Recurrent Calcium Oxalate Stone Research Articles

In vivo base editing rescues primary hyperoxaluria type 1 in rats

Primary hyperoxaluria type 1 (PH1) is a childhood-onset autosomal recessive disease, characterized by nephrocalcinosis, multiple recurrent urinary calcium oxalate stones, and a high risk of progressive kidney damage. PH1 is caused by inherent genetic defects of the alanine glyoxylate aminotransferase (AGXT) gene. The invivo repair of disease-causing genes was exceedingly inefficient before the invention of base editors which can efficiently introduce precisely targeted base alterations without double-strand DNA breaks. Adenine base editor (ABE) can precisely convert A·T to G·C with the assistance of specific guide RNA. Here, we demonstrated that systemic delivery of dual adeno-associated virus encoding a split-ABE8e could artificially repair 13% of the pathogenic allele in AgxtQ84X rats, a model of PH1, alleviating the disease phenotype. Specifically, ABE treatment partially restored the expression of alanine-glyoxylate-aminotransferase (AGT), reduced endogenous oxalate synthesis and alleviated calcium oxalate crystal deposition. Western blot and immunohistochemistry confirmed that ABE8e treatment restored AGT protein expression in hepatocytes. Moreover, the precise editing efficiency in the liver remained stable six months after treatment. Thus, our findings provided a prospect of invivo base editing as a personalized and precise medicine for PH1 by directly correcting the mutant Agxt gene.

Diagnostic value of urinary Tamm-Horsfall protein and 24 h urine osmolality for recurrent calcium oxalate stones of the upper urinary tract: Cross-sectional study.

We aimed to investigate the diagnostic value of urinary Tamm-Horsfall protein (THP) and 24 h urine osmolality for recurrent calcium oxalate (CaOx) stones. Clinical data of 120 patients with upper urinary tract stones admitted to our hospital between January 2020 and January 2022 were retrospectively reviewed. Patients were divided into recurrence (53 patients) and non-recurrence (67 patients) groups based on postoperative stone recurrence. Meanwhile, 50 healthy patients were selected as the control group. Urinary THP levels, 24 h urine osmolality, and biochemical indices were compared between the three groups; their diagnostic values for stone recurrence were evaluated using receiver operating characteristic (ROC) curves. Urinary THP, 24 h urine osmolality, and biochemical indices were significantly higher in the recurrence group than in the non-recurrence and control groups (P < 0.05). The 24 h urine osmolality was positively correlated with urinary oxalic acid and calcium excretion. ROC curve analysis showed that optimal cutoff values of urinary THP and 24 h urine osmolality for the diagnosis of stone development were ≥27.01 mg/L and ≥577.69 mOsm/(kg H2O), respectively. Furthermore, these indices combined significantly improved the accuracy of diagnosis. Urinary THP and 24 h urine osmolality were higher in patients with recurrent CaOx stones. Detection of both parameters combined can accurately diagnose stone recurrence.

The altered composition of gut microbiota and biochemical features as well as dietary patterns in a southern Chinese population with recurrent renal calcium oxalate stones.

The correlation among gut microbiota, biochemical features, and dietary patterns in recurrent stone formers has been inadequately investigated in the Chinese population. Forty-two patients with calcium oxalate stones (CaOxS group), including 34 recurrent stone formers (RS group), and 40 nonstone healthy subjects (NS group) from Changshu Hospital Affiliated with Soochow University, were prospectively recruited. Food frequency questionnaires were completed by participants, fasting vein blood was extracted, 24-h urine was collected for biochemical detection, and fecal samples were gathered for 16S ribosomal RNA (rRNA) gene sequencing. BMI; serum levels of triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), magnesium, and creatinine; and urine levels of magnesium in stone formers were significantly different from those of controls, and RS patients showed significantly low serum phosphate and high urine phosphate levels. Celery, bamboo shoots, and pickled food were the favored foods of local stone formers. Patients with recurrent stones had altered microbiota composition, with Escherichia, Fusobacterium, and Epulopiscium being the predominant pathogenic genera. The gut microbiota in RS patients had stronger functions in fatty acid and amino acid degradation but weaker functions in their biosynthesis. The pathogenic genera were positively correlated with BMI; serum levels of TGs and creatinine; urine levels of calcium, phosphate, and uric acid (UA); and celery, bamboo shoots, and pickled food intake. The abundance of Escherichia and Fusobacterium and the levels of serum magnesium and creatinine were the most relevant factors associated with stone recurrence and could be validated as biomarkers of recurrence. Our research provides a novel prevention strategy for the recurrence of renal calcium oxalate stones in the Han Chinese population of southern China.

