Net Acid Excretion and Urinary Organic Anions in Idiopathic Uric Acid Nephrolithiasis

Ion A Bobulescu, Sun K. Park, L. H.Richie Xu, Francisco Blanco, John Poindexter, Beverley A Huet, Taylor L. Davidson, Khashayar Sakhaee, Naim M Maalouf, Orson W Moe

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

BACKGROUND AND OBJECTIVES: Idiopathic uric acid nephrolithiasis, which is closely associated with obesity and the metabolic syndrome, is increasing in prevalence. Unduly acidic urine pH, the quintessential pathophysiologic feature of this disease, is in part explained by inadequate excretion of the principal urinary buffer ammonium. The role of net acid excretion in the pathogenesis of uric acid nephrolithiasis is incompletely understood. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We compared acid-base parameters of patients with idiopathic uric acid nephrolithiasis with matched control subjects under controlled diets in an inpatient metabolic unit. Measurements included fasting blood and 24-hour urine chemistries and 24-hour urine metabolomic analysis. Comparisons between groups included analysis of covariance models controlling for urine pH or body mass index. RESULTS: Subjects with idiopathic uric acid nephrolithiasis had lower urine pH (5.5 versus 5.9; P<0.001) and higher net acid excretion (60 versus 43 mEq/24 h; P<0.001), with the excess H+ carried by nonammonium buffers. In all subjects, there was a positive relationship of net acid excretion with higher body mass index in spite of strictly controlled equivalent dietary acid intake. This relationship was most evident among control subjects (r=0.36; P=0.03). It was attenuated in patients with idiopathic uric acid nephrolithiasis whose net acid excretion remained fixedly high and ammonium excretion remained low relative to net acid excretion, resulting in low urine pH over a wide body mass index range. Urinary metabolomics was performed to attempt to identify excess organic acids presented to the kidney in idiopathic uric acid nephrolithiasis. Among the tricarboxylic acid cycle intermediates and amino acid and lipid metabolites analyzed, 26 organic anions with acid dissociation constants values in the range of urine pH showed greater protonation. However, protons carried by the identified organic acids did not entirely account for the higher titratable acidity seen in idiopathic uric acid nephrolithiasis. CONCLUSIONS: Higher acid load to the kidney, resulting in higher urinary net acid excretion, is an important factor in the pathogenesis of idiopathic uric acid nephrolithiasis.

Original languageEnglish (US)
Pages (from-to)411-420
Number of pages10
JournalClinical journal of the American Society of Nephrology : CJASN
Volume14
Issue number3
DOIs
StatePublished - Mar 7 2019

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Nephrolithiasis
Uric Acid
Anions
Acids
Urine
Body Mass Index
Metabolomics
Ammonium Compounds
Buffers
Kidney
Citric Acid Cycle
Protons
Inpatients
Fasting
Obesity

Keywords

  • Amino Acids
  • Ammonium Compounds
  • Anions
  • Body Mass Index
  • Buffers
  • Citric Acid Cycle
  • Fasting
  • Inpatients
  • kidney
  • Kidney Calculi
  • kidney stones
  • lipids
  • metabolic study
  • Metabolic Syndrome
  • Metabolomics
  • obesity
  • Prevalence
  • Protons
  • uric acid
  • urine metabolomics

ASJC Scopus subject areas

  • Epidemiology
  • Critical Care and Intensive Care Medicine
  • Nephrology
  • Transplantation

Cite this

Net Acid Excretion and Urinary Organic Anions in Idiopathic Uric Acid Nephrolithiasis. / Bobulescu, Ion A; Park, Sun K.; Xu, L. H.Richie; Blanco, Francisco; Poindexter, John; Huet, Beverley A; Davidson, Taylor L.; Sakhaee, Khashayar; Maalouf, Naim M; Moe, Orson W.

In: Clinical journal of the American Society of Nephrology : CJASN, Vol. 14, No. 3, 07.03.2019, p. 411-420.

Research output: Contribution to journalArticle

Bobulescu, Ion A ; Park, Sun K. ; Xu, L. H.Richie ; Blanco, Francisco ; Poindexter, John ; Huet, Beverley A ; Davidson, Taylor L. ; Sakhaee, Khashayar ; Maalouf, Naim M ; Moe, Orson W. / Net Acid Excretion and Urinary Organic Anions in Idiopathic Uric Acid Nephrolithiasis. In: Clinical journal of the American Society of Nephrology : CJASN. 2019 ; Vol. 14, No. 3. pp. 411-420.
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AU - Park, Sun K.

AU - Xu, L. H.Richie

AU - Blanco, Francisco

AU - Poindexter, John

AU - Huet, Beverley A

AU - Davidson, Taylor L.

