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Project Title:  Renal Stone Risk During Spaceflight: Assessment and Countermeasure Validation Reduce
Fiscal Year: FY 2008 
Division: Human Research 
Research Discipline/Element:
HRP HHC:Human Health Countermeasures
Start Date: 07/01/1999  
End Date: 09/30/2008  
Task Last Updated: 10/21/2008 
Download report in PDF pdf
Principal Investigator/Affiliation:   Whitson, Peggy  Ph.D. / NASA Johnson Space Center 
Address:  2101 NASA Road 1 
 
Houston , TX 77058 
Email: peggy.a.whitson@nasa.gov 
Phone: 281-244-8950  
Congressional District: 22 
Web:  
Organization Type: NASA CENTER 
Organization Name: NASA Johnson Space Center 
Joint Agency:  
Comments:  
Co-Investigator(s)
Affiliation: 
Pietrzyk, Robert  Wyle/NASA Johnson Space Center 
Sams, Clarence  NASA Johnson Space Center 
Jones, Jeffrey  NASA Johnson Space Center 
Project Information: Grant/Contract No. None 
Responsible Center: NASA JSC 
Grant Monitor: Meck, J@n  
Center Contact: 281-244-5405 
janice.v.meck@nasa.gov 
Solicitation / Funding Source: 96-OLMSA-01 
Grant/Contract No.: None 
Project Type: FLIGHT 
Flight Program: Shuttle/ISS 
TechPort: No 
No. of Post Docs:
No. of PhD Candidates:
No. of Master's Candidates:
No. of Bachelor's Candidates:
No. of PhD Degrees:
No. of Master's Degrees:
No. of Bachelor's Degrees:
Human Research Program Elements: (1) HHC:Human Health Countermeasures
Human Research Program Risks: (1) Renal:Risk of Renal Stone Formation
Human Research Program Gaps: (1) B05:What is the current state of knowledge regarding renal stone formation due to spaceflight? (IRP Rev F)
(2) B06:What are the contributing factors other than loss of bone mineral density?
(3) B07:Is it necessary to increase crew fluid intake and, if possible, to what extent will it mitigate stone formation?
(4) B09:What is the frequency of post-flight stone formation; the incidence and types of stones; and the time course of stone formation? How does stone formation correlate with food intake and hydration status?
(5) B16:Can inhibitors of stone formation be sufficiently provided through dietary sources?
(6) N13:Can renal stone risk be decreased using nutritional countermeasures? (now Closed-2021)
Flight Assignment/Project Notes: ISS Increments 3-6, 8 and 11-14 (update 5/2007)

NOTE: End date is 9/30/2008 per PI and JSC (10/08)

Task Description: Exposure to the microgravity environment results in many metabolic and physiological changes to humans. Body fluid volumes, electrolyte levels, and bone and muscle undergo changes as the human body adapts to the weightless environment. Changes in the urinary biochemistry occurred as early as flight day 3-4 in the short duration crewmembers. Significant decreases were observed both in fluid intake and urinary output. During and following short duration Shuttle missions, significant changes were observed in the urinary pH, calcium, potassium and uric acid levels. During short duration missions, the risk of calcium oxalate stone formation increased early in the flight, continued at elevated levels throughout the flight and remained in the increased risk range on landing day. The risk returned to preflight levels one week following landing. The preflight calcium phosphate risk was significantly increased early in-flight and remained significantly elevated throughout the remainder of the mission. Results from the long duration Shuttle-Mir missions followed a similar trend. Most long duration crewmembers demonstrated increased urinary calcium levels despite lower dietary calcium intake. Fluid intake and urine volumes were significantly lower during the flight than during the preflight. The calcium oxalate risk was increased relative to the preflight levels during the early in-flight period and continued in the elevated risk range for the remainder of the space flight and through two weeks postflight. Calcium phosphate risk for these long duration crewmembers increased during flight and remained in the increased risk range throughout the flight and following landing. The complexity, expense and visibility of the human space program require that every effort be made to protect the health of the crewmembers and ensure the success of the mission. Results from our investigations clearly indicate that exposure to the microgravity environment of space significantly increases the risk of renal stone formation. These studies have indicated specific avenues for development of countermeasures for the increased renal stone risk observed during and following space flight. Increased hydration and implementation of pharmacological countermeasures should largely mitigate the in-flight risk of renal stones. The current study evaluated the efficacy of potassium citrate as a countermeasure to reduce this risk. Citrate, an important urinary inhibitor of calcium-containing renal stones binds with calcium in the urine, thereby reducing the amount of calcium available to form calcium oxalate stones. Urinary citrate also prevents calcium oxalate crystals from aggregating into larger crystals and into renal stones. In addition, citrate makes the urine less acidic which inhibits the development of uric acid stones. Potassium citrate supplementation has been successfully used to treat terrestrial patients with recurrent stone formation. The evaluation of potassium citrate as a countermeasure was performed during the ISS Expeditions 3-6, 8, and 11-14.

