Oxalate Stone Formation Research Articles

The oxalate content of fruit and vegetable juices, nectars and drinks

Fruit and vegetable juices are recommended for the treatment of hypocitraturia in calcium oxalate stone disease as alternatives to drugs containing alkaline citrate. Since dietary oxalate can contribute considerably to urinary oxalate excretion, the oxalate content of vegetable and fruit juices, nectars and drinks was analyzed using a validated HPLC-enzyme-reactor method. The highest oxalate concentrations were found in rhubarb nectar (198.3mg/100ml) and beetroot juices (60.1–70.0mg/100ml). The oxalate levels of all other beverages were below 10mg/100ml. Interestingly, except for carrot juice, the oxalate content of juices containing vegetables from organic farming was higher than from conventional farming. The consumption of even 500ml/d of certain vegetable juices can contribute to a considerable extent to the daily oxalate intake. Calcium oxalate stone formers should therefore pay attention not only to the oxalate content but also to the ingested amount of these beverages.

E67 Chronic stress and risk of recurrence in first calcium oxalate stone formers: A prospective study with five years of follow-up

E67 Chronic stress and risk of recurrence in first calcium oxalate stone formers: A prospective study with five years of follow-up

Experimental determination of multiple thermodynamic and kinetic risk factors for nephrolithiasis in the urine of healthy controls and calcium oxalate stone formers: does a universal discriminator exist?

Nephrolithiasis is thought to be governed by urinary thermodynamic and kinetic risk factors. However, identification of one or more of these factors which consistently and unambiguously differentiates between healthy subjects (N) and calcium oxalate (CaOx) renal stone patients (SF) remains elusive. The present study addresses this challenge. 24 h urines were collected from 15 N and 10 SF. Urine compositions were used to compute thermodynamic risk indices including urinary ratios, quotients and supersaturation (SS) values, while CaOx metastable limits (MSL) were determined experimentally. Crystallisation kinetics was determined by measuring rates of particle formation (number, volume, size) using a Coulter counter multisizer (CC) and a Coulter flow cytometer (FC). Particle shapes were qualitatively differentiated by FC and were viewed directly by scanning electron microscopy. Several urinary composition ratios and risk quotients were significantly different between the groups. However, there were no significant differences between CaOx MSL or SS values. Using transformed FC data, the rate of CaOx crystallisation in SF was significantly greater than in N. This was not supported by CC measurements. There were no significant differences between the groups with respect to particle size or CaOx crystal growth rates. Single and aggregated CaOx dihydrate crystals were observed in both groups with equal frequency and there were no differences in the kinetic properties of these deposits. A few CaOx monohydrate crystals were observed in SF. Although several risk factors were found to be significantly different between the groups, none of them were consistently robust when compared to other cognate factors. Arguments were readily invoked which demonstrated inter-factor inconsistencies and conflicts. We suspect that a unique discriminatory factor, such as any of those which we investigated in the present study, may not exist.

Nephrocalcinosis in Calcium Stone Formers Who Do Not have Systemic Disease

Nephrocalcinosis is commonly present in primary hyperparathyroidism, distal renal tubular acidosis and medullary sponge kidney disease. To our knowledge it has not been studied in patients with calcium phosphate stones who do not have systemic disease. We studied patients undergoing percutaneous nephrolithotomy who had calcium phosphate or calcium oxalate stones and did not have hyperparathyroidism, distal renal tubular acidosis or medullary sponge kidney disease. On postoperative day 1 all patients underwent noncontrast computerized tomography. If there were no residual calcifications, the patient was categorized as not having nephrocalcinosis. If there were residual calcifications, the patient underwent secondary percutaneous nephrolithotomy. If the calcifications were found to be stones, the patient was categorized as not having nephrocalcinosis. If the calcifications were not stones, the patient was categorized as having nephrocalcinosis. Patients were grouped based on the type of stones that formed, including hydroxyapatite, brushite and idiopathic calcium oxalate. The extent of nephrocalcinosis was quantified as 0--absent nephrocalcinosis to 3--extensive nephrocalcinosis. Patients with residual calcifications on postoperative day 1 noncontrast computerized tomography who did not undergo secondary percutaneous nephrolithotomy were excluded from analysis. The presence or absence of nephrocalcinosis was correlated with metabolic studies. A total of 67 patients were studied, including 14 with hydroxyapatite, 19 with brushite and 34 with idiopathic calcium oxalate calculi. Nephrocalcinosis was present in 10 of 14 (71.4%), 11 of 19 (57.9%) and 6 of 34 patients (17.6%) in the hydroxyapatite, brushite and idiopathic calcium oxalate groups, respectively (chi-square p = 0.01). The mean extent of nephrocalcinosis per group was 1.98, 1.32 and 0.18 for hydroxyapatite, brushite and idiopathic calcium oxalate, respectively (p ≤0.001). The presence of nephrocalcinosis positively correlated with urine calcium excretion (mean ± SD 287.39 ± 112.49 vs 223.68 ± 100.67 mg per day, p = 0.03). Patients without systemic disease who form hydroxyapatite and brushite stones commonly have coexistent nephrocalcinosis. Nephrocalcinosis can occur in calcium oxalate stone formers but the quantity and frequency of nephrocalcinosis in this group are dramatically less.

