Calcium Oxalate Supersaturation Research Articles

Beneficial effects of a prescription home-prepared diet and of zucchini on urine calcium oxalate supersaturation and urinary parameters in adult cats.

From the authors' experience, the consumption of a balanced prescription home-prepared diet that includes zucchini (courgette) benefits cats with recurrent urolithiasis, but there is no published evidence to support this. The aim was to study the effects on urinary parameters of (1) a balanced prescription home-prepared diet containing zucchini, and (2) the addition of zucchini to a dry food, compared with two commercial therapeutic diets. Eight healthy cats were included in a Latin-square designed protocol. Five diets were evaluated: two commercial diets, designed for cats with urinary disorders, one high-moisture (U-WET) and one high-sodium dry (U-DRY); one home-prepared diet (HOME); one commercial dry food for adult maintenance (DRY); and DRY given together with 10 g of zucchini per kg body weight (DRY-Zuc). After a 7-day adaptation period, urine was collected and daily food and water intakes were assessed for 12 days. Urinary parameters, and relative supersaturation (RSS) for calcium oxalate (CaOx) and struvite, were determined. Data underwent repeated measures ANOVA analysis. The digestibility of energy, dry matter, protein and fat was highest with the HOME diet. CaOx RSS was lowest in cats eating the HOME diet, but not significantly different from the U-WET or U-DRY diets. CaOx RSS was lower in cats eating the DRY-Zuc diet than in cats eating the DRY diet. Struvite RSS did not differ significantly among groups. This study shows that a balanced prescription home-prepared diet was safe and allowed a very low urinary CaOx RSS. It also showed that adding zucchini to dry food lowered the urine CaOx RSS.

Defining 24-hour urine parameters and kidney stone risk of student athletes.

Dehydration is a risk factor for kidney stone formation. Studying populations that may experience dehydration without a known increased incidence of stone formation may help understand stone formation and prevention. High-caliber athletes represent such a population. We characterized the urinary environment of high-caliber athletes utilizing 24-hour urine collections with comparison to non-athlete controls. After Institutional Review Board (IRB) and National Collegiate Athletic Association (NCAA) compliance officer approval, 74 college-student athletes and 20 non-athletes were enrolled. Demographics, medical history, and sport of participation were recorded. Participants were asked to provide 24-hour urine collections as well as diet and activity logs at the time of urine collection. Standard stone risk parameters were assessed and compared to litholink reference standards. 34 athletes and 10 non-athletes provided at least one 24-hour urine specimen for evaluation. Athletes had a high prevalence of urinary risks for stone formation including low volume (median 1.46L), low citrate, high sodium, high calcium (females), and high uric acid (males). However, athletes also had a high prevalence of known stone-protective factors such as high urine magnesium. Athletes had a lower urine pH but high supersaturation of uric acid and calcium oxalate compared to non-athletes. Student athletes appear to have a high prevalence of urinary risk factors for stone formation such as dehydration, high calcium, high uric acid, high sodium, and low citrate. Overall stone risk in this population may be offset by increased levels of stone-protective factors such as magnesium. Further study of this population may help generate hypotheses for effective stone prevention strategies in the general population.

Effect of Black Tea Consumption on Urinary Risk Factors for Kidney Stone Formation.

Copious fluid intake is the most essential nutritional measure in the treatment of urolithiasis, and is suggested to be a protective factor in the primary prevention of urinary stone formation. Although the intake of black tea contributes to daily fluid intake, the high oxalate content could outweigh the beneficial effect of urine dilution. The present study investigated the effect of black tea consumption on urinary risk factors for kidney stone formation. Ten healthy men received a standardized diet for a period of ten days. Subjects consumed 1.5 L/day of fruit tea (0 mg/day oxalate) during the 5-day control phase, which was replaced by 1.5 L/day of black tea (86 mg/day oxalate) during the 5-day test phase. Fractional and 24-h urines were obtained. The intake of black tea did not significantly alter 24-h urinary oxalate excretion. Urinary citrate, an important inhibitor of calcium stone formation, increased significantly, while the relative supersaturation of calcium oxalate, uric acid, and struvite remained unchanged. No significantly increased risk for kidney stone formation could be derived from the ingestion of black tea in normal subjects. Further research is needed to evaluate the impact of black tea consumption in kidney stone patients with intestinal hyperabsorption of oxalate.

