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Khashayar Sakhaee - One of the best experts on this subject based on the ideXlab platform.
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temporal changes in kidney Stone composition and in risk factors predisposing to Stone formation
The Journal of Urology, 2017Co-Authors: Beverley Adamshuet, Orson W. Moe, Naim M. Maalouf, John R Poindexter, Khashayar SakhaeeAbstract:Purpose: The prevalence of kidney Stones has increased globally in recent decades. However, studies investigating the association between temporal changes in the risk of Stone formation and Stone types are scarce. We investigated temporal changes in Stone composition, and demographic, serum and urinary parameters of kidney Stone formers from 1980 to 2015.Materials and Methods: We retrospectively analyzed the records of 1,516 patients diagnosed with either calcium or Uric Acid Stones at an initial visit to a university kidney Stone clinic from 1980 to 2015.Results: From 1980 to 2015, the proportion of Uric Acid Stones in all Stone formers increased from 7% to 14%. While age and body mass index increased with time in both Uric Acid and calcium Stone formers, Uric Acid Stone formers were consistently older and had a higher body mass index and lower urinary pH than calcium Stone formers. The proportion of females with Stones has increased over time but the increase in female gender was more prominent among ca...
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renal ammonium excretion after an acute Acid load blunted response in Uric Acid Stone formers but not in patients with type 2 diabetes
American Journal of Physiology-renal Physiology, 2013Co-Authors: Alexandru I Bobulescu, Orson W. Moe, Naim M. Maalouf, Beverley Adamshuet, Giovanna Capolongo, Tara R Rosenthal, Khashayar SakhaeeAbstract:Idiopathic Uric Acid nephrolithiasis is characterized by elevated urinary net Acid excretion and insufficient buffering by ammonium, resulting in excessively Acidic urine and titration of the relatively soluble urate anion to insoluble Uric Acid. Patients with type 2 diabetes have similar changes in urinary pH, net Acid excretion, and ammonium in 24-h urine collections at baseline, even after controlling for dietary factors, and are at increased risk for Uric Acid nephrolithiasis. However, not all patients with type 2 diabetes develop kidney Stones, suggesting that Uric Acid Stone formers may have additional urinary defects, perhaps not apparent at baseline. We performed a metabolic study of 14 patients with idiopathic Uric Acid nephrolithiasis, 13 patients with type 2 diabetes, and 8 healthy control subjects of similar body mass index. After equilibration on a fixed diet for 5 days, subjects were given a single oral Acid load (50 meq ammonium chloride), and urine was collected hourly for 4 h. Uric Acid Stone formers had a lower ammonium excretory response to acute Acid loading compared with diabetic and nondiabetic nonStone formers, suggesting that an ammonium excretory defect unique to Uric Acid Stone formers was unmasked by the Acid challenge. The Zucker diabetic fatty rat also did not show impaired urinary ammonium excretion in response to acute Acid challenge. A blunted renal ammonium excretory response to dietary Acid loads may contribute to the pathogenesis of idiopathic Uric Acid nephrolithiasis.
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the diurnal variation in urine Acidification differs between normal individuals and Uric Acid Stone formers
Kidney International, 2012Co-Authors: Mary Ann Cameron, Naim M. Maalouf, Beverley Adamshuet, John R Poindexter, Khashayar Sakhaee, Orson W. MoeAbstract:Many biological functions follow circadian rhythms driven by internal and external cues that synchronize and coordinate organ physiology to diurnal changes in the environment and behavior. Urinary Acid–base parameters follow diurnal patterns and it is thought these changes are due to periodic surges in gastric Acid secretion. Abnormal urine pH is a risk factor for specific types of nephrolithiasis and Uric Acid Stones result from excessively low urine pH. Here we placed 9 healthy volunteers and 10 Uric Acid Stone formers on fixed metabolic diets to study the diurnal pattern of urinary Acidification. All showed clear diurnal trends in urinary Acidification, but none of the patterns were affected by inhibitors of the gastric proton pump. Uric Acid Stone formers had similar patterns of change throughout the day but their urine pH was always lower compared to healthy volunteers. Uric Acid Stone formers excreted more Acid (normalized to Acid ingestion), with the excess excreted primarily as titratable Acid rather than ammonium. Urine base excretion was also lower in Uric Acid Stone formers (normalized to base ingestion), along with lower plasma bicarbonate concentrations during part of the day. Thus, increased net Acid presentation to the kidney and the preferential use of buffers, other than ammonium, result in much higher concentrations of undissociated Uric Acid throughout the day and consequently an increased risk of Uric Acid Stones.