MP41-14 IMPACT OF URINE PH ON URINARY SUPERSATUATION OF CALCIUM OXALATE

You have accessJournal of UrologyStone Disease: Medical Therapy1 Apr 2015MP41-14 IMPACT OF URINE PH ON URINARY SUPERSATUATION OF CALCIUM OXALATE Jodi A. Antonelli, Naim Maalouf, Jodi A. Antonelli, Monica S.C. Morgan, Adam Cohen, John Pointdexter, Beverley Adams-Huet, Khashayar Sakhaee, and Margaret S. Pearle Jodi A. AntonelliJodi A. Antonelli More articles by this author , Naim MaaloufNaim Maalouf More articles by this author , Jodi A. AntonelliJodi A. Antonelli More articles by this author , Monica S.C. MorganMonica S.C. Morgan More articles by this author , Adam CohenAdam Cohen More articles by this author , John PointdexterJohn Pointdexter More articles by this author , Beverley Adams-HuetBeverley Adams-Huet More articles by this author , Khashayar SakhaeeKhashayar Sakhaee More articles by this author , and Margaret S. PearleMargaret S. Pearle More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2015.02.1642AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES The role of urine pH in the formation of calcium oxalate stones is controversial. The benefit of increasing urine pH in calcium oxalate stone formers with low urine pH and normal urinary citrate is controversial. We sought to investigate the role of urine pH on estimates of urinary supersaturation by modeling and in a group of calcium oxalate stone formers with low urine pH and normal urinary citrate. METHODS Using mean values for urinary parameters derived from 1494 patients in our stone registry, we analyzed the effect of varying urine pH on estimates of urinary supersatuation over a range of urinary citrate while keeping other urinary parameters constant. We used 2 estimates of urinary supersaturation: relative saturation ratio (RSR) derived from EQUIL 2 and saturation index (SI) derived from JESS v8.2 (Joint Expert Speciation System). In addition, we obtained 24-hour urine values at baseline and after treatment with potassium citrate from 55 calcium oxalate stone formers with low urine pH (≤ 6.0) and normal urinary citrate (citrate ≥ 500 mg/day) and performed regression analysis, adjusting for calcium, oxalate, volume and citrate, to determine the independent effect of urine pH on RSR and SI calcium oxalate in this patient group. RESULTS Table 1 shows the results of the model. RSR and SI declined over a range of pH from 5.0 to 7.0 at all levels of urinary citrate when keeping the other urinary parameters constant. In the patient group, change in urine pH (from baseline to after treatment with potassium citrate) was a significant predictor of change in SI calcium oxalate (p=0.00125), but not of change in RSR calcium oxalate (p=0.413), with SI declining with increasing urine pH. CONCLUSIONS In a theoretical model, urine pH negatively correlated with urinary supersuration of calcium oxalate as estimated by RSR and SI. In a group of calcium oxalate stone formers with low pH and normal urinary citrate, treatment with potassium citrate reduced SI, but not RSR, independent of the effect on urinary citrate. Calcium oxalate stone formers may benefit from normalizing urine pH. The Effect of pH at Increasing Citrate levels pH 5.0 5.5 6.0 6.5 7.0 [Citrate] = 1.0 mmol/L SI CaOx 5.56 5.34 5.00 4.48 3.85 RSR CaOx 4.53 5.33 5.55 5.48 5.29 [Citrate] = 3.0 mml/L SI CaOx 4.37 3.98 3.48 2.77 1.76 RSR CaOx 3.90 4.24 4.14 3.93 3.73 [Citrate] = 5.0 SI CaOx 3.32 2.95 2.44 1.75 0.89 RSR CaOx 3.36 3.31 2.94 2.65 2.47 © 2015 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 193Issue 4SApril 2015Page: e505 Advertisement Copyright & Permissions© 2015 by American Urological Association Education and Research, Inc.MetricsAuthor Information Jodi A. Antonelli More articles by this author Naim Maalouf More articles by this author Jodi A. Antonelli More articles by this author Monica S.C. Morgan More articles by this author Adam Cohen More articles by this author John Pointdexter More articles by this author Beverley Adams-Huet More articles by this author Khashayar Sakhaee More articles by this author Margaret S. Pearle More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