Primary hyperoxaluria: Comprehensive mutation screening of the disease causing genes and spectrum of disease-associated pathogenic variants.

The primary hyperoxalurias are rare disorders of glyoxylate metabolism. Accurate diagnosis is essential for therapeutic and management strategies. We conducted a molecular study on patients suffering from recurrent calcium-oxalate stones and nephrocalcinosis and screened primary hyperoxaluria causing genes in a large cohort of early-onset cases. Disease-associated pathogenic-variants were defined as missense, nonsense, frameshift-indels, and splice-site variants with a reported minor allele frequency <1% in controls. We found pathogenic-variants in 34% of the cases. Variants in the AGXT gene causing PH-I were identified in 81% of the mutation positive cases. PH-II-associated variants in the GRHPR gene are found in 15% of the pediatric PH-positive population. Only 3% of the PH-positive cases have pathogenic-variants in the HOGA1 gene, responsible to cause PH-III. A population-specific AGXT gene variant c.1049G>A; p.Gly350Asp accounts for 22% of the PH-I-positive patients. Pathogenicity of the identified variants was evaluated by in-silico tools and ACMG guidelines. We have devised a rapid and low-cost approach for the screening of PH by using targeted-NGS highlighting the importance of an accurate and cost-effective screening platform. This is the largest study in Pakistani pediatric patients from South-Asian region that also expands the mutation spectrum of the three known genes.

Sequencing the CaSR locus in Pakistani stone formers reveals a novel loss-of-function variant atypically associated with nephrolithiasis

BackgroundNephrolithiasis (NL) affects 1 in 11 individuals worldwide and causes significant morbidity and cost. Common variants in the calcium sensing receptor gene (CaSR) have been associated with NL. Rare inactivating CaSR variants classically cause hyperparathyroidism, hypercalcemia and hypocalciuria. However, NL and familial hypercalciuria have been paradoxically associated with select inactivating CaSR variants in three kindreds from Europe and Australia.MethodsTo discover novel NL-associated CaSR variants from a geographically distinct cohort, 57 Pakistani families presenting with pediatric onset NL were recruited. The CaSR locus was analyzed by directed or exome sequencing.ResultsWe detected a heterozygous and likely pathogenic splice variant (GRCh37 Chr3:122000958A>G; GRCh38 Chr3:12228211A>G; NM_000388:c.1609-2A>G) in CaSR in one family with recurrent calcium oxalate stones. This variant would be predicted to cause exon skipping and premature termination (p.Val537Metfs*49). Moreover, a splice variant of unknown significance in an alternative CaSR transcript (GRCh37 Chr3:122000929G>C; GRCh38 Chr3:122282082G >C NM_000388:c.1609-31G >C NM_001178065:c.1609-1G >C) was identified in two additional families.ConclusionsSequencing of the CaSR locus in Pakistani stone formers reveals a novel loss-of-function variant, expanding the connection between the CaSR locus and nephrolithiasis.

Nephrolithiasis (part 2): Diagnosis, management and prevention of recurrent nephrolithiasis

Work-up of patients with calcium oxalate stones should be restricted to those who have multiple episodes (50% of stone formers). There are exceptions, such as pilots, fire-workers, people in the armed forces, those with a single kidney and children (&lt;19 years old). The most important aspect of therapy is to correct dietary aberrations, i.e. the ‘clinic effect’. The four golden rules to correct dietary influences are to maintain an adequate 24-hour urine volume, to restrict salt intake, to avoid red meat and to avoid a diet high in oxalate. In particular, Ceylon tea is contraindicated, as it contains excess oxalate. Drink coffee instead. In patients with hypocitraturia, the drug of choice is potassium citrate, which is the only acceptable urinary alkaliser. Other preparations, such as Urolyte-U, Citrosoda, etc., all have a high sodium content, which will influence urinary calcium excretion. In patients with ongoing hypercalciuria, thiazides are contraindicated in the management of recurrent calcium oxalate stones, and indapamide is the drug of choice. The treatment and follow-up are lifelong. In addition, poor adherence to treatment, coupled with repeated urological procedures, may result in renal functional deterioration and even occasionally renal failure.