Research Objectives:

1. Quantitate the pre- in- and postflight risk of renal stone formation associated with space flight.

2. Determine the efficacy of potassium citrate as a countermeasure in reducing the in-flight and postflight for renal stone formation.

3. Evaluate dietary impact on the urinary biochemistry.

4. Evaluate the potential benefit of citrate to inhibit bone loss

See also http://www.nasa.gov/mission_pages/station/science/experiments/Renal_Stone.html

Research Impact/Earth Benefits: Relevance to Space:

Previous data from studies of crewmembers have noted significant in-flight and postflight increases in the urinary stone-forming salts and decreases in the concentration of urinary inhibitors of renal stone formation. Results from this study have indicated that the risk of calcium-containing renal stones can be minimized and beneficial changes in the urinary chemistry can be accomplished with the use of potassium citrate.

Strategies to reduce the risk of renal stones should focus on prevention of stone formation and include education of crewmembers, dietary recommendations and pharmacological countermeasures. With humans participating in long duration ISS missions, extended habitation on the moon and exploration class missions to Mars, it is vital to maintain the health, safety and capabilities of all crewmembers.

Task Progress & Bibliography Information FY2008 
Task Progress: Subjects in this study were crewmembers from long duration missions to the International Space Station (ISS). During the 9 ISS missions, 20 subjects (19 male/1 female) participated in this study. Due to in-flight crew constraints 2 male crewmembers on ISS withdrew from the study. The remaining 18 crewmembers successfully completed the study protocol and participated in missions ranging from 93 to 175 days.

All in-flight urine samples have been returned to Earth and the urinary biochemistry, dietary and bone marker determination and statistical analysis of the data has been completed.

Preparation of the Final Report has also been completed and submitted to the NASA Human Research Program. Development of the manuscript for publication of the final results for submission to a scientific journal is underway.

Bibliography Type: Description: (Last Updated: 04/28/2010)  Show Cumulative Bibliography Listing
 
Abstracts for Journals and Proceedings Jones JA. "Urolithiasis in Space." 2nd International Urolithiasis Research Symposium, Indianapolis, Indiana, April 17 - 18, 2008.

2nd International Urolithiasis Research Symposium, Indianapolis, Indiana, April 17 - 18, 2008. , Apr-2008

Abstracts for Journals and Proceedings Sibonga JD, Pietrzyk RA, Johnston SL, Scheuring RA, Arrnaud SB. "Data Mining Activities for Bone Discipline-Current Status." NASA Human Research Program Investigators’ Workshop, League City, TX., February 4-6, 2008.

NASA Human Research Program Investigators’ Workshop, League City, TX., February 4-6, 2008. http://www.dsls.usra.edu/meetings/hrp2008/pdf/BoneMuscle/1084Sibonga.pdf , Feb-2008

Articles in Peer-reviewed Journals Whitson PA, Pietrzyk RA, Jones JA, Nelman-Gonzalez M, Hudson EK, Sams CF. "Effect of potassium citrate therapy on the risk of renal stone formation during spaceflight." J Urol. 2009 Nov;182(5):2490-6. PubMed PMID: 19765769 , Nov-2009
Articles in Peer-reviewed Journals Pietrzyk RA, Jones JA, Sams CF, Whitson PA. "Renal stone formation among astronauts." Aviat Space Environ Med. 2007 Apr;78(4 Suppl):A9-13. http://www.ingentaconnect.com/content/asma/asem/2007/00000078/A00104s1/art00004 ; PMID: 17511294 , Apr-2007
Books/Book Chapters Jones JA, Pietrzyk RA, Whitson PA. "Renal and Genitourinary Concerns." in "Principles of Clinical Medicine for Space Flight." Ed. M.R. Barratt, S.L. Pool. New York : Springer, c2008. p. 273-292., May-2008
Books/Book Chapters Jones, JA, Sargsyan A, Pietryzk R, Sams C, Stepaniak P, Whitson P. "Urolithiasis and Genitourinary Systems Issues for Spaceflight." in "Renal Stone Disease 2: 2nd International Urolithiasis Research Symposium." Ed. A.P. Evan, J.C. Williams, J.E. Lingeman, J.A. McAteer. Melville, N.Y. : American Institute of Physics, 2008. p. 293-307., Nov-2008
Project Title:  Renal Stone Risk During Spaceflight: Assessment and Countermeasure Validation Reduce
Fiscal Year: FY 2007 
Division: Human Research 
Research Discipline/Element:
HRP HHC:Human Health Countermeasures
Start Date: 07/01/1999  
End Date: 09/30/2008  
Task Last Updated: 05/07/2007 
Download report in PDF pdf
Principal Investigator/Affiliation:   Whitson, Peggy  Ph.D. / NASA Johnson Space Center 
Address:  2101 NASA Road 1 
 