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metabolic syndrome and Uric Acid nephrolithiasis
Seminars in Nephrology, 2008Co-Authors: Khashayar Sakhaee, Naim M. MaaloufAbstract:The metabolic syndrome describes a cluster of metabolic features that increases the risk for type 2 diabetes mellitus and cardiovascular disease. The prevalence of Uric Acid nephrolithiasis is higher among Stone-forming patients with features of the metabolic syndrome such as obesity and/or type 2 diabetes mellitus. The major determinant in the development of idiopathic Uric Acid Stones is an abnormally low urinary pH. The unduly urinary Acidity in Uric Acid Stone formers increasingly is recognized to be one of the features observed in the metabolic syndrome. Two major abnormalities have been implicated to explain this overly Acidic urine: (1) increased net Acid excretion, and (2) impaired buffering caused by defective urinary ammonium excretion, with the combination resulting in abnormally Acidic urine. New information is emerging linking these defects to changes in insulin signaling in the kidney. This article reviews the epidemiologic and metabolic studies linking Uric Acid nephrolithiasis with the metabolic syndrome, and examines the potential mechanisms underlying the unduly Acidic urine in these conditions.
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urine composition in type 2 diabetes predisposition to Uric Acid nephrolithiasis
Journal of The American Society of Nephrology, 2006Co-Authors: Mary Ann Cameron, Orson W. Moe, Naim M. Maalouf, Beverley Adamshuet, Khashayar SakhaeeAbstract:Type 2 diabetes is a risk factor for nephrolithiasis in general and has been associated with Uric Acid Stones in particular. The purpose of this study was to identify the metabolic features that place patients with type 2 diabetes at increased risk for Uric Acid nephrolithiasis. Three groups of individuals were recruited for this outpatient study: Patients who have type 2 diabetes and are not Stone formers ( n = 24), patients who do not have diabetes and are Uric Acid Stone formers (UASF; n = 8), and normal volunteers (NV; n = 59). Participants provided a fasting blood sample and a single 24-h urine collection for Stone risk analysis. Twenty-four-hour urine volume and total Uric Acid did not differ among the three groups. Patients with type 2 diabetes and UASF had lower 24-h urine pH than NV. Urine pH inversely correlated with both body weight and 24-h urine sulfate in all groups. Urine pH remained significantly lower in patients with type 2 diabetes and UASF than NV after adjustment for weight and urine sulfate ( P versus NV. With increasing urine sulfate, NV and patients with type 2 diabetes had a similar rise in urine ammonium, whereas in UASF, ammonium excretion remained unchanged. The main risk factor for Uric Acid nephrolithiasis in patients with type 2 diabetes is a low urine pH. Higher body mass and increased Acid intake can contribute to but cannot entirely account for the lower urine pH in patients with type 2 diabetes.
Naim M. Maalouf - One of the best experts on this subject based on the ideXlab platform.
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temporal changes in kidney Stone composition and in risk factors predisposing to Stone formation
The Journal of Urology, 2017Co-Authors: Beverley Adamshuet, Orson W. Moe, Naim M. Maalouf, John R Poindexter, Khashayar SakhaeeAbstract:Purpose: The prevalence of kidney Stones has increased globally in recent decades. However, studies investigating the association between temporal changes in the risk of Stone formation and Stone types are scarce. We investigated temporal changes in Stone composition, and demographic, serum and urinary parameters of kidney Stone formers from 1980 to 2015.Materials and Methods: We retrospectively analyzed the records of 1,516 patients diagnosed with either calcium or Uric Acid Stones at an initial visit to a university kidney Stone clinic from 1980 to 2015.Results: From 1980 to 2015, the proportion of Uric Acid Stones in all Stone formers increased from 7% to 14%. While age and body mass index increased with time in both Uric Acid and calcium Stone formers, Uric Acid Stone formers were consistently older and had a higher body mass index and lower urinary pH than calcium Stone formers. The proportion of females with Stones has increased over time but the increase in female gender was more prominent among ca...
