSK) is a renal malformation typically associated with nephrocalcinosis and recurrent calcium nephrolithiasis. Approximately 12% of recurrent stone formers have MSK, which is generally considered a sporadic disorder. Since its discovery, three pedigrees have been described in which an apparently autosomal dominant inheritance was suggested. Here, family members of 50 patients with MSK were systematically investigated by means of interviews, renal imaging, and biochemical studies in an effort to establish whether MSK is an inheritable disorder. Twenty-seven MSK probands had 59 first- and second-degree relatives of both genders with MSK in all generations. There were progressively lower mean levels of serum calcium, urinary sodium, pH, and volume, combined with higher serum phosphate and potassium from probands to relatives with bilateral, to those with unilateral, and to those unaffected by MSK. This suggests that most affected relatives have a milder form of MSK than the probands, which would explain why they had not been so diagnosed. Thus, our study provides strong evidence that familial clustering of MSK is common, and has an autosomal dominant inheritance, a reduced penetrance, and variable expressivity.

When to suspect a genetic disorder in a patient with renal stones, and why

Nephrolithiasis is a common disorder, with a rising prevalence in the general population. Its pathogenesis is still unclear, but a role for genetics has long been recognized, especially in cases of the more common calcium nephrolithiasis. Although relatively rare, monogenic causes of hypercalciuria and nephrolithiasis do exist and their timely recognition is important from a prognostic and therapeutic viewpoint. This article reviews the clinical and laboratory findings characterizing inherited causes of nephrolithiasis with a view to helping clinicians to recognize and manage these rare conditions.

Correlation of the body mass index and calcium nephrolithiasis in adult population.

ABSTRACTIntroduction:Prevalence of the kidney stones (renal calculi) increase in several countries in parallel with the increase of overweight, diabetes (type 2 diabetes) and hypertension.Goal:The goal of our research was to evaluate the connection between the calcium nephrolithiasis and overweight, as quantified using the Body Mass Index (BMI) of the adult population, with a particular reflection on the age groups within it.Material and methods:The research was prospective and it was implemented at the Clinical Center of Banja Luka, at the Urology Clinic in the period from 1st April 2012 to 1st January 2013. The trial encompassed 120 patients with calcium nephrolithiasis of the upper part of the urinary tract and 120 patients without nephrolithiasis. A group of patients with the calcium nephrolithiasis presented a working group, while a group of patients without nephrolithiasis presented a control group. The BMI obtained on the basis of bodily weight and height of the patient, where the age and sex of specific reference values of the BMI were developed by the Center for Disease Control and Prevention (CDC) were not used in the calculation of the BMI.Results:Analyzing the values of the BMI in relation to age groups, where there was a statistically significant difference in the working group, whereas in the control group there was a statistically high significant difference, testing of statistical significance of the average value of the BMI was done by observed age groups of working and control group, as well as to the total sample of work and control group using the Chi-Square test and T-test for independent samples. Having observed the age group of 20-40 years, statistically significant differences have been noted at the level of risk of 10%, which confirms that there is a connection between the categories of the BMI and the group, which the patient comes from (Chi-Square test p-0.05), that is, T-test has shown that the values are different at the level of 10%, i.e. p<0.1 (p=0.073). Having observed the age group 40-60, there was no dependency between the category of the BMI and the group, that is, the differences are not statistically significant, p>0.05 (t-test p=0.314). In addition to this, the average BMI values are not significantly different, p>0.05 (t-test p=0.871). Having observed the age group of the older than 60, there was no dependency between the category of the BMI and the group, that is, the differences are not statistically significant, p>0.05 (Chi-square test p=0.167). Having observed the total sample of the working and control group, there was no dependency of the category of the BMI and the group (or urolithiasis), p>0.05 (Chi-Square test p=1.208), whereas the results of the T-test showed that there was no statistically significant difference of the arithmetic mean values of the BMI working group and control group, p>0.05 (t-test p=0.620).Conclusion:Overweight in younger age groups of adult population may be connected to the occurrence of calcium nephrolithiasis, thus we suggest that urolithiasis should be considered with them, as part of overweight, by which a change of living habits and the manner of food consumption could prevent this disease.

