The Possible Roles of Inhibitors, Promoters, and Macromolecules in the Formation of Calcium Kidney Stones

Ryall, Rosemary L.

doi:10.1007/978-1-84800-362-0_4

Cited by 13 publications

(33 citation statements)

References 329 publications

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“…Pyrophosphate is also considered to be a leading inhibitor of CaOx growth (6,20,32). Meyer and Smith (20) provide valuable data with regard to direct inhibition of CaOx precipitation by pyrophosphates in terms of a modified/adjusted reaction rate constant, K g , as a function of the pyrophosphate concentrations.…”

Section: Effect Of Pyrophosphate Inhibitionmentioning

confidence: 99%

“…The list of substances that have been examined for their inhibition potential is numerous and includes, but is not limited to low-molecular-weight substances such as citrate, magnesium, pyrophosphate, and phytic acid; macromolecules like glycosaminoglycans; and proteins such as Tamm-Horsfall glycoprotein (THG) and osteopontin. Unfortunately, despite the vast amount of data collected with regard to these and other inhibitors, results have not been always consistent or conclusive (32).…”

mentioning

confidence: 96%

“…The progression from crystal nucleation and growth to a clinical colic situation is not yet well understood, but it is thought to occur by either free-or fixed-particle mechanisms (13,32). Recent studies by Kim et al (14) and Evan et al (7) using advanced endoscopic imaging and comprehensive physiological biopsies suggest three possible free/fixed pathways to stone formation: 1) nucleation and growth on the Randall plaque deposits in the papillae; 2) growth after adherence to a possibly injured section of collecting or Bellini ducts; and 3) homogeneous nucleation and growth in the urine during passage through the nephron.…”

mentioning

confidence: 99%

“…The idea that nephrolithiasis can be prevented by correcting the inhibitive deficiencies of the stone-former's urine through dietary or pharmacological means resulted in an intense research effort to identify natural and synthetic constituents that can act as effective inhibitors to CaOx stone formation (1,2,6,9,20,21,25,32). The list of substances that have been examined for their inhibition potential is numerous and includes, but is not limited to low-molecular-weight substances such as citrate, magnesium, pyrophosphate, and phytic acid; macromolecules like glycosaminoglycans; and proteins such as Tamm-Horsfall glycoprotein (THG) and osteopontin.…”

mentioning

confidence: 99%

“…The search for a natural dietary inhibitor for CaOx stone formation has also extended to the National Aeronautics and Space Administration (NASA)'s Human Research Program (HRP), where there is hope that an effective and safe dietary countermeasure to protect the astronaut against the risk of renal stone formation in space can be developed (32). Attention has been primarily focused on the use of citrate, potassium citrate, and potassium magnesium citrate as possible dietary countermeasures.…”

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confidence: 99%

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Prediction of renal crystalline size distributions in space using a PBE analytic model. 2. Effect of dietary countermeasures

Kassemi

Thompson

2016

American Journal of Physiology-Renal Physiology

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is used to assess the efficacy of citrate, pyrophosphate, and augmented fluid intake as dietary countermeasures aimed at reducing the risk of renal stone formation for astronauts. The model uses the measured biochemical profile of the astronauts as input and predicts the steady-state size distribution of the nucleating, growing, and agglomerating renal calculi subject to biochemical changes brought about by administration of these dietary countermeasures. Numerical predictions indicate that an increase in citrate levels beyond its average normal groundbased urinary values is beneficial but only to a limited extent. Unfortunately, results also indicate that any decline in the citrate levels during space travel below its normal urinary values on Earth can easily move the astronaut into the stone-forming risk category. Pyrophosphate is found to be an effective inhibitor since numerical predictions indicate that even at quite small urinary concentrations, it has the potential of shifting the maximum crystal aggregate size to a much smaller and plausibly safer range. Finally, our numerical results predict a decline in urinary volume below 1.5 liters/day can act as a dangerous promoter of renal stone development in microgravity while urinary volume levels of 2.5-3 liters/day can serve as effective space countermeasures.nephrolithiasis; gravity; weightlessness; crystal nucleation; crystal growth; agglomeration; inhibition; dietary countermeasures NEPHROLITHIASIS IS NOT ONLY a problem within the general population on Earth but is also a risk to the astronauts' health and survival during future long-duration missions where exposure to microgravity and other space conditions are likely to increase the risk of renal stone formation. The concern seems to be justified since a recent survey of renal stone formation in US astronauts has revealed 14 recorded postflight episodes (13, 26). Whether on Earth or in space, the development of calcium oxalate (CaOx) renal stones is initiated with nucleation of the sparingly soluble salt from a supersaturated urine as the necessary first step, followed by simultaneous growth and agglomeration of the crystals as two effective stone size-enhancing mechanisms. While the extent of urinary CaOx supersaturation in the nephron changes continuously depending on the level of hydration and the extent of other dietary intake, the urine of most individuals, healthy or stone former, remains supersaturated under normal everyday conditions.The progression from crystal nucleation and growth to a clinical colic situation is not yet well understood, but it is thought to occur by either free-or fixed-particle mechanisms (13, 32). Recent studies by Kim et al. (14) and Evan et al. (7) using advanced endoscopic imaging and comprehensive physiological biopsies suggest three possible free/fixed pathways to stone formation: 1) nucleation and growth on the Randall plaque deposits in the papillae; 2) growth after adherence to a possibly injured section of collecting or Bellini ducts; and 3) homogeneous nucleatio...

