Integrated Medical Model -- Renal Stone Module

The Exploration Medical Capability Element of the Human Research Program carries the risk of not being able to treat ill or injured crewmembers. Gap 4.13 in the Exploration Medical Capability Research Plan is the “Lack of lithotripsy or other capability to treat a renal stone.” The description of this gap states that, “Given the high probability of kidney stone formation in crew members during long duration missions the capability to perform Lithotripsy is highly desirable.”

During all spaceflight missions to date, renal stone incidence is actually lower than what would be expected in the general population or in the analog population utilized by the Lifetime Surveillance of Astronaut Health (LSAH). After astronauts return to Earth, however, the incidence rate increases and surpasses both the rate of the general population and the LSAH analog population, with the astronaut incidence rate of calcium oxalate stones approximately doubling that of the general US population. If these trends persist with the reintroduction of even fractional gravity, renal stones during a Mars mission could become a serious problem, not only in terms of astronaut health, but also in terms of the resources required to adequately treat the condition. A Bayesian update analysis of the data above suggested an approximately 5% probability of at least one crewmember developing a renal stone during a Mars mission.

Given the nature of these data, the Glenn Research Center (GRC) Integrated Medical Model (IMM) team developed a proof of concept probabilistic simulation of renal stone formation during a long duration exploration mission. While somewhat limited in scope, this simulation included both probabilistic and deterministic components. The deterministic components were developed to support the probabilistic analysis. Key findings from this work included:

1) As the stone grows larger, the governing equation says the rate of growth will increase, which is why the probabilistic analysis picks up the seed size as being influential.

2) The probabilistic model demonstrates identical sensitivity for Calcium and Oxalate, suggesting that a more detailed surface chemistry simulation needs to be conducted.

3) The sensitivities for the dwell time of a stone show pronounced differences between the 2.0 L/day and 2.5 L/day cases resulting in a 68.6% change in the probability of one stone reaching the effective diameter of a nephron from heterogeneous growth only. This result has a standard deviation of 0.237.

As part of the validation process for this module, the task underwent a subject matter expert review of the work done to date. The review was favorable with indication that an increase model fidelity was required, as outlined in Steps 1-3 below.

1. Determine expected incidence rate of renal stones during exploration missions and how this rate is affected by new countermeasure activities.

2. Provide a probabilistic simulation that allows the Exploration Medical Capabilities Element of the Human Research Program to develop medical kits appropriate to the level of risk of renal stone formation.

3. Provide a probabilistic simulation that allows the Exploration Medical Capabilities Element of the Human Research Program the ability to quantitatively evaluate the effect of different operations scenarios on the ability of a given medical kit to adequately treat an ill or injured crew member.

The GRC IMM task team is currently working to extend the capabilities of the deterministic model used as the parameter integration function to include both promoters, inhibitors, agglomeration, wall interaction effects, and gravity components. Once this is matured, it will be wrapped with a probabilistic simulation representing the scenarios and physiological parameter variation typical of spaceflight to assess the likelihood of renal stone formation.

Once completed, The Renal Stone Formation Simulation Module (RSFSM) will provide a state-of-the-art computational capability that can not only be used to more directly investigate the renal stone size distributions and the statistical propensities for developing a critical stone incident for future mission scenarios but also help to devise and evaluate different systematic chemical or physical intervention countermeasures for preventing their occurrence in future.

Nephrolithiasis constitutes as one of the most common diseases that has afflicted man for centuries. Indeed, one of the first evidences of renal stones in humans was found in an Egyptian mummy at El- Amrah dating back to 4800 B.C. Today, approximately 5% of the U.S. population develops clinically significant urinary calculi in their lifetime. However, renal stone disease is not only a concern on Earth, but could conceivably pose as a serious risk to the astronauts’ health and safety in space. The physiological, environmental, and dietary conditions imposed by space travel and weightlessness can easily increase this risk as a recent survey of renal stone formation in U.S. astronauts has revealed 14 recorded episodes. Russian medical science investigators have also noted multiple stone events among the Soviet cosmonauts. The most serious one was an in-flight renal stone occurrence that nearly caused the the Russian mission to be aborted.

The Renal Stone Formation Simulation Module (RSFSM) developed as part of this task is designed to inform NASA's Integrated Medical Model (IMM) with the likelihood and associated uncertainty of astronauts developing kidney stones upon long-term exposure to microgravity, as well as upon re-entry to a gravitational field. The computational module will be able to assess the effects of various design reference mission scenarios, thus allowing mission planners, medical kit designers, and clinicians to compare the efficacy of various countermeasures devised to reduce the probability of developing renal stone incident during the mission. The understanding that these simulations provide will also help to improve the astronauts' screening protocols.

The benefits of developing this computational capability is not limited to space applications but will extend back to impact clinical and scientific medicine on Earth. As a state-of-the-art research tool and virtual hypothesis-tester, RSFSM will expand the current level of understanding of renal stone disease. It will also serve as a tool to help improve clinical procedures for screening and treating nephrolithiasis on Earth and devise physical and/or pharmaceutical interventions to help the nearly 15 million Americans who currently suffer from this ailment today.

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