Bone and Metabolic Markers in Women With Recurrent Calcium Stones

PurposeThe target of our work was to study several biochemical parameters in phospho-calcic and bone metabolism in blood and urine and the bone mineral density of women with recurrent calcium nephrolithiasis.Materials and MethodsWe conducted a cross-sectional study with a control group of 85 women divided into 3 groups: group 1 consisted of 25 women without a history of nephrolithiasis, group 2 consisted of 35 women with only one episode of calcium nephrolithiasis, and group 3 consisted of 25 women with a history of recurrent calcium nephrolithiasis. Blood and urine biochemical study was performed, including markers related to lithiasis, and a bone mineral density study was done by use of bone densitometry.ResultsPatients in group 3 showed statistically significantly elevated calciuria (15.4 mg/dL), fasting calcium/creatinine ratio (0.14), and 24-hour calcium/creatinine ratio (0.21) compared with groups 1 and 2. Moreover, this group of women with recurrent calcium nephrolithiasis had significantly elevated values of beta-crosslaps, a bone resorption marker, compared with groups 1 and 2 (p=0.000) and showed more bone mineral density loss than did these groups.ConclusionsRecurrent calcium nephrolithiasis in women has a significant association with bone mineral density loss and with values of calciuria, both fasting and 24-hour.

Role of carbonic anhydrase and urine acidification in calcium nephrolithiasis

Role of carbonic anhydrase and urine acidification in calcium nephrolithiasis

The Role of Claudin in Hypercalciuric Nephrolithiasis

Calcium nephrolithiasis is a common condition. Family-based genetic linkage studies and genome-wide association studies (GWASs) have uncovered a run of important candidate genes involved in renal Ca(++) disorders and kidney stone diseases. The susceptible genes include NKCC2, ROMK and ClCkb/Barttin that underlie renal salt excretion; claudin-14, -16 and -19 that underlie renal Ca(++) excretion; and CaSR that provides a sensing mechanism for the kidney to regulate salt, water and Ca(++) homeostasis. Biological and physiological analyses have revealed the cellular mechanism for transepithelial Ca(++) transport in the kidney that depends on the concerted action of these gene products. Although the individual pathogenic weight of the susceptible genes in nephrolithiasis remains unclear, perturbation of their expression or function compromises the different steps within the integrated pathway for Ca(++) reabsorption, providing a physiological basis for diagnosing and managing kidney stone diseases.

Osteopenia/osteoporosis in patients with calcium nephrolithiasis

The objective of this study is to analyze the alterations in bone mineral density and bone and calcium-phosphorus metabolism in patients with calcium nephrolithiasis. We designed a study with 182 patients who were distributed among three groups: group O, 56 patients without nephrolithiasis; group A, 67 patients with calcium nephrolithiasis and mild lithogenic activity; and group B, 59 patients with calcium nephrolithiasis and severe lithogenic activity. Metabolic parameters of blood and urine that were related to calcium-phosphorous and bone metabolism and bone densitometry were assessed in all patients. A comparative study was performed on the variables of bone and calcium-phosphorus metabolism and bone densitometry as well as the presence or absence of osteopenia/osteoporosis. The patients in group B had a greater loss of bone mineral density, measured by the T-score, than the patients in groups O and A. Moreover, the proportion of patients in group B with osteopenia/osteoporosis was statistically significantly higher than the proportion of patients in groups O and A. We observed higher values of calciuria, fasting calcium/creatinine ratio, and 24-h calcium/creatinine among the patients in group B compared to the other two groups. Calciuria, citraturia, and fasting calcium/creatinine were independent factors that showed a relationship with severe lithogenic activity compared to the control group, and β-crosslaps is an independent factor that has a relationship with severe lithogenic activity as compared to mild lithogenic activity. Patients with calcium lithiasis and severe lithogenic activity have a greater loss in bone mineral density and therefore a greater risk of osteopenia/osteoporosis.

