Recurrent Calcium Nephrolithiasis Research Articles

Investigation of Allopurinol binding mechanism to allele HLA-A*33:03 by using Molecular Dynamics simulation

Allopurinol (ALP), a xanthine oxidase inhibitor, is an FDA-approved urate-lowering medication used to treat Gout, prevent tumor lysis syndrome, and prevent recurrent calcium nephrolithiasis in hyperuricosuria patients. However, it has been known as a common cause of severe cutaneous adverse drug reactions (SCAR) including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms (HSS/DRESS), especially in patients carrying the Human Leukocyte Antigens allele HLA-B*58:01, which is more prevalent in Asian population. However, although patients do not carry the HLA-B*58:01 allele, they still exhibit allopurinol-induced SCAR. Surprisingly, a large number of these patients have the HLA-A*33:03 allele. In this research, we investigated the binding of ALP to the HLA-A*33:03 structure using Molecular Dynamics (MD) simulation. Our results showed that the complex of HLA-A*33:03 and ALP was stable after 100000 ps simulation time. ALP had strong interactions with three important residues locating in the active site of HLA-A*33:03, which include the seven amino acid residues Val 76, Asp 77, Leu 81, Ile 95, Gln 96, Asp 116, and Tyr 123. This data suggests that ALP has strong binding affinity for this allele. Thus, in addition to HLA-B*58:01, HLA-A*33:03 may be a potential screening marker before prescribing Allopurinol for Gout treatment.

The Relationship Between Renal Stones and Primary Aldosteronism.

IntroductionThe association between primary aldosteronism (PA) and nephrolithiasis is still unclear. The hypercalciuria and hypocitraturia of PA patients might be the reason leading to recurrent calcium nephrolithiasis. This study aimed to evaluate the relationship between PA and renal stones, including stone size and density.Materials and MethodsFrom February 2010 to March 2021, we retrospectively collected 610 patients who presented to our medical center with hypertension history, and all these patients, suspicious of PA, had PA data survey. In total, 147 patients had kidney stone and were divided into 44 patients with essential hypertension as group 1 and 103 patients with PA as group 2. Pearson χ2 test and independent Student’s t-test were performed to examine the differences among variables.ResultsThe mean age was 54.4 ± 12.0 years in group 1 and 53.0 ± 11.1 years in group 2. The incidence rate of renal stones in the PA group was around 24%. No significant differences between the two groups were found for gender, systolic/diastolic blood pressure, duration of hypertension, diabetes mellitus history, and laterality of kidney stone; however, mean stone size was 4.0 ± 3.3 mm in group 1 and 6.5 ± 7.2 mm in group 2, with a significantly larger renal stone size noted in the PA group than that in the essential hypertension group (p = 0.004). Hounsfield unit (HU) density was higher in the PA group vis-à-vis the essential hypertension cohort, although this did not reach a significant difference (p = 0.204).ConclusionsOur study revealed that PA patients had a higher incidence rate of renal stones compared to that of the general population. Besides, the PA-related renal stones also presented as larger and harder than those of the essential hypertension group. Further investigation concerning the association between PA and renal stones is warranted.

Nephrectomy in a Patient with Medullary Sponge Kidney Associated with Severe Nephrocalcinosis and Nephrolithiasis: A Rare Condition

Background: Medullary sponge kidney (MSK) is a disturbance of renal development characterized by cystic dilation and diffuse precalyceal duct ectasia. The disease affects both genders in equal proportions and is generally diagnosed in adulthood, as a result of recurrent calcium nephrolithiasis and nephrocalcinosis. The most frequently encountered manifestations being renal colic, microscopic or macroscopic hematuria, and fever. The intravenous pyelogram is standard for diagnosis and metabolic workup is required to identify the underlying cause. The main goal of treatment is to prevent recurrence and disease progression. Though considered a benign condition, a nephrectomy may often be required in patients presenting late with irreversible complications and end-stage renal disease. Aim: To highlight and discuss the presentation and management of a rare case of nephrocalcinosis and nephrolithiasis secondary to the medullary sponge kidney. Case presentation: We report herein the case of a 56-year-old male with long-standing hematuria in whom a diagnosis of medullary sponge kidney disease was made and he underwent a left total nephrectomy. The postoperative course was uneventful. Conclusion: Nephrocalcinosis and nephrolithiasis are complications of MSK and can result in irreversible renal damage. A high index of suspicion is necessary for patients presenting with renal colic, recurrent urinary tract infections, or hematuria for prompt diagnosis and management.