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renal ammonium excretion after an acute Acid load blunted response in Uric Acid Stone formers but not in patients with type 2 diabetes
American Journal of Physiology-renal Physiology, 2013Co-Authors: Alexandru I Bobulescu, Orson W. Moe, Naim M. Maalouf, Beverley Adamshuet, Giovanna Capolongo, Tara R Rosenthal, Khashayar SakhaeeAbstract:Idiopathic Uric Acid nephrolithiasis is characterized by elevated urinary net Acid excretion and insufficient buffering by ammonium, resulting in excessively Acidic urine and titration of the relatively soluble urate anion to insoluble Uric Acid. Patients with type 2 diabetes have similar changes in urinary pH, net Acid excretion, and ammonium in 24-h urine collections at baseline, even after controlling for dietary factors, and are at increased risk for Uric Acid nephrolithiasis. However, not all patients with type 2 diabetes develop kidney Stones, suggesting that Uric Acid Stone formers may have additional urinary defects, perhaps not apparent at baseline. We performed a metabolic study of 14 patients with idiopathic Uric Acid nephrolithiasis, 13 patients with type 2 diabetes, and 8 healthy control subjects of similar body mass index. After equilibration on a fixed diet for 5 days, subjects were given a single oral Acid load (50 meq ammonium chloride), and urine was collected hourly for 4 h. Uric Acid Stone formers had a lower ammonium excretory response to acute Acid loading compared with diabetic and nondiabetic nonStone formers, suggesting that an ammonium excretory defect unique to Uric Acid Stone formers was unmasked by the Acid challenge. The Zucker diabetic fatty rat also did not show impaired urinary ammonium excretion in response to acute Acid challenge. A blunted renal ammonium excretory response to dietary Acid loads may contribute to the pathogenesis of idiopathic Uric Acid nephrolithiasis.
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the diurnal variation in urine Acidification differs between normal individuals and Uric Acid Stone formers
Kidney International, 2012Co-Authors: Mary Ann Cameron, Naim M. Maalouf, Beverley Adamshuet, John R Poindexter, Khashayar Sakhaee, Orson W. MoeAbstract:Many biological functions follow circadian rhythms driven by internal and external cues that synchronize and coordinate organ physiology to diurnal changes in the environment and behavior. Urinary Acid–base parameters follow diurnal patterns and it is thought these changes are due to periodic surges in gastric Acid secretion. Abnormal urine pH is a risk factor for specific types of nephrolithiasis and Uric Acid Stones result from excessively low urine pH. Here we placed 9 healthy volunteers and 10 Uric Acid Stone formers on fixed metabolic diets to study the diurnal pattern of urinary Acidification. All showed clear diurnal trends in urinary Acidification, but none of the patterns were affected by inhibitors of the gastric proton pump. Uric Acid Stone formers had similar patterns of change throughout the day but their urine pH was always lower compared to healthy volunteers. Uric Acid Stone formers excreted more Acid (normalized to Acid ingestion), with the excess excreted primarily as titratable Acid rather than ammonium. Urine base excretion was also lower in Uric Acid Stone formers (normalized to base ingestion), along with lower plasma bicarbonate concentrations during part of the day. Thus, increased net Acid presentation to the kidney and the preferential use of buffers, other than ammonium, result in much higher concentrations of undissociated Uric Acid throughout the day and consequently an increased risk of Uric Acid Stones.
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metabolic syndrome and Uric Acid nephrolithiasis
Seminars in Nephrology, 2008Co-Authors: Khashayar Sakhaee, Naim M. MaaloufAbstract:The metabolic syndrome describes a cluster of metabolic features that increases the risk for type 2 diabetes mellitus and cardiovascular disease. The prevalence of Uric Acid nephrolithiasis is higher among Stone-forming patients with features of the metabolic syndrome such as obesity and/or type 2 diabetes mellitus. The major determinant in the development of idiopathic Uric Acid Stones is an abnormally low urinary pH. The unduly urinary Acidity in Uric Acid Stone formers increasingly is recognized to be one of the features observed in the metabolic syndrome. Two major abnormalities have been implicated to explain this overly Acidic urine: (1) increased net Acid excretion, and (2) impaired buffering caused by defective urinary ammonium excretion, with the combination resulting in abnormally Acidic urine. New information is emerging linking these defects to changes in insulin signaling in the kidney. This article reviews the epidemiologic and metabolic studies linking Uric Acid nephrolithiasis with the metabolic syndrome, and examines the potential mechanisms underlying the unduly Acidic urine in these conditions.