MP80-17 DO 24-HOUR URINE SUPERSATURATIONS PREDICT STONE COMPOSITION?

You have accessJournal of UrologyStone Disease: Evaluation II1 Apr 2015MP80-17 DO 24-HOUR URINE SUPERSATURATIONS PREDICT STONE COMPOSITION? Mohamed Omar, Alaa El Mahdy, Ahmed Gamal, and Manoj Monga Mohamed OmarMohamed Omar More articles by this author , Alaa El MahdyAlaa El Mahdy More articles by this author , Ahmed GamalAhmed Gamal More articles by this author , and Manoj MongaManoj Monga More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2015.02.2853AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES To evaluate the correlation between 24 hour urine supersaturation levels and the crystalline stone composition. METHODS We retrospectively reviewed the results of stone analysis of 386 patients who had completed 24 hour urine stone risk profiles within 6 months of stone analysis. Patients were characterized as calcium oxalate, calcium phosphate or Uric acid stone formers based on the predominant component (>60%) of their stone. Patients with <50% of one stone composition were characterized as a mixed stone former. Sensitivity, specificity and accuracy of the 24-hour urine supersaturation for predicting the corresponding stone component were calculated. RESULTS The distribution of stone compositions was 235(61%) CAOX, 98(25%) CAPH, 35(9%) Uric acid and 18(5%) mixed stone group. The accuracy of supersaturation for predicting the predominant stone composition was 52.5% for CAOX, 70% for CAPH and 67% for Uric acid group. Even when the predominant stone composition exceeded 90%, the accuracy of supersaturation didn't change remarkably, coax (49 %, p=0.6641), cap (77%, p= 0.361) and uric acid (67%, p=0.9593) CONCLUSIONS 24-hour urine supersaturation has a poor accuracy to predict the predominant stone composition. Accuracy is highest for patients with calcium phosphate stone compositions. Bivariate comparison of 24-hour urine elements across stone type groups Demographics CaOx CaP Uric A Mixed P Value No. of patients (%) 235 (61%) 98 (25%) 35 (9%) 18 (5%) 386 Gender: Male 151 (64%) 31 (32%) 24 (69%) 10 (56%) <.0001 Gender: Female 84 (36%) 67 (68%) 11 (31%) 8 (44%) <.0001 Mean age 56±15 54±17 60±10 50±14 0.390 BMI 29±7.5 29.3±9.3 31.2±6.4 30.5±7.4 0.3781 pH 5.9±0.4 6.4±0.6 5.8±0.6 6.4±0.6 <.0001 Urine volume 2±0.9 2.1±1 1.9±0.8 1.9±1 0.6195 CaOx SS 6.74±3.6 6.6±3.7 5.9±3.7 5.6±3.2 0.3202 CaP SS 1±0.96 1.6±1.2 0.7±1.1 1.5±1.2 <.0001 Uric Acid SS 1±0.87 0.46±0.5 1.4±1 0.5±0.87 <.0001 Accuracy of supersaturation at different cut-off values of predominant stone composition Mineral Calcium oxalate Calcium phosphate Uric Acid >60% 52.5% 70% 67% >70% 54% 72% 67% >80% 54% 76% 67% >90% 49% 77% 67% © 2015 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 193Issue 4SApril 2015Page: e1025-e1026 Advertisement Copyright & Permissions© 2015 by American Urological Association Education and Research, Inc.MetricsAuthor Information Mohamed Omar More articles by this author Alaa El Mahdy More articles by this author Ahmed Gamal More articles by this author Manoj Monga More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Endoscopic and Histologic Findings in a Cohort of Uric Acid and Calcium Oxalate Stone Formers

