Idiopathic Calcium Stone Formers Research Articles

The Vitamin D Metabolite Diagnostic Ratio Associates With Phenotypic Traits of Idiopathic Hypercalciuria

IntroductionUnderlying mechanisms for hypercalciuria remain unknown in most cases, hence the designation “idiopathic”. We hypothesized that the Vitamin D-inactivating enzyme CYP24A1 contributes to the pathogenesis of hypercalciuria in kidney stone formers. MethodsWe conducted association analyses between CYP24A1 activity, estimated by the Vitamin D metabolite diagnostic ratio (25(OH) Vitamin D3/total 24,25 (OH)2 Vitamin D ratio; VMDR), and the phenotype of participants in two observational cohorts of kidney stone formers, the Swiss Kidney Stone Cohort and the Bern Kidney Stone Registry. Circulating 25(OH)- and 24,25 (OH)2 Vitamin D were quantified using a validated LC-MS/MS assay. Results974 participants were included in the analysis. We found a positive association of VMDR (and hence negative association of CYP24A1 activity) with total (β 0.009 mmol/L; 95% CI 0.002, 0.016; p = 0.02) and ionized plasma calcium (β 0.005 mmol/L; 95% CI 0.002, 0.008; p < 0.01), absolute and fractional excretion of urinary calcium (β 0.054 mmol/24h; 95% CI 0.010, 0.097; p = 0.02 and β 0.046 %; 95% CI 0.018, 0.074; p < 0.01, respectively). Further, VMDR was associated with an increased likelihood of forming calcium oxalate dihydrate stones (Odds ratio 1.64; 95% CI 1.22, 2.35; p < 0.01) and reduced bone mineral density at the femoral neck (β -0.005 g/cm2; 95% CI -0.010, -0.001; p = 0.04). The described associations became stronger when the analysis was confined to idiopathic calcium stone formers. ConclusionOur study reveals that CYP24A1 activity, estimated by VMDR, is associated with clinical traits previously linked to idiopathic hypercalciuria.

Water Loading and Uromodulin Secretion in Healthy Individuals and Idiopathic Calcium Stone Formers.

Uromodulin is a protein made only by the kidney and released in urine, circulating in polymerizing and nonpolymerizing forms. This protein's multiple functions include inhibition of stone formation in the urine. The physiological determinants of uromodulin production are incompletely understood. We investigated changes in uromodulin levels and key factors governing its production and release in urine and serum. We performed an experiment to determine whether water loading, a common intervention to prevent stone formation, will alter the rate of uromodulin production. During a 2-day period, 17 stone forming participants and 14 control participants were subjected to water loading (day 1) and normal fluid intake (day 2). Uromodulin levels were measured on timed hourly collections in urine and plasma during the period of the study. Water loading increased urinary uromodulin secretion (33±4 versus 10±4 μ g/min at baseline, P < 0.0001) in stone formers and control participants. Despite high urine volumes, most participants maintained relatively stable urinary uromodulin concentrations. Native Western blots for polymerizing and nonpolymerizing uromodulin suggest that polymerizing uromodulin was the predominant form at higher urinary flow volumes. Urine flow rates and sodium excretion were significant correlates of urinary uromodulin production. Water loading did not affect serum uromodulin levels, which were also not associated with urinary uromodulin. Water loading increases the secretion of polymerizing urinary uromodulin. This increased secretion reduces the variability of urinary uromodulin concentrations despite high urine volumes. Serum uromodulin levels were not affected by this treatment.

Prospective long-term evaluation of incomplete distal renal tubular acidosis in idiopathic calcium nephrolithiasis diagnosed by low-dose NH4CL loading – gender prevalences and impact of alkali treatment

