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Elaine M. Worcester - One of the best experts on this subject based on the ideXlab platform.
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evidence for disordered acid base handling in Calcium Stone forming patients
American Journal of Physiology-renal Physiology, 2020Co-Authors: Elaine M. Worcester, Kristin J. Bergsland, Daniel L Gillen, Fredric L CoeAbstract:In Stone formers (SFs) with idiopathic hypercalciuria, urine pH governs the mineral phase of Stones. Calcium phosphate (CaP) SFs have higher urine pH than Calcium oxalate (CaOx) SFs. Normal women h...
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Evidence for a role of PDZ domain-containing proteins to mediate hypophosphatemia in Calcium Stone formers
Nephrology Dialysis Transplantation, 2017Co-Authors: Kristin J. Bergsland, Joan H Parks, John R. Asplin, Elaine M. WorcesterAbstract:Background:Hypophosphatemia (HYP) is common among Calcium Stone formers (SFs) and in rare cases is associated with mutations in sodium-phosphate cotransporters or in Na+/H+ exchanger regulatory factor 1 (NHERF1), but the majority of cases are unexplained. We hypothesized that reduced sodium-phosphate cotransporter activity mediated via NHERF1 or a similar PDZ domain-containing protein, causes HYP. If so, other transport activities controlled by NHERF1, such as NHE3 and URAT1, might be reduced in HYP. Methods:To test this idea, we analyzed two large but separate sets of 24-h urine samples and paired serums of 2700 SFs from the University of Chicago and 11 073 SFs from Litholink, a national laboratory. Patients were divided into quintiles based on serum phosphate. Results:Males were more common in the lowest phosphate tiles in both datasets. Phosphate excretion did not vary across the quintiles, excluding diet as a cause of HYP. Tubule maximum (Tm) phosphate per unit glomerular filtration rate decreased and fractional excretion increased with decreasing phosphate quintiles, indicating reduced tubule phosphate reabsorption was responsible for HYP. Urine pH and serum chloride increased with decreasing serum phosphate, suggesting a coordinate change in NHE3 activity. Serum uric acid and Tm uric acid decreased significantly with decreasing serum phosphate, while uric acid excretion did not vary. Conclusion. HYP in SFs results from decreased tubule phosphate reabsorption and, being associated with related changes in other proximal tubule transporters, may arise from alterations in or signaling to PDZ-containing proteins.
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nephrocalcinosis in Calcium Stone formers who do not have systemic disease
Author, 2015Co-Authors: Naeem Bhojani, Elaine M. Worcester, Andrew P. Evan, Fredric L Coe, Jessica E Paonessa, Tariq A Hameed, Michael S Borofsky, James E LingemanAbstract:Purpose: 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.Materials and Methods: 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 t...
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biopsy proven medullary sponge kidney clinical findings histopathology and role of osteogenesis in Stone and plaque formation
Anatomical Record-advances in Integrative Anatomy and Evolutionary Biology, 2015Co-Authors: Andrew P. Evan, Elaine M. Worcester, James E Lingeman, James C Williams, Andre J Sommer, Carrie L Phillips, Fredric L CoeAbstract:Medullary sponge kidney (MSK) is associated with recurrent Stone formation, but the clinical phenotype is unclear because patients with other disorders may be incorrectly labeled MSK. We studied 12 patients with histologic findings pathognomonic of MSK. All patients had an endoscopically recognizable pattern of papillary malformation, which may be segmental or diffuse. Affected papillae are enlarged and billowy, due to markedly enlarged inner medullary collecting ducts (IMCD), which contain small, mobile ductal Stones. Patients had frequent dilation of Bellini ducts, with occasional mineral plugs. Stones may form over white (Randall's) plaque, but most renal pelvic Stones are not attached, and have a similar morphology as ductal Stones, which are a mixture of Calcium oxalate and apatite. Patients had no abnormalities of urinary acidification or acid excretion; the most frequent metabolic abnormality was idiopathic hypercalciuria. Although both Runx2 and Osterix are expressed in papillae of MSK patients, no mineral deposition was seen at the sites of gene expression, arguing against a role of these genes in this process. Similar studies in idiopathic Calcium Stone formers showed no expression of these genes at sites of Randall's plaque. The most likely mechanism for Stone formation in MSK appears to be crystallization due to urinary stasis in dilated IMCD with subsequent passage of ductal Stones into the renal pelvis where they may serve as nuclei for Stone formation.
