Urinary Citrate Levels Research Articles

Impact of geographical region on urinary metabolomic and plasma fatty acid profiles in subjects with the metabolic syndrome across Europe: the LIPGENE study

The application of metabolomics in multi-centre studies is increasing. The aim of the present study was to assess the effects of geographical location on the metabolic profiles of individuals with the metabolic syndrome. Blood and urine samples were collected from 219 adults from seven European centres participating in the LIPGENE project (Diet, genomics and the metabolic syndrome: an integrated nutrition, agro-food, social and economic analysis). Nutrient intakes, BMI, waist:hip ratio, blood pressure, and plasma glucose, insulin and blood lipid levels were assessed. Plasma fatty acid levels and urine were assessed using a metabolomic technique. The separation of three European geographical groups (NW, northwest; NE, northeast; SW, southwest) was identified using partial least-squares discriminant analysis models for urine (R² X: 0·33, Q²: 0·39) and plasma fatty acid (R² X: 0·32, Q²: 0·60) data. The NW group was characterised by higher levels of urinary hippurate and N-methylnicotinate. The NE group was characterised by higher levels of urinary creatine and citrate and plasma EPA (20 : 5 n-3). The SW group was characterised by higher levels of urinary trimethylamine oxide and lower levels of plasma EPA. The indicators of metabolic health appeared to be consistent across the groups. The SW group had higher intakes of total fat and MUFA compared with both the NW and NE groups (P≤ 0·001). The NE group had higher intakes of fibre and n-3 and n-6 fatty acids compared with both the NW and SW groups (all P< 0·001). It is likely that differences in dietary intakes contributed to the separation of the three groups. Evaluation of geographical factors including diet should be considered in the interpretation of metabolomic data from multi-centre studies.

SLC26A6 and NaDC-1 Transporters Interact to Regulate Oxalate and Citrate Homeostasis

The combination of hyperoxaluria and hypocitraturia can trigger Ca(2+)-oxalate stone formation, even in the absence of hypercalciuria, but the molecular mechanisms that control urinary oxalate and citrate levels are not understood completely. Here, we examined the relationship between the oxalate transporter SLC26A6 and the citrate transporter NaDC-1 in citrate and oxalate homeostasis. Compared with wild-type mice, Slc26a6-null mice exhibited increased renal and intestinal sodium-dependent succinate uptake, as well as urinary hyperoxaluria and hypocitraturia, but no change in urinary pH, indicating enhanced transport activity of NaDC-1. When co-expressed in Xenopus oocytes, NaDC-1 enhanced Slc26a6 transport activity. In contrast, Slc26a6 inhibited NaDC-1 transport activity in an activity dependent manner to restricted tubular citrate absorption. Biochemical and physiologic 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. These findings reveal a molecular pathway that senses and tightly regulates oxalate and citrate levels and may control Ca(2+)-oxalate stone formation.

Nutrition in calcium nephrolithiasis

Idiopathic calcium nephrolithiasis is a multifactorial disease with a complex pathogenesis due to genetic and environmental factors. The importance of social and health effects of nephrolithiasis is further highlighted by the strong tendency to relapse of the disease. Long-term prospective studies show a peak of disease recurrence within 2–3 years since onset, 40-50% of patients have a recurrence after 5 years and more than 50-60% after 10 years. International nutritional studies demonstrated that nutritional habits are relevant in therapy and prevention approaches of nephrolithiasis. Water, right intake of calcium, low intake of sodium, high levels of urinary citrate are certainly important for the primary and secondary prevention of nephrolithiasis.In this review is discussed how the correction of nutritional mistakes can reduce the incidence of recurrent nephrolithiasis.