The Effect of Lemonade and Diet Lemonade Upon Urinary Parameters Affecting Calcium Urinary Stone Formation.

To determine the effects of regular and diet lemonade upon urinary parameters affecting kidney stone formation. In this prospective blinded crossover study, 12 healthy participants consumed either 2 L of regular or diet lemonade daily while on a standardized low sodium moderate calcium diet. Twenty four-hour urine collections were obtained at baseline on the controlled diet only and on days 4 and 5 of each treatment phase. There was a 1-week washout period between regular and diet lemonade treatments. Primary outcomes were urine citrate, pH, and volume determined by 24-hour urine collections. Secondary outcomes included the supersaturation of calcium oxalate, calcium phosphate, and uric acid. Urine volume was significantly higher with both regular and diet lemonade consumption compared with baseline values. Urinary citrate significantly increased from baseline with diet lemonade only. Urine pH was unchanged with both beverages. The supersaturation of calcium oxalate significantly decreased with diet lemonade only, whereas supersaturation of calcium phosphate decreased with both beverages. Daily consumption of 2 L of regular and diet lemonade resulted in an intake of 168.4 and 170.2 mEq of citrate but a total alkali intake of 12.2 and 16.0 mEq, respectively. Compared with diet lemonade, regular lemonade provided subjects with 805 additional calories and 225 g of sugar per day. Diet lemonade may provide a low-calorie sugar-free cost-effective option for decreasing the risk of recurrent calcium nephrolithiasis through a significant increase in urine volume, increase in urinary citrate, and reduction in supersaturation of calcium oxalate and calcium phosphate.

Sodium chloride pica causing recurrent nephrolithiasis in a patient with iron deficiency anemia: a case report

BackgroundIron deficiency anemia is a common finding in women of child-bearing age. Pica, or the ingestion of non-food or non-nutritive items, is a well-known manifestation of iron deficiency. A high sodium diet increases risk for nephrolithiasis. We describe the case of a 31-year-old woman with recurrent calcium nephrolithiasis and anemia who ate ice chips as well as spoons of salt daily. Treatment of pica may prove effective in preventing recurrent nephrolithiasis.Case presentationA 31-year-old white woman with a past medical history of menorrhagia, anemia, and recurrent calcium nephrolithiasis presented for preoperative evaluation prior to ureterolithotomy. She described a daily pattern of eating continually from a cup of ice chips accompanied by multiple spoons of salt directly out of a salt shaker. These cravings had been present for many years, were bothersome to her, and interfered with her daily life. Laboratory findings revealed hemoglobin of 10.9 g/dL with ferritin of 3 ng/mL. History, physical, and laboratory data were consistent with pica secondary to iron deficiency anemia. She was prescribed orally administered ferrous sulfate 325 mg three times a day with meals. She continues to struggle with the symptoms of pica and orally administered supplementation.ConclusionsIt is important that clinicians consider the possible diagnosis of sodium chloride pica in patients with iron deficiency anemia and recurrent nephrolithiasis. Treatment of anemia and resolution of pica may prove effective in preventing future nephrolithiasis. Specific questioning about pica symptoms in patients with iron deficiency anemia and recurrent nephrolithiasis may be helpful diagnostically and therapeutically.

Calcium nephrolithiasis and bone demineralization: pathophysiology, diagnosis, and medical management.

To establish the relationship between calcium nephrolithiasis, bone densitometry scoring, and bone mineral density (BMD) loss according to bone turnover markers (BTMs) and urinary metabolites. Patients with recurrent calcium nephrolithiasis and idiopathic fasting hypercalciuria (urinary calcium/creatinine ratio >0.11) are more likely to have BMD loss that may lead to osteopenia or osteoporosis. In these patients, BTMs may be used as a surrogate for both bone health and stone recurrence. Suspect higher lithogenic states when calcium stone formers have serum beta-crosslaps (resorptive marker) greater than 0.311 ng/ml, serum osteocalcin (formative marker) greater than 13.2 ng/ml, and beta-crosslaps/osteocalcin ratio greater than 0.024. Patients with recurrent calcium nephrolithiasis and fasting hypercalciuria have a higher incidence of osteopenia and osteoporosis, measured by the dual-energy X-ray absorptiometry. These patients present not only with hypercalciuria and increased BTMs (mainly resorptive), but also up to 30% have hypocitraturia and increased urinary calcium/citrate ratio (>0.25). On the basis of these results, a diagnostic algorithm was created, classifying hypercalciurics according to their fasting calcium/creatinine and calcium/citrate ratio. Medical therapy for these patients is aimed at improving the dietary habits (normocalcemic, low salt, low animal protein diet), prescribing combinations of potassium citrate, thiazides, and bisphosphonates, and correcting bone and urinary abnormalities that may lower future skeletal and kidney stone risk.

