The Influence of Urinary Ionic Strength on Phosphate Pk2′ and the Determination of Titratable Acid*

Schwartz, William B.; Bank, Norman; Cutler, Robert

doi:10.1172/jci103808

Cited by 40 publications

(25 citation statements)

References 6 publications

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“…Urinary ammonium was analyzed by ion chromatography. 38 Titratable acidity in urine was calculated from urinary PO4 excretion, urine pH, and blood pH, with the pK' of PO4 corrected for ionic strength by the method of Schwartz et al 39 Urinary NAE was calculated as ammonium plus titratable acid minus bicarbonate excretion. We measured 1,25(OH) 2 Laboratories, Inc., Minneapolis, MN).…”

Section: Discussionmentioning

confidence: 99%

The Human Response to Acute Enteral and Parenteral Phosphate Loads

Scanni

vonRotz

Jehle

et al. 2014

Journal of the American Society of Nephrology

107

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The human response to acute phosphate (PO4) loading is poorly characterized, and it is unknown whether an intestinal phosphate sensor mechanism exists. Here, we characterized the human mineral and endocrine response to parenteral and duodenal acute phosphate loads. Healthy human participants underwent 36 hours of intravenous (IV; 1.15 [low dose] and 2.30 [high dose] mmol of PO4/kg per 24 hours) or duodenal (1.53 mmol of PO4/kg per 24 hours) neutral sodium PO4 loading. Control experiments used equimolar NaCl loads. Maximum PO4 urinary excretory responses occurred between 12 and 24 hours and were similar for low-dose IV and duodenal infusion. Hyperphosphatemic responses were also temporally and quantitatively similar for low-dose IV and duodenal PO4 infusion. Fractional renal PO4 clearance increased approximately 6-fold (high-dose IV group) and 4-fold (low-dose IV and duodenal groups), and significant reductions in plasma PO4 concentrations relative to peak values occurred by 36 hours, despite persistent PO4 loading. After cessation of loading, frank hypophosphatemia occurred. The earliest phosphaturic response occurred after plasma PO4 and parathyroid hormone concentrations increased. Plasma fibroblast growth factor-23 concentration increased after the onset of phosphaturia, followed by a decrease in plasma 1,25(OH)2D levels; a-Klotho levels did not change. Contrary to results in rodents, we found no evidence for intestinal-specific phosphaturic control mechanisms in humans. Complete urinary phosphate recovery in the IV loading groups provides evidence against any important extrarenal response to acute PO4 loads. Plasma phosphate (PO4) concentration is regulated within narrow limits and is the result of intestinal absorption, influx into and efflux from bone, renal excretion, and modest intestinal secretion. 1 Rapid changes in transcellular distribution are effected primarily by systemic acid-base equilibrium and hormones such as insulin and catecholamines. 2 1,25(OH) 2 D stimulates intestinal PO4 absorption, 4 while parathyroid hormone (PTH) and osteocytederived fibroblast growth factor-23 (FGF-23) are the best-characterized phosphaturic factors. Both inhibit proximal tubular sodium-dependent PO4 reabsorption (via Na/PO4 cotransport, NaPi2a and NaPi2c). 5,6 In addition, a-Klotho is a renal transmembrane and secreted protein that functions as an FGF-23 coreceptor and is phosphaturic independently of However, the relative roles of other phosphaturic agents, such as secreted frizzled related protein (sFRP-4), matrix extracellular phosphoglycoprotein, and FGF-8 are not yet defined in humans.1,25(OH) 2 D, PTH, and FGF-23 regulate PO4 metabolism within a complex system of positive and negative feedback mechanisms (for review, see Bergwitz and Jüppner 8 ). Increases in plasma PO4 concentration stimulate PTH secretion, while proximal tubule 1a-hydroxylase and, therefore,

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Section: Discussionmentioning

confidence: 99%

The Human Response to Acute Enteral and Parenteral Phosphate Loads

Scanni

vonRotz

Jehle

et al. 2014

Journal of the American Society of Nephrology

107

View full text Add to dashboard Cite

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“…PTH was then administered i.v., as in the preceding experiments, and two additional timed urine collections were obtained. Each urine sample was analyzed for pH, CO2 content, ammonium (25), and titratable acid (26). The values in individual animals were averaged before and after PTH administration and analyzed statistically by paired t test.…”

Section: Methodsmentioning

confidence: 99%

A micropuncture study of the effect of parathyroid hormone on renal bicarbonate reabsorption.

Bank¹,

Aynediian²

1976

J. Clin. Invest.

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A B S T R A C T Renal micropuncture and clearance experiments were carried out in rats to study the effect of parathyroid hormone (PTH) on renal tubular HCOreabsorption. The rats were studied during an initial period of parathyroid deficiency (acute thyroidparathyroidectomy, TPTX) and during infusion of large amounts of bovine PTH. Under normal acid-base conditions, PTH administration to TPTX rats caused a significant rise in proximal tubular fluid HCO3 concentration (TFHco-), a decrease in fluid reabsorption, and a fall in proximal HCO-reabsorption from 94.0 to 88.2% (P < 0.01). In control experiments with mannitol infusion, a comparable reduction in proximal fluid reabsorption occurred without any significant effect on intraluminal HCO-concentration. During acute intravenous HCO-loading, PTH inhibited proximal HCO-reabsorption. However, no change in whole kidney HCO-reabsorption was observed in these experiments or in the animals studied under normal acid-base conditions. The findings are consistent with the view that PTH inhibits proximal tubular HCO-3 reabsorption with normal or high filtered loads of HCO-, but distal segments of the nephron are able to reabsorb the excess delivered from the proximal tubule. Measurements of urinary ammonium and titratable acid indicate that net acid excretion (NH+ + TA -HCO) increases significantly after PTH administration. These results do not provide support for the view that PTH excess causes metabolic acidosis by reducing renal acid excretion.

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“…It has been proposed that excretion of αKG and other organic anions (e.g., citrate) in the urine represents the loss of "potential HCO 3 -," which provides the advantage of minimizing bicarbonaturia under alkali load (6). The latter is important because it allows the excretion of base at a lower urinary pH, thereby diminishing the risk of nephrolithiasis due to the formation of calciumphosphate precipitates [αKG: pKa 1 (1.9), pKa 2 (4.4); bicarbonate: pKa 1 (6.1); HPO 4 2-: pKa 2 (6.7-6.8)] in the urine (5,7). Collectively, these results demonstrated that acid-base status is a major factor determining blood levels of αKG and the rate of αKG excretion into urine.…”

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confidence: 99%