Changes in renal papillary density after hydration therapy in calcium stone formers

BackgroundPrevious studies have shown that, compared with non-stone formers, stone formers have a higher papillary density measured with computer tomography (CT) scan. The effect of increased hydration on such papillary density in idiopathic calcium stone formers is not known.MethodsPatients with recurrent calcium oxalate stones undergoing endourological procedures for renal stones at our Institution from June 2013 to June 2014 were considered eligible for enrolment. Enrolled patients underwent a baseline unenhanced CT scan before the urological procedure; after endoscopic removal of their stones, the patients were instructed to drink at least 2 L/day of a hypotonic, oligomineral water low in sodium and minerals (fixed residue at 180 °C < 200 mg/L) for at least 12 months. Finally, the patients underwent a follow-up unenhanced CT scan during hydration regimen.ResultsTwenty-five patients were prospectively enrolled and underwent baseline and follow-up CT scans. At baseline, mean papillary density was 43.2 ± 6.6 Hounsfield Units (HU) (43.2 ± 6.7 for the left kidney and 42.8 ± 7.1 HU for the right kidney). At follow-up and after at least 12 months of hydration regimen, mean papillary density was significantly reduced at 35.4 ± 4.2 HU (35.8 ± 5.0 for the left kidney and 35.1 ± 4.2 HU for the right kidney); the mean difference between baseline and follow-up was − 7.8 HU (95% confidence interval − 10.6 to − 5.1 HU, p < 0.001).ConclusionsIncreased fluid intake in patients with recurrent calcium oxalate stones was associated with a significant reduction in renal papillary density.Trial registrationNCT03343743, 15/11/2017 (Retrospectively registered).

Short-Term Changes in Urinary Relative Supersaturation Predict Recurrence of Kidney Stones: A Tool to Guide Preventive Measures in Urolithiasis

Kidney stone disease is characterized by a relatively high rate of recurrence. In our study we analyzed the association between relative supersaturation and the risk of stone recurrence. Additionally, we examined the association between the risk of recurrence and changes in relative supersaturation and urinary composition after 1 week of medical treatment. We performed a post hoc analysis of data from a previously published randomized controlled trial comparing the effect of 2 diets in 120 men with recurrent calcium oxalate stones and hypercalciuria. Baseline and followup 24-hour urine parameters were used to calculate the relative supersaturation of calcium oxalate, calcium phosphate and uric acid using the EQUIL2, JESS and LithoRisk computer programs. Cox models were used to calculate the estimated association between each baseline relative supersaturation, and 1-week changes and the risk of recurrence during followup. During a 5-year followup 35 patients (34%) experienced recurrence. A reduction in calcium oxalate relative supersaturation at 1 week was significantly associated with a lower risk of recurrence using the EQUIL2 calculation (for every 10% reduction from baseline HR 0.92, 95% CI 0.86-1.00, p = 0.044). However, there was no association for relative supersaturation calculated by other methods or for the relative supersaturation of other salts. Changes in the 24-hour urine excretion of citrate, potassium and magnesium were significantly associated with a risk of recurrence. In recurrent stone formers with hypercalciuria baseline values and changes in the relative supersaturation of calcium oxalate may be associated with the risk of recurrence. Changes in urinary citrate, potassium and magnesium following dietary intervention may also be predictive.

Designer probiotic Lactobacillus plantarum expressing oxalate decarboxylase developed using group II intron degrades intestinal oxalate in hyperoxaluric rats