Antiurolithiasis, Antioxidant, Anti-inflammatory, Analgesic, and Diuretic Activity of Ethanolic Extract of Seeds of Caesalpinia bonducella

Background: Urolithiasis, commonly known as nephrolithiasis, kidney stone, or renal stone, is a disorder caused by a decrease in anti-oxidant capability, damaged renal epithelium or consistently supersaturated urine, which leads to increased crystallisation. The aim of this study was to evaluate antiurolithiatic, antioxidant, analgesic, anti-inflammatory and diuretic property of ethanolic extract of C. bonducella seeds (EECB). Methods: For the probable molecules in EECB, GC-MS analysis was performed. Antioxidant property was investigated using DPPH and FRAP assays. Nucleation and aggregation assays were used for in vitro urolithiatic study. The diuretic, anti-inflammatory and analgesic activity were performed in animal model. Results: GC–MS analysis of EECB identified the presence of Vitamin E, steroidal ring containing compounds and hydrocarbons. EECB was found to be effective in scavenging free radicals. EECB exhibited significant inhibition of nucleation and aggregation of calcium oxalate crystals. The anti-inflammatory and analgesic activity of EECB were found to be significant effective at dose of 400 mg/kg. Further, EECB exhibited a significant increase in urinary output and electrolytes Na+, Cl- excretion at dose of 400 mg/kg. Conclusion: The finding of this study suggested that EECB possess significant pharmacological activities like antioxidant, anti-inflammatory, analgesic, diuretic, and antiurolithiatic activities. Antioxidants property of EECB could be used in preventing oxidative stress; the anti-inflammatory and analgesic properties could be used in the prevention of inflammation and pain of damaged epithelial cells of nephrons, which are caused by intra-papillary calcifications; the diuretic activity could be used in reducing supersaturation of calcium oxalate.

24-Hour Urine Calcium Oxalate Supersaturation Risk Correlates with Computerized Tomography Volumetric Calcium Oxalate Stone Growth.

In vitro experiments demonstrate calcium oxalate (CaOx) supersaturation (SS) drives CaOx nucleation and growth. We investigated the link between 24-hour urine SS CaOx and in vivo stone growth through a natural history, imaging study. Using an institutional review board-approved database, we sought >80% CaOx stone formers who prior to stone intervention obtained 2 separate computerized tomography (CT) scans with at least one 24-hour urine collection between scans. Two blinded reviewers calculated bilateral 3-dimensional stone volume using the Visage 7® region of interest pen tool. CT volume difference was divided by time between scans, and SS CaOx was grouped into low (<5), medium (5-10) and high risk (>10). Statistical significance between groups was assessed by Kruskal-Wallis test. We identified 80 individuals with stone growth measured by 3-dimensional CT (mean ∼7 months between studies). Inter-reviewer reliability of CT volume measurement was well correlated (0.98, Gwet's AC2), and an arbitrator was only needed in 13/160 (8%) cases. Median stone volume growth/year was 15%, 71% and 177% for low, medium and high risk groups, respectively (p <0.001). Despite inter-individual variation, best fit of mean SS CaOx vs stone volume growth was moderately correlated (Spearman's rho=0.53, p <0.001). In a population of pure CaOx stone formers, increased 24-hour SS CaOx risk was associated with increased in vivo stone growth. Further investigations using CT volumetric stone growth may allow for the noninvasive study of stone growth modulators, improved stone risk prediction and development of a kidney stone simulator.