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evidence for net renal tubule oxalate secretion in patients with Calcium kidney Stones
American Journal of Physiology-renal Physiology, 2011Co-Authors: Kristin J. Bergsland, Elaine M. Worcester, John R. Asplin, Anna L Zisman, Fredric L CoeAbstract:Little is known about the renal handling of oxalate in patients with idiopathic hypercalciuria (IH). To explore the role of tubular oxalate handling in IH and to evaluate whether differences exist between IH and normal controls, we studied 19 IH subjects, 8 normal subjects, and 2 bariatric Stone formers (BSF) during a 1-day General Clinical Research Center protocol utilizing a low-oxalate diet. Urine and blood samples were collected at 30- to 60-min intervals while subjects were fasting and after they ate three meals providing known amounts of Calcium, phosphorus, sodium, protein, oxalate, and calories. Plasma oxalate concentrations and oxalate-filtered loads were similar between patients (includes IH and BSF) and controls in both the fasting and fed states. Urinary oxalate excretion was significantly higher in patients vs. controls regardless of feeding state. Fractional excretion of oxalate (FEOx) was >1, suggesting tubular secretion of oxalate, in 6 of 19 IH and both BSF, compared with none of the controls (P < 0.00001). Adjusted for water extraction along the nephron, urine oxalate rose more rapidly among patients than normal subjects with increases in plasma oxalate. Our findings identify tubular secretion of oxalate as a key mediator of hyperoxaluria in Calcium Stone formers, potentially as a means of maintaining plasma oxalate in a tight range.
Ita Pfeferman Heilberg - One of the best experts on this subject based on the ideXlab platform.
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Influence of nutritional status, laboratory parameters and dietary patterns upon urinary acid excretion in Calcium Stone formers.
2018Co-Authors: Carolini Zanette Warmling Tessaro, Christiane Ishikawa Ramos, Ita Pfeferman HeilbergAbstract:ABSTRACT Introduction: Obesity and Metabolic Syndrome (MS) are associated with low urinary pH and represent risk factors for nephrolithiasis, especially composed by uric acid. Acidogenic diets may also contribute to a reduction of urinary pH. Propensity for Calcium oxalate precipitation has been shown to be higher with increasing features of the MS. Objective: A retrospective evaluation of anthropometric and body composition parameters, MS criteria and the dietary patterns of overweight and obese Calcium Stone formers and their impact upon urinary pH and other lithogenic parameters was performed. Methods: Data regarding anthropometry, body composition, serum and urinary parameters and 3-days dietary records were obtained from medical records of 102(34M/68F) Calcium Stone formers. Results: A negative correlation was found between urinary pH, waist circumference and serum uric acid levels (males). The endogenous production of organic acids (OA) was positively correlated with triglycerides levels and number of features of MS (males), and with glucose, uric acid and triglycerides serum levels, and number of features of MS (females). No significant correlations were detected between Net Acid Excretion (NAE) or Potential Renal Acid Load of the diet with any of the assessed parameters. A multivariate analysis showed a negative association between OA and urinary pH. Conclusion: The endogenous production of OA and not an acidogenic diet were found to be independently predictive factors for lower urinary pH levels in Calcium Stone formers. Hypercalciuric and/or hyperuricosuric patients presented higher OA levels and lower levels of urinary pH.
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the effect of sodium bicarbonate upon urinary citrate excretion in Calcium Stone formers
Urology, 2013Co-Authors: Vivian Barbosa Pinheiro, Alessandra Calabria Baxmann, Hansgoeran Tiselius, Ita Pfeferman HeilbergAbstract:Objective To evaluate the effects of oral sodium bicarbonate (NaBic) supplementation upon urinary citrate excretion in Calcium Stone formers (CSFs). Methods Sixteen adult Calcium Stone formers with hypocitraturia were enrolled in a randomized, double-blind, crossover protocol using 60 mEq/day of NaBic during 3 days compared to the same period and doses of potassium citrate (KCit) supplementation. Blood and 24-hour urine samples were collected at baseline and during the third day of each alkali salt. Results NaBic, similarly to KCit supplementation, led to an equivalent and significant increase in urinary citrate and pH. Compared to baseline, NaBic led to a significant increase in sodium excretion without concomitant increases in urinary Calcium excretion, whereas KCit induced a significant increase in potassium excretion coupled with a significant reduction in urinary Calcium. Although NaBic and KCit both reduced Calcium oxalate supersaturation (CaOxSS) significantly vs baseline, KCit reduced Calcium oxalate supersaturation significantly further vs NaBic. Both KCit and NaBic significantly reduced urinary phosphate and increased Calcium phosphate supersaturation (CaPSS) compared to baseline. Finally, a significantly higher sodium urate supersaturation (NaUrSS) was observed after the use of the 2 drugs. Conclusion This short-term study suggests that NaBic represents an effective alternative for the treatment of hypocitraturic Calcium oxalate Stone formers who cannot tolerate or afford the cost of KCit. In view of the increased sodium urate supersaturation, patients with pure uric acid Stones and high urate excretion may be less suited for treatment with NaBic.