To characterize the endoscopic and histologic renal papillary lesions in a cohort of uric acid (UA) stone formers (SF). Data were prospectively obtained during percutaneous nephrolithotomy between 2009 and 2013. Renal papillae were endoscopically analyzed to quantitate surface area occupied by plaque or plug, and biopsies were obtained. UA SF were compared with non-SF controls and patients with >50% calcium oxalate (CaOx) in the absence of UA. There were 23 UA SF; of which 19 stones (83%) were admixed with CaOx and 4 (17%) were pure. Compared with CaOx SF and controls, UA SF had a higher prevalence of diabetes and obesity, greater serum creatinine and UA levels, lower estimated glomerular filtration rate and urine pH, and elevated UA supersaturation. Characteristics of UA SF were compared with 95 CaOx SF and 19 controls. Overall, 23 (100%) UA SF had endoscopic plaque and 13 (57%) plugs. Endoscopically, UA SF displayed a greater incidence of plugging (57% vs 45% vs 11%; P=.006) relative to CaOx SF and controls. Likewise, UA SF had a greater percentage surface area of plugging (0.1 vs 0.0; P= .002) and plaque (2.0 vs 0.9; P= .006) than controls but similar amounts to CaOx SF. Histologic plugs were similar in UA and CaOx SF, although CaOx SF demonstrated greater interstitial inflammation on endoscopic biopsy. UA and CaOx SF have similar amounts of plaque, whereas UA SF have more endoscopic but not histologic collecting duct plugs. These data suggest an overlap between the pathogenesis of UA and CaOx stones. The anchoring site for UA stones remains uncertain.

Physiological Implications of Transepithelial Carboxylic Acid Absorption and Regulation by Slc26a6

The combination of increased urinary oxalate and attenuated urinary citrate concentration are a major risk factor for Ca2+-oxalate kidney stone formation, even when urinary Ca2+ levels are not elevated. Nevertheless, the molecular mechanisms that regulate urinary oxalate and citrate levels are not well understood. We studied the role of the oxalate transporter, slc26a6, and the citrate transporter, NaDC-1, in regulating oxalate/citrate homeostasis. We found that Slc26a6-null mice exhibited increased renal and intestinal sodium-dependent succinate uptake which is attributed to NaDC-1 function. Furthermore, we monitored urinary hyperoxaluria and hypocitraturia, but no change in urinary pH, indicating enhanced transport activity of NaDC-1 in slc26a6-null mice. When co-expressed in xenopus oocytes, Slc26a6 dramatically inhibited NaDC-1 transport activity in an activity dependent manner. Finally, biochemical and physiological analysis revealed that the STAS domain of Slc26a6 and the first intracellular loop of NaDC-1 mediated both the physical and functional interactions of these transporters. Our findings reveal a molecular pathway that tightly regulates oxalate and citrate concentration and may control biological Ca2+-oxalate stone formation in the kidney and other organs like, for example, salivary glands.

Does 24-Hour Urine Supersaturation Predict Stone Composition?

Background: The aim of the study was to evaluate the correlation between 24-hour urine supersaturation (SS) levels and the crystalline stone composition. Methods: We retrospectively reviewed the results of stone analysis of 386 patients who had completed 24-hour urine stone risk profiles within 2 months of stone analysis. Patients were characterized as calcium oxalate (CAOX), calcium phosphate (CAPH) or uric acid (UA) stone formers based on the predominant component (> 60%) of their stone. Patients with < 50% of one stone composition were characterized as a mixed stone former. Sensitivity, specificity and accuracy of the 24-hour urine SS for predicting the corresponding stone component were calculated. Results: The distribution of stone compositions was 235 (61%) CAOX, 98 (25%) CAPH, 35 (9%) UA and 18 (5%) mixed stone group. At predominant stone mineral concentration ? 60%, the accuracy of 24-hour urine SS for predicting the predominant stone composition was 52.5% for CAOX, 70% for CAPH and 67% for UA group. Even when the predominant stone mineral concentration was ? 90%, the accuracy of SS did not improve: COAX (49%, P = 0.6641), CAPH (77%, P = 0.361) and UA (67%, P = 0.9593). Conclusions: Twenty-four-hour urine SS has a poor accuracy to predict the predominant stone composition. Accuracy is highest for patients with CAPH stones. World J Nephrol Urol. 2015;4(1):169-172 doi: http://dx.doi.org/10.14740/wjnu206w