Houston , TX 77058 
Email: peggy.a.whitson@nasa.gov 
Phone: 281-244-8950  
Congressional District: 22 
Web:  
Organization Type: NASA CENTER 
Organization Name: NASA Johnson Space Center 
Joint Agency:  
Comments:  
Co-Investigator(s)
Affiliation: 
Pietrzyk, Robert  NASA Johnson Space Center 
Sams, Clarence  NASA Johnson Space Center 
Jones, Jeffrey  NASA Johnson Space Center 
Project Information: Grant/Contract No. None 
Responsible Center: NASA JSC 
Grant Monitor: McCollum, Suzanne  
Center Contact: 281 483-7307 
suzanne.g.mccollum@nasa.gov 
Solicitation / Funding Source: 96-OLMSA-01 
Grant/Contract No.: None 
Project Type: FLIGHT 
Flight Program: Shuttle/ISS 
TechPort: No 
No. of Post Docs:
No. of PhD Candidates:
No. of Master's Candidates:
No. of Bachelor's Candidates:
No. of PhD Degrees:
No. of Master's Degrees:
No. of Bachelor's Degrees:
Human Research Program Elements: (1) HHC:Human Health Countermeasures
Human Research Program Risks: (1) Renal:Risk of Renal Stone Formation
Human Research Program Gaps: (1) B05:What is the current state of knowledge regarding renal stone formation due to spaceflight? (IRP Rev F)
(2) B06:What are the contributing factors other than loss of bone mineral density?
(3) B07:Is it necessary to increase crew fluid intake and, if possible, to what extent will it mitigate stone formation?
(4) B09:What is the frequency of post-flight stone formation; the incidence and types of stones; and the time course of stone formation? How does stone formation correlate with food intake and hydration status?
(5) B16:Can inhibitors of stone formation be sufficiently provided through dietary sources?
(6) N13:Can renal stone risk be decreased using nutritional countermeasures? (now Closed-2021)
Flight Assignment/Project Notes: ISS Increments 3-6, 8 and 11-14 (update 5/2007)

NOTE: End date is 9/30/2008 per PI and JSC (10/08)

Task Description: Exposure to the microgravity environment results in many metabolic and physiological changes to humans. Body fluid volumes, electrolyte levels, and bone and muscle undergo changes as the human body adapts to the weightless environment. Changes in the urinary biochemistry occurred as early as flight day 3-4 in the short duration crewmembers. Significant decreases were observed both in fluid intake and urinary output. During and following short duration Shuttle missions, significant changes were observed in the urinary pH, calcium, potassium and uric acid levels. During short duration missions, the risk of calcium oxalate stone formation increased early in the flight, continued at elevated levels throughout the flight and remained in the increased risk range on landing day. The risk returned to preflight levels one week following landing. The preflight calcium phosphate risk was significantly increased early in-flight and remained significantly elevated throughout the remainder of the mission. Results from the long duration Shuttle-Mir missions followed a similar trend. Most long duration crewmembers demonstrated increased urinary calcium levels despite lower dietary calcium intake. Fluid intake and urine volumes were significantly lower during the flight than during the preflight. The calcium oxalate risk was increased relative to the preflight levels during the early in-flight period and continued in the elevated risk range for the remainder of the space flight and through two weeks postflight. Calcium phosphate risk for these long duration crewmembers increased during flight and remained in the increased risk range throughout the flight and following landing. The complexity, expense and visibility of the human space program require that every effort be made to protect the health of the crewmembers and ensure the success of the mission. Results from our investigations clearly indicate that exposure to the microgravity environment of space significantly increases the risk of renal stone formation. These studies have indicated specific avenues for development of countermeasures for the increased renal stone risk observed during and following space flight. Increased hydration and implementation of pharmacological countermeasures should largely mitigate the in-flight risk of renal stones. Maintaining the health and well-being of crewmembers during space flight requires a means of minimizing potential detrimental health effects of microgravity. The formation of a renal stone during flight obviously has severe consequences for the affected crewmember as well as the success of the mission. The studies planned in this investigation will not only provide a better understanding of the stone-forming risk crewmembers experience during and after space flight, but will take the next step to test the efficacy of potassium citrate as a countermeasures to reduce this risk. Based on the known increased risk crewmembers experience, it is imperative that countermeasures to reduce or alleviate this risk are developed and tested.