MO119COMPUTER-DERIVED SOFTWARE IN CLINICAL PRACTICE: RESULTS FROM A SHORT-TERM FOLLOW-UP ACCORDING TO KIDNEY STONE COMPOSITION IN KIDNEY STONE FORMERS

Abstract Background and Aims Urinary supersaturation (SS) contributes to stone formation, and its assessment in stone formers may be helpful in clinical practice. Several computer programs are available for SS calculation, including EQUIL2, JESS and Lithorisk1. The aim of this study was to evaluate changes in SS in 24-hour urine in patients with known stone composition before and after about three months of regular treatment. Method Patients who submitted their stone/s for composition analysis and had provided an adequate 24-hour urine collection (creatinine 15-20 mg/kg/24-hour) before and around 90 days under regular treatment were included. Stone composition was defined using morphoconstitutional and infrared spectroscopy. The treatment was initiated in accordance with specific guidelines, and included dietary advices and medications2. SS for calcium oxalate (CaOx), calcium phosphate (CaP) and uric acid (UA) using EQUIL2, JESS and Lithorisk were calculated at baseline and after about 90 days on treatment. Continuous variables were reported as means (SD) while categorical variables were reported as frequencies and percentages. Baseline and follow-up SS urine values were compared using the Wilcoxon signed-rank test. 3D graphs were plotted using mean SS values of CaOx, CaP and UA obtained from each program before and after treatment, dividing the stones into 4 groups1: calcium oxalate monohydrate (COM), calcium oxalate dihydrate (COD), calcium phosphate (CaP), and uric acid (UA). Ethical Committee approval was obtained. Results 105 patients (61 men, 58%) were followed and provided 24h urine collection. Of these, 101 (96%) were recurrent patients. The mean (SD) follow-up was 94 (14) days. 48 (46%) of all calculi were made of CaOx, either COM or COD, 36 (34%) of UA, and 21 (20%) of CaP. A significant reduction in SS values during treatment was observed in patients with COM (p&amp;lt;0.05) , COD (p&amp;lt;0.001), and UA stones (p&amp;lt;0.001) with all programs. The reduction in SS values over time in patients with CaP stones was not significant (Table 1). Figure 1 shows 3D plots with SS before and after treatment into 4 groups of stone formers. Conclusion EQUIL2, JESS and Lithorisk are suitable software currently used for clinical and research purposes. SS values calculated by EQUIL2, JESS and Lithorisk during follow-up showed a significant reduction among COM, COD and UA stone formers. CaP stone formers did not show significant changes in SS over time.

Sex Differences of Kidney Stone Urine Risk Factors after Roux-en-Y Gastric Bypass

Introduction: Roux-en-Y gastric bypass (RYGB) is a bariatric surgical procedure that is associated with higher risk of kidney stones after surgery. We examined urine composition in 18 men and women before and after RYGB to examine differences in kidney stone risk. Methods: Three 24-h urine collections were performed before and 1 year after RYGB. We analyzed mean urinary values for pre- and post-RYGB collections and compared men and women. Results: Seven men and eleven women completed pre- and post-RYGB urine collections. Pre-RYGB, men had higher calcium oxalate supersaturation (CaOx SS) (7.0 vs. 5.0, p = 0.04) compared with women. Post-RYGB, women had higher urine CaOx SS (13.1 vs. 4.6, p = 0.002), calcium phosphate supersaturation (1.04 vs. 0.59, p = 0.05), and lower urine volumes (1.7 vs. 2.7L, p < 0.001) compared with men. Discussion/Conclusion: There are important differences in urine composition by sex that may contribute to higher kidney stone risk in women after RYGB compared with men.

Evaluation of fasting impact during Ramadan month on patients with a history of kidney stones in a military hospital