Dietary habits may influence oxalate degradation by intestinal bacteria commentary on: the role of Oxalobacter formigenes colonization in calcium oxalate stone disease.

The purpose of this article was to assess the role of Oxalobacter formigenes (O formigenes) on the intestinal absorption, plasma concentration, and urinary excretion of oxalate in calcium oxalate stone formers and to better understand oxalate metabolism in the presence or absence of this bacterial species.

Cystine stones: a single tertiary center experience.

To analyze the epidemiological and clinical characteristics and therapeutic outcomes of patients with cystine stones and to compare them with the characteristics of patients with calcium oxalate stones. We identified 30 patients with cystine stones who were consulted in our department from January 1972 until December 2013. These patients were matched and paired, based on age and gender, to 30 calcium oxalate stone formers who were diagnosed and treated in our department from January 2011 until December 2013. Cystine stones were significantly large in size (p<0.001) and most of them were found in the kidney (p=0.002). Patients with cystinuria had their first stone episode at an early age (p<0.001) compared with patients with calcium oxalate stones. No significant differences were observed regarding the frequency and the severity of symptoms. Both groups had similar visits per year in outpatient clinics, emergency room admissions, and episodes of febrile urinary tract infections. Cystine stone formers had undergone significantly higher number of procedures for stone removal (p<0.001). No statistical differences were found in the compliance rates between the groups. Patients with cystine stones had significantly higher serum creatinine levels (p=0.005). Cystine stones present in an earlier age and have the likelihood to be large in size. Patients with cystine stones undergo a greater number of procedures, and they have a greater risk to develop chronic renal impairment.

Urinary oxalate, citrate, and gamma glutamyl transferase alterations after administration of Cynodon dactylon extract in cats

BACKGROUND: Urinary oxalate and citrate are the keyfactors in caox urolithiasis of cats and Gamma GlutamylTransferase is a good test for assessment of kidney damage.Favorable effects of Cynodon dactylon on calcium oxalate stoneformation have recently been proved in rats. OBJECTIVES: Thepresent study was designed to investigate the alteration ofurinary oxalate, citrate, and GGT after administration of thehydroalcoholic extract of Cynodon dactylon to experimentalhyperoxaluric cats. No scientific study has been done so far todemonstrate the beneficial effect of this plant in cats. METHODS:13 mature male cats were randomly divided into 3 groups: groupAreceived standard diet and drinking water while, group B andC also received ethylene glycol at sub-toxic dose (130 mg/kg)daily for 30 days. Group C received hydroalcoholic extract ofC.dactylon (400 mg/kg) from day 0 to 30, as well. Urine sampleswere collected on days 0, 15, and 30 and were analyzed foroxalate, citrate, and GGT levels. RESULTS: Urine oxalate levelin group B was significantly higher than group C on days 15 and30. Urinary citrate excretion was significantly higher in group Ccompared to the other groups on day 15; however, it decreasedduring the entire experiment in groups B and C. Urinary GammaGlutamyl Transferase level was increased in hyperoxaluric catsand decreased in the treated group during the experiment.CONCLUSIONS: Based on our results, C.dactylon extract couldreduce the hyperoxaluria and has beneficial effects onpreventing the renal damage in cats. Such findings provide ascientific explanation for applying C.dactylon in prevention andpossible treatment of CaOx kidney stones in cats and humans.

Association of serum biochemical metabolic panel with stone composition.