PurposeProspective evaluation of the prevalence of incomplete distal renal tubular acidosis (idRTA) in idiopathic calcium stone formers (ICSF) diagnosed by half-dose ammonium chloride loading (NH4Cl, 0.05 g/kg body weight/day) and impact of alkali treatment of idRTA.MethodsEvaluation of 386 consecutive idiopathic calcium stone formers (ICSF) (280 males, 106 females) for idRTA. If screening fasting urine pH was > 5.80, 1-day NH4Cl loading was performed without severe adverse effects. Normally, urine pH falls below 5.45.ResultsSixty-four idiopathic calcium stone formers exhibited idRTA, one complete dRTA. Prevalence was higher in women (25.4%) than in men (13.6%). Thus, for more equilibrated comparisons, we formed pairs of 62 idiopathic calcium stone formers (ICSF) with and 62 without idRTA, matched for gender, age, BMI and serum creatinine. Idiopathic calcium stone formers with idRTA more often had hypercalciuria (p < 0.025) and urine citrate < 2 mmol/d (p < 0.05), formed calcium phosphate stones more frequently, exhibited higher numbers of stones/year (1.4 ± 1.5 vs. 0.9 ± 0.8, p = 0.034) and 2.5 times more intrarenal calcifications (4.6 ± 5.9 vs. 1.8 ± 3.6, p = 0.002). All idiopathic calcium stone formers with idRTA were recommended chronic alkali therapy. After 4–15 years of follow-up, stone events /years follow-up (stone passage or urologic intervention) were higher in patients non-adherent to alkali therapy (0.61 ± 0.92) than in patients adherent to treatment (0.11 ± 0.21, p = 0.006).Conclusion Incomplete distal renal tubular acidosis is 1.8-fold more prevalent among female idiopathic calcium stone formers, predicts more stone recurrences, predisposes to calcium phosphate stones and is associated with 2.5 times more intrarenal calcifications vs. non-idRTA patients. Chronic alkali treatment reduces clinical stone recurrences by 5.5 times.Graphical abstract

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).

Understanding the gut–kidney axis in nephrolithiasis: an analysis of the gut microbiota composition and functionality of stone formers

ObjectivesThe involvement of the gut microbiota in the pathogenesis of calcium nephrolithiasis has been hypothesised since the discovery of the oxalate-degrading activity of Oxalobacter formigenes, but never comprehensively studied with...

PD03-06 PLAQUE, PITTING, CONTOUR LOSS - A PATHOGENETIC SEQUENCE IN RENAL PAPILLAE OF IDIOPATHIC CALCIUM STONE FORMERS

You have accessJournal of UrologyStone Disease: Basic Research & Pathophysiology I1 Apr 2018PD03-06 PLAQUE, PITTING, CONTOUR LOSS - A PATHOGENETIC SEQUENCE IN RENAL PAPILLAE OF IDIOPATHIC CALCIUM STONE FORMERS Melanie Adamsky, Andrew Cohen, Christopher Riedinger, Glenn Gerber, Elaine Worcester, and Frederic Coe Melanie AdamskyMelanie Adamsky More articles by this author , Andrew CohenAndrew Cohen More articles by this author , Christopher RiedingerChristopher Riedinger More articles by this author , Glenn GerberGlenn Gerber More articles by this author , Elaine WorcesterElaine Worcester More articles by this author , and Frederic CoeFrederic Coe More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2018.02.272AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Renal papillary abnormalities are thought to have deeper roots in renal physiology and stone pathogenesis. A unifying hypothesis is that Randall′s plaque (RP) production is continuous, plaque loss gives rise to pitting, and this loss of tissue gives rise to changes in papillary contour (Figure 1). We have tested these predictions in a cohort of idiopathic calcium stone formers (ICSF). METHODS A previously described renal papillary grading system, which quantifies the degree of RP, pitting, plugging, and contour on each papillum, was applied to ICSF during ureteroscopy. We performed 2x2 table analysis of relationships between the scores for each papillary feature at the level of the papillum and the level of the kidney. Finally, we calculated mean scores for each feature by kidney and used Pearson correlation coefficients to measure relationships between features at the kidney level. RESULTS 85 patients were included with a total of 361 papillae graded. In table analysis of pitting scores by plaque scores, values deviated powerfully from chance (X2=63.997, p<0.00001). Increasing plaque scores were associated with decreasing percentage of pitting score zero. The presence of plaque without pitting is more often seen than pitting without plaque. A similar but less pronounced relationship was seen in the analysis of contour loss by pitting scores (X2= 35.9461, p=0.0029). Furthermore, contour loss and plaque scores showed a very strong relationship (X2 = 57.2033, p<0.00001). Results of the papillum-level analysis are summarized in Figure 2. At the level of the kidney, the strongest relationship exists between mean RP and mean contour scores (rp=0.4630, p=0.0003). CONCLUSIONS These data support our critical hypothesis that RP and attached calcium stone complex are shed from the papillum leaving behind a pitting defect on the papillary surface, which can then either heal over or, with repeated insult, progress to loss of papillary contour. We believe that understanding this sequence helps link renal physiology to a urologic endpoint. © 2018FiguresReferencesRelatedDetails Volume 199Issue 4SApril 2018Page: e72-e73 Advertisement Copyright & Permissions© 2018MetricsAuthor Information Melanie Adamsky More articles by this author Andrew Cohen More articles by this author Christopher Riedinger More articles by this author Glenn Gerber More articles by this author Elaine Worcester More articles by this author Frederic Coe More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Biopsy proven medullary sponge kidney: clinical findings, histopathology, and role of osteogenesis in stone and plaque formation.