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)

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.

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.

Dietary habits in women with recurrent idiopathic calcium nephrolithiasis

BackgroundNutrition has been widely recognized to influence the risk of kidney stone formation. Therefore the aim of our study was to assess: a) whether usual diet of women with idiopathic calcium nephrolithiasis (ICN) living in Parma (Northern-Italy) is different compared to healthy controls, b) how their diet differs from Italian National guidelines and c) whether it is related to nephrolithiasis clinical course.Methods143 women with recurrent ICN (mean age 43 ± 13 ys) and 170 healthy women (mean age 42 ± 11 ys) were enrolled. All women completed a food frequency questionnaire for the last 60-days and a 3-day dietary diary analysed with a dedicated software.ResultsStone formers showed a higher consumption of sausages, ham, meat and sweets than healthy controls (43.1% vs 11.1%, 29.4% vs 13.9%, 21.6% vs 4.2%, 66.7% vs 18.1%, p < 0.001). The 3-day diary analysis showed an intake of calories, carbohydrates, lipids and non-discretionary sodium about 10% higher than healthy controls (p < 0.001). Finally, after dividing the population into 3 age groups (≤30, 31-40, > 40 years), the differences described above were amplified in the class ≤30 years, where nephrolithiasis presented a more serious course (shorter recurrence interval, greater stone-rate). In this age group the intake of fruit and vegetables was notably lower than guideline recommendations.ConclusionsWe conclude that the usual diet of women with recurrent ICN is different from controls and characterized by low intake of fruits and vegetables and higher consumption of simple sugars and foods with high protein and salt content. This dietary imbalance could play a role in the ICN pathogenesis, especially in younger women.This work was financed by grants from Italian Ministry of University and Research as part of a larger project about the prevention of kidney stones (PRIN 2005063822) and by Fondazione per la Ricerca Scientifica Termale (FoRST). No potential conflict of interest relevant to this paper was reported.

Biochemical Determinants of Severe Lithogenic Activity in Patients With Idiopathic Calcium Nephrolithiasis

To analyze the biochemical alterations in plasma and the urine determinants of severe lithogenic activity in patients with idiopathic calcium nephrolithiasis. We performed a cross-sectional study of 120 patients divided into 2 groups: group 1, 60 patients without nephrolithiasis; and group 2, 60 patients with severe and/or recurrent calcium nephrolithiasis. In all patients, a study of renal function, calcium metabolism, and bone remodeling markers, and a study of the lithogenic factors were performed in urine after fasting and in 24-hour urine samples. We observed greater values for phosphorus in group 1 than in group 2 (P=.03). Also, we found greater values for intact parathyroid hormone (P=.01), osteocalcin (P=.000), and β-crosslaps (P=.000) in group 2 than in group 1. In the 24-hour urine samples, significant differences were found between groups 1 and 2 in calciuria (11.7 vs 17.4 mg/dL; P=.000), citraturia (50.6 vs 33.5 mg/dL; P=.002), calcium/creatinine quotient (0.14 vs 0.20; P=.001), calcium/citrate quotient (0.05 vs 0.13; P=.04), and calcium/creatinine quotient after fasting (0.09 vs 0.16; P=.000). We consider the determinants of severe and/or recurrent calcium lithiasis to be hypercalciuria and hypocitraturia and a calcium/citrate quotient>0.06. As risk markers we can consider phosphatemia<2.9 mg/dL, phosphate/chlorine quotient>35, alkaline phosphatase>80 U/L, intact parathyroid hormone>60 pg/mL, osteocalcin>16 ng/mL, β-crosslaps>0.400 ng/mL, and β-crosslaps/osteocalcin quotient>0.028.

