Acid and mineral balances and bone in familial proximal renal tubular acidosis

Lemann, Jacob; Adams, Nancy D.; Wilz, Donald R.; Brenes, Luis Guillermo

doi:10.1046/j.1523-1755.2000.00282.x

Cited by 70 publications

(47 citation statements)

References 52 publications

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“…Net fixed acid production was normal and appropriate for their body weights, averaging 0.9 and 10.2 mEq/kg per d. Acid balance was near zero, at 1.9 Ϯ 2.3 and Ϫ2.2 Ϯ 2.2 mEq/d. Urine calcium excretion was normal (29). Associated clinical findings were limited growth retardation and reduced bone densities.…”

Section: Autosomal Dominant Prtamentioning

confidence: 97%

Unraveling the Molecular Pathogenesis of Isolated Proximal Renal Tubular Acidosis

Igarashi¹,

Sekine²,

Inatomi³

et al. 2002

Journal of the American Society of Nephrology

117

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Section: Autosomal Dominant Prtamentioning

confidence: 97%

Unraveling the Molecular Pathogenesis of Isolated Proximal Renal Tubular Acidosis

Igarashi¹,

Sekine²,

Inatomi³

et al. 2002

Journal of the American Society of Nephrology

117

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“…Decreased proximal tubule bicarbonate absorption causes proximal renal tubular acidosis (1)(2)(3)(4). Familial autosomal recessive proximal renal tubular acidosis results from mutations in the electrogenic sodium bicarbonate cotransporter NBCe1-A encoded by the SLC4A4 gene (5,6).…”

Section: T442cmentioning

confidence: 99%

Oligomeric Structure and Minimal Functional Unit of the Electrogenic Sodium Bicarbonate Cotransporter NBCe1-A

Kao

Sassani

Azimov

et al. 2008

Journal of Biological Chemistry

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The electrogenic sodium bicarbonate cotransporter NBCe1-A mediates the basolateral absorption of sodium and bicarbonate in the proximal tubule. In this study the oligomeric state and minimal functional unit of NBCe1-A were investigated. Wildtype (wt) NBCe1-A isolated from mouse kidney or heterologously expressed in HEK293 cells was predominantly in a dimeric state as was shown using fluorescence energy transfer, pulldown, immunoprecipitation, cross-linking experiments, and nondenaturing perfluorooctanoate-PAGE. NBCe1-A monomers were found to be covalently linked by S-S bonds. When each of the 15 native cysteine residues were individually removed on a wt-NBCe1-A backbone, dimerization of the cotransporter was not affected. In experiments involving multiple native cysteine residue removal, both Cys 630 and Cys 642 in extracellular loop 3 were shown to mediate S-S bond formation between NBCe1-A monomers. When native NBCe1-A cysteine residues were individually reintroduced into a cysteineless NBCe1-A mutant backbone, the finding that a Cys 992 construct that lacked S-S bonds functioned normally indicated that stable covalent linkage of NBCe1-A monomers was not a necessary requirement for functional activity of the cotransporter. Studies using concatameric constructs of wt-NBCe1-A, whose activity is resistant to methanesulfonate reagents, and an NBCe1-A T442C mutant, whose activity is completely inhibited by methanesulfonate reagents, confirmed that NBCe1-A monomers are functional. Our results demonstrate that wt-NBCe1-A is predominantly a homodimer, dependent on S-S bond formation that is composed of functionally active monomers.

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“…Patients with isolated familial proximal RTA have been observed to exhibit normal rates of both acid production and net acid excretion and thus are in acid balance. Moreover, they also exhibit normal rates of urinary and fecal Ca 2ϩ excretion relative to their Ca 2ϩ intakes and are in Ca 2ϩ balance (32). Thus it appears that both positive acid balances and increased Ca 2ϩ excretion rates are necessary for the development of negative Ca 2ϩ balances in the presence of metabolic acidosis.…”

Section: Evaluation Of the Acidosis Of Chronic Azotemic Kidney Diseasmentioning

confidence: 99%

Bone buffering of acid and base in humans

Lemann

Bushinsky²,

Hamm³

2003

American Journal of Physiology-Renal Physiology

Self Cite

222

197

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The sources and rates of metabolic acid production in relation to renal net acid excretion and thus acid balance in humans have remained controversial. The techniques and possible errors in these measurements are reviewed, as is the relationship of charge balance to acid balance. The results demonstrate that when acid production is experimentally increased among healthy subjects, renal net acid excretion does not increase as much as acid production so that acid balances become positive. These positive imbalances are accompanied by equivalently negative charge balances that are the result of bone buffering of retained H+ and loss of bone Ca2+ into the urine. The data also demonstrate that when acid production is experimentally reduced during the administration of KHCO3, renal net acid excretion does not decrease as much as the decrease in acid production so that acid balances become negative, or, in opposite terms, there are equivalently positive [Formula: see text] balances. Equivalently positive K+ and Ca2+ balances, and thus positive charge balances, accompany these negative acid imbalances. Similarly, positive Na+ balances, and thus positive charge balances, accompany these negative acid balances during the administration of NaHCO3. These charge balances are likely the result of the adsorption of [Formula: see text] onto the crystal surfaces of bone mineral. There do not appear to be significant errors in the measurements.

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Acid and mineral balances and bone in familial proximal renal tubular acidosis

Cited by 70 publications

References 52 publications

Unraveling the Molecular Pathogenesis of Isolated Proximal Renal Tubular Acidosis

Unraveling the Molecular Pathogenesis of Isolated Proximal Renal Tubular Acidosis

Oligomeric Structure and Minimal Functional Unit of the Electrogenic Sodium Bicarbonate Cotransporter NBCe1-A

Bone buffering of acid and base in humans

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