Medullary sponge kidney (MSK) is associated with recurrent stone formation, but the clinical phenotype is unclear because patients with other disorders may be incorrectly labeled MSK. We studied 12 patients with histologic findings pathognomonic of MSK. All patients had an endoscopically recognizable pattern of papillary malformation, which may be segmental or diffuse. Affected papillae are enlarged and billowy, due to markedly enlarged inner medullary collecting ducts (IMCD), which contain small, mobile ductal stones. Patients had frequent dilation of Bellini ducts, with occasional mineral plugs. Stones may form over white (Randall's) plaque, but most renal pelvic stones are not attached, and have a similar morphology as ductal stones, which are a mixture of calcium oxalate and apatite. Patients had no abnormalities of urinary acidification or acid excretion; the most frequent metabolic abnormality was idiopathic hypercalciuria. Although both Runx2 and Osterix are expressed in papillae of MSK patients, no mineral deposition was seen at the sites of gene expression, arguing against a role of these genes in this process. Similar studies in idiopathic calcium stone formers showed no expression of these genes at sites of Randall's plaque. The most likely mechanism for stone formation in MSK appears to be crystallization due to urinary stasis in dilated IMCD with subsequent passage of ductal stones into the renal pelvis where they may serve as nuclei for stone formation.

The relationship between calcium kidney stones, arterial stiffness and bone density: unraveling the stone-bone-vessel liaison.

Kidney stone disease is associated with a higher incidence of cardio-vascular (CV) events for still unclear reasons. Reduced bone density is also a frequent finding in calcium kidney stones. The association of reduced bone density with increased vascular stiffness and calcification has been discovered in a number of conditions. We investigated the hypothesis that patients with calcium kidney stones have increased arterial stiffness, which would be associated with reduced bone density and higher CV risk. We compared measures of arterial stiffness [carotid-radial pulse-wave velocity (CR-PWV), carotid-femoral pulse-wave velocity (CF-PWV) and augmentation index (AI)] and of bone density (T-scores determined at lumbar spine, neck and hip) among 42 idiopathic calcium stone formers compared with 42 age- and sex-matched healthy volunteers. Stone formers had higher values of CR-PWV, CF-PWV and AI, and lower values of all T-scores. Furthermore, the prevalence of abnormal arterial stiffness and reduced bone density was significantly higher among stone formers. Statistical adjustment for age, sex, body mass index and other covariates did not change the results. Our study confirms that stone formers have increased arterial stiffness and reduced bone density. Abnormal arterial stiffness appears to be independent of reduced bone density and may explain the higher CV risk observed in stone formers.