Increased intestinal absorption of oxalate causes hyperoxaluria, a major risk factor for kidney stone disease. Intestinal colonization of recombinant probiotic bacteria expressing oxalate-degrading gene (OxdC) is an effective therapeutic option for recurrent calcium oxalate (CaOx) stone disease. Therefore, we aimed to develop food-grade probiotic L. plantarum secreting OxdC using lactococcal group II intron, Ll.LtrB and evaluate its oxalate degradation ability in vivo. Male Wistar albino rats were divided into four groups. The rats of group I received normal rat chow and drinking water. Groups II, III and IV rats received 5% potassium oxalate containing diet for 28 days. Groups III and IV rats received L. plantarum and food-grade recombinant L. plantarum respectively from 15 to 28 days. Biochemical parameters and crystalluria were analysed in 24 h urine samples. At the end of experimental period, rats were sacrificed; intestine and kidneys were dissected out for colonization studies and histopathological analysis. Herein, we found that the administration of recombinant probiotics significantly reduced the urinary oxalate, calcium, urea, and creatinine levels in rats of group IV compared to group II. Furthermore, colonization studies indicated that recombinant probiotics have gastrointestinal transit and intestinal colonization ability similar to that of wild-type bacteria. In addition, gene expression studies revealed down-regulation of OPN and KIM-1 among group IV rats. Histopathological analysis showed less evidence of nephrocalcinosis in group IV rats. In conclusion, the study demonstrates that food-grade L. plantarum secreting OxdC is capable of degrading intestinal oxalate and thereby prevent CaOx stone formation in experimental rats.

Изменение концентрации маркеров мочекаменной болезни в зависимости от степени активности камнеобразования у пациентов с рецидивирующим уролитиазом

The study comprised 152 patients with recurrent calcium oxalate stones at various localizations. Patients of the study group (n=78) were administered complex preventive treatment (water load, Blamaren, thiazide diuretics, oral calcium supplementation) aimed at reducing the activity of urolithiasis. Patients of the control group (n=74) received no treatment. The studied parameters included concentrations of urine bikunin, osteopontin, and nephrocalcin in using ELISA. The follow-up period was six months. By the end of the follow-up, the bikunin concentration in the control group was significantly higher than in the study group (7.0+/-0.81 mg/ml vs. 3.28+/-0.86 mg/ml, respectively, p<0.05) while osteopontin level was significantly lower (2.4+/-0.39 mg/ml vs. 3.4+/-0.36 mg/ml, p<0.05). The nephrocalcin concentrations during the follow-up period did not change significantly (p>0.05). The presence of hypercalciuria did not lead to significant changes in the concentration of stone formation inhibitors. The increase in bikunin concentration in control patients is associated with an increase in the expression of this stone formation inhibitor due to the rise in the urolithiasis activity. Reduction in the osteopontin concentration in patients with high urolithiasis activity is a consequence of osteopontin being a constituent of calcium oxalate stones. In patients with calcium oxalate urolithiasis, testing for urine concentrations of bikunin and osteopontin as potential markers can be used to estimate the risk of stone recurrence.

Changes in urinary risk profile after short-term low sodium and low calcium diet in recurrent Swiss kidney stone formers

BackgroundKidney stone disease is common in industrialized countries. Recently, it has attracted growing attention, because of its significant association with adverse renal outcomes, including end stage renal disease. Calcium-containing kidney stones are frequent with high recurrence rates. While hypercalciuria is a well-known risk factor, restricted intake of animal protein and sodium, combined with normal dietary calcium, has been shown to be more effective in stone prevention compared with a low-calcium diet. Notably, the average sodium intake in Switzerland is twice as high as the WHO recommendation, while the intake of milk and dairy products is low.MethodsWe retrospectively analyzed Swiss recurrent kidney stone formers (rKSF) to test the impact of a low-sodium in combination with a low-calcium diet on the urinary risk profile. In patients with recurrent calcium oxalate containing stones, we investigated both, the consequence of a low-sodium diet on urinary volume and calcium excretion, and the influence of a low-sodium low-calcium diet on urinary oxalate excretion.ResultsOf the 169 patients with CaOx stones, 49 presented with hypercalciuria at baseline. The diet resulted in a highly significant reduction in 24-h urinary sodium and calcium excretion: from 201 ± 89 at baseline to 128 ± 88 mmol/d for sodium (p < 0.0001), and from 5.67 ± 3.01 to 4.06 ± 2.46 mmol/d (p < 0.0001) for calcium, respectively. Urine volume remained unchanged. Notably, no increase in oxalate excretion occurred on the restricted diet (0.39 ± 0.26 vs 0.39 ± 0.19 mmol/d, p = 0.277). Calculated Psf (probability of stone formation) values were only predictive for the risk of calcium phosphate stones.ConclusionA diet low in sodium and calcium in recurrent calcium oxalate stone formers resulted in a significant reduction of urinary calcium excretion, but no change in urine volume. In this population with apparently low intake of dairy products, calcium restriction does not necessarily result in increased urinary oxalate excretion. However, based on previous studies, we recommend a normal dietary calcium intake to avoid a potential increase in urinary oxalate excretion and unfavorable effects on bone metabolism in hypercalciuric KSFs.