To determine the association of the basic metabolic panel with stone type. The present study was a retrospective review of 492 stone formers with both stone composition analysis and basic metabolic panel available. Analysis of a basic metabolic panel across stone types was carried out using Fisher's exact test and analysis of variance. Multinomial logistic regression was used to predict stone type based on a basic metabolic panel. A total of 272 (55%) patients had predominantly calcium oxalate stones, 100 (21%) had uric acid stones, 93 (19%) had calcium phosphate stones, 16 (3%) had mixed stones and 11 (2%) had other types of stones. Uric acid stone formers had the highest serum glucose, blood urea nitrogen and creatinine levels. Calcium oxalate stone formers had the highest serum sodium. No significant differences in mean serum calcium levels across different stone types were identified. The predicted risk of uric acid stone over the other stone types increased with an increase in serum glucose and decreased with an increase in carbon dioxide levels. The predicted risk of calcium oxalate stones increased with an increase in serum sodium and chloride levels. The predicted risk of calcium phosphate and oxalate stones over the other stone types increased with an increase in serum calcium levels. The overall accuracy of the basic metabolic panel alone to predict stone type was 59%. A basic metabolic panel alone or in combination with 24-h urinalysis and demographics does not accurately predict stone type. However, it can be used in combination with other variables to predict stone composition.

Alexander Randall may have had it right after all.

Several theories exist regarding the pathogenesis of urinary calculi, and the early incipient events leading to calculus formation remain the most controversial. The authors detail a theory by which microscopic Randall plaques (RP) lead to calcium oxalate calculi in idiopathic calcium oxalate stone formers (1). Outlined is a process by which RP form in the basement membrane of the loops of Henle and spread through the interstitium through mineral deposition in an organic matrix, eventually eroding through the urothelium. Once exposed to the urinary milieu, precipitation of minerals and organic substances occurs based on urinary constituents. The process leading to RP formation is not yet fully defined, but one must consider an alternative theory based on a more vascular process. In short, formation may be RP due to a process similar to how atherosclerotic lesions form in arteries as the vasa recta that surround the tubules have turbulent flow, relative hypoxia, and hyperosmolarity which is an ideal environment for vascular injury and a calcifying process. The early events leading to RP and calcium oxalate stone formation has yet to be determined, but is likely multifactorial and represents an area of research fit for collaboration beyond our fellow urologic colleagues.

Biomimetic Randall’s plaque as an in vitro model system for studying the role of acidic biopolymers in idiopathic stone formation

Randall's plaque (RP) deposits seem to be consistent among the most common type of kidney stone formers, idiopathic calcium oxalate stone formers. This group forms calcium oxalate renal stones without any systemic symptoms, which contributes to the difficulty of understanding and treating this painful and recurring disease. Thus, the development of an in vitro model system to study idiopathic nephrolithiasis, beginning with RP pathogenesis, can help in identifying how plaques and subsequently stones form. One main theory of RP formation is that calcium phosphate deposits initially form in the basement membrane of the thin loops of Henle, which then fuse and spread into the interstitial tissue, and ultimately make their way across the urothelium, where upon exposure to the urine, the mineralized tissue serves as a nidus for overgrowth with calcium oxalate into a stone. Our group has found that many of the unusual morphologies found in RP and stones, such as concentrically laminated spherulites and mineralized collagenous tissue, can be reproduced in vitro using a polymer-induced liquid precursor (PILP) process, in which acidic polypeptides induce a liquid phase amorphous precursor to the mineral, yielding non-equilibrium crystal morphologies. Given that there are many acidic proteins and polysaccharides present in the renal tissue and urine, we have put forth the hypothesis that the PILP system may be involved in urolithiasis. Therefore, our goal is to develop an in vitro model system of these two stages of composite stone formation to study the role that various acidic macromolecules may play. In our initial experiments presented here, the development of "biomimetic" RP was investigated, which will then serve as a nidus for calcium oxalate overgrowth studies. To mimic the tissue environment, MatriStem(®) (ACell, Inc.), a decellularized porcine urinary bladder matrix was used, because it has both an intact epithelial basement membrane surface and a tunica propria layer, thus providing the two types of matrix constituents found associated with mineral in the early stages of RP formation. We found that when using the PILP process to mineralize this tissue matrix, the two sides led to dramatically different mineral textures, and they bore a striking resemblance to native RP, which was not seen in the tissue mineralized via the classical crystal nucleation and growth process. The interstitium side predominantly consisted of collagen-associated mineral, while the luminal side had much less mineral, which appeared to be tiny spherules embedded within the basement membrane. Although these studies are only preliminary, they support our hypothesis that kidney stones may involve non-classical crystallization pathways induced by the large variety of macromolecular species in the urinary environment. We believe that mineralization of native tissue scaffolds is useful for developing a model system of stone formation, with the ultimate goal of developing strategies to avoid RP and its detrimental consequences in stone formation, or developing therapeutic treatments to prevent or cure the disease. Supported by NIDDK grant RO1DK092311.