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Effects of Calcium supplementation on body weight reduction in overweight Calcium Stone formers
Urological Research, 2009Co-Authors: Viviane Barcellos Menon, Alessandra Calabria Baxmann, Leila Froeder, Lígia Araújo Martini, Ita Pfeferman HeilbergAbstract:A randomized, placebo-controlled trial was conducted in overweight Calcium Stone-forming (CSF) patients, to evaluate the effect of Calcium supplementation associated with a calorie-restricted diet on body weight (BW) and fat reduction and its potential changes upon serum and urinary parameters. Fifteen patients were placed on a hypocaloric diet for 3 months, supplemented with either Calcium carbonate (CaCO_3, n = 8) or placebo ( n = 7), 500 mg bid. Blood and 24-h urine samples were collected and body composition was assessed at baseline and after the intervention. At the end of the study, final BW was significantly lower vs baseline in both CaCO_3 (74 ± 14 vs. 80 ± 14 kg, P = 0.01) and placebo groups (80 ± 10 vs. 87 ± 9 kg, P = 0.02) but the mean percentage of loss of body weight and body fat did not differ between CaCO_3 and placebo (7.0 ± 2.0 vs. 8.0 ± 3.0%, P = 0.40 and 13.0 ± 7.0 vs. 13.0 ± 10.0%; P = 0.81, respectively). After CaCO_3 or placebo, no significant differences versus baseline were observed for urinary parameters in both CaCO_3 and placebo, except for a higher mean urinary citrate in placebo group. These data suggest that increasing Calcium intake by Calcium carbonate supplementation did not contribute to a further reduction of BW and fat in overweight CSF patients submitted to a hypocaloric diet nor altered urinary lithogenic parameters.
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phyllanthus niruri normalizes elevated urinary Calcium levels in Calcium Stone forming csf patients
Urological Research, 2004Co-Authors: Jose Luiz Nishiura, Alexandre H Campos, Mirian A Boim, Ita Pfeferman Heilberg, Nestor SchorAbstract:Phyllanthus niruri is a plant used for years in Brazil to treat urinary calculi. We prospectively evaluated the effect of P. niruri intake on 24 h urinary biochemical parameters in an attempt to assess its in vivo effect in Calcium Stone forming (CSF) patients. A total of 69 CSF patients (39 males and 30 females, 38±8 years old) were randomized to take either P. niruri (n=33) (450 mg capsules, td) or placebo (n=36) for 3 months. Blood Calcium, uric acid, citrate, magnesium, oxalate, sodium and potassium were determined at baseline and at the end of the study. A subset analysis was made in patients classified according to the presence of metabolic abnormalities (hypercalciuria, hyperuricosuria, hyperoxaluria, hypocitraturia and hypomagnesiuria). Overall, there were no significant differences in the mean values of urinary parameters between the urine samples before and after P. niruri intake, except for a slight reduction in mean urinary magnesium after P. niruri, which was within the normal range. However, in the subset analysis, we observed that P. niruri induced a significant reduction in the mean urinary Calcium in hypercalciuric patients (4.8±1.0 vs 3.4±1.1 mg/kg/24 h, P<0.05). In this short-term follow-up, no significant differences in calculi voiding and/or pain relief between the groups taking P. niruri or the placebo were detected. Our data suggest that P. niruri intake reduces urinary Calcium based on the analysis of a subset of patients presenting with hypercalciuria. Larger trials including primary hypercalciuric Stone formers should be performed in order to confirm these findings and to determine the possible clinical consequences of urinary Calcium reduction during P. niruri administration.