Introduction: One of the cornerstones and common causes of kidney stone formation is the volume of fluid consumed during a 24- hour that influences on forming that by several mechanisms. Since fluid intake decreases during Ramadan, one of the common questions posed is whether Ramadan fasting is associated with the precipitating of stone formation. The present study was aimed to investigate the effect of Ramadan fasting on precipitating and Inhibitors of stone formation in patients with a history of renal kidney disease. Methods: The study population included all of the patients with kidney stone diseases who were seen at the Clinic of Urology and Nephrology affiliated with Baqiyatallah hospital during the month of Ramadan in 2014 and 2015. The number of 66 patients was chosen and included in the study through randomized simple sampling. All subjects underwent blood tests like serum uric acid, serum phosphate, serum calcium, and serum sodium. Samples were tested in terms of volume, magnesium, uric acid, Calcium, Phosphate, Sodium, citrate, oxalate, Calcium oxalate supersaturation, Calcium Phosphate supersaturation, Uric acid supersaturation. Results: Sixty-six eligible patients were included that the mean age was 48.35±12.10 years. Fourteen men and 52 women were included. There were no significant differences in the mean pH of urine, urinary sodium, urinary oxalate, supersaturated levels of calcium oxalate in the urine, urinary phosphate levels, and super-saturated levels of urinary calcium phosphate between the two groups (P&gt;0.05). The average volume of urine, urinary magnesium, urinary calcium, urinary citrate, the uric acid level in the non-fasting group was higher than the fasting group (P&lt;0.05). There were no differences in the average blood calcium levels, blood sodium, blood phosphate levels, blood acidic levels between the two groups (P&gt;0.05). There was no difference in the mean super-saturated level of uric acid between the two groups (P=0.035). Conclusion: There was controversial evidence on the effect of Ramadan fasting on kidney stone formation and there is not enough evidence in the present study that Ramadan fasting precipitates risk factors associated with calculus formation.

Chlorthalidone with potassium citrate decreases calcium oxalate stones and increases bone quality in genetic hypercalciuric stone-forming rats

To study human idiopathic hypercalciuria we developed an animal model, genetic hypercalciuric stone-forming rats, whose pathophysiology parallels that of human idiopathic hypercalciuria. Fed the oxalate precursor, hydroxyproline, every rat in this model develops calcium oxalate stones. Using this rat model, we tested whether chlorthalidone and potassium citrate combined would reduce calcium oxalate stone formation and improve bone quality more than either agent alone. These rats (113 generation) were fed a normal calcium and phosphorus diet with hydroxyproline and divided into four groups: diets plus potassium chloride as control, potassium citrate, chlorthalidone plus potassium chloride, or potassium citrate plus chlorthalidone. Urine was collected at six, 12, and 18 weeks and kidney stone formation and bone parameters were determined. Compared to potassium chloride, potassium citrate reduced urinary calcium, chlorthalidone reduced it further and potassium citrate plus chlorthalidone even further. Potassium citrate plus chlorthalidone decreased urine oxalate compared to all other groups. There were no significant differences in calcium oxalate supersaturation in any group. Neither potassium citrate nor chlorthalidone altered stone formation. However, potassium citrate plus chlorthalidone significantly reduced stone formation. Vertebral trabecular bone increased with chlorthalidone and potassium citrate plus chlorthalidone. Cortical bone area increased with chlorthalidone but not potassium citrate or potassium citrate plus chlorthalidone. Mechanical properties of trabecular bone improved with chlorthalidone, but not with potassium citrate plus chlorthalidone. Thus in genetic hypercalciuric stone-forming rats fed a diet resulting in calcium oxalate stone formation, potassium citrate plus chlorthalidone prevented stone formation better than either agent alone. Chlorthalidone alone improved bone quality, but adding potassium citrate provided no additional benefit.

Urolithiasis and sleeve gastrectomy: a prospective assessment of urinary biochemical variables.

to evaluate urinary biochemical alterations related to urolithogenesis processes after sleeve gastrectomy (SG). : prospective study with 32 individuals without previous diagnosis of urolithiasis who underwent SG. A 24-h urine test was collected seven days prior to surgery and at 6-month follow-up. The studied variables were urine volume, urinary pH, oxalate, calcium, citrate, and magnesium and calcium oxalate super saturation (CaOx SS). patients were mainly women (81.2%), with mean age of 40.6 years. Mean pre- and postoperative BMI were 47.1 ± 8.3 Kg/m2 and 35.5 ± 6.1 Kg/m2, respectively (p<0.001). Urine volume was significantly lower at the postoperative evaluation in absolute values (2,242.50 ± 798.26 mL x 1,240.94 ± 352.39 mL, p<0.001) and adjusted to body weight (18.58 ± 6.92 mL/kg x 13.92 ± 4.65 mL/kg, p<0.001). CaOx SS increased significantly after SG (0.11 ± 0.10 x 0.24 ± 0.18, p<0.001). Moreover, uric acid levels were significantly lower at the postoperative evaluation (482.34 ± 195.80 mg x 434.75 ± 158.38 mg, p=0.027). Urinary pH, oxalate, calcium, citrate, and magnesium did not present significant variations between the pre- and postoperative periods. SG may lead to important alterations in the urinary profile. However, it occurs in a much milder way than that of RYGB.