MP73-01 NON-CONTRAST CT ATTENUATION VALUE OF RENAL PAPILLA IS A NOVEL PREDICTOR FOR RECURRENCE IN KIDNEY STONE DISEASE

You have accessJournal of UrologyStone Disease: Evaluation III1 Apr 2014MP73-01 NON-CONTRAST CT ATTENUATION VALUE OF RENAL PAPILLA IS A NOVEL PREDICTOR FOR RECURRENCE IN KIDNEY STONE DISEASE Yasuo Kohjimoto, Akinori Iba, Shinpei Yamashita, Nagahide Matsumura, and Isao Hara Yasuo KohjimotoYasuo Kohjimoto More articles by this author , Akinori IbaAkinori Iba More articles by this author , Shinpei YamashitaShinpei Yamashita More articles by this author , Nagahide MatsumuraNagahide Matsumura More articles by this author , and Isao HaraIsao Hara More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2014.02.2354AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES In idiopathic calcium stone formers (ICSFs), most stones are known to grow attached to Randall′s plaque, which can be identified by measuring computed tomography (CT) attenuation value of renal papilla. The purpose of the present study was to test the hypothesis that CT attenuation value of renal papilla can predict the severity and recurrence of the stone disease. METHODS We retrospectively reviewed the charts of ICSFs who underwent non-contrast CT scan from February 2005 to May 2012. Two observers independently measured the Hounsfield unit (HU) of the renal papilla from the upper pole, middle region and lower pole in both kidneys. Patients were classified into high- and low-HU value groups based on the mean HU values of all papillae. The median value was used for differentiation. Proportions of patients with severe disease (recurrent and/or multiple stones), urine chemistries and recurrence rates were compared between the groups. RESULTS A total of 134 patients, 89 men and 45 women, with at least one-year follow-up, were included in the analysis. Median HU value of all papillae was 49.3. The proportion of patients with recurrent and/or multiple stones was significantly higher in high-HU group compared to low-HU group (94.0% vs. 76.1%, p<0.01). AP (CaOx) index in high-HU group was higher than that in low-HU group, although the difference was marginally significant (p=0.06, Table 1). Recurrence rate in high-HU value group (0.62 person-year) was significantly higher than that of low-HU value group (0.09 person-year, p<0.01). Multivariate analysis revealed that high-HU value was an independent predictor of stone recurrence (OR 8.48, 95% CI 3.45-22.88, Table 2). CONCLUSIONS These results demonstrated that the HU value of renal papilla was correlated with disease severity, AP (CaOx) index and recurrence in ICSFs. This may allow us to identify patients with a higher risk of recurrent stone formations and change the clinical management of these patients if necessary. Table 1. Urine parameters (n=53) Low-HU group (<48.3) High-HU group (>48.3) p= Volume, mL/day 1695±606 1674±841 0.91 Oxalate, mg/day 32.4±15.1 39.5±26.9 0.25 Calcium, mg/day 183.1±108.4 207.8±128.7 0.45 Uric acid, mg/day 585.3±187.3 499.7±223.1 0.14 Magnesium, mg/day 76.4±29.0 81.4±28.9 0.53 Citrate, mg/day 383.9±258.1 554.9±614.9 0.20 AP (CaOx) 0.811±0.494 1.191±0.865 0.06 Table 2. Multivariate analysis of stone recurrence (n=134) Odds ratio 95% confidence interval p= Age 0.95 0.90-0.98 <0.01 Male 1.76 0.68-4.70 0.24 Multiple stones 1.35 0.48-3.87 0.56 Recurrent stone former 0.88 0.31-2.39 0.81 Medication 3.98 1.51-11.07 <0.01 High-HU (≥49.3) 8.48 3.45-22.88 <0.01 © 2014FiguresReferencesRelatedDetails Volume 191Issue 4SApril 2014Page: e865 Advertisement Copyright & Permissions© 2014MetricsAuthor Information Yasuo Kohjimoto More articles by this author Akinori Iba More articles by this author Shinpei Yamashita More articles by this author Nagahide Matsumura More articles by this author Isao Hara More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Male hypercalciuric stone formers with low renal calcium reabsorption

AimsHypercalciuria is a common poorly understood abnormality among stone formers. We aimed to identify hypercalciuric male stone formers with a primary defect in renal calcium reabsorption and to look for...

Twenty-five years of idiopathic calcium nephrolithiasis: has anything changed?