The role of Randall plaques on kidney stone formation.

Randall’s plaque is microscopically a plaque of calcium deposited in the interstitial tissue of the renal papilla. These plaques are thought to serve as a nidus for urinary stone formation. Large amounts of Randall’s plaque are unique to idiopathic calcium oxalate stone formers. Although Randall’s plaques can be found in other stone formers, only in idiopathic calcium oxalate stone formers, the detailed mechanism of stone overgrow on plaque was thoroughly studied. Calcification is invariably located in the basement membrane of the loops of Henle and from there plaques spread through the interstitium toward urothelium. Within the basement membrane, mineral deposits are individual laminated particles in which zones of crystal and organic matrix overlay each other. In the interstitium, the particles appear to fuse on the collagen bundles to form a syncytium of crystal islands in an organic sea. By loss of integrity of urothelium, regions of plaque are exposed to urine. The exposed surface will touch and be covered by molecules of urine origin, including osteopontin, Tamm Horsfall protein, and crystals formed under urine supersaturations, resulting in a ribbon of alternating matrix and crystal. Eventually crystallization escapes from matrix modulation and crystals extend outward into the space of urine and begin to form a calcium oxalate stone proper. Randall’s plaque plays an important role and is prerequisite of kidney stone formation in idiopathic calcium oxalate stone formers.

Comparison of the Metabolic Profile of Mixed Calcium Oxalate/Uric Acid Stone Formers to That of Pure Calcium Oxalate and Pure Uric Acid Stone Formers

To compare the metabolic profile of patients who form mixed calcium oxalate (CaOx)/uric acid (UA) stones to those of pure CaOx and pure UA stone formers. We performed a retrospective review of 232 patients, with both stone composition analysis and 24-hour urine collection, seen between March 2002 and April 2012. Analysis of 24-hour urine constituents across the 3 stone groups (pure UA, pure CaOx, and mixed CaOx/UA) was performed using univariate analysis of variance and multivariate linear regression models adjusting for clinical and demographic factors and 24-hour urine collection elements. A total of 27 patients (11.6%) had mixed CaOx/UA, 122 (52.6%) had pure CaOx, and 83 (35.8%) had pure UA calculi. Univariate analysis demonstrated significant differences between mixed CaOx/UA patients and pure CaOx patients for urine pH (mixed, 5.63 ± 0.49 vs pure, CaOx 5.93 ± 0.51; P= .009) and supersaturation (SS) UA (mixed, 1.84 ± 1.09 vs pure, CaOx 1.26 ± 0.93; P= .01), and a significant difference between mixed CaOx/UA patients and pure UA patients for SS CaOx (mixed, 7.18 ± 4.23 vs pure, UA 4.90 ± 2.96; P= .005). Multivariate analysis demonstrated that mixed CaOx/UA patients had no significant difference in SS CaOx as compared with pure CaOx patients (difference,-0.27; P= .66), whereas at the same time had no significant difference in SS UA as compared with pure UA patients (-0.07; P=.69). The metabolic profile of patients who form mixed CaOx/UA stones demonstrates abnormalities that promote both CaOx and UA stone formation. Dietary and medical management for this group of patients should address treatment of both defects.