Comparison of Supersaturation Outputs from Different Programs and Their Application in Testing Correspondence with Kidney Stone Composition.

Introduction: Relative supersaturation (SS) for calcium oxalate (CaOx), calcium phosphate (CaP), and uric acid (UA) has been used for assessing urinary crystallization and estimated by programs, including EQUIL, Joint Expert Speciation System (JESS), and Lithorisk. We compared outputs from these programs and their correspondence with stone composition. Materials and Methods: SS of CaOx, CaP, and UA, using EQUIL, JESS, and Lithorisk were calculated from stone-forming patients. Pearson correlation coefficients were used to ascertain the correspondence between the outputs. Fractional regression models evaluated the relationship between SS and the percentage of each compound in the stones. Results: Two hundred eleven patients were included. Pearson correlation coefficients for CaOx (r ≥ 0.96), CaP (r ≥ 0.99), and UA SS (r ≥ 0.99) showed a high correspondence between all programs. We observed a significant correspondence between CaOx SS and the percentage of CaOx dihydrate in the stone (p < 0.001), as well as between the percentage of brushite and apatite and CaP SS. UA SS showed the strongest correspondence with the percentage of UA in the stones (p < 0.001). Conclusions: Good correlation between EQUIL, JESS, and Lithorisk was observed and good correspondence with stone composition. The magnitude of the association demonstrated by fractional regression models supports evidence for applying SS in clinical practice.

Association of Chronic Kidney Disease Stage with 24-Hour Urine Values Among Patients with Nephrolithiasis.

Introduction: Nephrolithiasis is a known risk factor for chronic kidney disease (CKD); however, it is unknown how CKD affects urinary parameters related to stone risk. The purpose of this study was to assess the relationship of diminishing glomerular filtration rate (GFR) and kidney stone-related 24-hour urine (24H urine) composition. Materials and Methods: A single-institution retrospective review of patients (n = 2057) who underwent 24H urine analysis was performed. The serum creatinine within 1 year of the first 24H urine was used to determine estimated GFR and stratify patients by CKD stage. We performed analysis of variance and multivariable linear regression to assess the relationship of GFR and urinary analytes. Results: Among all patients, there were 184 (8.9%), 1537 (74.7%), 245 (11.9%), 70 (3.4%), 17 (0.8%), and 4 (0.2%) in CKD stage I, II, IIIa, IIIb, IV, and V groups, respectively. On analysis of 24H urine composition, as CKD increased, changes in urinary parameters protective against crystallization included decreased calcium and uric acid (UA) (P < 0.001). In addition, parameters favoring crystallization included decreased citrate and magnesium (P = 0.002 and P < 0.001, respectively). The net effect with increasing GFR was decreasing supersaturation of calcium oxalate and phosphate. On linear regression, urinary excretion of calcium, oxalate, citrate, UA, phosphate, and ammonia all decreased with decreasing GFR (all P < 0.05). Conclusions: Higher CKD stage was associated with changes in urinary analytes that both promoted and inhibited stone formation, with the net effect of decreasing calcium oxalate and phosphate supersaturation. These patients may benefit from medical therapy that targets improving urinary citrate instead of lowering calcium or UA.