Stone management in children

Children constitute only a small number of the total patients with urolithiasis. Nevertheless, pediatric stone disease is an important health care problem because of its high recurrence rate. In recent years, the incidence of pediatric stone disease has increased several-fold, mostly owing to hypercalciuria and hypocitraturia. Chang Kit and colleagues’1 article highlights the pattern of nephrolithiasis in developed countries and depicts the major differences in presentation, predisposing factors and treatment options in children presenting with urinary stones. Children can present with a wide range of symptoms varying from flank pain and hematuria to nonspecific symptoms such as irritability and nausea. Ultrasonography and plain radiography play a role in diagnosis and follow-up. As shown by Chang Kit and colleagues, the most common diagnostic radiological methods used were abdominal ultrasonography (74%) and (or) abdominal plain film radiography (56%). Approaching pediatric urolithiasis requires a thorough metabolic and environmental evaluation of all patients on an individual basis, and as shown by Chang Kit and coworkers, 41% (28/69) had a metabolic abnormality. In addition, since there is a high recurrence rate, metabolic evaluation of every child with a urinary stone should be undertaken, medical treatment should be given when indicated and children should be followed closely to avoid stone recurrence. The medical treatment is based on the chemical composition of the stone and the biochemical abnormalities causing its formation; hence, chemical analysis of the stone, urine and blood is of paramount importance and should be done when the first stone is detected. The nonpharmacological means to address stone disease include high fluid intake and, frequently, modification of nutritional habits. Urine volume increases in parallel with body mass index, and medical therapeutic agents that increase urine citrate levels should be encouraged. Limiting salt in the diet and drinking plenty of water are the best ways to prevent the most common types of kidney stones or to slow their growth, but the ease in applying these dietary guidelines in children is not known. Furthermore, obstructive pathologies such as ureteropelvic junction obstruction have to be corrected concomitantly when present, and apparent metabolic abnormalities should also be treated adequately. The goal of medical treatment is not only to decrease recurrence but also to decrease the expansion of existing stones. It is thought that children have elastic ureters, allowing them to pass stones easily. In Chang Kit and colleagues’ study, 47% of patients spontaneously passed their stones even when they were as big as 11 mm. Nevertheless, more than one-half of the patients needed surgical intervention. With recent advances in technology, stone management has changed from an open surgical approach to less-invasive approaches such as extracorporeal shock wave lithotripsy and endoscopic techniques. In children, clearance of stones after extracorporeal shock wave lithotripsy especially in the presence of metabolic abnormality is necessary because residual fragments are clinically significant in children and increase the chance of adverse clinical outcomes.2 Thus these patients, particularly those with identifiable predisposing disorders, require close follow-up. Traditionally, upper urinary tract calculi that are too large to treat with extracorporeal shock wave lithotripsy are most commonly cleared with percutaneous endoscopic techniques. Recently, improved ureteroscopic access to stones throughout the pediatric urinary tract and stone-free rates that are comparable to the adult population have led to the adoption of ureteroscopy as first-line therapy in children at our institution.3 In a select group of patients who are poor candidates for percutaneous nephrostolithotomy, retrograde endoscopic lithotripsy is becoming an attractive option. Thus with miniaturization and advances in technology, large and complex upper urinary tract calculi can be addressed safely and efficiently with retrograde endoscopic techniques. For instance, ureteroscopy achieves reasonable results with minimal complications in pediatric patients with renal pelvic calculi. On the other hand, polar stones require multiple sessions for complete clearance, and staghorn calculi may not be amenable to ureteroscopy. In their article, Chang Kit and colleagues do not report the number of procedures performed that lead to full success for each surgical approach, nor do they report the complications that occurred when they approached the patients surgically.