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urine composition in type 2 diabetes predisposition to Uric Acid nephrolithiasis
Journal of The American Society of Nephrology, 2006Co-Authors: Mary Ann Cameron, Orson W. Moe, Naim M. Maalouf, Beverley Adamshuet, Khashayar SakhaeeAbstract:Type 2 diabetes is a risk factor for nephrolithiasis in general and has been associated with Uric Acid Stones in particular. The purpose of this study was to identify the metabolic features that place patients with type 2 diabetes at increased risk for Uric Acid nephrolithiasis. Three groups of individuals were recruited for this outpatient study: Patients who have type 2 diabetes and are not Stone formers ( n = 24), patients who do not have diabetes and are Uric Acid Stone formers (UASF; n = 8), and normal volunteers (NV; n = 59). Participants provided a fasting blood sample and a single 24-h urine collection for Stone risk analysis. Twenty-four-hour urine volume and total Uric Acid did not differ among the three groups. Patients with type 2 diabetes and UASF had lower 24-h urine pH than NV. Urine pH inversely correlated with both body weight and 24-h urine sulfate in all groups. Urine pH remained significantly lower in patients with type 2 diabetes and UASF than NV after adjustment for weight and urine sulfate ( P versus NV. With increasing urine sulfate, NV and patients with type 2 diabetes had a similar rise in urine ammonium, whereas in UASF, ammonium excretion remained unchanged. The main risk factor for Uric Acid nephrolithiasis in patients with type 2 diabetes is a low urine pH. Higher body mass and increased Acid intake can contribute to but cannot entirely account for the lower urine pH in patients with type 2 diabetes.
Orson W. Moe - One of the best experts on this subject based on the ideXlab platform.
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temporal changes in kidney Stone composition and in risk factors predisposing to Stone formation
The Journal of Urology, 2017Co-Authors: Beverley Adamshuet, Orson W. Moe, Naim M. Maalouf, John R Poindexter, Khashayar SakhaeeAbstract:Purpose: The prevalence of kidney Stones has increased globally in recent decades. However, studies investigating the association between temporal changes in the risk of Stone formation and Stone types are scarce. We investigated temporal changes in Stone composition, and demographic, serum and urinary parameters of kidney Stone formers from 1980 to 2015.Materials and Methods: We retrospectively analyzed the records of 1,516 patients diagnosed with either calcium or Uric Acid Stones at an initial visit to a university kidney Stone clinic from 1980 to 2015.Results: From 1980 to 2015, the proportion of Uric Acid Stones in all Stone formers increased from 7% to 14%. While age and body mass index increased with time in both Uric Acid and calcium Stone formers, Uric Acid Stone formers were consistently older and had a higher body mass index and lower urinary pH than calcium Stone formers. The proportion of females with Stones has increased over time but the increase in female gender was more prominent among ca...
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renal ammonium excretion after an acute Acid load blunted response in Uric Acid Stone formers but not in patients with type 2 diabetes
American Journal of Physiology-renal Physiology, 2013Co-Authors: Alexandru I Bobulescu, Orson W. Moe, Naim M. Maalouf, Beverley Adamshuet, Giovanna Capolongo, Tara R Rosenthal, Khashayar SakhaeeAbstract:Idiopathic Uric Acid nephrolithiasis is characterized by elevated urinary net Acid excretion and insufficient buffering by ammonium, resulting in excessively Acidic urine and titration of the relatively soluble urate anion to insoluble Uric Acid. Patients with type 2 diabetes have similar changes in urinary pH, net Acid excretion, and ammonium in 24-h urine collections at baseline, even after controlling for dietary factors, and are at increased risk for Uric Acid nephrolithiasis. However, not all patients with type 2 diabetes develop kidney Stones, suggesting that Uric Acid Stone formers may have additional urinary defects, perhaps not apparent at baseline. We performed a metabolic study of 14 patients with idiopathic Uric Acid nephrolithiasis, 13 patients with type 2 diabetes, and 8 healthy control subjects of similar body mass index. After equilibration on a fixed diet for 5 days, subjects were given a single oral Acid load (50 meq ammonium chloride), and urine was collected hourly for 4 h. Uric Acid Stone formers had a lower ammonium excretory response to acute Acid loading compared with diabetic and nondiabetic nonStone formers, suggesting that an ammonium excretory defect unique to Uric Acid Stone formers was unmasked by the Acid challenge. The Zucker diabetic fatty rat also did not show impaired urinary ammonium excretion in response to acute Acid challenge. A blunted renal ammonium excretory response to dietary Acid loads may contribute to the pathogenesis of idiopathic Uric Acid nephrolithiasis.