Research Impact/Earth Benefits: Relevance to Space and/or Earth Based Research:

Previous studies of Skylab and Shuttle crews have demonstrated significant changes in the urinary chemical composition. Increase in urinary calcium and phosphorus are well documented and probably represent bone resorption due to exposure to the weightless environment. Studies of Shuttle mission of varying duration noted significant postflight increases in the urinary stone-forming salts and decreases in the concentration of urinary inhibitors of renal stone formation. This study is expected to show the in-flight effects of microgravity on the risk factors associated with renal stone development. It is expected that space flight will significantly enhance renal stone formation by providing an environment that is saturated with the stone-forming salts, primarily calcium and phosphorus, in the presence of a reduced concentration of renal stone inhibitors. The postflight renal stone profiles completed on Shuttle crewmembers (n = 323) indicated substantial changes from preflight levels and from normal non-stone formers. With the previous in-flight history (n = 6) of some of the known urinary analytes that influence renal stone formation, we expect an increase in calcium-containing stones (both calcium oxalate and calcium phosphate stones), and sodium-containing stones (sodium urate). It is predicted that the increased risk observed during space flight can be minimized and beneficial changes in the urinary chemistry can be accomplished with the use of potassium citrate. Renal stone disease affects approximately 12% of the human population on Earth with recurrence rates of renal stones reaching 75% in untreated individuals. Morbidity is high and related health costs have been estimated to exceed two billion dollars a year. Understanding how the disease may form in otherwise healthy crewmembers under varying environmental conditions may lead to additional clues as to how crystals form in the urine and develop into renal stones.

Task Progress & Bibliography Information FY2007 
Task Progress: This investigation was successfully completed by 19 crewmembers during the ISS Expeditions 3-6, 8, and 11-14 missions. Preflight, in-flight and postflight sample collections and dietary monitoring have been completed through the ISS Expedition 13 missions. Data analysis is completed through the ISS Expedition 13 missions. All preflight and in-flight sample collection sessions have been completed for the one crewmember participating during the ISS Expedition 14 mission. At this time, postflight activities are in progress. Due to down mass constraints and re-scheduled shuttle launch dates, in-flight samples from the ISS Expedition 14 will not return to until approximately June 2007.

Approval for elimination of the double blind requirement was received in December, 2005. As a result, the participating crewmembers ingested only potassium citrate as a countermeasure to the risk of renal stone formation. Since the majority of this study was performed as a double-blind investigation, the effect of potassium citrate on renal stone risk has not been determined at this time. Upon completion of the study, data from all the ISS missions will be combined for a detailed analysis involving statistical analysis and evaluation of the pharmacologic countermeasure to reduce the risk of stone formation.

Bibliography Type: Description: (Last Updated: 04/28/2010)  Show Cumulative Bibliography Listing
 
Abstracts for Journals and Proceedings Whitson PA, Pietrzyk RA, Sams CF, Jones JA, Nelman-Gonzalez MA, Hudson EK. "Renal Stone Risk During Space Flight: Assessment and Countermeasure Validation." NASA Human Research Program Investigators’ Workshop, League City, Texas, February 12-14, 2007.

NASA Human Research Program Investigators’ Workshop, 2007. http://www.dsls.usra.edu/meetings/hrp2007/pdf/SmartMed/3087Pietrzyk.pdf , Feb-2007

Abstracts for Journals and Proceedings Zwart SR, Watts SM, Sams CF, Whitson PA, Smith SM. "Reducing Dietary Acid Load as a Potential Countermeasure for Bone Loss Associated with Spaceflight." International Astronautical Congress, Valencia, Spain, October 3, 2006.

International Astronautical Congress, October 2006. , Oct-2006

Articles in Peer-reviewed Journals Pietrzyk RA, Jones JA, Sams CF, Whitson PA. "Renal stone formation among astronauts." Aviat Space Environ Med. 2007 Apr;78(4 Suppl):A9-13. http://www.ingentaconnect.com/content/asma/asem/2007/00000078/A00104s1/art00004 ; PMID: 17511294 , Apr-2007
Project Title:  Renal Stone Risk During Spaceflight: Assessment and Countermeasure Validation Reduce
Fiscal Year: FY 2006 
Division: Human Research 
Research Discipline/Element:
HRP HHC:Human Health Countermeasures
Start Date: 07/01/1999  
End Date: 04/01/2008  
Task Last Updated: 05/08/2007 
Download report in PDF pdf
Principal Investigator/Affiliation:   Whitson, Peggy  Ph.D. / NASA Johnson Space Center 
Address:  2101 NASA Road 1 
 