Idiopathic calcium nephrolithiasis (ICN) is a disease whose prevalence is rising. Our aim was to assess whether lifestyle indicators and habits of calcium stone formers in Italy have changed over the last 25 years, trying to establish a connection with the diffusion of Internet access. Therefore we examined the database of the Stone Clinic of Parma University Hospital and extracted 1952 (1192 M, 760 F) patients with ICN who underwent a full clinical and laboratory evaluation from 1986 to 2010. Laboratory evaluation included data on urinary 24-h volume, pH, sodium, potassium, chloride, calcium, phosphate, uric acid, magnesium, oxalate, and citrate. Patients were split in three groups on a chronological basis, according to official EUROSTAT-ISTAT data of Internet connection among families in Italy: Group 1, pre-Internet era (1986-1998, 853 patients); Group 2, narrow-band era (1999-2004, 467 patients); Group 3, broad-band era (2005-2010, 632 patients). Over the time we found a significant increase in water intake (1.37 vs. 1.78 L in men and 1.21 vs. 1.55 L in women, Group 1 vs. Group 3, p-trend<0.001) and a decrease in urinary sodium and chloride for both genders and calcium and magnesium only for males, while females experienced a slight increase in oxalate excretion. Supersaturation indexes for calcium and uric acid stones dramatically fell for both genders. The percentage of stone formers performing physical activity significantly rise (41% Group 3 vs. 8% Group 1, p<0.001) and we also found a trend of reduction in mean blood pressure. Therefore, the lifestyle of Italian idiopathic calcium stone formers has changed over the last 25 years, and the rising Internet access may have played a great role in driving this change.

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.

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.

2077 NON-CONTRAST CT ATTENUATION VALUE OF RENAL PAPILLA PREDICTS THE SEVERITY AND RECURRENCE OF KIDNEY STONE DISEASE

You have accessJournal of UrologyStone Disease: Basic Research (I)1 Apr 20132077 NON-CONTRAST CT ATTENUATION VALUE OF RENAL PAPILLA PREDICTS THE SEVERITY AND RECURRENCE OF KIDNEY STONE DISEASE Yasuo Kohjimoto, Akinori Iba, Satoshi Nishizawa, Nagahide Matsumura, and Isao Hara Yasuo KohjimotoYasuo Kohjimoto Wakayama, Japan More articles by this author , Akinori IbaAkinori Iba Wakayama, Japan More articles by this author , Satoshi NishizawaSatoshi Nishizawa Wakayama, Japan More articles by this author , Nagahide MatsumuraNagahide Matsumura Wakayama, Japan More articles by this author , and Isao HaraIsao Hara Wakayama, Japan More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2013.02.2496AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES In idiopathic calcium stone formers (ICSFs), most stones are known to grow attached to Randall's plaque, which can be identified by measuring computed tomography (CT) attenuation value of renal papilla. The purpose of the present study was to test the hypothesis that CT attenuation value of renal papilla can predict the severity and recurrence of the stone disease. METHODS We retrospectively reviewed the charts of ICSFs who underwent non-contrast CT scan from May 2010 to April 2011. Two observers independently measured the Hounsfield unit (HU) of the renal papilla from the upper pole, middle region and lower pole in both kidneys. Patients were classified into high- and low-HU value groups based on the mean HU values of all papillae. The median value was used for differentiation. Proportions of patients with severe disease (recurrent and/or multiple stones), urine chemistries and recurrence rates were compared between the groups. RESULTS A total of 80 patients, 50 men and 30 women, were included in the analysis. Median HU value of all papillae was 50.5. The proportion of patients with recurrent and/or multiple stones was significantly higher in high-HU group compared to low-HU group (p<0.01). No significant differences were noted in urine parameters except for urinary uric acid. Recurrence rate in high-HU value group (0.40 person-year) was higher than that of low-HU value group (0.23, p=0.11). CONCLUSIONS These results demonstrated that the HU value of renal papilla was correlated with disease severity and recurrence in ICSFs. This may allow us to identify patients with a higher risk of recurrent stone formations and change the clinical management of these patients if necessary. Low-HU (< 50.5) group High-HU (≥ 50.5) group p= Recurrent and/or multiple stones, % 40 90 < 0.01 U-Volume, mL/day 1694 ± 548 1428 ± 650 0.25 U-oxalate, mg/day 32 ± 19 38 ± 23 0.42 U-calcium, mg/day 190 ± 111 197 ± 108 0.86 U-uric acid, mg/day 621 ± 220 424 ± 141 < 0.01 U-magnesium, mg/day 79 ± 30 79 ± 32 0.94 U-citrate, mg/day 453 ± 314 566 ± 843 0.65 AP(CaOx) 0.80 ± 0.49 1.13 ± 0.71 0.17 Recurrence rate, person-year (95% confidence interval) 0.23 (0.12 - 0.39) 0.40 (0.24 - 0.63) 0.11 © 2013 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 189Issue 4SApril 2013Page: e852 Advertisement Copyright & Permissions© 2013 by American Urological Association Education and Research, Inc.MetricsAuthor Information Yasuo Kohjimoto Wakayama, Japan More articles by this author Akinori Iba Wakayama, Japan More articles by this author Satoshi Nishizawa Wakayama, Japan More articles by this author Nagahide Matsumura Wakayama, Japan More articles by this author Isao Hara Wakayama, Japan More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Who makes uric acid stones and why—observations from a renal stones clinic