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Section: Effect Of Pyrophosphate Inhibitionmentioning

confidence: 99%

mentioning

confidence: 96%

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Prediction of renal crystalline size distributions in space using a PBE analytic model. 2. Effect of dietary countermeasures

Kassemi

Thompson

2016

American Journal of Physiology-Renal Physiology

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Successful urinary discrimination between calcium oxalate kidney stone patients and healthy subjects using ¹H NMR spectroscopy: Suggestion of a possible link to protein content

2019

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Stone formation in the urinary tract is a multifactorial world‐wide disease afflicting between 8 and 20% of population groups in different geographical locations. Discrimination between stone formers and healthy persons on the basis of urine composition remains a crucial goal among researchers. Since 1H NMR is able to monitor the metabolic function of the kidney we applied it to the urine of 60 stone formers (34 females, 26 males) and 38 healthy persons (14 females, 24 males). Spectra were normalized relative to an internal standard and integrated over 37 consecutive regions. The resulting data were subjected to principal component and canonical discriminant analysis. Excellent discrimination between patient and controls for both genders was achieved, with all the data falling within the 95% confidence interval. The most important variables allowing for this inter‐group separation correspond to those associated with protein signals. We therefore speculate that the discrimination between patients and controls may be due to the presence or absence of macromolecular stone promoters and/or inhibitors. This supports numerous in vitro studies demonstrating that urinary macromolecules play significant roles in stone formation and prevention. Our finding that 1H NMR analysis of urine differentiates between stone formers and healthy persons represents an important breakthrough for rapid screening of individuals who are at risk for this disease.

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Experimental determination of multiple thermodynamic and kinetic risk factors for nephrolithiasis in the urine of healthy controls and calcium oxalate stone formers: does a universal discriminator exist?

2015

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Nephrolithiasis is thought to be governed by urinary thermodynamic and kinetic risk factors. However, identification of one or more of these factors which consistently and unambiguously differentiates between healthy subjects (N) and calcium oxalate (CaOx) renal stone patients (SF) remains elusive. The present study addresses this challenge. 24 h urines were collected from 15 N and 10 SF. Urine compositions were used to compute thermodynamic risk indices including urinary ratios, quotients and supersaturation (SS) values, while CaOx metastable limits (MSL) were determined experimentally. Crystallisation kinetics was determined by measuring rates of particle formation (number, volume, size) using a Coulter counter multisizer (CC) and a Coulter flow cytometer (FC). Particle shapes were qualitatively differentiated by FC and were viewed directly by scanning electron microscopy. Several urinary composition ratios and risk quotients were significantly different between the groups. However, there were no significant differences between CaOx MSL or SS values. Using transformed FC data, the rate of CaOx crystallisation in SF was significantly greater than in N. This was not supported by CC measurements. There were no significant differences between the groups with respect to particle size or CaOx crystal growth rates. Single and aggregated CaOx dihydrate crystals were observed in both groups with equal frequency and there were no differences in the kinetic properties of these deposits. A few CaOx monohydrate crystals were observed in SF. Although several risk factors were found to be significantly different between the groups, none of them were consistently robust when compared to other cognate factors. Arguments were readily invoked which demonstrated inter-factor inconsistencies and conflicts. We suspect that a unique discriminatory factor, such as any of those which we investigated in the present study, may not exist.

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The Possible Roles of Inhibitors, Promoters, and Macromolecules in the Formation of Calcium Kidney Stones

Cited by 13 publications

References 329 publications

Prediction of renal crystalline size distributions in space using a PBE analytic model. 2. Effect of dietary countermeasures

Prediction of renal crystalline size distributions in space using a PBE analytic model. 2. Effect of dietary countermeasures

Successful urinary discrimination between calcium oxalate kidney stone patients and healthy subjects using ¹H NMR spectroscopy: Suggestion of a possible link to protein content

Experimental determination of multiple thermodynamic and kinetic risk factors for nephrolithiasis in the urine of healthy controls and calcium oxalate stone formers: does a universal discriminator exist?

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The Possible Roles of Inhibitors, Promoters, and Macromolecules in the Formation of Calcium Kidney Stones

Cited by 13 publications

References 329 publications

Prediction of renal crystalline size distributions in space using a PBE analytic model. 2. Effect of dietary countermeasures

Prediction of renal crystalline size distributions in space using a PBE analytic model. 2. Effect of dietary countermeasures

Successful urinary discrimination between calcium oxalate kidney stone patients and healthy subjects using 1H NMR spectroscopy: Suggestion of a possible link to protein content

Experimental determination of multiple thermodynamic and kinetic risk factors for nephrolithiasis in the urine of healthy controls and calcium oxalate stone formers: does a universal discriminator exist?

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Successful urinary discrimination between calcium oxalate kidney stone patients and healthy subjects using ¹H NMR spectroscopy: Suggestion of a possible link to protein content