Animal Protein and the Risk of Kidney Stones: A Comparative Metabolic Study of Animal Protein Sources

We compared the effect of 3 animal protein sources on urinary stone risk. A total of 15 healthy subjects completed a 3-phase randomized, crossover metabolic study. During each 1-week phase subjects consumed a standard metabolic diet containing beef, chicken or fish. Serum chemistry and 24-hour urine samples collected at the end of each phase were compared using mixed model repeated measures analysis. Serum and urinary uric acid were increased for each phase. Beef was associated with lower serum uric acid than chicken or fish (6.5 vs 7.0 and 7.3 mg/dl, respectively, each p <0.05). Fish was associated with higher urinary uric acid than beef or chicken (741 vs 638 and 641 mg per day, p = 0.003 and 0.04, respectively). No significant difference among phases was noted in urinary pH, sulfate, calcium, citrate, oxalate or sodium. Mean saturation index for calcium oxalate was highest for beef (2.48), although the difference attained significance only compared to chicken (1.67, p = 0.02) but not to fish (1.79, p = 0.08). Consuming animal protein is associated with increased serum and urine uric acid in healthy individuals. The higher purine content of fish compared to beef or chicken is reflected in higher 24-hour urinary uric acid. However, as reflected in the saturation index, the stone forming propensity is marginally higher for beef compared to fish or chicken. Stone formers should be advised to limit the intake of all animal proteins, including fish.

Contrasting Histopathology and Crystal Deposits in Kidneys of Idiopathic Stone Formers Who Produce Hydroxy Apatite, Brushite, or Calcium Oxalate Stones

Our previous work has shown that stone formers who form calcium phosphate (CaP) stones that contain any brushite (BRSF) have a distinctive renal histopathology and surgical anatomy when compared with idiopathic calcium oxalate stone formers (ICSF). Here we report on another group of idiopathic CaP stone formers, those forming stone containing primarily hydroxyapatite, in order to clarify in what ways their pathology differs from BRSF and ICSF. Eleven hydroxyapatite stone formers (HASF) (2 males, 9 females) were studied using intra-operative digital photography and biopsy of papillary and cortical regions to measure tissue changes associated with stone formation. Our main finding is that HASF and BRSF differ significantly from each other and that both differ greatly from ICSF. Both BRSF and ICSF patients have significant levels of Randall's plaque compared with HASF. Intra-tubular deposit number is greater in HASF than BRSF and nonexistent in ICSF while deposit size is smaller in HASF than BRSF. Cortical pathology is distinctly greater in BRSF than HASF. Four attached stones were observed in HASF, three in 25 BRSF and 5-10 per ICSF patient. HASF and BRSF differ clinically in that both have higher average urine pH, supersaturation of CaP, and calcium excretion than ICSF. Our work suggests that HASF and BRSF are two distinct and separate diseases and both differ greatly from ICSF.

Evaluation of biochemical parameters in calcium oxalate renal stone formers

Background: Calcium oxalate renal stones are the most predominant cases of renal stones, their formation is more complex and no specific cause for the stone can be identified so called 'idiopathic'. This study was designed to analyze the metabolic and biochemical alterations in serum, urine and their relation to pathophysiology of calcium oxalate stone formation Patients and Methods : In this study, individuals have been classified into three groups: Group (A) included (29) apparently healthy persons of non calcium oxalate stone formers aged (20-35 years), group (B) included (16) patients with calcium oxalate renal stone aged (20-35 years) and group(C) included (15) patients with calcium oxalate renal stone aged (40-70 years). Fasting serum, random urine and 24hours urine samples were collected from all individuals to determine urine volume, creatinine clearance, serum and urine levels of calcium, phosphate ,uric acid ,zinc, copper and serum levels of total cholesterol, high density lipoproprotien-cholesterol and urea . Results: Calcium oxalate stone formers group (B) exhibited significantly decreased serum levels of uric acid (P=0.015),zinc (P=0.031) with increased serum level of total cholesterol(P=0.034) when compared to similar age group of healthy control ,group (A). Urinary parameters in calcium oxalate stone formers also showed significantly increased levels of 24-hour urine calcium(P=0.05) and urine calcium: creatinine ratio (P=0.05)when compared to healthy control. While, older age calcium oxalate stone formers, group (C) showed significantly decreased urine volume (P=0.015)with increased kidney stone size(P=0.03) when compared to younger age calcium oxalate stone formers, group (B). Conclusions: Level of urinary calcium and urine volume are the most important urinary factors in enhancing calcium oxalate stone formation. While the observed changes in biochemical measurements of serum in calcium oxalate stone formers may indicate a probable metabolic relation in pathogenesis of this disease.