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the diurnal variation in urine Acidification differs between normal individuals and Uric Acid Stone formers
Kidney International, 2012Co-Authors: Mary Ann Cameron, Naim M. Maalouf, Beverley Adamshuet, John R Poindexter, Khashayar Sakhaee, Orson W. MoeAbstract:Many biological functions follow circadian rhythms driven by internal and external cues that synchronize and coordinate organ physiology to diurnal changes in the environment and behavior. Urinary Acid–base parameters follow diurnal patterns and it is thought these changes are due to periodic surges in gastric Acid secretion. Abnormal urine pH is a risk factor for specific types of nephrolithiasis and Uric Acid Stones result from excessively low urine pH. Here we placed 9 healthy volunteers and 10 Uric Acid Stone formers on fixed metabolic diets to study the diurnal pattern of urinary Acidification. All showed clear diurnal trends in urinary Acidification, but none of the patterns were affected by inhibitors of the gastric proton pump. Uric Acid Stone formers had similar patterns of change throughout the day but their urine pH was always lower compared to healthy volunteers. Uric Acid Stone formers excreted more Acid (normalized to Acid ingestion), with the excess excreted primarily as titratable Acid rather than ammonium. Urine base excretion was also lower in Uric Acid Stone formers (normalized to base ingestion), along with lower plasma bicarbonate concentrations during part of the day. Thus, increased net Acid presentation to the kidney and the preferential use of buffers, other than ammonium, result in much higher concentrations of undissociated Uric Acid throughout the day and consequently an increased risk of Uric Acid Stones.
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urine composition in type 2 diabetes predisposition to Uric Acid nephrolithiasis
Journal of The American Society of Nephrology, 2006Co-Authors: Mary Ann Cameron, Orson W. Moe, Naim M. Maalouf, Beverley Adamshuet, Khashayar SakhaeeAbstract:Type 2 diabetes is a risk factor for nephrolithiasis in general and has been associated with Uric Acid Stones in particular. The purpose of this study was to identify the metabolic features that place patients with type 2 diabetes at increased risk for Uric Acid nephrolithiasis. Three groups of individuals were recruited for this outpatient study: Patients who have type 2 diabetes and are not Stone formers ( n = 24), patients who do not have diabetes and are Uric Acid Stone formers (UASF; n = 8), and normal volunteers (NV; n = 59). Participants provided a fasting blood sample and a single 24-h urine collection for Stone risk analysis. Twenty-four-hour urine volume and total Uric Acid did not differ among the three groups. Patients with type 2 diabetes and UASF had lower 24-h urine pH than NV. Urine pH inversely correlated with both body weight and 24-h urine sulfate in all groups. Urine pH remained significantly lower in patients with type 2 diabetes and UASF than NV after adjustment for weight and urine sulfate ( P versus NV. With increasing urine sulfate, NV and patients with type 2 diabetes had a similar rise in urine ammonium, whereas in UASF, ammonium excretion remained unchanged. The main risk factor for Uric Acid nephrolithiasis in patients with type 2 diabetes is a low urine pH. Higher body mass and increased Acid intake can contribute to but cannot entirely account for the lower urine pH in patients with type 2 diabetes.