Importance of citrate and the calcium : citrate ratio in patients with calcium renal lithiasis and severe lithogenesis

Different studies have shown the importance of citrate in the formation of calcium stones. It has further been shown that the states of metabolic acidosis result in an increase in bone resorption and lower urinary citrate levels. Increasing the intake of citrate in these patients can reduce the lithogenic risk and improve bone mineral density (BMD), contributing to control of both diseases. The study shows the importance of citrate in patients with calcium stones and BMD loss. The deficit in citrate excretion is associated with a decrease in bone mineralization and increased β-crosslaps. A calcium : citrate ratio >0.25 in patients with calcium stones and loss of mineral density may predict severe lithogenic activity. To analyse the importance of urinary citrate and the urinary calcium : citrate ratio in patients with calcium renal lithiasis and severe lithogenesis compared with a control group of patients without lithiasis. A cross-sectional study of 115 patients in eastern Andalusia, Spain was conducted. The patients were divided into two groups: Group A: 56 patients aged 25-60 years without calcium renal lithiasis; Group B: 59 patients aged 25-60 years, presenting with calcium renal lithiasis and severe lithogenesis. The citrate levels and the calcium : citrate ratio in the patients' urine and the relationship of these two factors to lithiasic activity were analysed and compared. In Group B, 32.2% of the patients presented with hypocitraturia, compared with 14.3% of the patients in Group A (P = 0.02). The urinary citrate levels were lower in Group B than in Group A (P = 0.001) and the calcium : citrate ratio was higher in Group B than in Group A (P = 0.005). The results suggest that a patient urinary calcium : citrate ratio > 0.25 indicates severe lithogenesis (with a sensitivity of 89% and a specificity of 57%). After linear regression analysis, we found that the urinary citrate level is an independent factor associated with the changes in bone densitometry T-score values of patients. The patients with severe lithogenesis presented with hypocitraturia, which was associated with lower bone mineral density. The calcium : citrate ratio, which is linearly related to the bone resorption marker β-crosslaps, could be useful in evaluating the risk of severe lithogenesis when this ratio is >0.25.

Importance of citrate and the calcium : citrate ratio in patients with calcium renal lithiasis and severe lithogenesis

Stone disease and osteopaenia are both common conditions, and reduced bone mineral density (BMD) is an increasingly recognized complication in stone formers; indeed, in a previous paper in BJUI, Arrabal-Polo et al. 1 reported that patients with recurrent stones have lower BMD compared with controls or patients with just a single episode of urolithiasis. Although the exact pathogenesis of bone loss in stone disease is yet to be determined, the conceptually obvious relationship with hypercalciuria is well documented 2. In the present study, Arrabal-Polo et al. emphasise that hypocitraturia is also associated with reduced BMD. Furthermore, they found a higher calcium : citrate ratio in patients with a cumulative maximum stone diameter >20 mm, or in those with frequent recurrences than in controls, and found that this correlated with higher levels of β-crosslaps, consistent with increased bone resorption in these patients. We commented in our previous editorial that metabolic abnormalities should be sought in recurrent stone formers, and managed in a multi-disciplinary setting 3. In addition to dietary advice, options for treatment include bisphosphonates (which inhibit bone resorption, and are commonly used in osteoporosis), thiazide diuretics (which reduce calcium excretion and can increase BMD) and potassium citrate (which acts as an alkalinizing agent mitigating the bone restorative effect of acidosis) 2. This approach is supported by recent data in medullary sponge kidneys, in which hypercalciuria and hypocitraturia were commonly detected in association with reduced BMD. Patients who were treated with potassium citrate were found to have increased urinary pH citrate levels, and an improvement in their BMD 4. In the present article, Arrabal-Polo et al. suggest using a calcium : citrate ratio of 0.25 for predicting the risk of future recurrent stone formation, but this value could equally be used to predict the risk of patients having reduced BMD and the complications that may follow. Either way, their findings strengthen the argument for metabolic screening of recurrent stone formers, and for an assessment of these patients' BMD. Patients can then be appropriately treated with a thiazide diuretic, potassium citrate, or a bisphosphonate, either singly or in combination, according to the abnormalities detected and their progress on treatment.