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effect of vitamin c supplements on urinary oxalate and ph in Calcium Stone forming patients
Kidney International, 2003Co-Authors: Alessandra Calabria Baxmann, Claudia De O G Mendonca, Ita Pfeferman HeilbergAbstract:Effect of vitamin C supplements on urinary oxalate and pH in Calcium Stone-forming patients. Background The contribution of ascorbate to urinary oxalate is controversial. The present study aimed to determine whether urinary oxalate and pH may be affected by vitamin C supplementation in Calcium Stone-forming patients. Methods Forty-seven adult Calcium Stone-forming patients received either 1 g ( N = 23) or 2 g ( N = 24) of vitamin C supplement for 3 days and 20 healthy subjects received 1 g. A 24-hour urine sample was obtained both before and after vitamin C for Calcium, oxalate, magnesium, citrate, sodium, potassium, and creatinine determination. The Tiselius index was used as a Calcium oxalate crystallization index. A spot fasting morning urine sample was also obtained to determine the urinary pH before and after vitamin C. Results Fasting urinary pH did not change after 1 g (5.8 ± 0.6 vs. 5.8 ± 0.7) or 2 g vitamin C (5.8 ± 0.8 vs. 5.8 ± 0.7). A significant increase in mean urinary oxalate was observed in Calcium Stone-forming patients receiving either 1 g (50 ± 16 vs. 31 ± 12 mg/24 hours) or 2 g (48 ± 21 vs. 34 ± 12 mg/24 hours) of vitamin C and in healthy subjects (25 ± 12 vs. 39 ± 13 mg/24 hours). A significant increase in mean Tiselius index was observed in Calcium Stone-forming patients after 1 g (1.43 ± 0.70 vs. 0.92 ± 0.65) or 2 g vitamin C (1.61 ± 1.05 vs. 0.99 ± 0.55) and in healthy subjects (1.50 ± 0.69 vs. 0.91 ± 0.46). Ancillary analyses of spot urine obtained after vitamin C were performed in 15 control subjects in vessels with or without ethylenediaminetetraacetic acid (EDTA) with no difference in urinary oxalate between them (28 ± 23 vs. 26 ± 21 mg/L), suggesting that the in vitro conversion of ascorbate to oxalate did not occur. Conclusion These data suggest that vitamin C supplementation may increase urinary oxalate excretion and the risk of Calcium oxalate crystallization in Calcium Stone-forming patients.
Fredric L Coe - One of the best experts on this subject based on the ideXlab platform.
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evidence for disordered acid base handling in Calcium Stone forming patients
American Journal of Physiology-renal Physiology, 2020Co-Authors: Elaine M. Worcester, Kristin J. Bergsland, Daniel L Gillen, Fredric L CoeAbstract:In Stone formers (SFs) with idiopathic hypercalciuria, urine pH governs the mineral phase of Stones. Calcium phosphate (CaP) SFs have higher urine pH than Calcium oxalate (CaOx) SFs. Normal women h...
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nephrocalcinosis in Calcium Stone formers who do not have systemic disease
Author, 2015Co-Authors: Naeem Bhojani, Elaine M. Worcester, Andrew P. Evan, Fredric L Coe, Jessica E Paonessa, Tariq A Hameed, Michael S Borofsky, James E LingemanAbstract:Purpose: 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.Materials and Methods: 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 t...
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biopsy proven medullary sponge kidney clinical findings histopathology and role of osteogenesis in Stone and plaque formation
Anatomical Record-advances in Integrative Anatomy and Evolutionary Biology, 2015Co-Authors: Andrew P. Evan, Elaine M. Worcester, James E Lingeman, James C Williams, Andre J Sommer, Carrie L Phillips, Fredric L CoeAbstract:Medullary sponge kidney (MSK) is associated with recurrent Stone formation, but the clinical phenotype is unclear because patients with other disorders may be incorrectly labeled MSK. We studied 12 patients with histologic findings pathognomonic of MSK. All patients had an endoscopically recognizable pattern of papillary malformation, which may be segmental or diffuse. Affected papillae are enlarged and billowy, due to markedly enlarged inner medullary collecting ducts (IMCD), which contain small, mobile ductal Stones. Patients had frequent dilation of Bellini ducts, with occasional mineral plugs. Stones may form over white (Randall's) plaque, but most renal pelvic Stones are not attached, and have a similar morphology as ductal Stones, which are a mixture of Calcium oxalate and apatite. Patients had no abnormalities of urinary acidification or acid excretion; the most frequent metabolic abnormality was idiopathic hypercalciuria. Although both Runx2 and Osterix are expressed in papillae of MSK patients, no mineral deposition was seen at the sites of gene expression, arguing against a role of these genes in this process. Similar studies in idiopathic Calcium Stone formers showed no expression of these genes at sites of Randall's plaque. The most likely mechanism for Stone formation in MSK appears to be crystallization due to urinary stasis in dilated IMCD with subsequent passage of ductal Stones into the renal pelvis where they may serve as nuclei for Stone formation.