E137 2-year follow-up of patients with recurrent calcium nephrolithiasis and treated with alendronate sodium

E137 2-year follow-up of patients with recurrent calcium nephrolithiasis and treated with alendronate sodium

UP-03.084 Effect of Alendronate Sodium and 2-Year Follow-Up of Patients with Recurrent Calcium Nephrolithiasis

UP-03.084 Effect of Alendronate Sodium and 2-Year Follow-Up of Patients with Recurrent Calcium Nephrolithiasis

Prevalence and densitometric characteristics of incomplete distal renal tubular acidosis in men with recurrent calcium nephrolithiasis

The aim of this study was to assess the prevalence of incomplete distal renal tubular acidosis (idRTA) in men with recurrent calcium nephrolithiasis and its potential impact on bone mineral density. We conducted a retrospective analysis of 150 consecutive, male idiopathic recurrent calcium stone formers (RCSFs), which had originally been referred to the tertiary care stone center of the University Hospital of Berne for further metabolic evaluation. All RCSFs had been maintained on a free-choice diet while collecting two 24-h urine samples and delivered second morning urine samples after 12 h fasting. Among 12 RCSFs with a fasting urine pH >5.8, a modified 3-day ammonium chloride loading test identified idRTA in 10 patients (urine pH >5.32, idRTA group). We matched to each idRTA subject 5 control subjects from the 150 RCSFs, primary by BMI and then by age, i.e., 50 patients, without any acidification defect (non-RTA group) for comparative biochemistry and dual energy X-ray absorptiometry (DEXA) analyses. The prevalence of primary idRTA among RCSFs was 6.7% (10/150). Patients with idRTA had significantly higher 2-h fasting and 24-h urine pH (2-h urine pH: 6.6 ± 0.4 vs. 5.2 ± 0.1, p = 0.001; 24-h urine pH: 6.1 ± 0.2 vs. 5.3 ± 0.3, p = 0.001), 24-h urinary calcium excretion (7.70 ± 1.75 vs. 5.69 ± 1.73 mmol/d, p = 0.02), but significantly lower 24-h urinary urea excretion (323 ± 53 vs. 399 ± 114 mmol/d, p = 0.01), urinary citrate levels (2.32 ± 0.82 vs. 3.01 ± 0.72 mmol/d, p = 0.04) and renal phosphate threshold normalized for the glomerular filtration rate (TmPO(4)/GFR: 0.66 ± 0.17 vs. 0.82 ± 0.21, p = 0.03) compared to non-RTA patients. No significant difference in bone mineral density (BMD) was found between idRTA and non-RTA patients for the lumbar spine (LS BMD (g/cm(2)): 1.046 ± 0.245 SD vs. 1.005 ± 0.119 SD, p = 0.42) or femoral neck (FN BMD (g/cm(2)): 0.830 ± 0.135 SD vs. 0.852 ± 0.127 SD). Thus, idRTA occurs in 1 in 15 male RCSFs and should be sought in all recurrent calcium nephrolithiasis patients. Bone mineral density, however, does not appear to be significantly affected by idRTA.

The melatonin receptor 1A (MTNR1A) gene is associated with recurrent and idiopathic calcium nephrolithiasis

Experimental evidence indicate that melatonin regulates some renal tubular functions via specific melatonin receptors (MTNRs) located in the kidney of several avian and mammalian species, including humans. We hypothesized that single nucleotide polymorphisms (SNPs) in the melatonin receptor 1A gene (MTNR1A) might influence the risk of calcium nephrolithiasis. We performed a systematic analysis of the MTNR1A gene in 246 recurrent calcium stone formers (136 men, 110 women; mean age 40.2 ± 12.0 years; body mass index 25.8 ± 4.5 kg/m2) and 269 healthy controls comparable for age and gender without a history of nephrolithiasis. Two SNPs in Intron 1 of MTNR1A were significantly associated with calcium nephrolithiasis: rs13140012 (P = 0.0004) and rs6553010 (P = 0.009). The haplotypes resulting from the two SNPs were also differently distributed between stone formers and controls, the haplotype A-T being more represented among stone formers (P = 0.00001) and the haplotype T-C being more common in healthy controls (P = 0.00001). Preliminary functional studies showed that the SNP rs13140012 could modify the binding sites for transcription factors. The results of this case-control study indicate a strong association between allelic variants of MTNR1A and recurrent calcium nephrolithiasis.