2094 TREATMENT RESPONSE IN STONE PATIENTS WITH GOUTHY DIATHESIS STRATIFIED BY BODY MASS INDEX

You have accessJournal of UrologyStone Disease: Evaluation & Medical Management (I)1 Apr 20132094 TREATMENT RESPONSE IN STONE PATIENTS WITH GOUTHY DIATHESIS STRATIFIED BY BODY MASS INDEX Gastón Astroza, Andreas Neisius, Matvey Tsivian, Muhammad Iqbal, Nicholas Kuntz, Ramy Youssef, Glenn Preminger, and Michael Lipkin Gastón AstrozaGastón Astroza Durham, NC More articles by this author , Andreas NeisiusAndreas Neisius Durham, NC More articles by this author , Matvey TsivianMatvey Tsivian Durham, NC More articles by this author , Muhammad IqbalMuhammad Iqbal Durham, NC More articles by this author , Nicholas KuntzNicholas Kuntz Durham, NC More articles by this author , Ramy YoussefRamy Youssef Durham, NC More articles by this author , Glenn PremingerGlenn Preminger Durham, NC More articles by this author , and Michael LipkinMichael Lipkin Durham, NC More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2013.02.2003AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Hypocitraturia (hypocit) and gouthy diathesis (GD) are common metabolic abnormalities in patients with urolithiasis. Since different physiologic pathways may be associated with GD in obese and non-obese patients we hypothesized that therapeutic response to treatment with potassium citrate (KCit) could differ by body mass index (BMI). METHODS We performed a retrospective review of patients with urolithiasis who had undergone metabolic evaluation from 2001-2011. Patients with hypocit/GD defined as urinary citrate ≤500mg and urinary pH≤5.6, respectively, who were treated with KCit were included. Metabolic data from 24 hour urine collections was recorded at baseline, 3, 6, 9, 12, 18, 24 and 36 months. The cohort was divided into 4 groups based on BMI: BMI<25kg/m2, II: BMI 25-29.9, III: BMI 30-34.9 and IV: BMI≥35kg/m2. Metabolic data was compared between groups at baseline and subsequent visits. We compared urinary pH and citrate both in absolute values and the relative change in these parameters from baseline, as well as the rate at which patients required an increase of KCit. Fisher's exact and rank sum tests were used for comparisons. Trend analyses were performed using Cochran-Armitage and Cuzick's tests. RESULTS A total of 3166 patients with urolithiasis who had undergone metabolic evaluation were identified, of which 125 had both hypocit/GD. Median patient age was 61 (52-68) yrs, 80 (64%) were males and median BMI was 30.4kg/m2 (26.1-35.0). Urine pH increased from 5.4 (5.2-5.5) to 6.0 (5.5-6.6) at first follow up (p<0.001). Similarly, citrate levels rose from 247mg/d (125-355) to 534 (318-728) (p<0.001). The median change in pH on KCit treatment was 0.7 (0.2-1.2). PH values and their absolute change from baseline were lower as BMI increased (p≤0.001). Similarly, an association between increasing BMI category and lower urinary citrate levels was accompanied by a significant trend indicating lower absolute changes in citrate with increasing BMI (p≤0.001). KCit doses and therapy modifications were increased more frequently among higher BMI groups being 9% for normal weight and overweight, 17% for obese and 38% for morbidly obese patients (p=0.002). Overall, pH and citrate levels normalized in 61% and 51% with no apparent differences between the BMI groups. CONCLUSIONS In patients with hypocit/GD, KCit appears to be less effective at raising pH as BMI increases and more frequent dose adjustments are needed in obese patients. Obese patients with hypocit/GD treated with KCit require close follow up with repeat 24 hour urine collections to ensure adequate response. © 2013 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 189Issue 4SApril 2013Page: e859 Advertisement Copyright & Permissions© 2013 by American Urological Association Education and Research, Inc.MetricsAuthor Information Gastón Astroza Durham, NC More articles by this author Andreas Neisius Durham, NC More articles by this author Matvey Tsivian Durham, NC More articles by this author Muhammad Iqbal Durham, NC More articles by this author Nicholas Kuntz Durham, NC More articles by this author Ramy Youssef Durham, NC More articles by this author Glenn Preminger Durham, NC More articles by this author Michael Lipkin Durham, NC More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Patient-centered Medical Therapy for Nephrolithiasis

To elucidate the effect of a patient-centered combined nutritional and medical therapy approach on stone disease management, guided by 24-hour urinary stone risk. We retrospectively analyzed the records of patients treated at our multidisciplinary stone clinic from July 2007 to February 2009. Included were adult stone formers who presented with severe urinary abnormalities or whose urinary parameters failed to improve with dietary changes. Urinary risk factors for stone disease were evaluated before and after intervention with 24-hour urine collections. Hypercalciuria was treated with hydrochlorothiazide/indapamide, hypocitraturia with potassium/calcium citrate, and hyperuricosuria with allopurinol. The primary end point was the effect of combined dietary and medical intervention on levels of urinary metabolites. Statistical comparisons of postintervention urine collection values with baseline values were performed using a paired t test. Two-tailed P <.05 was considered statistically significant. Data for 137 patients with a mean follow-up of 14.39 months were analyzed. Mean age was 47.2 years, and the male-to-female ratio was 1.04. Hypocitraturia was detected in 70 patients (51%), hypercalciuria in 49 (37%) and hyperuricosuria in 18 (13%). A significant improvement was found in 67% of patients with hypocitraturia (urinary citrate levels: 380.28 to 663.96 mg/d; P <.0001), in 82% of patients with hypercalciuria (urinary calcium levels: 337.4 to 183.6 mg/d; P <.0001), and in 72% of patients with hyperuricosuria (urinary citric acid level: 927 to 600 mg/d; P <.0001). Medical management of stone disease instituted based on individual risk factors impacts subsequent urinary stone risk, supporting its use for stone disease when patients do not respond to lifestyle and dietary changes.

Importance of citrate and the calcium : citrate ratio in patients with calcium renal lithiasis and severe lithogenesis