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evidence for net renal tubule oxalate secretion in patients with Calcium kidney Stones
American Journal of Physiology-renal Physiology, 2011Co-Authors: Kristin J. Bergsland, Elaine M. Worcester, John R. Asplin, Anna L Zisman, Fredric L CoeAbstract:Little is known about the renal handling of oxalate in patients with idiopathic hypercalciuria (IH). To explore the role of tubular oxalate handling in IH and to evaluate whether differences exist between IH and normal controls, we studied 19 IH subjects, 8 normal subjects, and 2 bariatric Stone formers (BSF) during a 1-day General Clinical Research Center protocol utilizing a low-oxalate diet. Urine and blood samples were collected at 30- to 60-min intervals while subjects were fasting and after they ate three meals providing known amounts of Calcium, phosphorus, sodium, protein, oxalate, and calories. Plasma oxalate concentrations and oxalate-filtered loads were similar between patients (includes IH and BSF) and controls in both the fasting and fed states. Urinary oxalate excretion was significantly higher in patients vs. controls regardless of feeding state. Fractional excretion of oxalate (FEOx) was >1, suggesting tubular secretion of oxalate, in 6 of 19 IH and both BSF, compared with none of the controls (P < 0.00001). Adjusted for water extraction along the nephron, urine oxalate rose more rapidly among patients than normal subjects with increases in plasma oxalate. Our findings identify tubular secretion of oxalate as a key mediator of hyperoxaluria in Calcium Stone formers, potentially as a means of maintaining plasma oxalate in a tight range.
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a test of the hypothesis that the collecting duct Calcium sensing receptor limits rise of urine Calcium molarity in hypercalciuric Calcium kidney Stone formers
American Journal of Physiology-renal Physiology, 2009Co-Authors: Kristin J. Bergsland, Daniel L Gillen, Fredric L Coe, Elaine M. WorcesterAbstract:The process of kidney Stone formation depends on an imbalance between excretion of water and insoluble Stone-forming salts, leading to high concentrations that supersaturate urine and inner medullary collecting duct (IMCD) fluid. For common Calcium-containing Stones, a critical mechanism that has been proposed for integrating water and Calcium salt excretions is activation of the cell surface Calcium-sensing receptor (CaSR) on the apical membranes of IMCD cells. High deliveries of Calcium into the IMCD would be predicted to activate CaSR, leading to reduced membrane abundance of aquaporin-2, thereby limiting water conservation and protecting against Stone formation. We have tested this hypothesis in 16 idiopathic hypercalciuric Calcium Stone formers and 14 matched normal men and women in the General Clinical Research Center. Subjects were fed identical diets; we collected 14 urine samples at 1-h intervals during a single study day, and one sample overnight. Hypercalciuria did not increase urine volume, so urine Calcium molarity and supersaturation with respect to Calcium oxalate and Calcium phosphate rose proportionately to Calcium excretion. Thus CaSR modulation of urine volume via IMCD CaSR activation does not appear to be an important mechanism of protection against Stone formation. The overnight period, one of maximal water conservation, was a time of maximal Stone risk and perhaps a target of specific clinical intervention.
John R. Asplin - One of the best experts on this subject based on the ideXlab platform.
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Evidence for a role of PDZ domain-containing proteins to mediate hypophosphatemia in Calcium Stone formers
Nephrology Dialysis Transplantation, 2017Co-Authors: Kristin J. Bergsland, Joan H Parks, John R. Asplin, Elaine M. WorcesterAbstract:Background:Hypophosphatemia (HYP) is common among Calcium Stone formers (SFs) and in rare cases is associated with mutations in sodium-phosphate cotransporters or in Na+/H+ exchanger regulatory factor 1 (NHERF1), but the majority of cases are unexplained. We hypothesized that reduced sodium-phosphate cotransporter activity mediated via NHERF1 or a similar PDZ domain-containing protein, causes HYP. If so, other transport activities controlled by NHERF1, such as NHE3 and URAT1, might be reduced in HYP. Methods:To test this idea, we analyzed two large but separate sets of 24-h urine samples and paired serums of 2700 SFs from the University of Chicago and 11 073 SFs from Litholink, a national laboratory. Patients were divided into quintiles based on serum phosphate. Results:Males were more common in the lowest phosphate tiles in both datasets. Phosphate excretion did not vary across the quintiles, excluding diet as a cause of HYP. Tubule maximum (Tm) phosphate per unit glomerular filtration rate decreased and fractional excretion increased with decreasing phosphate quintiles, indicating reduced tubule phosphate reabsorption was responsible for HYP. Urine pH and serum chloride increased with decreasing serum phosphate, suggesting a coordinate change in NHE3 activity. Serum uric acid and Tm uric acid decreased significantly with decreasing serum phosphate, while uric acid excretion did not vary. Conclusion. HYP in SFs results from decreased tubule phosphate reabsorption and, being associated with related changes in other proximal tubule transporters, may arise from alterations in or signaling to PDZ-containing proteins.