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the metabolic syndrome and Uric Acid nephrolithiasis novel features of renal manifestation of insulin resistance
Kidney International, 2004Co-Authors: Orson W. Moe, Nicola Abate, Manisha Chandalia, Alberto V Cabochan, Khashayar SakhaeeAbstract:The metabolic syndrome and Uric Acid nephrolithiasis: Novel features of renal manifestation of insulin resistance. Background Uric Acid nephrolithiasis primarily results from low urinary pH, which increases the concentration of the insoluble undissociated Uric Acid, causing formation of both Uric Acid and mixed Uric Acid/calcium oxalate Stones. These patients have recently been described as exhibiting features of insulin resistance. This study was designed to evaluate if insulin resistance is associated with excessively low urinary pH in overtly healthy volunteers (non-Stone formers) and if insulin resistance may explain the excessively low urinary pH in patients with Uric Acid nephrolithiasis. Methods Fifty-five healthy volunteers (non Stone-formers) with a large range of body mass index and 13 patients with recurrent Uric Acid nephrolithiasis underwent hyperinsulinemic euglycemic clamp, 24-hour urinary studies, and anthropometric measurements of adiposity. A subgroup of 35 non-Stone formers had 2-hour timed urinary collection before and during the hyperinsulinemic phase of the clamp studies. Results For the non-Stone former population, low insulin sensitivity measured as glucose disposal rate significantly correlated with low 24-hour urinary pH ( r = 0. 35; P = 0.01). In addition to the previously described Acidic urine pH and hypoUricosuria, patients with recurrent Uric Acid nephrolithiasis were found to be severely insulin resistant (glucose disposal rate: Uric Acid Stone-formers vs. normals; 4.1 ± 1.3 vs. 6.9 ± 2.1mg/min/kg of lean body mass, P = 0.008). Acute hyperinsulinemia was associated with higher urinary pH (6.1 ± 0.7 at baseline to 6.8 ± 0.7 during hyperinsulinemia; P P = 0.002) and urinary citrate excretion (48 ± 33mg/2hr at baseline and 113 ± 68mg/2hr P Conclusion We conclude that one renal manifestation of insulin resistance may be low urinary ammonium and pH. This defect can result in increased risk of Uric Acid precipitation despite normoUricosuria.
Beverley Adamshuet - One of the best experts on this subject based on the ideXlab platform.
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temporal changes in kidney Stone composition and in risk factors predisposing to Stone formation
The Journal of Urology, 2017Co-Authors: Beverley Adamshuet, Orson W. Moe, Naim M. Maalouf, John R Poindexter, Khashayar SakhaeeAbstract:Purpose: The prevalence of kidney Stones has increased globally in recent decades. However, studies investigating the association between temporal changes in the risk of Stone formation and Stone types are scarce. We investigated temporal changes in Stone composition, and demographic, serum and urinary parameters of kidney Stone formers from 1980 to 2015.Materials and Methods: We retrospectively analyzed the records of 1,516 patients diagnosed with either calcium or Uric Acid Stones at an initial visit to a university kidney Stone clinic from 1980 to 2015.Results: From 1980 to 2015, the proportion of Uric Acid Stones in all Stone formers increased from 7% to 14%. While age and body mass index increased with time in both Uric Acid and calcium Stone formers, Uric Acid Stone formers were consistently older and had a higher body mass index and lower urinary pH than calcium Stone formers. The proportion of females with Stones has increased over time but the increase in female gender was more prominent among ca...
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renal ammonium excretion after an acute Acid load blunted response in Uric Acid Stone formers but not in patients with type 2 diabetes
American Journal of Physiology-renal Physiology, 2013Co-Authors: Alexandru I Bobulescu, Orson W. Moe, Naim M. Maalouf, Beverley Adamshuet, Giovanna Capolongo, Tara R Rosenthal, Khashayar SakhaeeAbstract:Idiopathic Uric Acid nephrolithiasis is characterized by elevated urinary net Acid excretion and insufficient buffering by ammonium, resulting in excessively Acidic urine and titration of the relatively soluble urate anion to insoluble Uric Acid. Patients with type 2 diabetes have similar changes in urinary pH, net Acid excretion, and ammonium in 24-h urine collections at baseline, even after controlling for dietary factors, and are at increased risk for Uric Acid nephrolithiasis. However, not all patients with type 2 diabetes develop kidney Stones, suggesting that Uric Acid Stone formers may have additional urinary defects, perhaps not apparent at baseline. We performed a metabolic study of 14 patients with idiopathic Uric Acid nephrolithiasis, 13 patients with type 2 diabetes, and 8 healthy control subjects of similar body mass index. After equilibration on a fixed diet for 5 days, subjects were given a single oral Acid load (50 meq ammonium chloride), and urine was collected hourly for 4 h. Uric Acid Stone formers had a lower ammonium excretory response to acute Acid loading compared with diabetic and nondiabetic nonStone formers, suggesting that an ammonium excretory defect unique to Uric Acid Stone formers was unmasked by the Acid challenge. The Zucker diabetic fatty rat also did not show impaired urinary ammonium excretion in response to acute Acid challenge. A blunted renal ammonium excretory response to dietary Acid loads may contribute to the pathogenesis of idiopathic Uric Acid nephrolithiasis.
