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Human Research Program

Probabilistic Analysis of Renal Stones in US Astronauts (PI=Kassemi)

Completed Technology Project

Project Introduction

A combined transport-kinetics model for nucleation, growth, and agglomeration of calcium oxalate crystals was developed in the framework of the population balance equation whereupon the nephron was treated as a continuous crystallizer. The model was used to investigate the growth rates and size distributions of renal calculi based on parametric simulation case studies for normal and stone-forming subjects in 1g and microgravity. To investigate the transport effects of gravity on the formation and development of renal calculi in the nephron, the Population Balance Equation (PBE)-agglomeration model was further incorporated into the multipurpose computational fluid dynamics (CFD) code Ansys-Fluent and coupled to the Navier-Stokes and species equations that describe the urinary flow and transport of calcium and oxalate ions through the nephron. Numerical results indicate that the typical renal biochemistry of normal subjects on Earth as exemplified by low urinary calcium and oxalate concentrations, higher relative velocities between urinary flow and the calculi, and lower reaction rates due to presence of normal concentration of inhibitors will lead to surface reaction limited crystal growth rates. However, in microgravity, due to the possibility of increased supersaturation levels arising from lower urine volumes and higher calcium and oxalate concentrations, a negligible relative velocity between the stone and the urinary flow, and the lower inhibitor concentrations, the stone growth will be limited by the transport of ions in the bulk liquid. The numerical simulations further indicate that: 1. The distribution of stone sizes and their respective population densities are both quite sensitive to the different biochemistries of normal and stone-forming subjects in 1g and microgravity. 2. Stone formers exhibit parabolic distributions with peak of stone populations shifting from 2 microns in 1g to about 5-7 microns in reduced-gravity and when precipitation is the main mechanism for growth. 3. Normal subjects exhibit a monotonic decrease in precipitating stone size populations from seed size to about 8 microns in microgravity. 4. As a result of the shift in the renal biochemistry upon exposure to microgravity, a normal subject in space can exhibit stone growth rates and size distributions that are comparable to a stone-former on Earth -- a finding that may prove important to the astronaut screening protocols. 5. Agglomeration is likely to be the most important and critical mechanism in development and enlargement of renal stones causing around ten-fold increase in the resulting stone sizes. 6. Stone size distribution is quite sensitive to the magnitude of the agglomeration coefficient – a quantity that unfortunately may vary substantially for different urine biochemistries and therefore not well-quantified in published literature. 7. The gravitational field plays an adverse effect increasing the transit time of renal calculi in the nephron with a possibility of a nearly two-fold stone size enhancement. In summary, the results so far imply that while a typical stone-former may form considerably larger renal stones on Earth, the normal subject in microgravity tends to make significantly more stones below the 2 micron range by nucleation and precipitation. Agglomeration of these crystals in the nephron may result in a 10 fold further increase in the stone sizes in microgravity. The stones in this size range will still clear through the nephron. But unfortunately, upon re-entry into a gravitational field, further growth and agglomeration of the renal calculi combined with increased transit times due to the lagging of the stones behind the urinary flow in tubule sections where gravitational vector is acting in the adverse direction can result in size increases alarmingly close to the critical dimension for retention. In this case, the risk for a clinical stone occurrence may be greatly enhanced. The development of the Renal Stone Formation Simulation Module (RSFSM) and its validation has been nearly completed in 2013. In the final year of the project (2014), this model will be used to perform a series of comprehensive parametric simulation case studies to investigate effect of hydration and inhibition. Furthermore, the core deterministic PBE model will be coupled to front and back end probabilistic wrapper models. Simulations performed using the combined deterministic-probabilistic model will be used to provide a probabilistic assessment of the risks of clinical stone incidents for future space mission scenarios. More »

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