AU - Sakhaee, Khashayar

AU - Maalouf, Naim M

AU - Moe, Orson W

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N2 - BACKGROUND AND OBJECTIVES: Idiopathic uric acid nephrolithiasis, which is closely associated with obesity and the metabolic syndrome, is increasing in prevalence. Unduly acidic urine pH, the quintessential pathophysiologic feature of this disease, is in part explained by inadequate excretion of the principal urinary buffer ammonium. The role of net acid excretion in the pathogenesis of uric acid nephrolithiasis is incompletely understood. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We compared acid-base parameters of patients with idiopathic uric acid nephrolithiasis with matched control subjects under controlled diets in an inpatient metabolic unit. Measurements included fasting blood and 24-hour urine chemistries and 24-hour urine metabolomic analysis. Comparisons between groups included analysis of covariance models controlling for urine pH or body mass index. RESULTS: Subjects with idiopathic uric acid nephrolithiasis had lower urine pH (5.5 versus 5.9; P<0.001) and higher net acid excretion (60 versus 43 mEq/24 h; P<0.001), with the excess H+ carried by nonammonium buffers. In all subjects, there was a positive relationship of net acid excretion with higher body mass index in spite of strictly controlled equivalent dietary acid intake. This relationship was most evident among control subjects (r=0.36; P=0.03). It was attenuated in patients with idiopathic uric acid nephrolithiasis whose net acid excretion remained fixedly high and ammonium excretion remained low relative to net acid excretion, resulting in low urine pH over a wide body mass index range. Urinary metabolomics was performed to attempt to identify excess organic acids presented to the kidney in idiopathic uric acid nephrolithiasis. Among the tricarboxylic acid cycle intermediates and amino acid and lipid metabolites analyzed, 26 organic anions with acid dissociation constants values in the range of urine pH showed greater protonation. However, protons carried by the identified organic acids did not entirely account for the higher titratable acidity seen in idiopathic uric acid nephrolithiasis. CONCLUSIONS: Higher acid load to the kidney, resulting in higher urinary net acid excretion, is an important factor in the pathogenesis of idiopathic uric acid nephrolithiasis.

AB - BACKGROUND AND OBJECTIVES: Idiopathic uric acid nephrolithiasis, which is closely associated with obesity and the metabolic syndrome, is increasing in prevalence. Unduly acidic urine pH, the quintessential pathophysiologic feature of this disease, is in part explained by inadequate excretion of the principal urinary buffer ammonium. The role of net acid excretion in the pathogenesis of uric acid nephrolithiasis is incompletely understood. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We compared acid-base parameters of patients with idiopathic uric acid nephrolithiasis with matched control subjects under controlled diets in an inpatient metabolic unit. Measurements included fasting blood and 24-hour urine chemistries and 24-hour urine metabolomic analysis. Comparisons between groups included analysis of covariance models controlling for urine pH or body mass index. RESULTS: Subjects with idiopathic uric acid nephrolithiasis had lower urine pH (5.5 versus 5.9; P<0.001) and higher net acid excretion (60 versus 43 mEq/24 h; P<0.001), with the excess H+ carried by nonammonium buffers. In all subjects, there was a positive relationship of net acid excretion with higher body mass index in spite of strictly controlled equivalent dietary acid intake. This relationship was most evident among control subjects (r=0.36; P=0.03). It was attenuated in patients with idiopathic uric acid nephrolithiasis whose net acid excretion remained fixedly high and ammonium excretion remained low relative to net acid excretion, resulting in low urine pH over a wide body mass index range. Urinary metabolomics was performed to attempt to identify excess organic acids presented to the kidney in idiopathic uric acid nephrolithiasis. Among the tricarboxylic acid cycle intermediates and amino acid and lipid metabolites analyzed, 26 organic anions with acid dissociation constants values in the range of urine pH showed greater protonation. However, protons carried by the identified organic acids did not entirely account for the higher titratable acidity seen in idiopathic uric acid nephrolithiasis. CONCLUSIONS: Higher acid load to the kidney, resulting in higher urinary net acid excretion, is an important factor in the pathogenesis of idiopathic uric acid nephrolithiasis.

KW - Amino Acids

KW - Ammonium Compounds

KW - Anions

KW - Body Mass Index

KW - Buffers

KW - Citric Acid Cycle

KW - Fasting

KW - Inpatients

KW - kidney

KW - Kidney Calculi

KW - kidney stones

KW - lipids

KW - metabolic study

KW - Metabolic Syndrome

KW - Metabolomics

KW - obesity

KW - Prevalence

KW - Protons

KW - uric acid

KW - urine metabolomics

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