Houston , TX 77058 
Email: peggy.a.whitson@nasa.gov 
Phone: 281-244-8950  
Congressional District: 22 
Web:  
Organization Type: NASA CENTER 
Organization Name: NASA Johnson Space Center 
Joint Agency:  
Comments:  
Co-Investigator(s)
Affiliation: 
Pietrzyk, Robert  NASA Johnson Space Center 
Sams, Clarence  NASA Johnson Space Center 
Jones, Jeffrey  NASA Johnson Space Center 
Project Information: Grant/Contract No. None 
Responsible Center: NASA JSC 
Grant Monitor: McCollum, Suzanne  
Center Contact: 281 483-7307 
suzanne.g.mccollum@nasa.gov 
Solicitation / Funding Source: 96-OLMSA-01 
Grant/Contract No.: None 
Project Type: FLIGHT 
Flight Program: Shuttle/ISS 
TechPort: No 
No. of Post Docs:
No. of PhD Candidates:  
No. of Master's Candidates:  
No. of Bachelor's Candidates:  
No. of PhD Degrees:  
No. of Master's Degrees:  
No. of Bachelor's Degrees:  
Human Research Program Elements: (1) HHC:Human Health Countermeasures
Human Research Program Risks: (1) Renal:Risk of Renal Stone Formation
Human Research Program Gaps: (1) B05:What is the current state of knowledge regarding renal stone formation due to spaceflight? (IRP Rev F)
(2) B06:What are the contributing factors other than loss of bone mineral density?
(3) B07:Is it necessary to increase crew fluid intake and, if possible, to what extent will it mitigate stone formation?
(4) B09:What is the frequency of post-flight stone formation; the incidence and types of stones; and the time course of stone formation? How does stone formation correlate with food intake and hydration status?
(5) B16:Can inhibitors of stone formation be sufficiently provided through dietary sources?
(6) N13:Can renal stone risk be decreased using nutritional countermeasures? (now Closed-2021)
Flight Assignment/Project Notes: ISS Increments 3-10 In flight development phase (data collection has begun)

Task Description: Exposure to the microgravity environment results in many metabolic and physiological changes to humans. Body fluid volumes, electrolyte levels, and bone and muscle undergo changes as the human body adapts to the weightless environment. Changes in the urinary biochemistry occurred as early as flight day 3-4 in the short duration crewmembers. Significant decreases were observed both in fluid intake and urinary output. During and following short duration Shuttle missions, significant changes were observed in the urinary pH, calcium, potassium and uric acid levels. During short duration missions, the risk of calcium oxalate stone formation increased early in the flight, continued at elevated levels throughout the flight and remained in the increased risk range on landing day. The risk returned to preflight levels one week following landing. The preflight calcium phosphate risk was significantly increased early in-flight and remained significantly elevated throughout the remainder of the mission. Results from the long duration Shuttle-Mir missions followed a similar trend. Most long duration crewmembers demonstrated increased urinary calcium levels despite lower dietary calcium intake. Fluid intake and urine volumes were significantly lower during the flight than during the preflight. The calcium oxalate risk was increased relative to the preflight levels during the early in-flight period and continued in the elevated risk range for the remainder of the space flight and through two weeks postflight. Calcium phosphate risk for these long duration crewmembers increased during flight and remained in the increased risk range throughout the flight and following landing. The complexity, expense and visibility of the human space program require that every effort be made to protect the health of the crewmembers and ensure the success of the mission. Results from our investigations clearly indicate that exposure to the microgravity environment of space significantly increases the risk of renal stone formation. These studies have indicated specific avenues for development of countermeasures for the increased renal stone risk observed during and following space flight. Increased hydration and implementation of pharmacological countermeasures should largely mitigate the in-flight risk of renal stones. Maintaining the health and well-being of crewmembers during space flight requires a means of minimizing potential detrimental health effects of microgravity. The formation of a renal stone during flight obviously has severe consequences for the affected crewmember as well as the success of the mission. The studies planned in this investigation will not only provide a better understanding of the stone-forming risk crewmembers experience during and after space flight, but will take the next step to test the efficacy of potassium citrate as a countermeasures to reduce this risk. Based on the known increased risk crewmembers experience, it is imperative that countermeasures to reduce or alleviate this risk are developed and tested.