Simple dietary advice targeting five urinary parameters reduces urinary supersaturation in idiopathic calcium oxalate stone formers

Among 208 kidney stone patients referred within 2 years, 75 patients (66 men, nine women) with truly idiopathic calcium oxalate stones (ICSF) were recruited. Dietary advice (DA) aimed at (1) urine dilution, (2) reduced crystallization promotion (lowering oxalate), and (3) increased crystallization inhibition (increasing citrate). We recommended higher intakes of fluid and calcium with meals/snacks (reducing intestinal oxalate absorption) as well as increased alkali and reduced meat protein (acid) for increasing urinary citrate. The intended effects of DA were elevations in urine volume, calcium (U-Ca) and citrate (U-Cit) as well as reductions in oxalate (U-Ox) and uric acid (U-UA). We retrospectively calculated an adherence score (AS), awarding + 1 point for parameters altered in the intended direction and − 1 point for opposite changes. Calcium oxalate supersaturation (CaOx-SS) was calculated using Tiselius’ AP(CaOx) index EQ. DA induced changes (all p < 0.0001) in urine volume (2057 ± 79 vs. 2573 ± 71 ml/day) and U-Ca (5.49 ± 0.24 vs. 7.98 ± 0.38 mmol/day) as well as in U-Ox (0.34 ± 0.01 vs. 0.26 ± 0.01 mmol/day) and U-UA (3.48 ± 0.12 vs. 3.13 ± 0.10 mmol/day). U-Cit only tendentially increased (3.07 ± 0.17 vs. 3.36 ± 0.23 mmol/day, p = 0.06). DA induced a 21.5% drop in AP(CaOx) index, from 0.93 ± 0.05 to 0.73 ± 0.05 (p = 0.0005). Decreases in CaOx-SS correlated with AS (R = 0.448, p < 0.0005), and highest AS (+ 5) always indicated lowering of CaOx-SS. Thus, simple DA can reduce CaOx-SS which may be monitored by AS.

Effect of water composition and timing of ingestion on urinary lithogenic profile in healthy volunteers: a randomized crossover trial

Kidney stone disease is a common condition with a high recurrence rate and elevated costs. Despite the well-known positive effects of high fluid intake, there are little data about the roles of water composition and timing of ingestion during the day. This study examines the effect of two different waters [calcium-bicarbonate water (CBW) and oligomineral water (OW)] consumed at different times during the day on urine composition in a group of healthy volunteers. In a cross-over randomized trial, 12 healthy volunteers were assigned to a different sequence of four combined interventions (1 L of water consumed during fasting and 1 L of water consumed with meals): CBW/OW; OW/CBW; CBW/CBW; OW/OW. Participants were instructed to follow the same diet and to avoid smoking, caffeine and other beverages during the day of intervention, and to collect their urine every 2h during the day, followed by a single overnight collection. The relative supersaturation for calcium oxalate was higher for CBW/CBW compared with all other interventions, while relative supersaturation for calcium phosphate was lower for the combination OW/CBW with meals. Urinary excretion of oxalate was lower in all interventions including CBW, while no significant differences were found for urinary calcium. Water composition and timing of ingestion have complex and interacting effects on lithogenic risk. Depending on individual characteristics, a strategy involving either OW or a mix of CBW during meals and OW outside of meals could be effective in modulating the lithogenic profile.Trial registered at clinicaltrial.gov: Protocol ID NCT03447847.

Mediterranean diet adherence and risk of incident kidney stones

Diet plays an important role in kidney stone formation. Several individual components have been associated with the risk of kidney stone formation, but there is limited evidence regarding the role of healthful dietary patterns. To prospectively study the association between adherence to the Mediterranean diet and the risk of incident kidney stones. We conducted a longitudinal study using 3 different cohorts: the Health Professionals Follow-up Study (n=42,902 men), the Nurses' Health Study I (n=59,994 women), and the Nurses' Health Study II (n=90,631 women). We assessed diet every 4 y using an FFQ and calculated adherence to a Mediterranean diet using the alternate Mediterranean diet score (aMED). A subgroup of 6077 participants provided ≥1 24-h urine sample, and urinary solute excretion was analyzed. We used Cox proportional hazards regression to examine the independent association between the aMED and incidence of kidney stones, adjusting for potential confounders. We used adjusted linear regression models to study the relation between aMED and urine composition. During 3,316,633 person-years of follow-up, 6576 cases of incident kidney stones were identified. For participants in the highest aMED score category, the risk of developing a kidney stone was between 13% and 41% lower compared with participants in the lowest score (pooled HR: 0.72, 95% CI: 0.59, 0.87; P value for trend<0.001). A higher aMED score was associated with higher urinary citrate, magnesium, oxalate, phosphate, uric acid, volume, and pH, and lower urinary sodium, resulting in lower supersaturation for calcium oxalate, calcium phosphate, and uric acid. Adherence to a Mediterranean diet is associated with a lower risk of developing a kidney stone.