Different studies have shown the importance of citrate in the formation of calcium stones. It has further been shown that the states of metabolic acidosis result in an increase in bone resorption and lower urinary citrate levels. Increasing the intake of citrate in these patients can reduce the lithogenic risk and improve bone mineral density (BMD), contributing to control of both diseases. The study shows the importance of citrate in patients with calcium stones and BMD loss. The deficit in citrate excretion is associated with a decrease in bone mineralization and increased β-crosslaps. A calcium : citrate ratio >0.25 in patients with calcium stones and loss of mineral density may predict severe lithogenic activity. To analyse the importance of urinary citrate and the urinary calcium : citrate ratio in patients with calcium renal lithiasis and severe lithogenesis compared with a control group of patients without lithiasis. A cross-sectional study of 115 patients in eastern Andalusia, Spain was conducted. The patients were divided into two groups: Group A: 56 patients aged 25-60 years without calcium renal lithiasis; Group B: 59 patients aged 25-60 years, presenting with calcium renal lithiasis and severe lithogenesis. The citrate levels and the calcium : citrate ratio in the patients' urine and the relationship of these two factors to lithiasic activity were analysed and compared. In Group B, 32.2% of the patients presented with hypocitraturia, compared with 14.3% of the patients in Group A (P = 0.02). The urinary citrate levels were lower in Group B than in Group A (P = 0.001) and the calcium : citrate ratio was higher in Group B than in Group A (P = 0.005). The results suggest that a patient urinary calcium : citrate ratio > 0.25 indicates severe lithogenesis (with a sensitivity of 89% and a specificity of 57%). After linear regression analysis, we found that the urinary citrate level is an independent factor associated with the changes in bone densitometry T-score values of patients. The patients with severe lithogenesis presented with hypocitraturia, which was associated with lower bone mineral density. The calcium : citrate ratio, which is linearly related to the bone resorption marker β-crosslaps, could be useful in evaluating the risk of severe lithogenesis when this ratio is >0.25.

Importance of citrate and the calcium : citrate ratio in patients with calcium renal lithiasis and severe lithogenesis

Stone disease and osteopaenia are both common conditions, and reduced bone mineral density (BMD) is an increasingly recognized complication in stone formers; indeed, in a previous paper in BJUI, Arrabal-Polo et al. 1 reported that patients with recurrent stones have lower BMD compared with controls or patients with just a single episode of urolithiasis. Although the exact pathogenesis of bone loss in stone disease is yet to be determined, the conceptually obvious relationship with hypercalciuria is well documented 2. In the present study, Arrabal-Polo et al. emphasise that hypocitraturia is also associated with reduced BMD. Furthermore, they found a higher calcium : citrate ratio in patients with a cumulative maximum stone diameter >20 mm, or in those with frequent recurrences than in controls, and found that this correlated with higher levels of β-crosslaps, consistent with increased bone resorption in these patients. We commented in our previous editorial that metabolic abnormalities should be sought in recurrent stone formers, and managed in a multi-disciplinary setting 3. In addition to dietary advice, options for treatment include bisphosphonates (which inhibit bone resorption, and are commonly used in osteoporosis), thiazide diuretics (which reduce calcium excretion and can increase BMD) and potassium citrate (which acts as an alkalinizing agent mitigating the bone restorative effect of acidosis) 2. This approach is supported by recent data in medullary sponge kidneys, in which hypercalciuria and hypocitraturia were commonly detected in association with reduced BMD. Patients who were treated with potassium citrate were found to have increased urinary pH citrate levels, and an improvement in their BMD 4. In the present article, Arrabal-Polo et al. suggest using a calcium : citrate ratio of 0.25 for predicting the risk of future recurrent stone formation, but this value could equally be used to predict the risk of patients having reduced BMD and the complications that may follow. Either way, their findings strengthen the argument for metabolic screening of recurrent stone formers, and for an assessment of these patients' BMD. Patients can then be appropriately treated with a thiazide diuretic, potassium citrate, or a bisphosphonate, either singly or in combination, according to the abnormalities detected and their progress on treatment.

The effect of citrate replacement in hypocitraturic cases on the results of SWL: a preliminary prospective randomized study

To evaluate the possible effects of citrate replacement on the efficacy of shockwave lithotripsy (SWL) in the management of kidney stones in cases with hypocitraturia. Forty hypocitraturic cases with renal pelvic stones were randomized into two groups; while citrate replacement has been done before and at the time of SWL in Study Group I (n: 20), SWL was performed without any additional specific management for hypocitraturia in Study Group II (n: 20). Twenty normocitraturic cases were also chosen as the control group (Group III). Data of the patients were evaluated comparatively. Patient, stone, and urinary pH characteristics of the groups were similar. Pre-SWL urinary citrate levels were 0.71 (0.1-1.3), 0.86 (0.1-1.4), and 3.12 (1.8-4.4) mmol/24 h in Group I, II, and III, respectively. Urinary citrate value increased from 0.71 (0.1-1.3) to 1.96 (1.6-4.1) mmol/24 h following replacement therapy (before and at the time of SWL) in Group I. Mean number of SW (p = 0.461), rate of stone-street formation (p = 0.146), and Double-J placement (p = 0.291) were similar in Group I and Group II. While the mean number of SWL sessions (2.27 ± 0.71 in Group I vs. 2.94 ± 0.59 in Group II; p = 0.027), and time to stone-free status [29.1 (16-47) days in Group I vs. 38.4(21-63) days in Group II; p = 0.043], was significantly different between study groups, these parameters were found similar between Group I and Group III. In our study, the patients with hypocitraturia, who did receive replacement therapy, tended to require lower number of SWL sessions and became stone free in a shorter period than the others who underwent SWL without any specific management of hypocitraturia.

