ORCID Profile
0000-0003-0434-3855
Current Organisation
Murdoch University
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Publisher: Public Library of Science (PLoS)
Date: 08-2022
DOI: 10.1371/JOURNAL.PONE.0272380
Abstract: Secondary hyperparathyroidism (SHPT) complicates advanced chronic kidney disease (CKD) and causes skeletal and other morbidity. In animal models of CKD, SHPT was prevented and reversed by reduction of dietary phosphate in proportion to GFR, but the phenomena underlying these observations are not understood. The tradeoff-in-the-nephron hypothesis states that as GFR falls, the phosphate concentration in the distal convoluted tubule ([P] DCT ]) rises, reduces the ionized calcium concentration in that segment ([Ca ++ ] DCT ), and thereby induces increased secretion of parathyroid hormone (PTH) to maintain normal calcium reabsorption. In patients with CKD, we previously documented correlations between [PTH] and phosphate excreted per volume of filtrate (E P /C cr ), a surrogate for [P] DCT . In the present investigation, we estimated [P] DCT from physiologic considerations and measurements of phosphaturia, and sought evidence for a specific chemical phenomenon by which increased [P] DCT could lower [Ca ++ ] DCT and raise [PTH]. We studied 28 patients (“CKD”) with eGFR of 14–49 mL/min/1.73m 2 (mean 29.9 ± 9.5) and 27 controls (“CTRL”) with eGFR 60 mL/min/1.73m 2 (mean 86.2 ± 10.2). In each subject, total [Ca] DCT and [P] DCT were deduced from relevant laboratory data. The Joint Expert Speciation System (JESS) was used to calculate [Ca ++ ] DCT and concentrations of related chemical species under the assumption that a solid phase of amorphous calcium phosphate (Ca 3 (PO 4 ) 2 (am., s.)) could precipitate. Regressions of [PTH] on eGFR, [P] DCT , and [Ca ++ ] DCT were then examined. At filtrate pH of 6.8 and 7.0, [P] DCT was found to be the sole determinant of [Ca ++ ] DCT , and precipitation of Ca 3 (PO 4 ) 2 (am., s.) appeared to mediate this result. At pH 6.6, total [Ca] DCT was the principal determinant of [Ca ++ ] DCT , [P] DCT was a minor determinant, and precipitation of Ca 3 (PO 4 ) 2 (am., s.) was predicted in no CKD and five CTRL. In CKD, at all three pH values, [PTH] varied directly with [P] DCT and inversely with [Ca ++ ] DCT , and a reduced [Ca ++ ] DCT was identified at which [PTH] rose unequivocally. Relationships of [PTH] to [Ca ++ ] DCT and to eGFR resembled each other closely. As [P] DCT increases, chemical speciation calculations predict reduction of [Ca ++ ] DCT through precipitation of Ca 3 (PO 4 ) 2 (am., s.). [PTH] appears to rise unequivocally if [Ca ++ ] DCT falls sufficiently. These results support the tradeoff-in-the-nephron hypothesis, and they explain why proportional phosphate restriction prevented and reversed SHPT in experimental CKD. Whether equally stringent treatment can be as efficacious in humans warrants investigation.
Publisher: Springer Science and Business Media LLC
Date: 12-04-2023
DOI: 10.1007/S10953-023-01259-2
Abstract: Critically assessed data regarding Sn(IV) dioxides and hydroxy complexes have recently been challenged. Differences as large as nine orders of magnitude occur in certain of the published solubility products and other equilibrium constants, despite supposedly being derived from the same ‘reliable’ measurements. We show how these differing conclusions depend on the assignments of uncertainty in the respective experimental observations and that the ergence is due to error propagation in identifiable thermodynamic analyses. The use of Sn 4+ as a ‘basis’/‘master’ species in thermodynamic modelling is deprecated. Automatic methods which enable the necessary calculations to be properly evaluated, as well as easily repeated, help uncover such mistakes. The results from the comprehensive NEA review are substantially confirmed.
Publisher: Springer Science and Business Media LLC
Date: 28-06-2023
DOI: 10.1007/S10953-023-01302-2
Abstract: The JESS (Joint Expert Speciation System) Thermodynamic Database (v8.9) is now available as a set of freely available PDF files. This reaction database contains about 280,000 thermodynamic parameters (equilibrium constants, enthalpies, etc.) as published in the literature for over 80,000 chemical reactions. It is grounded in the tradition of the Stability Constants Special Publications (by the Chemical Society) but it has become much more extensive and it includes some quantitative indication of parameter reliability based mainly on intra- and extra-reaction consistency.
Publisher: Elsevier BV
Date: 08-2023
Publisher: American Chemical Society (ACS)
Date: 22-03-2017
Publisher: American Chemical Society (ACS)
Date: 12-06-2019
Publisher: American Chemical Society (ACS)
Date: 30-12-2021
Publisher: Royal Society of Chemistry (RSC)
Date: 2018
DOI: 10.1039/C7NJ03597G
Abstract: A large, open-access, sustainable database of relative Gibbs energies is developed for over 50 000 aqueous chemical species, including many metal–ligand complexes.
Publisher: American Chemical Society (ACS)
Date: 08-02-2018
Publisher: Royal Society of Chemistry (RSC)
Date: 2018
DOI: 10.1039/C8CC00187A
Abstract: S 2− (aq) is a widespread but deleterious artefact which needs to be eliminated by the chemical community.
Publisher: Springer Science and Business Media LLC
Date: 26-11-2019
DOI: 10.1007/S00240-019-01172-8
Abstract: Although most kidney stones are found in the calyx, they are usually initiated upstream in the nephron by precipitation there of certain incipient mineral phases. The risk of kidney stone formation can thus be indicated by changes in the degree of saturation of these minerals in the nephron fluid. To this end, relevant concentration profiles in the fluid along the nephron have been calculated by starting with specified urine compositions and imposing constraints from the corresponding, much less variable, blood compositions. A model for supersaturation within ten sections of both long and short nephrons has accordingly been developed based on this 'reverse engineering' of the necessary substance concentrations coupled with chemical speciation distributions calculated by our Joint Expert Speciation System (JESS). This allows the likelihood of precipitation to be assessed based on Ostwald's 'Rule of Stages'. Differences between normal and stone-former profiles have been used to identify sections in the nephron where conditions seem most likely to induce heterogeneous nucleation.
Publisher: Springer Science and Business Media LLC
Date: 07-10-2023
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Peter May.