Research Impact/Earth Benefits: Relevance to Space and/or Earth Based Research:

Previous studies of Skylab and Shuttle crews have demonstrated significant changes in the urinary chemical composition. Increase in urinary calcium and phosphorus are well documented and probably represent bone resorption due to exposure to the weightless environment. Studies of Shuttle mission of varying duration noted significant postflight increases in the urinary stone-forming salts and decreases in the concentration of urinary inhibitors of renal stone formation. This study is expected to show the in-flight effects of microgravity on the risk factors associated with renal stone development. It is expected that space flight will significantly enhance renal stone formation by providing an environment that is saturated with the stone-forming salts, primarily calcium and phosphorus, in the presence of a reduced concentration of renal stone inhibitors. The postflight renal stone profiles completed on Shuttle crewmembers (n = 323) indicated substantial changes from preflight levels and from normal non-stone formers. With the previous in-flight history (n = 6) of some of the known urinary analytes that influence renal stone formation, we expect an increase in calcium-containing stones (both calcium oxalate and calcium phosphate stones), and sodium-containing stones (sodium urate). It is predicted that the increased risk observed during space flight can be minimized and beneficial changes in the urinary chemistry can be accomplished with the use of potassium citrate. Renal stone disease affects approximately 12% of the human population on Earth with recurrence rates of renal stones reaching 75% in untreated individuals. Morbidity is high and related health costs have been estimated to exceed two billion dollars a year. Understanding how the disease may form in otherwise healthy crewmembers under varying environmental conditions may lead to additional clues as to how crystals form in the urine and develop into renal stones.

Task Progress & Bibliography Information FY2006 
Task Progress: See FY2007 report.

Bibliography Type: Description: (Last Updated: 04/28/2010)  Show Cumulative Bibliography Listing
 
 None in FY 2006
Project Title:  Renal Stone Risk During Spaceflight: Assessment and Countermeasure Validation Reduce
Fiscal Year: FY 2005 
Division: Human Research 
Research Discipline/Element:
HRP HHC:Human Health Countermeasures
Start Date: 07/01/1999  
End Date: 04/01/2008  
Task Last Updated: 05/03/2006 
Download report in PDF pdf
Principal Investigator/Affiliation:   Whitson, Peggy  Ph.D. / NASA Johnson Space Center 
Address:  2101 NASA Road 1 
 
Houston , TX 77058 
Email: peggy.a.whitson@nasa.gov 
Phone: 281-244-8950  
Congressional District: 22 
Web:  
Organization Type: NASA CENTER 
Organization Name: NASA Johnson Space Center 
Joint Agency:  
Comments:  
Co-Investigator(s)
Affiliation: 
Pietrzyk, Robert  NASA Johnson Space Center 
Sams, Clarence  NASA Johnson Space Center 
Jones, Jeffrey  NASA Johnson Space Center 
Project Information: Grant/Contract No. None 
Responsible Center: NASA JSC 
Grant Monitor: McCollum, Suzanne  
Center Contact: 281 483-7307 
suzanne.g.mccollum@nasa.gov 
Solicitation / Funding Source: 96-OLMSA-01 
Grant/Contract No.: None 
Project Type: FLIGHT 
Flight Program: Shuttle/ISS 
TechPort: No 
No. of Post Docs:
No. of PhD Candidates:  
No. of Master's Candidates:  
No. of Bachelor's Candidates:  
No. of PhD Degrees:  
No. of Master's Degrees:  
No. of Bachelor's Degrees:  
Human Research Program Elements: (1) HHC:Human Health Countermeasures
Human Research Program Risks: (1) Renal:Risk of Renal Stone Formation
Human Research Program Gaps: (1) B05:What is the current state of knowledge regarding renal stone formation due to spaceflight? (IRP Rev F)
(2) B06:What are the contributing factors other than loss of bone mineral density?
(3) B07:Is it necessary to increase crew fluid intake and, if possible, to what extent will it mitigate stone formation?
(4) B09:What is the frequency of post-flight stone formation; the incidence and types of stones; and the time course of stone formation? How does stone formation correlate with food intake and hydration status?
(5) B16:Can inhibitors of stone formation be sufficiently provided through dietary sources?
(6) N13:Can renal stone risk be decreased using nutritional countermeasures? (now Closed-2021)
Flight Assignment/Project Notes: ISS Increments 3-10 In flight development phase (data collection has begun)

