Prediction of renal crystalline size distributions in space using a PBE analytic model. 1. Effect of microgravity-induced biochemical alterations

Kassemi, Mohammad; Thompson, David A.

doi:10.1152/ajprenal.00401.2015

Cited by 12 publications

(30 citation statements)

References 31 publications

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“…PBE renal stone formation model used in this analysis has been described and verified in detail in our previous paper (13). The model uses the renal biochemistry of the subject and determines the size distribution of renal calculi as they form through nucleation and enlarge due to growth and agglomeration through the renal system.…”

Section: Methodsmentioning

confidence: 99%

“…As described previously in detail (13), Eq. 1 is amenable to an analytic solution that in dimensionless terms can be written as follows:…”

Section: Methodsmentioning

confidence: 99%

“…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.…”

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confidence: 99%

“…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%

“…CaOx stones account for ϳ85% of the clinical occurrences of nephrolithiasis on Earth, and the majority of the 14 stones developed by the astronauts postflight (13,26,33). The most important aggravating factor in space is hypercalciuria due to bone catabolism (22).…”

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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: Methodsmentioning

confidence: 99%

“…As described previously in detail (13), Eq. 1 is amenable to an analytic solution that in dimensionless terms can be written as follows:…”

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%