AimsExcessively acidic urine is the dominant factor in uric acid stone formation. Recent evidence implicating insulin resistance has revived interest in its causation. We reviewed data on uric acid stone...

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 most important metabolic risk factors in recurrent urinary stone formers.

To evaluate different urinary factors contributing to idiopathic calcium stone disease for determining appropriate medical treatments. Two 24-hour urine samples were collected from 106 male recurrent idiopathic calcium stone formers and another 109 randomly selected men as the control group matching for age. Cases had significantly higher mean urine oxalate, calcium, uric acid, and chloride in comparison with the healthy controls (P < .001). After necessary adjustment, only mean urine levels of oxalate and uric acid were higher in stone formers than those in controls. The mean value of supersaturation for calcium oxalate was significantly higher in patients than the controls (P = .001); whereas supersaturation for calcium phosphate and uric acid did not reach statistical significance (P = .675 and P = .675, respectively). Hyperoxaluria and hypercalciuria were among the most frequent abnormalities. After categorizing urine parameter values into four quartiles, the risk of stone formation was found to increase as the urine calcium, oxalate, uric acid, chloride, and citrate rise. In contrast, the risk of stone formation decreased with the increase of urine potassium. Oxalate seems to play the most important role as urinary stone risk factor in our population followed by calcium and uric acid. In addition to the risk factors, it seems that supersaturation as the sum of all risk factors probably has a high predictive value.

Sodium Restriction as Initial Conservative Treatment for Urinary Stone Disease

Sodium restriction is widely recommended to prevent urinary stone recurrence. However, the effect of urinary sodium excretion has not been fully evaluated. We investigated the relationship between urinary sodium, urinary metabolite excretion and the risk of recurrence in urinary stone formers. Selected for study were 798 stone formers with no evidence of metabolic disorders as the cause of abnormal urinary solutes. We analyzed the relationship between urinary sodium and other metabolic parameters by gender. Values were adjusted by covariates according to correlation status. Patients were divided into stone formers with hypernatriuresis or normal natriuresis (less than 220 mEq daily) and urinary parameters were compared. Kaplan-Meier analysis was done to determine the cumulative incidence of recurrent stones by urinary sodium. Patients were considered recurrence-free at a minimum followup of 3 years without incidence. In the 492 men and 306 women mean ± SD age was 40.0 ± 11.4 and 45.4 ± 12.7 years, and mean body mass index was 23.9 ± 3.1 and 23.0 ± 3.0 kg/m(2), respectively. Using covariate adjusted partial correlation coefficients urinary sodium was noted to influence volume, pH, calcium, uric acid, oxalate and citrate in men, and volume, pH, calcium, uric acid and citrate in women (each p <0.05). At a median followup of 56.1 months 46 of 98 stone formers (46.9%) with normal natriuresis experienced stone recurrence vs 60 of 93 (64.5%) with hypernatriuresis. Patients with hypernatriuresis also had significantly decreased time to recurrence than those with normal natriuresis (log rank test p = 0.043). Results show that urinary sodium is an important determinant of other stone forming parameters and of the risk of recurrent stones. These findings suggest that a sodium restricted diet should be the initial step when treating stone formers.