Task Description: Exposure to the microgravity environment results in many metabolic and physiological changes to humans. Body fluid volumes, electrolyte levels, and bone and muscle undergo changes as the human body adapts to the weightless environment. Changes in the urinary biochemistry occurred as early as flight day 3-4 in the short duration crewmembers. Significant decreases were observed both in fluid intake and urinary output. During and following short duration Shuttle missions, significant changes were observed in the urinary pH, calcium, potassium and uric acid levels. During short duration missions, the risk of calcium oxalate stone formation increased early in the flight, continued at elevated levels throughout the flight and remained in the increased risk range on landing day. The risk returned to preflight levels one week following landing. The preflight calcium phosphate risk was significantly increased early in-flight and remained significantly elevated throughout the remainder of the mission. Results from the long duration Shuttle-Mir missions followed a similar trend. Most long duration crewmembers demonstrated increased urinary calcium levels despite lower dietary calcium intake. Fluid intake and urine volumes were significantly lower during the flight than during the preflight. The calcium oxalate risk was increased relative to the preflight levels during the early in-flight period and continued in the elevated risk range for the remainder of the space flight and through two weeks postflight. Calcium phosphate risk for these long duration crewmembers increased during flight and remained in the increased risk range throughout the flight and following landing. The complexity, expense and visibility of the human space program require that every effort be made to protect the health of the crewmembers and ensure the success of the mission. Results from our investigations clearly indicate that exposure to the microgravity environment of space significantly increases the risk of renal stone formation. These studies have indicated specific avenues for development of countermeasures for the increased renal stone risk observed during and following space flight. Increased hydration and implementation of pharmacological countermeasures should largely mitigate the in-flight risk of renal stones. Maintaining the health and well-being of crewmembers during space flight requires a means of minimizing potential detrimental health effects of microgravity. The formation of a renal stone during flight obviously has severe consequences for the affected crewmember as well as the success of the mission. The studies planned in this investigation will not only provide a better understanding of the stone-forming risk crewmembers experience during and after space flight, but will take the next step to test the efficacy of potassium citrate as a countermeasures to reduce this risk. Based on the known increased risk crewmembers experience, it is imperative that countermeasures to reduce or alleviate this risk are developed and tested.

Research Impact/Earth Benefits: Relevance to Space and/or Earth Based Research:

Previous studies of Skylab and Shuttle crews have demonstrated significant changes in the urinary chemical composition. Increase in urinary calcium and phosphorus are well documented and probably represent bone resorption due to exposure to the weightless environment. Studies of Shuttle mission of varying duration noted significant postflight increases in the urinary stone-forming salts and decreases in the concentration of urinary inhibitors of renal stone formation. This study is expected to show the in-flight effects of microgravity on the risk factors associated with renal stone development. It is expected that space flight will significantly enhance renal stone formation by providing an environment that is saturated with the stone-forming salts, primarily calcium and phosphorus, in the presence of a reduced concentration of renal stone inhibitors. The postflight renal stone profiles completed on Shuttle crewmembers (n = 323) indicated substantial changes from preflight levels and from normal non-stone formers. With the previous in-flight history (n = 6) of some of the known urinary analytes that influence renal stone formation, we expect an increase in calcium-containing stones (both calcium oxalate and calcium phosphate stones), and sodium-containing stones (sodium urate). It is predicted that the increased risk observed during space flight can be minimized and beneficial changes in the urinary chemistry can be accomplished with the use of potassium citrate. Renal stone disease affects approximately 12% of the human population on Earth with recurrence rates of renal stones reaching 75% in untreated individuals. Morbidity is high and related health costs have been estimated to exceed two billion dollars a year. Understanding how the disease may form in otherwise healthy crewmembers under varying environmental conditions may lead to additional clues as to how crystals form in the urine and develop into renal stones.

Task Progress & Bibliography Information FY2005 
Task Progress: No progress report this period.

Bibliography Type: Description: (Last Updated: 04/28/2010)  Show Cumulative Bibliography Listing
 
 None in FY 2005
Project Title:  Renal Stone Risk During Spaceflight: Assessment and Countermeasure Validation Reduce
Fiscal Year: FY 2004 
Division: Human Research 
Research Discipline/Element:
HRP HHC:Human Health Countermeasures
Start Date: 10/01/2000  
End Date: 09/30/2005  
Task Last Updated: 03/30/2006 
Download report in PDF pdf
Principal Investigator/Affiliation:   Whitson, Peggy  Ph.D. / NASA Johnson Space Center 
Address:  2101 NASA Road 1 
 