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A Pilot Study of the Effect of Sodium Thiosulfate on Urinary Lithogenicity and Associated Metabolic Acid Load in Non-Stone
2016Co-Authors: Stone Formers, John R. Asplin, Ignacio Granja, Onyeka W Okonkwo, Ruchika Batwara, David S. GoldfarbAbstract:Background and Objectives: Sodium thiosulfate (STS) reduced Calcium Stone formation in both humans and genetic hypercalciuric Stone forming (GHS) rats. We sought to measure urine chemistry changes resulting from STS administration in people. Design, Setting, Participants & Measurements: STS was given to healthy and hypercalciuric Stone forming adults. Five normal non-Stone forming adults (mean age 33 years), and 5 people with idiopathic hypercalciuria and Calcium kidney Stones (mean age 66 years) participated. Two baseline 24-hour urine collections were performed on days 2 and 3 of 3 days of self-selected diets. Subjects then drank STS 10 mmol twice a day for 7 days and did urine collections while repeating the self-selected diet. Results were compared by non-parametric Wilcoxon signed rank test. The primary outcome was the resulting change in urine chemistry. Results: STS administration did not cause a significant change in urinary Calcium excretion in either group. In both groups, 24 hour urinary ammonium (P = 0.005) and sulfate excretion (P = 0.007) increased, and urinary pH fell (P = 0.005); citrate excretion fell (P,0.05) in hypercalciuric participants but not in non-Stone formers. Among Stone formers with hypercalciuria, 3 of 5 patients had measurement of serum HCO3 concentration after the STS period: it did not change. The net effect was an increase in supersaturation of uric acid, and no change in supersaturation of Calcium oxalate or Calcium phosphate
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evidence for net renal tubule oxalate secretion in patients with Calcium kidney Stones
American Journal of Physiology-renal Physiology, 2011Co-Authors: Kristin J. Bergsland, Elaine M. Worcester, John R. Asplin, Anna L Zisman, Fredric L CoeAbstract:Little is known about the renal handling of oxalate in patients with idiopathic hypercalciuria (IH). To explore the role of tubular oxalate handling in IH and to evaluate whether differences exist between IH and normal controls, we studied 19 IH subjects, 8 normal subjects, and 2 bariatric Stone formers (BSF) during a 1-day General Clinical Research Center protocol utilizing a low-oxalate diet. Urine and blood samples were collected at 30- to 60-min intervals while subjects were fasting and after they ate three meals providing known amounts of Calcium, phosphorus, sodium, protein, oxalate, and calories. Plasma oxalate concentrations and oxalate-filtered loads were similar between patients (includes IH and BSF) and controls in both the fasting and fed states. Urinary oxalate excretion was significantly higher in patients vs. controls regardless of feeding state. Fractional excretion of oxalate (FEOx) was >1, suggesting tubular secretion of oxalate, in 6 of 19 IH and both BSF, compared with none of the controls (P < 0.00001). Adjusted for water extraction along the nephron, urine oxalate rose more rapidly among patients than normal subjects with increases in plasma oxalate. Our findings identify tubular secretion of oxalate as a key mediator of hyperoxaluria in Calcium Stone formers, potentially as a means of maintaining plasma oxalate in a tight range.
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citrate malate and alkali content in commonly consumed diet sodas implications for nephrolithiasis treatment
The Journal of Urology, 2010Co-Authors: David S. Goldfarb, John R. Asplin, Brian H Eisner, Ardalanejaz Ahmad, Marshall L StollerAbstract:Purpose: Citrate is a known inhibitor of Calcium Stone formation. Dietary citrate and alkali intake may have an effect on citraturia. Increasing alkali intake also increases urine pH, which can help prevent uric acid Stones. We determined citrate, malate and total alkali concentrations in commonly consumed diet sodas to help direct dietary recommendations in patients with hypocitraturic Calcium or uric acid nephrolithiasis.Materials and Methods: Citrate and malate were measured in a lemonade beverage commonly used to treat hypocitraturic Calcium nephrolithiasis and in 15 diet sodas. Anions were measured by ion chromatography. The pH of each beverage was measured to allow calculation of the unprotonated anion concentration using the known pK of citric and malic acid. Total alkali equivalents were calculated for each beverage. Statistical analysis was done using Pearson's correlation coefficient.Results: Several sodas contained an amount of citrate equal to or greater than that of alkali and total alkali as...
