Effect of Potassium Citrate Therapy on the Risk of Renal Stone Formation During Spaceflight

Whitson, Peggy A.; Pietrzyk, Robert A.; Jones, Jeffrey A.; Nelman-Gonzalez, Mayra; Hudson, Edgar K.; Sams, Clarence F.

doi:10.1016/j.juro.2009.07.010

Cited by 56 publications

(41 citation statements)

References 10 publications

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“…Despite the use of exercise, decreases in bone density and bone strength, together with muscle volume, continue to occur in crewmembers during long-duration missions on the ISS (Convertino, 2002;Holick, 1998;Keyak et al, 2009;Lang et al, 2004;LeBlanc et al, 2000LeBlanc et al, , 1998Whedon et al, 1974;Trappe et al, 2009). The risks associated with these deleterious effects of microgravity include bone fracture, renal stone formation, increased fatigue, decreases in strength, and limited physical working capacity (Whitson et al, 2009;Convertino and Sandler, 1995;Convertino, 2002). Data from the first 6 expeditions on-board the ISS indicated that bone mineral density (BMD) was lost at a monthly rate of 1.4-1.5% at the hip and 0.9% at the spine (Lang et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

Foot forces during exercise on the International Space Station

Genc

Gopalakrishnan

Kuklis

et al. 2010

Journal of Biomechanics

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Section: Introductionmentioning

confidence: 99%

Foot forces during exercise on the International Space Station

Genc

Gopalakrishnan

Kuklis

et al. 2010

Journal of Biomechanics

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“…The physiological, environmental, and dietary conditions imposed by space travel and weightlessness have a considerable potential for increasing the risk of renal stone development (11,26,(37)(38)(39)40). 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).…”

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confidence: 99%

“…Citrate is one of the main contributors to urine's intrinsic inhibitory capacity (40,42). It can protect against CaOx crystallization in two ways.…”

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confidence: 99%

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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“…These renal data form the basis of the third subject designated as a "microgravity astronaut." Finally, the last subject represents a microgravity stone former and was constructed using the long-duration flight data provided by Whitson et al (38) as extracted from the 24-h postflight (return ϩ 0 -2) urine samples obtained from astronauts who were subject to the placebo test. In this case, the SDs associated with the respective excretion rates were used to construct a hypothetical "worst case" microgravity scenario as given by the entries for this case in Table 1.…”

Section: Resultsmentioning

confidence: 99%

“…There are other contributing factors such as the astronauts' high protein and sodium level that in addition to inducing higher calcium and pH levels can also provide nidi that may serve as nucleation sites, thus promoting CaOx precipitation (37,41). The higher pH levels will also lower the concentration of citrate, one of the primary inhibitors of CaOx growth and agglomeration (38,41). In short, alterations in the renal biochemistry of astronauts tend to provide favorable conditions for increased nucleation, growth, and agglomeration of CaOx crystals in the renal system.…”

mentioning

confidence: 99%

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

Kassemi

Thompson

2016

American Journal of Physiology-Renal Physiology

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Numerical results indicate that the model is successful in clearly distinguishing between 1-G normal and 1-G recurrent stone-former subjects based solely on their published 24-h urine biochemical profiles. Numerical case studies further show that the predicted renal calculi size distribution for a microgravity astronaut is closer to that of a recurrent stone former on Earth rather than to a normal subject in 1 G. This interestingly implies that the increase in renal stone risk level in microgravity is relatively more significant for a normal person than a stone former. However, numerical predictions still underscore that the stone-former subject carries by far the highest absolute risk of critical stone formation during space travel.

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Effect of Potassium Citrate Therapy on the Risk of Renal Stone Formation During Spaceflight

Abstract: Results from this investigation suggest that supplementation with potassium citrate may decrease the risk of renal stone formation during and immediately after spaceflight.

Cited by 56 publications

References 10 publications

Foot forces during exercise on the International Space Station

Foot forces during exercise on the International Space Station

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. 1. Effect of microgravity-induced biochemical alterations

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