A test of the hypothesis that the collecting duct calcium-sensing receptor limits rise of urine calcium molarity in hypercalciuric calcium kidney stone formers

The process of kidney stone formation depends on an imbalance between excretion of water and insoluble stone-forming salts, leading to high concentrations that supersaturate urine and inner medullary collecting duct (IMCD) fluid. For common calcium-containing stones, a critical mechanism that has been proposed for integrating water and calcium salt excretions is activation of the cell surface calcium-sensing receptor (CaSR) on the apical membranes of IMCD cells. High deliveries of calcium into the IMCD would be predicted to activate CaSR, leading to reduced membrane abundance of aquaporin-2, thereby limiting water conservation and protecting against stone formation. We have tested this hypothesis in 16 idiopathic hypercalciuric calcium stone formers and 14 matched normal men and women in the General Clinical Research Center. Subjects were fed identical diets; we collected 14 urine samples at 1-h intervals during a single study day, and one sample overnight. Hypercalciuria did not increase urine volume, so urine calcium molarity and supersaturation with respect to calcium oxalate and calcium phosphate rose proportionately to calcium excretion. Thus CaSR modulation of urine volume via IMCD CaSR activation does not appear to be an important mechanism of protection against stone formation. The overnight period, one of maximal water conservation, was a time of maximal stone risk and perhaps a target of specific clinical intervention.

New insights into the pathogenesis of bone loss in recurrent calcium stone formers

Background/aims: Urolithiasis is one of the leading social and economical problems of modern society. It is estimated that 10% of males and 4 % of females between 30 and 50 years of age have urinary tract stone disease. Recurrence rate of urolithiasis is 75% at 15 years with no treatment. Calcium is the major calculus component since 75-80% of renal stones are composed of calcium oxalate, while idiopathic metabolic hypercalciuria is one of the most frequent causes of recurrent calcium urolithiasis. Numerous studies showed that urolithiasis patients have higher rate of bone resorption and lower bone mineral content as well as bone mineral density, which is more evident in idiopathic calcium stone formers. However, mechanisms of action and factors involved in bone loss in these patients are still unknown. Increased production of cytokines such as IL-1, IL-6, TNF as well as osteopontin (OPN), osteoprotegerin (OPG) and RANKL (receptor activator of NF-kappaB ligand) may enhance bone resorption and therefore lower bone mass in patients with idiopathic calcium urolithiasis. Aim of this study is to assess changes of cytokines involved in bone turnover and increased bone resorption, as that might play role in bone loss in recurrent calcium stone formers. Methods: 49 recurrent calcium stone formers were involved in the study and compared to healthy age and sex matched controls. Anthropometrical measurements and metabolic evaluation were performed. Bone mineral density (BMD ; g/cm2) was assessed by dual-energy x-ray absorptiometry (« Lunar Prodigy» ). BMD measurements were performed at the lumbar spine, femoral neck, forearm and total body. Results are presented as bone mineral content (BMC ; g) and bone area (BA ; cm2). Ca2+, Mg2+, P, creatinine, Na+, K+, Cl-, proteins, uric acid, alkaline phosphatase, osteocalcin, calcitonin, PTH, 25-OH D vitamin and 1, 25-OH D vitamin were assessed by standard biochemical serum analysis. IL-1, IL-6, TNF-α , OPG, RANKL and OPN serum levels were determined by quantitive enzyme-linked immunosorbent assay (ELISA) according to manufacture’ s protocol (Quantikine, R&D Systems, Inc., Minneapolis, USA). Results: The frequency of low BMD between male and female recurrent calcium stone formers was 36.4% to 45.8%, respectiveley. Different calcium excretion levels influenced the frequency of low BMD and ranged from 31.6% in normocalciuric patients to 50% in patients with hypercalciuria, respectiveley. The frequency of increased bone turnover markers showed differences between recurent stone formers with and without low BMD as well as between male and female participants. PTH was increased in 54.5% female participants with low BMD and in 25%