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the diurnal variation in urine Acidification differs between normal individuals and Uric Acid Stone formers
Kidney International, 2012Co-Authors: Mary Ann Cameron, Naim M. Maalouf, Beverley Adamshuet, John R Poindexter, Khashayar Sakhaee, Orson W. MoeAbstract:Many biological functions follow circadian rhythms driven by internal and external cues that synchronize and coordinate organ physiology to diurnal changes in the environment and behavior. Urinary Acid–base parameters follow diurnal patterns and it is thought these changes are due to periodic surges in gastric Acid secretion. Abnormal urine pH is a risk factor for specific types of nephrolithiasis and Uric Acid Stones result from excessively low urine pH. Here we placed 9 healthy volunteers and 10 Uric Acid Stone formers on fixed metabolic diets to study the diurnal pattern of urinary Acidification. All showed clear diurnal trends in urinary Acidification, but none of the patterns were affected by inhibitors of the gastric proton pump. Uric Acid Stone formers had similar patterns of change throughout the day but their urine pH was always lower compared to healthy volunteers. Uric Acid Stone formers excreted more Acid (normalized to Acid ingestion), with the excess excreted primarily as titratable Acid rather than ammonium. Urine base excretion was also lower in Uric Acid Stone formers (normalized to base ingestion), along with lower plasma bicarbonate concentrations during part of the day. Thus, increased net Acid presentation to the kidney and the preferential use of buffers, other than ammonium, result in much higher concentrations of undissociated Uric Acid throughout the day and consequently an increased risk of Uric Acid Stones.
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urine composition in type 2 diabetes predisposition to Uric Acid nephrolithiasis
Journal of The American Society of Nephrology, 2006Co-Authors: Mary Ann Cameron, Orson W. Moe, Naim M. Maalouf, Beverley Adamshuet, Khashayar SakhaeeAbstract:Type 2 diabetes is a risk factor for nephrolithiasis in general and has been associated with Uric Acid Stones in particular. The purpose of this study was to identify the metabolic features that place patients with type 2 diabetes at increased risk for Uric Acid nephrolithiasis. Three groups of individuals were recruited for this outpatient study: Patients who have type 2 diabetes and are not Stone formers ( n = 24), patients who do not have diabetes and are Uric Acid Stone formers (UASF; n = 8), and normal volunteers (NV; n = 59). Participants provided a fasting blood sample and a single 24-h urine collection for Stone risk analysis. Twenty-four-hour urine volume and total Uric Acid did not differ among the three groups. Patients with type 2 diabetes and UASF had lower 24-h urine pH than NV. Urine pH inversely correlated with both body weight and 24-h urine sulfate in all groups. Urine pH remained significantly lower in patients with type 2 diabetes and UASF than NV after adjustment for weight and urine sulfate ( P versus NV. With increasing urine sulfate, NV and patients with type 2 diabetes had a similar rise in urine ammonium, whereas in UASF, ammonium excretion remained unchanged. The main risk factor for Uric Acid nephrolithiasis in patients with type 2 diabetes is a low urine pH. Higher body mass and increased Acid intake can contribute to but cannot entirely account for the lower urine pH in patients with type 2 diabetes.