Patient Satisfaction and Clinical Efficacy of an Advanced Practice Provider Stone Prevention Clinic.

The benefits of a multidisciplinary stone prevention clinic are well established. However, the outcomes of advanced practice provider integration into this model have not been reported. Our goal was to assess the feasibility of an advanced practice provider managed stone prevention clinic. High risk kidney stone patients were evaluated by an advanced practice provider and registered dietitian. Medical and dietary interventions were formulated based on medical and dietary history, labs and imaging. Post-intake surveys assessed patient satisfaction and educational impact. Survey results, stone risk parameters and acute stone events were retrospectively reviewed. Paired samples t-tests were used to assess changes in 24-hour urine parameters. We followed 77 patients over an average of 4.34 visits (750±464 days). Of the 63 surveys completed 100% found their visit helpful and 98.4% would recommend the clinic. Of the 65 patients with multiple 24-hour urine studies significant reductions were seen in stone supersaturation profiles for uric acid (54.2%, p <0.01) and calcium phosphate (31.8%, p=0.04). Supersaturation profiles for uric acid, calcium phosphate and calcium oxalate decreased with each followup visit. Number of registered dietician appointments was associated with reduced supersaturation of calcium oxalate (-2.29, p=0.04). Number of advanced practice provider appointments was associated with reduced supersaturation of uric acid (-0.34, p=0.02). In all, 15 patients experienced an acute stone event and 8 patients had 1 or more emergency room visit. The implementation of an advanced practice provider managed stone prevention clinic is feasible in the community setting. This is supported by positive feedback, educational impact and reductions in stone risk parameters.

Urinary supersaturation on fractioned urine collections: which urine sample can explain better the variability observed on 24-h urine? A proof-of-concept study.

Due to the difficulty of collecting 24-h urines in the stone-forming patient, some authors have suggested other types of urine collection, but their usefulness is not yet well studied. The objective of this study is to evaluate the variation of urinary supersaturation (SS) throughout the day and to analyze whether timed urine collections offer accurate information. 48 urine samples were collected from 12 young adults. Each 24-h urine was collected on 7 2-h urine fractions and a 10-h overnight sample. Solute concentrations and SS for calcium oxalate (CaOx), calcium phosphate (CaP), and uric acid (UA) were determined. Linear regression and relative importance of predictors were used to determine the percentage of R2 attributed to each timed collection (individual SS). 43 24-h urine samples were included in the study. The highest SS values were: for CaOx, night period and first morning urine; for CaP, between 2 and 6pm and at night; for UA, between 8 am and 12pm. For CaOx, the SS from the samples between 8pm and 8 am accounted for more than 40% of the R2; for CaP, the results were more equally distributed throughout the day, and for UA, the SS values from 12 to 4pm accounted for more than 45% of the observed variability. In conclusion, urinary SS varies throughout the day, being higher for CaOx and CaP at night, and in the early morning for UA. For CaOx and UA, the overnight and 12-4pm urine samples, respectively, contribute most to the variability observed in the SS of 24-h urine.

Idiopathic calcium nephrolithiasis with pure calcium oxalate composition: clinical correlates of the calcium oxalate dihydrate/monohydrate (COD/COM) stone ratio.