Nephrectomy as a cause of chronic kidney disease in the treatment of urolithiasis: a case–control study

To analyze the clinical course of nephrectomized patients due to complications related to nephrolithiasis and ascertain the prevalence of chronic kidney disease (CKD) in this population. From 2005 to 2010, 658 patients were treated with urolithiasis. Among these, 30 (4.6%) were nephrectomized. For each case, a control was selected and matched to the case by age, sex and disease duration. All data were collected from medical records, which contained the clinical, laboratory evaluation and diagnostic imaging. Age of the study group was 51.5 ± 10.4 years and the control group 47.1 ± 5.2 years. There were 17 (85%) women and three men in each group. Patients from the study group reported 3 (range, 1-5) episodes of acute renal colic before nephrectomy. Urinary tract infection and hematuria was detected in 70% of cases before surgery. In addition, half of the patients had at least one previous urological procedure. The control group showed higher urinary levels of calcium (216.1 ± 114.3 vs. 130.9 ± 72.2), uric acid (530.2 ± 197.4 vs. 424 ± 75.2) and citrate (755 ± 533 vs. 380.2 ± 260.7), p < 0.01, 0.03 and 0.01, respectively. The creatinine clearance was lower in the study group, 52.5 ± 18.8 ml/min vs. 92.9 ± 24.2 ml/min in the control group (p < 0.001). There was a decrease in kidney function in nephrectomized patients compared to a control group of stone-forming patients with both kidneys. Prospective studies are needed to assess the incidence of CKD in patients with nephrolithiasis submitted to nephrectomy.

Influence of Overweight on 24-Hour Urine Chemistry Studies and Recurrent Urolithiasis in Children

PurposeWe investigated the influence of overweight on 24-hour urine chemistry studies and recurrent urolithiasis (UL) in children.Materials and MethodsA retrospective cohort study was designed to assess children who presented with UL at a pediatric institution between 1985 and 2010. We calculated body mass index percentile (BMIp) adjusted for gender and age according to the 2007 Korean Children and Adolescents Growth Chart and stratified the children into 3 BMI categories: lower body weight (LBW, BMIp≤10), normal BW (NBW, 10<BMIp<85), and upper BW (UBW, BMIp≥85). Twenty-four hour urine chemistry studies (urine volume, creatinine, calcium, oxalate, citrate, and pH) were compared between the 3 BMIp groups. Univariate and multivariate analyses were performed to assess independent risk factors for stone recurrence.ResultsA total of 125 patients were included. The age of the patients in the NBW group was older than that of patients in the LBW group, but 24-hour urine chemistry studies did not differ significantly between the three groups. Mean urine citrate levels were lower (0.273±0.218 mg/mg/d vs. 0.429±0.299 mg/mg/d, p<0.05) and the incidence of hypocitraturia was higher (81.5% vs. 45.7%, p<0.05)) in the recurrent stone former group. In the univariate analysis, hypocitraturia and acidic urinary pH were risk factors, but in the multivariate analysis, only hypocitraturia was a risk factor for stone recurrence (hazard ratio, 3.647; 95% confidence interval, 1.047 to 12.703). In the Kaplan-Meier curve, the hypocitraturia group showed higher recurrence than did the normocitraturia group (p<0.05).ConclusionsUnlike in adults, in children, overweight adjusted for gender and age was not associated with 24-hour urine chemistry studies and was not a risk factor for recurrent UL. Hypocitraturia was the only risk factor for UL in children.

Why is hypercalciuria absent at diagnosis in some children with ATP6V1B1 mutation?

We try to explain why hypercalciuria is absent at diagnosis in some children with an ATP6V1B1 mutation. A 5-month-old girl presented with distal renal tubular acidosis (dRTA) and sensorineural hearing loss. Direct sequencing of the ATP6V1B1 genes disclosed a new homozygous mutation (452 delT) in exon 13. In particular, an absence of hypercalciuria and a normal level of parathyroid hormones were noted. After alkaline therapy, the signs of nephrocalcinosis improved on ultrasound during follow-up. After a review of the literature regarding patients with ATP6V1B1 gene mutations, a young age seemed to be an important factor for normocalciuria. The probable mechanism of normocalciuria and a dynamic mode of calcium excretion in patients with dRTA is proposed. The determinant factors include the degree of systemic acidosis, urine pH, genetic polymorphisms, age, dietary factors, and volume status. Low sodium intake may be a major determinant of normocalciuria in these patients. It is suggested that hypercalciuria is usually absent at diagnosis of dRTA in young infants. Blood pH, plasma bicarbonate concentration, urinary citrate levels, and growth catch-up may be better indicators of adequate alkali therapy in normocalciuric children. Volume contraction, low salt content in infant formula, and alkaline urine in young infants are likely to account for the increased calcium reabsorption.