MP90-04 A NOVEL USE OF STRUCTURED WATER FOR THE PREVENTION OF RECURRENT STONES IN IDIOPATHIC HYPERCALCIURIA.

You have accessJournal of UrologyStone Disease: Medical & Dietary Therapy1 Apr 2017MP90-04 A NOVEL USE OF STRUCTURED WATER FOR THE PREVENTION OF RECURRENT STONES IN IDIOPATHIC HYPERCALCIURIA. Ali Sami Ali SamiAli Sami More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2017.02.2823AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES The majority of stones (85%) contain primarily calcium oxalate. Most renal stones are idiopathic calcium stones, and the most common predisposing factor in these patients is hypercalciuria. Structured water is a new type of water that has been prepared using different types of energy fields and modulators to produce this structured water that has new and different characteristics from the ordinary water. In this study, we compared the efficacy of the structured water (Magnalife®) with hydrochlorothiazide and with ordinary bottled water in the prevention of recurrent renal stones in patients with idiopathic hypercalciuria. METHODS We conducted a three-year randomized trial comparing the effect of structured water with the effect of hydrochlorothiazide and ordinary bottled water in 300 patients with recurrent calcium oxalate stones and hypercalciuria. 100 men used structured water (Magnalife®). The other 100 men used 50 mg hydrochlorothiazide, and 100 men used ordinary bottled water. Urine analysis with renal ultrasonography and radiology were done at baseline and at yearly intervals and any time of recurrence and at the end of the 3 years (36th month). All patients were informed and signed a written informed consent form. RESULTS Of the 300 men included in this study, 95 had recurrent stones, 15 men (15%) in the group of structured water ,31 men (31%) in the hydrochlorothiazide group, and 49 men (49%) in the group of ordinary bottled water. The difference in the recurrence rate between the structured water group and the hydrochlorothiazide group is significant (P=0.007) Also the difference between the difference between the structured water group and the ordinary water group is significant (p<0.001), furthermore the hydrochlorothiazide group and the ordinary bottled water group recurrence rate is significantly different (P=0.009). CONCLUSIONS Structured water is a safe, effective, and affordable new way to prevent recurrent urinary stones without the need for medications that are expensive and have many side effects. Furthermore, it is more potent than some preventive measures and drugs as a prophylactic way against recurrent urinary stones. It is far more effective than ordinary bottled water in preventing recurrent stones. Further studies are recommended to explore its role in other fields of urology. © 2017FiguresReferencesRelatedDetails Volume 197Issue 4SApril 2017Page: e1211 Advertisement Copyright & Permissions© 2017MetricsAuthor Information Ali Sami More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Evidence for epistatic interaction between VDR and SLC13A2 genes in the pathogenesis of hypocitraturia in recurrent calcium oxalate stone formers.

Genetic factors play a key role in the pathogenesis of hypocitraturia, a common risk factor for nephrolithiasis. The Na+-dicarboxylate cotransporter NaDC1, encoded by the sodium-dicarboxylate cotransporter (SLC13A2) gene, is a major determinant of urinary citrate excretion and its biological functions are regulated also by the vitamin D/Vitamin D receptor (VDR) biological system. The aim of this case-control study was to evaluate the possible epistatic interaction between VDR rs731236and SLC13A2 rs11567842 allelic variants in the pathogenesis of hypocitraturia. Recurrent calcium-oxalate stone formers (SF) with or without hypocitraturia and healthy controls (C) were genotyped. Gene-gene interactions were estimated by the 1.0 software package of multifactor dimensionality reduction (MDR). The prevalence of VDR TT and SLC13A2 GG genotypes was higher in hypocitraturic SF compared to C (odds ratio [OR] 3.24, 95 % confidence interval [CI] 1.38-7.60 for VDR TT vs. VDR tt and OR 4.06, 95 % CI 1.75-9.42 for SLC13A2 GG vs. SLC13A2 AA ). MDR analysis indicated a significant interaction between VDR TT and SLC13A2 GG in hypocitraturic SF compared to C [OR 3.81 (2.11-6.88)]. These data are compatible with an epistatic interaction between the VDR TT and SLC13A2 GG genotypes with a significant impact on the magnitude of the effect (suppressive effect). These results point to an epistatic interaction between the VDR and the SLC13A2 alleles in the pathogenesis of idiopathic hypocitraturia in calcium-oxalate SF.