Pure calcium oxalate is the most frequent type of idiopathic kidney stone composition. Fourier transform infrared spectroscopy (FT-IR) allows to detect the ratio of calcium oxalate dihydrate (COD) and monohydrate (COM) crystals in stones, but the clinical significance of this parameter remains uncertain. The objective of this observational study was to verify the association of clinical and laboratory parameters of kidney stone disease with COD/COM ratio in a group of 465 (322M, age 46 ± 14) patients suffering from idiopathic calcium nephrolithiasis with pure calcium oxalate stones (≥ 97%). Each participant underwent a complete clinical examination, serum chemistry, 24-h urine collection for the determination of the profile of lithogenic risk, and had stones analyzed by FT-IR. Most (62%) of the stones had a COD/COM ratio ≤ 0.25, and the urine chemistry of the corresponding patients showed a low prevalence of urinary metabolic abnormalities. With increasing COD/COM ratio intervals (0-0.25, 0.26-0.50, 0.51-0.75, 0.76-1), a significant association was observed for the number of urological procedures, serum calcium, 24-h urinary calcium excretion, prevalence of hypercalciuria and relative calcium oxalate supersaturation, and a negative trend was detected for the age of the first stone episode (all p values < 0.05). A linear regression model showed that the only parameters significantly associated with COD/COM ratio were 24-h urinary calcium excretion (standardized β = 0.464, p < 0.001) and urine pH (standardized β = 0.103, p = 0.013). In pure calcium oxalate idiopathic stones, COD/COM ratio may reflect the presence of urinary metabolic risk factors, and represent a guide for the prescription of urinary analyses.

Analysis of Factors Associated with Large Kidney Stones: Stone Composition, Comorbid Conditions, and 24-H Urine Parameters—a Machine Learning-Aided Approach

We aim to describe factors that are associated with kidney stones 20 mm or larger. This information would potentially guide research regarding factors of kidney stone growth. We retrospectively reviewed a patient cohort who underwent surgical treatment for kidney stones. Patients with detailed demographics, 24-h urine testing, and kidney stone profiling were included. Large stone was defined as measuring 20 mm or more. Univariate analysis was conducted to assess variables associated with kidney stones larger than 20 mm. Multivariate logistic regression and statistical machine learning methods were used to infer prediction models. The specific composition of kidney stones, laboratory testing results, and detailed demographics of 277 patients were included in our analysis. Multiple variables were significantly associated with large stones in univariate analysis. The final model that predicts large stone size includes several variables from different domains: hypertension (OR = 1.91; 95% CI 1.06, 3.43), older age (60+ vs 20–40) (OR = 2.46; 95% CI 1.07, 5.63), decreased calcium oxalate supersaturation (OR = 0.92; 95% CI 0.85, 0.99), and higher percentage of protein in stone composition (OR = 5.64; 95% CI 2.04, 15.58). This model yields a sensitivity 83% and specificity of 56%. Models using machine learning algorithms identified similar predictors, but the performance varies. Our model yielded good performance, and it could potentially be used as a clinical tool for predicting large stones and identifying factors affecting kidney stone growth. Similar analysis in other cohorts should be pursued to externally validate findings.

Theoretical and laboratory investigations of the effects of hydroxyproline ingestion on the metabolic and physicochemical risk factors for calcium oxalate kidney stone formation in a small group of healthy subjects.

Dietary hydroxyproline may be involved in the endogenous synthesis of oxalate. Glycolate, produced during the metabolism of hydroxyproline, may exert physicochemical effects on urinary calcium by virtue of its dihydroxycarboxylic acid structure. The aim of this study was to investigate these possible stone-risk scenarios. We modelled the effect of different glycolic acid concentrations on ionized calcium (iCa2+) and relative supersaturation (RSS) of calcium oxalate (CaOx) using the program JESS. Thereafter, three healthy white males and two healthy black males ingested 30g gelatin for 3days. 24-h urines were collected at baseline and after completion of the protocol. Urines were analysed for physicochemical risk factors and for iCa2+ and glycolic acid. Speciation concentrations and RSS values were calculated. Theoretical modelling showed that binding between calcium and glycolate does not occur and that iCa2+ and RSS CaOx are unaffected. However, after ingestion of hydroxyproline, iCa2+ decreased significantly. Urinary pH and glycolate increased significantly. Oxalate excretion and RSS CaOx did not change CONCLUSIONS: We attribute the decrease in iCa2+ to increases in the concentrations of several Ca-phosphate species, the formation of which is due to the increase in pH. We speculate that the absence of an increase in oxalate excretion despite an increase in glycolate excretion may be due to the mixed racial composition of our test group in which some pathways may be preferred to others. Our findings alert stone researchers to the importance of measuring urinary pH in their workup of subjects and to select racially homogenous groups for investigation.