Effect of diet orange soda on urinary lithogenicity

Studies have shown that certain beverages decrease urinary lithogenicity by increasing urine citrate excretion. Diet Sunkist Orange soda had the highest concentration of citrate and total alkali content among 12 diet sodas previously assayed. We studied the effect of Diet Sunkist Orange soda consumption on urinary chemistry. Nine healthy men and women ages 26-54 years completed the study. During the control period, subjects drank 36 oz of water for 3 days in addition to their own, self-selected diet and recorded a food diary. During the study period, the subjects drank three 12-oz cans of Diet Sunkist Orange soda a day instead of water, and replicated their diets from the control period. In each period, the subjects performed 24-h urine collections on days 2 and 3. Urine chemical analysis was performed, including urinary citrate levels and pH. Diet Sunkist Orange soda increased urinary citrate excretion by 60 mg/day, which was not statistically significant (95% CI -75 to 195, P value 0.34). There was no significant change in pH from the control period to the study period (pH: 6.29-6.21; 95% CI: -0.09 to 0.25, P = 0.30). Urine volumes and creatinine excretions were not significantly different between the control and study periods. Despite the relatively high citrate and total alkali content of Diet Sunkist Orange soda, the volume consumed in this study (36 oz per day) did not provide sufficient potential base to significantly alter urine composition in healthy subjects with normocitraturia. The effect of Diet Sunkist Orange soda on urinary chemistry in patients with hypocitraturia and nephrolithiasis is not likely to have a clinically significant effect to prevent calcium or uric acid stones.

Metabolic profiling study of ketoprofen-induced toxicity using1H NMR spectroscopy coupled with multivariate analysis

H nuclear magnetic resonance (NMR) spectroscopy of biological samples has been proven to be an effective and nondestructive approach to probe drug toxicity within an organism. In this study, ketoprofen toxicity was investigated using 1 H-NMR spectroscopy coupled with multivariate statistical analysis. Histopathologic test of ketoprofen-induced acute gastrointestinal damage in rats demonstrated a significant dose-dependent effect. Furthermore, principal component analysis (PCA) derived from 1 HNMR spectra of urinary samples showed clear separation between the vehicle-treated control and ketoprofen-treated groups. Moreover, PCA derived from endogenous metabolite concentrations through targeted profiling revealed a dose-dependent metabolic shift between the vehicletreated control, low-dose ketoprofen-treated (10 mg/kg body weight), and high-dose ketoprofen-treated (50 mg/kg) groups coinciding with their gastric damage scores after ketoprofen administration. The resultant metabolic profiles demonstrated that the ketoprofen-induced gastric damage exhibited energy metabolism perturbations that increased urinary levels of citrate, cis-aconitate, succinate, and phosphocreatine. In addition, ketoprofen administration induced an enhancement of xenobiotic activity in fatty oxidation, which caused increase levels of N-isovalerylglycine, adipate, phenylacetylglycine, dimethylamine, betaine, hippurate, 3-indoxylsulfate, N,N-dimethylglycine, trimethyl-N-oxide, and glycine. These findings demonstrate that 1 H-NMR–based urinary metabolic profiling can be used