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the risk of recurrent nephrolithiasis in children is dependent on urinary Calcium and citrate
The Journal of Urology, 2008Co-Authors: William Defoor, John R. Asplin, Alexandre Caillat, Elizabeth Jackson, Eugene Minevich, Curtis SheldonAbstract:Objectives To determine which risk factors help predict recurrent Stone formation. Urinary Stone disease is relatively rare in children. At our institution, a full urinary metabolic evaluation is initiated after the first Stone episode. Methods A retrospective cohort study was performed to assess urinary metabolic profiles in children with urolithiasis. Twenty-four–hour urine collections were performed and evaluated. Urine chemistries were adjusted for creatinine and weight. Abnormal thresholds were obtained from the available published data. The patients were stratified into solitary or recurrent Stone formers by review of the medical record. Multivariate analysis was performed with a logistic regression model to assess for independent risk factors for Stone recurrence. Results A total of 148 samples from 88 patients with solitary Stones and 84 samples from 51 patients with recurrent Stones were evaluated. Age and gender were well-matched between the 2 groups. Most known Stones were Calcium oxalate, and there were no radiolucent Stones in those with unknown composition. A significantly higher number of patients with recurrent Stones had abnormal values for Calcium (73% vs 57%) and citrate (30% vs 13%) by univariate analysis. Both Calcium (odds ratio, 2.3, P P Conclusions There are significant differences in the urinary Calcium and citrate levels between children with solitary and recurrent Calcium Stone formation. This may allow identification of patients at risk for Stone recurrence that may benefit from more aggressive dietary and/or pharmacologic intervention.
David S. Goldfarb - One of the best experts on this subject based on the ideXlab platform.
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A Pilot Study of the Effect of Sodium Thiosulfate on Urinary Lithogenicity and Associated Metabolic Acid Load in Non-Stone
2016Co-Authors: Stone Formers, John R. Asplin, Ignacio Granja, Onyeka W Okonkwo, Ruchika Batwara, David S. GoldfarbAbstract:Background and Objectives: Sodium thiosulfate (STS) reduced Calcium Stone formation in both humans and genetic hypercalciuric Stone forming (GHS) rats. We sought to measure urine chemistry changes resulting from STS administration in people. Design, Setting, Participants & Measurements: STS was given to healthy and hypercalciuric Stone forming adults. Five normal non-Stone forming adults (mean age 33 years), and 5 people with idiopathic hypercalciuria and Calcium kidney Stones (mean age 66 years) participated. Two baseline 24-hour urine collections were performed on days 2 and 3 of 3 days of self-selected diets. Subjects then drank STS 10 mmol twice a day for 7 days and did urine collections while repeating the self-selected diet. Results were compared by non-parametric Wilcoxon signed rank test. The primary outcome was the resulting change in urine chemistry. Results: STS administration did not cause a significant change in urinary Calcium excretion in either group. In both groups, 24 hour urinary ammonium (P = 0.005) and sulfate excretion (P = 0.007) increased, and urinary pH fell (P = 0.005); citrate excretion fell (P,0.05) in hypercalciuric participants but not in non-Stone formers. Among Stone formers with hypercalciuria, 3 of 5 patients had measurement of serum HCO3 concentration after the STS period: it did not change. The net effect was an increase in supersaturation of uric acid, and no change in supersaturation of Calcium oxalate or Calcium phosphate
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Randomized Controlled Trial of Febuxostat Versus Allopurinol or Placebo in Individuals with Higher Urinary Uric Acid Excretion and Calcium Stones
Clinical Journal of The American Society of Nephrology, 2013Co-Authors: David S. Goldfarb, Patricia A. Macdonald, Lhanoo Gunawardhana, Solomon Chefo, Lachy McleanAbstract:Summary Background and objectives Higher urinary uric acid excretion is a suspected risk factor for Calcium oxalate Stone formation. Febuxostat, a xanthine oxidoreductase inhibitor, is effective in lowering serum urate concentration and urinary uric acid excretion in healthy volunteers and people with gout. This work studied whether febuxostat, compared with allopurinol and placebo, would reduce 24-hour urinary uric acid excretion and prevent Stone growth or new Stone formation. Design, setting, participants, & measurements In this 6-month, double-blind, multicenter, randomized controlled trial, hyperuricosuric participants with a recent history of Calcium Stones and one or more radio-opaque Calcium Stone ≥3 mm (as seen by multidetector computed tomography) received daily febuxostat at 80 mg, allopurinol at 300 mg, or placebo. The primary end point was percent change from baseline to month 6 in 24-hour urinary uric acid. Secondary end points included percent change from baseline to month 6 in size of index Stone and change from baseline in the mean number of Stones and 24-hour creatinine clearance. Results Of 99 enrolled participants, 86 participants completed the study. Febuxostat led to significantly greater reduction in 24-hour urinary uric acid (−58.6%) than either allopurinol (−36.4%; P=0.003) or placebo (−12.7%; P Conclusions Febuxostat (80 mg) lowered 24-hour urinary uric acid significantly more than allopurinol (300 mg) in Stone formers with higher urinary uric acid excretion after 6 months of treatment. There was no change in Stone size or number over the 6-month period.