Mineral density and bone remodelling markers in patients with calcium lithiasis

What's known on the subject? and What does the study add? Hypercalciuria is related with bone mineral density loss. This study demonstrates the relationship between recurrent calcium nephrolithiasis and bone mineral density loss and their correlation with bone markers. • To show that a relationship exists between the loss of bone mineral density (BMD) and calcium renal lithiasis and that bone remodelling markers correlate with changes in BMD. • It is possible that many cases hypercalciuria are related to the increase of bone turnover and the predominance of bone resorption phenomena. • The present study comprised a transversal investigation in three groups: group O, without lithiasis; group A, with a single episode of lithiasis; and group B, with relapsed calcium renal lithiasis. • An analysis was made of body mass index; abdominal X-ray and/or urography and renal ultrasonography; osteocalcin and β-crosslaps bone markers; calcium and citrate concentrations in the urine; and femur and spinal column bone densitometry. • The results were analyzed by analysis of variance and Pearson's correlation coefficient. • Patients with relapsed calcium renal lithiasis present a greater BMD loss than those in the O or A groups. • Densitometry: T-score femur -0.2 group O, -0.5 group A, -1.2 group B (P= 0.001); T-score column -0.6 group O, -0.6 group A, -1.3 group B (P= 0.05). • A statistically significant negative correlation exists between values of β-crosslaps and T-score femur (R=-0.251; P= 0.009) and T-score column (R=-0.324; P= 0.001); thus, a higher concentration of β-crosslaps was accompanied by a lower value of the T-score and a greater loss of BMD. • A positive relationship is observed between β-crosslaps and osteocalcin (R= 0.611; P < 0.001) and between calciuria and cocient β-crosslaps/osteocalcin (R= 0.303; P= 0.001). • A statistically significant relationship is shown between the loss of BMD and relapsed calcium renal lithiasis. • Determination of bone remodelling markers (i.e. osteocalcin and β-crosslaps) facilitates the diagnosis of osteopaenia/osteoporosis in these patients.

Pharmacotherapy of urolithiasis: evidence from clinical trials

Urolithiasis is a worldwide problem with significant health and economic burdens. Medical therapy that alters the course of stone disease has enormous medical and financial impact. Urolithiasis is a final manifestation of a broad range of etiologies and pathogenesis. The modest progress in understanding the pathophysiology has hampered successful development of targeted therapy. Current regimens are based mostly on rational alteration of urinary biochemistry and physical chemistry to lower the risk of precipitation. In terms of pharmacotherapy, there are drugs to successfully improve hypercalciuria, hypocitraturia, aciduria, hyperuricosuria, and hypercystinuria. These agents have been proven to be effective in randomized controlled trials in improving urinary biochemical and physicochemical risk factors, as well as clinical outcomes. Although our current regimens have clearly improved the management and lives of stone formers, there are still clearly identifiable immense voids in the knowledge of pathophysiology of stone disease that can be filled with combined basic science and clinical studies.

Diagnosis of hypercalciuria in calcium nephrolithiasis (author's transl)

An increased calcium excretion in 24-hour urine was found in 32 of 42 out-patients with recurrent calcium nephrolithiasis (calcium excretion > 300 mg in males, > 250 mg in females). Subsequent hospitalization of the 32 patients revealed the following diagnosis after a calcium tolerance test: absorptive hypercalciuria in 18, renal hypercalciuria in 4, primary hyperparathyroidism in 2 and dietary hypercalciuria in 7. Normocalciuria in 10 out-patients was confirmed in 6; in one instance there was, however, primary hyperparathyroidism, in 3 there was absorptive hypercalciuria. In one patient it was not possible to classify the hypercalciuria. Total as well as nephrogenic cAMP showed wide scatter and was unsuitable, therefore, in differential diagnosis. In 2 of 3 cases of hyperparathyroidism the serum level of parathormone was distinctly elevated.

Bone Involvement in Patients with Idiopathic Calcium Nephrolithiasis

While bone involvement is more evident in case of secondary calcium calculosis, such as hyperparathyroidism, medullary sponge disease, hypercalcemic systemic illness and chronic diarrhea syndrome, less known and more controversial is still the link between bone loss and idiopathic calcium nephrolithiasis. In this study 46 patients with idiopathic calcium nephrolithiasis were consecutively enrolled at their customer diet. Our data show that dietary habits, especially an high sodium and animal protein intake, could seem to influence bone loss of the lumbar spine and of the neck. Furthemore a negative correlation has been found between citrate urinary excretion and bone loss, that suggests a protective role of potassium citrate not only on prevention of recurrent calcium nephrolithiasis, but also on bone loss.

Recurrent calcium nephrolithiasis associated with primary aldosteronism

Typical manifestations of hyperaldosteronism include salt retention, hypokalemia, and metabolic alkalosis. However, a consequence infrequently recognized and described is hypocitraturia. In combination with hypercalciuria, aldosterone-induced hypocitraturia can trigger calcium nephrolithiasis. The authors report a case of an individual with primary hyperaldosteronism from an adrenal adenoma that resulted in hypocitraturia. The patient had severe recurrent renal calcium calculi that corrected with adrenalectomy. The clinical physiology of renal calcium and citrate handling in hyperaldosteronism is reviewed.