2043 BONE MINERAL LOSS IN PATIENTS WITH CALCIUM NEPHROLITHIASIS. IS THERE A RELATIONSHIP?

INTRODUCTION AND OBJECTIVES: The recurrent calcium lithiasis has a multifactorial origin. The phosphorus/calcium metabolism is regulated by blood calcium levels and two main hormones, parathyroid hormone and vitamin D. Bone mineral loss and hypercalciuria in patients with renal lithiasis may be associated with tubular changes and hormone synthesis or action of calcium metabolism, nutritional factors or genetic factors through the CLDN14 gene. The objective of this study is to demonstrate the clinical relationship between bone loss and recurrent calcium lithiasis. METHODS: We conducted a cross sectional study by dividing the patients into 3 groups: Group O: 50 patients (25–60 years) without lithiasis. Group A: 50 patients (25–60 years) with a first episode of lithiasis. Group B: 50 patients (25–60 years) with recurrent lithiasis. We consider recurrent lithiasis as two or more episodes of lithiasis within five years. In all cases, bone densitometry, radiography and abdominal ultrasonography or urography were performed. Plasma concentrations of creatinine, calcium, phosphorus, alkaline phosphatase, iPTH, osteocalcin, beta-crosslaps along with urine determination of calcium, phosphorus, citrate, oxalate. Statistical analysis was performed with SPSS 17.0. RESULTS: The mean age was 49.4 years in group 0, 45.3 years in group A, 46 in group B, so the groups were considered homogeneous (p 0.189). Significant differences were observed regarding blood levels of iPTH (group O, 44.98 pg/ml, group A, 49.70 pg/ml, group B, 56.59 pg/ml, p 0.013), osteocalcin (group O, 13.90 ng/ml, group A, 14.01 ng/ml, group B, 17.44 ng/ml, p 0,001), â-crosslaps (group O, 0.343 ng/ml, group A , 0.354 ng/ml, group B, 0.518 ng/ml, p 0.001) and alkaline phosphatase (group O, 64.19 U/l, group A, 63.29 U/l, group B, 74.15 U/l, p 0.027); no statistically significant differences for calcium, phosphorus and creatinine were observed. We found significant differences in urinary levels of calcium (group O, 10.7 mg/dl, group A, 15.8 mg/dl, group B: 16.7 mg/dl, p 0.001) and citrate (group O , 501.56 mg/dl, group A, 447.41 mg/dl, group B: 336.80 mg/dl, p 0.009) with no differences for phosphorus and oxalate. There are significant differences in bone mineral density (group O, T-score 0,427 and 0,572 for spine and the hip respectively, group A 0,558 and 0,768, group B 1.382 and 1.037, p 0002). CONCLUSIONS: We observed a significant relationship between bone mineral density loss and recurrent calcium lithiasis. A correlation between the marker of bone resorption and bone mineral density is found.

Dietary therapy for patients with hypocitraturic nephrolithiasis

Citrate is an inhibitor of urinary stone formation. Clinical and in vitro data suggest that increasing urine citrate levels will decrease the precipitation of calcium stones. Historically, low urinary citrate has been treated with oral potassium citrate or sodium citrate supplementation, but recent studies have shown the potential of dietary interventions to raise urine citrate levels. Dietary therapy with commercial or homemade beverages is attractive to patients who would prefer nonpharmacological intervention. To date, several drinks have shown promise but no single beverage has been found to consistently raise urine citrate levels in a reproducible fashion. Further research is necessary to develop the ideal dietary therapy for hypocitraturic calcium nephrolithiasis.

The Effectiveness of Lemon Solution versus Potassium Citrate in the Management of Hypocitraturic Calcium Kidney Stones: A Systematic Review

Review Questions/Objectives The objective of this systematic review is to critically analyse the quantitative research studies and present the best available evidence related to the effectiveness of lemon solution compared with the effectiveness of potassium citrate in the management of hypocitraturic calcium kidney stones for adults. The more specific review question is: Is lemon solution as effective as potassium citrate in the management of hypocitraturic calcium kidney stones for adults? Types of participants The participants of interest include adult and elderly patients who are 18 years or above. There is no limitation with gender, ethnicity, and settings. Patients who are required to have surgical intervention or have acute symptoms such as acute pain, obstruction, bleeding, and severe infection are also included. Participants are diagnosed with the types of calcium oxalate and/or calcium phosphate kidney stones based on stone analysis and presenting total daily urinary citrate excretion of less than 320 mg or 500 mg. Other diagnostic methods for stone analysis are specified by research investigators will be included. Types of interventions The intervention of interest is lemon solution in the management of hypocitraturic calcium kidney stones. For instance, lemon solution includes commercial beverages of lemonade, and using fresh lemon juice with water only and/or sugar. Approximately 85cc of lemon juice contains 60 mEq (4.2 gm) citrate. The daily dose of lemons’ citrate is given as equal as comparator-potassium citrate. Nursing staff daily make a jug of lemon water (1,000ml - 2,000ml) and delivery to participants. The participants have to finish the jug of lemon water in 24 hours. Lemon water also can be delivered as a single serve (e.g. 250-350 ml) after 3 meals. Participants in communities or homes are trained to administrate this intervention. Types of comparator The comparator is the drug intervention of potassium citrate administered orally in the management of hypocitraturic calcium kidney stones. A typical dose of potassium citrate for adults is from 40 to 60 mEq daily. The dose of potassium citrate can be increased or decreased based on inpatient monitored changes in urinary citrate level. Nursing staff daily delivery TRUNCATED AT 350 WORDS

Alterations in urinary metabolites due to unilateral ureteral obstruction in a rodent model