Probiotic properties of Oxalobacter formigenes: an in vitro examination.

Oxalobacter formigenes (O. formigenes) is a nonpathogenic, Gram-negative, obligate anaerobic bacterium that commonly inhabits the human gut and degrades oxalate as its major energy and carbon source. Results from a case-controlled study suggested that lack of O. formigenes colonization is a risk factor for recurrent calcium oxalate stone formation. Hence, O. formigenes colonization may prove to be an efficacious method for limiting calcium oxalate stone risk. However, challenges exist in the preparation of O. formigenes as a successful probiotic due to it being an anaerobe with fastidious growth requirements. Here we examine in vitro properties expected of a successful probiotic strain. The data show that the Group 1 O. formigenes strain OxCC13 is sensitive to pH<5.0, persists in the absence of oxalate, is aerotolerant, and survives for long periods when freeze-dried or mixed with yogurt. These findings highlight the resilience of this O. formigenes strain to some processes and conditions associated with the manufacture, storage and distribution of probiotic strains.

Metabolic assessment of recurrent and first renal calcium oxalate stone formers.

This study aimed to demonstrate the dominant role of metabolic disorders in the formation of calcium oxalate stones in patients with recurrent urolithiasis, as well as in patients experiencing their first episode of urolithiasis. The records of the patients who attended our kidney stone outpatient clinics between 2008 and 2012 were reviewed, and the data of 318 calcium oxalate stone patients who had undergone a metabolic assessment were retrospectively analysed. The patients were divided in two groups. The first group included the patients who presented with their first episode of urolithiasis (Group 1, n = 170), and the second group included patients with recurrent urolithiasis (Group 2, n = 148); intergroup comparisons of metabolic disorders were performed. A significant difference was found between the two groups in mean urine calcium levels (Group 1, 0.25; Group 2, 0.31; p = 0.001); the mean serum calcium level was found to be significantly higher although at less extent in Group 2 (Group 1, 9.4; Group 2, 9.6); p = 0.04). Significant differences were also found in mean urine citrate (Group 1, 481.9; Group 2, 397.2, p &lt; 0.0001) and oxalate levels (Group 1, 22.1; Group 2, 28.5; p &lt; 0.0001) . This study revealed a metabolic tendency to hypercalciuria in calcium oxalate stone patients, predominantly in those with recurrent calcium oxalate urolithiasis. Urinary oxalate excretion was found to be higher in recurrent urolithiasis in comparison to the first episode of calcium oxalate urolithiasis and urinary citrate excretion lower in recurrent urolithiasis.

Should we modify the principles of risk evaluation and recurrence preventive treatment of patients with calcium oxalate stone disease in view of the etiologic importance of calcium phosphate?

Prevention of recurrent calcium oxalate (CaOx) stone formation in the urinary tract is important to avoid negative effects on renal function, patient suffering and to reduce health care cost. Present shortcomings in this regard can be explained both by insufficient understanding of the mechanisms of stone formation and by poor patient compliance to those regimens that nevertheless have proven effective. During the past years, we have got increased insights in the nature of CaOx stone formation and it is suggested that the improved understanding of this process can be used for a more dynamic risk evaluation and treatment regimen directed to specific risk periods that can be identified in the individual patients. Some of the possibilities with regard to the important role of calcium phosphate are discussed in this article.

How much calcium supplement is recommended in a patient with osteoporosis and a history of calcium oxalate kidney stones?

Evidence-Based Answer The answer is unclear. When extrapolating from trials with postmenopausal women or patients with history of kidney stones, calcium intake alone does not appear to greatly increase the risk of recurrent calcium oxalate stones (SOR: C, extrapolation from RCTs).