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potential pharmacologic treatments for cystinuria and for Calcium Stones associated with hyperuricosuria
Clinical Journal of The American Society of Nephrology, 2011Co-Authors: David S. GoldfarbAbstract:Summary Two new potential pharmacologic therapies for recurrent Stone disease are described. The role of hyperuricosuria in promoting Calcium Stones is controversial with only some but not all epidemiologic studies demonstrating associations between increasing urinary uric acid excretion and Calcium Stone disease. The relationship is supported by the ability of uric acid to “salt out” (or reduce the solubility of) Calcium oxalate in vitro. A randomized, controlled trial of allopurinol in patients with hyperuricosuria and normocalciuria was also effective in preventing recurrent Stones. Febuxostat, a nonpurine inhibitor of xanthine oxidase (also known as xanthine dehydrogenase or xanthine oxidoreductase) may have advantages over allopurinol and is being tested in a similar protocol, with the eventual goal of determining whether urate-lowering therapy prevents recurrent Calcium Stones. Treatments for cystinuria have advanced little in the past 30 years. Atomic force microscopy has been used recently to demonstrate that effective inhibition of cystine crystal growth is accomplished at low concentrations of L-cystine methyl ester and L-cystine dimethyl ester, structural analogs of cystine that provide steric inhibition of crystal growth. In vitro, L-cystine dimethyl ester had a significant inhibitory effect on crystal growth. The drug’s safety and effectiveness will be tested in an Slc3a1 knockout mouse that serves as an animal model of cystinuria. Clin J Am Soc Nephrol 6: 2093–2097, 2011. doi: 10.2215/CJN.00320111
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potential pharmacologic treatments for cystinuria and for Calcium Stones associated with hyperuricosuria
Clinical Journal of The American Society of Nephrology, 2011Co-Authors: David S. GoldfarbAbstract:Two new potential pharmacologic therapies for recurrent Stone disease are described. The role of hyperuricosuria in promoting Calcium Stones is controversial with only some but not all epidemiologic studies demonstrating associations between increasing urinary uric acid excretion and Calcium Stone disease. The relationship is supported by the ability of uric acid to "salt out" (or reduce the solubility of) Calcium oxalate in vitro. A randomized, controlled trial of allopurinol in patients with hyperuricosuria and normocalciuria was also effective in preventing recurrent Stones. Febuxostat, a nonpurine inhibitor of xanthine oxidase (also known as xanthine dehydrogenase or xanthine oxidoreductase) may have advantages over allopurinol and is being tested in a similar protocol, with the eventual goal of determining whether urate-lowering therapy prevents recurrent Calcium Stones. Treatments for cystinuria have advanced little in the past 30 years. Atomic force microscopy has been used recently to demonstrate that effective inhibition of cystine crystal growth is accomplished at low concentrations of l-cystine methyl ester and l-cystine dimethyl ester, structural analogs of cystine that provide steric inhibition of crystal growth. In vitro, l-cystine dimethyl ester had a significant inhibitory effect on crystal growth. The drug's safety and effectiveness will be tested in an Slc3a1 knockout mouse that serves as an animal model of cystinuria.
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citrate malate and alkali content in commonly consumed diet sodas implications for nephrolithiasis treatment
The Journal of Urology, 2010Co-Authors: David S. Goldfarb, John R. Asplin, Brian H Eisner, Ardalanejaz Ahmad, Marshall L StollerAbstract:Purpose: Citrate is a known inhibitor of Calcium Stone formation. Dietary citrate and alkali intake may have an effect on citraturia. Increasing alkali intake also increases urine pH, which can help prevent uric acid Stones. We determined citrate, malate and total alkali concentrations in commonly consumed diet sodas to help direct dietary recommendations in patients with hypocitraturic Calcium or uric acid nephrolithiasis.Materials and Methods: Citrate and malate were measured in a lemonade beverage commonly used to treat hypocitraturic Calcium nephrolithiasis and in 15 diet sodas. Anions were measured by ion chromatography. The pH of each beverage was measured to allow calculation of the unprotonated anion concentration using the known pK of citric and malic acid. Total alkali equivalents were calculated for each beverage. Statistical analysis was done using Pearson's correlation coefficient.Results: Several sodas contained an amount of citrate equal to or greater than that of alkali and total alkali as...