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pathophysiologic basis for normoUricosUric Uric Acid nephrolithiasis
Kidney International, 2002Co-Authors: Beverley Adamshuet, Orson W. Moe, Charles Y C PakAbstract:Pathophysiologic basis for normoUricosUric Uric Acid nephrolithiasis. Background: Low urinary pH is the commonest and by far the most important factor in Uric Acid nephrolithiasis but the reason(s) for this defect is (are) unknown. Patients with Uric Acid nephrolithaisis have normal Acid-base parameters according conventional clinical tests. Methods: We studied steady-state plasma and urinary parameters of Acid-base balance in subjects with normoUricosUric pure Uric Acid Stones. We also tested the ability of these subjects to excrete ammonium in response to an acute Acid load. We compared these parameters in patients with pure Uric Acid Stones to patients with mixed Uric Acid/calcium oxalate Stones, pure calcium Stones, and normal volunteers. Results: Pure Uric Acid Stone formers have a much higher incidence of either diabetes or glucose intolerance. After equilibration to a control diet, patients with Uric Acid Stones have lower urinary pH and they excrete less of their Acid as ammonium. This is compensated by higher titratable Acidity and hypocitraturia. Despite their low baseline urinary pH, Uric Acid Stone formers further Acidify their urine after an Acid load because of a severely impaired ammonia excretory response. Their characteristics are significantly different from normal volunteers and pure calcium Stone formers. Patients with mixed Uric Acid/calcium Stones exhibit intermediate characteristics. Conclusion: We propose that certain patients with normoUricosUric Uric Acid nephrolithiasis have a renal Acidification disease. The primary defect lies in renal ammonium excretion, which may be linked to the insulin-resistant state. Although net Acid excretion is maintained at the expense of increased titratable Acidity and to some degree hypocitraturia, the compromise is Acid urine pH and may result in Uric Acid nephrolithiasis.
Mary Ann Cameron - One of the best experts on this subject based on the ideXlab platform.
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the diurnal variation in urine Acidification differs between normal individuals and Uric Acid Stone formers
Kidney International, 2012Co-Authors: Mary Ann Cameron, Naim M. Maalouf, Beverley Adamshuet, John R Poindexter, Khashayar Sakhaee, Orson W. MoeAbstract:Many biological functions follow circadian rhythms driven by internal and external cues that synchronize and coordinate organ physiology to diurnal changes in the environment and behavior. Urinary Acid–base parameters follow diurnal patterns and it is thought these changes are due to periodic surges in gastric Acid secretion. Abnormal urine pH is a risk factor for specific types of nephrolithiasis and Uric Acid Stones result from excessively low urine pH. Here we placed 9 healthy volunteers and 10 Uric Acid Stone formers on fixed metabolic diets to study the diurnal pattern of urinary Acidification. All showed clear diurnal trends in urinary Acidification, but none of the patterns were affected by inhibitors of the gastric proton pump. Uric Acid Stone formers had similar patterns of change throughout the day but their urine pH was always lower compared to healthy volunteers. Uric Acid Stone formers excreted more Acid (normalized to Acid ingestion), with the excess excreted primarily as titratable Acid rather than ammonium. Urine base excretion was also lower in Uric Acid Stone formers (normalized to base ingestion), along with lower plasma bicarbonate concentrations during part of the day. Thus, increased net Acid presentation to the kidney and the preferential use of buffers, other than ammonium, result in much higher concentrations of undissociated Uric Acid throughout the day and consequently an increased risk of Uric Acid Stones.
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urine composition in type 2 diabetes predisposition to Uric Acid nephrolithiasis
Journal of The American Society of Nephrology, 2006Co-Authors: Mary Ann Cameron, Orson W. Moe, Naim M. Maalouf, Beverley Adamshuet, Khashayar SakhaeeAbstract:Type 2 diabetes is a risk factor for nephrolithiasis in general and has been associated with Uric Acid Stones in particular. The purpose of this study was to identify the metabolic features that place patients with type 2 diabetes at increased risk for Uric Acid nephrolithiasis. Three groups of individuals were recruited for this outpatient study: Patients who have type 2 diabetes and are not Stone formers ( n = 24), patients who do not have diabetes and are Uric Acid Stone formers (UASF; n = 8), and normal volunteers (NV; n = 59). Participants provided a fasting blood sample and a single 24-h urine collection for Stone risk analysis. Twenty-four-hour urine volume and total Uric Acid did not differ among the three groups. Patients with type 2 diabetes and UASF had lower 24-h urine pH than NV. Urine pH inversely correlated with both body weight and 24-h urine sulfate in all groups. Urine pH remained significantly lower in patients with type 2 diabetes and UASF than NV after adjustment for weight and urine sulfate ( P versus NV. With increasing urine sulfate, NV and patients with type 2 diabetes had a similar rise in urine ammonium, whereas in UASF, ammonium excretion remained unchanged. The main risk factor for Uric Acid nephrolithiasis in patients with type 2 diabetes is a low urine pH. Higher body mass and increased Acid intake can contribute to but cannot entirely account for the lower urine pH in patients with type 2 diabetes.