Lack of evidence for the association of ornithine decarboxylase (+316 G&gt;A), spermidine/spermine acetyl transferase (−1415 T&gt;C) gene polymorphisms with calcium oxalate stone disease

Urolithiasis is a complex and multifactorial disorder characterized by the presence of stones in the urinary tract. Urea cycle is an important process involved in disease progression. L-ornithine is a key amino acid in the urea cycle and is converted to putrescine by ornithine decarboxylase (ODC). Putrescine, spermidine and spermine are natural polyamines that are catabolized by a specific enzyme, spermidine/spermine acetyltransferase (SSAT). The single-nucleotide polymorphisms (SNPs) in the intron region of ODC (+316 G>A) and promoter region of SSAT (-1415 T>C) genes have been found to be associated with the polyamines expression levels. The aim of this study was to examine whether the ODC (+316 G>A) intron 1 region gene polymorphism and SAT-1 promoter region (-1415 T>C) gene polymorphisms are potential genetic markers for susceptibility to urolithiasis. A control group of 104 healthy subjects and a group of 65 patients with recurrent idiopathic calcium oxalate stone disease were enrolled into this study. Polymerase chain reaction (PCR)-based restriction analysis was performed for the ODC intron 1 (+316 G>A) region and SAT-1 (-1415 T>C) promoter gene polymorphisms by PstI and MspI restriction enzyme digestion, respectively. The genotype distribution of polymorphisms studied in the ODC intron 1 region (+316 G>A) and SAT-1 -1415 T>C promoter region did not reveal a significant difference between urolithiasis and the control groups (P=0.713 and 0.853), respectively. Furthermore, no significant difference was observed between the control and patient groups for ODC +316 G>A and SAT-1 -1415 T>C allele frequencies (P=0.877 and 0.644), respectively. In conclusion, results of the present study suggest that ODC + 316 G>A and SAT-1 -1415 T>C gene polymorphisms might not be a risk factor for urolithiasis.

HumanSLC26A1Gene Variants: A Pilot Study

Kidney stones are a global health problem, incurring massive health costs annually. Why stones recur in many patients remains unknown but likely involves environmental, physiological, and genetic factors. The solute linked carrier (SLC) 26A1 gene has previously been linked to kidney stones in mice. SLC26A1 encodes the sulfate anion transporter 1 (SAT1) protein, and its loss in mice leads to hyperoxaluria and calcium oxalate renal stones. To investigate the possible involvement of SAT1 in human urolithiasis, we screened the SLC26A1 gene in a cohort of 13 individuals with recurrent calcium oxalate urolithiasis, which is the commonest type. DNA sequence analyses showed missense mutations in seven patients: one individual was heterozygous R372H; 4 individuals were heterozygous Q556R; one patient was homozygous Q556R; and one patient with severe nephrocalcinosis (requiring nephrectomy) was homozygous Q556R and heterozygous M132T. The M132 amino acid in human SAT1 is conserved with 15 other species and is located within the third transmembrane domain of the predicted SAT1 protein structure, suggesting that this amino acid may be important for SAT1 function. These initial findings demonstrate genetic variants in SLC26A1 of recurrent stone formers and warrant wider independent studies of SLC26A1 in humans with recurrent calcium oxalate stones.

Effects of dietary interventions on 24-hour urine parameters in patients with idiopathic recurrent calcium oxalate stones

The aim of this study is to investigate the effects of dietary factors on 24-hour urine parameters in patients with idiopathic recurrent calcium oxalate stones. A total of 108 of idiopathic recurrent calcium oxalate stones were included in the study. A 24-hour urinalysis was performed and metabolic abnormalities were measured for all of the patients. All of the patients were given specialized diets for their 24-hour urine abnormalities. At the end of first month, the same parameters were examined in another 24-hour urinalysis. Hyperoxaluria, hypernatruria, and hypercalciuria were found in 84 (77%), 43 (39.8%), and 38 (35.5%) of the patients, respectively. The differences between the oxalate, sodium, volume, uric acid, and citrate parameters before and after the dietary intervention were significant (p < 0.05). The calcium parameters were not significantly different before and after the intervention. We found that oxalate, sodium, volume, uric acid, and citrate—but not calcium—abnormalities in patients with recurrent calcium oxalate stones can be corrected by diet. The metabolic profiles of idiopathic calcium oxalate stone patients should be evaluated and the appropriate dietary interventions should be implemented to decrease stone recurrence.