Urinary tract obstruction (UTO) results in renal compensatory mechanisms and may progress to irrecoverable functional loss and histologic alterations. The pathophysiology of this progression is poorly understood. We identified urinary metabolite alterations in a rodent model of partial and complete UTO using (1)H nuclear magnetic resonance ((1)H-NMR) spectroscopy. Principal component analysis (PCA) was used for classification and discovery of differentiating metabolites. UTO was associated with elevated urinary levels of alanine, succinate, dimethylglycine (DMG), creatinine, taurine, choline-like compounds, hippurate, and lactate. Decreased urinary levels of 2-oxoglutarate and citrate were noted. The patterns of alteration in partial and complete UTO were similar except that an absence of elevated urinary osmolytes (DMG and hippurate) was noted in complete UTO. This pattern of metabolite alteration indicates impaired oxidative metabolism of the mitochondria in renal proximal tubules and production of renal protective osmolytes by the medulla. Decreased production of osmolytes in complete obstruction better elucidates the pathophysiology of progression from renal compensatory mechanisms to irrecoverable changes. Further confirmation of these potential biomarkers in children with UTO is necessary.

Identification of urinary metabolites that distinguish membranous lupus nephritis from proliferative lupus nephritis and focal segmental glomerulosclerosis

IntroductionSystemic lupus erythematosus (SLE or lupus) is a chronic autoimmune disease, and kidney involvement with SLE, a.k.a. lupus nephritis (LN), is a frequent and severe complication of SLE that increases patient morbidity and mortality. About 50% of patients with SLE encounter renal abnormalities which, if left untreated, can lead to end-stage renal disease. Kidney biopsy is considered the criterion standard for diagnosis and staging of LN using the International Society of Nephrology/Renal Pathology Society (ISN/RPS) classification, which was developed to help predict renal outcomes and assist with medical decision-making. However, kidney biopsy-based classification of LN is highly invasive and impractical for real-time monitoring of LN status. Here, nuclear magnetic resonance (NMR) spectroscopy-based metabolic profiling was used to identify urinary metabolites that discriminated between proliferative and pure membranous LN as defined by the ISN/RPS classification, and between LN and primary focal segmental glomerulosclerosis (FSGS).MethodsMetabolic profiling was conducted using urine samples of patients with proliferative LN without membranous features (Class III/IV; n = 7) or pure membranous LN (Class V; n = 7). Patients with primary FSGS and proteinuria (n = 10) served as disease controls. For each patient, demographic information and clinical data was obtained and a random urine sample collected to measure NMR spectra. Data and sample collection for patients with LN occurred around the time of kidney biopsy. Metabolic profiling analysis was done by visual inspection and principal component analysis.ResultsUrinary citrate levels were 8-fold lower in Class V LN compared to Class III/IV patients, who had normal levels of urinary citrate (P < 0.05). Class III/IV LN patients had > 10-fold lower levels of urinary taurine compared to Class V patients, who had mostly normal levels (P < 0.01). Class V LN patients had normal urinary hippurate levels compared to FSGS patients, who completely lacked urinary hippurate (P < 0.001).ConclusionsThis pilot study indicated differences in urinary metabolites between proliferative LN and pure membranous LN patients, and between LN and FSGS patients. If confirmed in larger studies, these urine metabolites may serve as biomarkers to help discriminate between different classes of LN, and between LN and FSGS.

1H NMR-based metabolic profiling of naproxen-induced toxicity in rats

The dose-dependent perturbations in urinary metabolite concentrations caused by naproxen toxicity were investigated using 1H NMR spectroscopy coupled with multivariate statistical analysis. Histopathologic evaluation of naproxen-induced acute gastrointestinal damage in rats demonstrated a significant dose-dependent effect. Furthermore, principal component analysis (PCA) of 1H NMR from rat urine revealed a dose-dependent metabolic shift between the vehicle-treated control rats and rats treated with low-dose (10 mg/kg body weight), moderate-dose (50 mg/kg), and high-dose (100 mg/kg) naproxen, coinciding with their gastric damage scores after naproxen administration. The resultant metabolic profiles demonstrate that the naproxen-induced gastric damage exhibited energy metabolism perturbations that elevated their urinary levels of citrate, cis–aconitate, creatine, and creatine phosphate. In addition, naproxen administration decreased choline level and increased betaine level, indicating that it depleted the main protective constituent of the gastric mucosa. Moreover, naproxen stimulated the decomposition of tryptophan into kynurenate, which inhibits fibroblast growth factor-1 and delays ulcer healing. These findings demonstrate that 1H NMR-based urinary metabolic profiling can facilitate noninvasive and rapid diagnosis of drug side effects and is suitable for elucidating possible biological pathways perturbed by drug toxicity.