Houston , TX 77058 
Email: peggy.a.whitson@nasa.gov 
Phone: 281-244-8950  
Congressional District: 22 
Web:  
Organization Type: NASA CENTER 
Organization Name: NASA Johnson Space Center 
Joint Agency:  
Comments:  
Co-Investigator(s)
Affiliation: 
Pietrzyk, Robert  NASA Johnson Space Center 
Sams, Clarence  NASA Johnson Space Center 
Jones, Jeffrey  NASA Johnson Space Center 
Project Information: Grant/Contract No. None 
Responsible Center: NASA JSC 
Grant Monitor: McCollum, Suzanne  
Center Contact: 281 483-7307 
suzanne.g.mccollum@nasa.gov 
Solicitation / Funding Source: 99-HEDS-02 
Grant/Contract No.: None 
Project Type: FLIGHT 
Flight Program: Shuttle/ISS 
TechPort: No 
No. of Post Docs:
No. of PhD Candidates:
No. of Master's Candidates:
No. of Bachelor's Candidates:
No. of PhD Degrees:  
No. of Master's Degrees:  
No. of Bachelor's Degrees:  
Human Research Program Elements: (1) HHC:Human Health Countermeasures
Human Research Program Risks: (1) Renal:Risk of Renal Stone Formation
Human Research Program Gaps: (1) B05:What is the current state of knowledge regarding renal stone formation due to spaceflight? (IRP Rev F)
(2) B06:What are the contributing factors other than loss of bone mineral density?
(3) B07:Is it necessary to increase crew fluid intake and, if possible, to what extent will it mitigate stone formation?
(4) B09:What is the frequency of post-flight stone formation; the incidence and types of stones; and the time course of stone formation? How does stone formation correlate with food intake and hydration status?
(5) B16:Can inhibitors of stone formation be sufficiently provided through dietary sources?
(6) N13:Can renal stone risk be decreased using nutritional countermeasures? (now Closed-2021)
Flight Assignment/Project Notes: ISS Increments 3-10

Task Description: Exposure to the microgravity environment results in many metabolic and physiological changes to humans. Body fluid volumes, electrolyte levels, and bone and muscle undergo changes as the human body adapts to the weightless environment. Changes in the urinary biochemistry occurred as early as flight day 3-4 in the short duration crewmembers. Significant decreases were observed both in fluid intake and urinary output. During and following short duration Shuttle missions, significant changes were observed in the urinary pH, calcium, potassium and uric acid levels. During short duration missions, the risk of calcium oxalate stone formation increased early in the flight, continued at elevated levels throughout the flight and remained in the increased risk range on landing day. The risk returned to preflight levels one week following landing. The preflight calcium phosphate risk was significantly increased early in-flight and remained significantly elevated throughout the remainder of the mission. Results from the long duration Shuttle-Mir missions followed a similar trend. Most long duration crewmembers demonstrated increased urinary calcium levels despite lower dietary calcium intake. Fluid intake and urine volumes were significantly lower during the flight than during the preflight. The calcium oxalate risk was increased relative to the preflight levels during the early in-flight period and continued in the elevated risk range for the remainder of the space flight and through two weeks postflight. Calcium phosphate risk for these long duration crewmembers increased during flight and remained in the increased risk range throughout the flight and following landing. The complexity, expense and visibility of the human space program require that every effort be made to protect the health of the crewmembers and ensure the success of the mission. Results from our investigations clearly indicate that exposure to the microgravity environment of space significantly increases the risk of renal stone formation. These studies have indicated specific avenues for development of countermeasures for the increased renal stone risk observed during and following space flight. Increased hydration and implementation of pharmacological countermeasures should largely mitigate the in-flight risk of renal stones. Maintaining the health and well-being of crewmembers during space flight requires a means of minimizing potential detrimental health effects of microgravity. The formation of a renal stone during flight obviously has severe consequences for the affected crewmember as well as the success of the mission. The studies planned in this investigation will not only provide a better understanding of the stone-forming risk crewmembers experience during and after space flight, but will take the next step to test the efficacy of potassium citrate as a countermeasures to reduce this risk. Based on the known increased risk crewmembers experience, it is imperative that countermeasures to reduce or alleviate this risk are developed and tested.

Research Impact/Earth Benefits: Relevance to Space and/or Earth Based Research:

Previous studies of Skylab and Shuttle crews have demonstrated significant changes in the urinary chemical composition. Increase in urinary calcium and phosphorus are well documented and probably represent bone resorption due to exposure to the weightless environment. Studies of Shuttle mission of varying duration noted significant postflight increases in the urinary stone-forming salts and decreases in the concentration of urinary inhibitors of renal stone formation. This study is expected to show the in-flight effects of microgravity on the risk factors associated with renal stone development. It is expected that space flight will significantly enhance renal stone formation by providing an environment that is saturated with the stone-forming salts, primarily calcium and phosphorus, in the presence of a reduced concentration of renal stone inhibitors. The postflight renal stone profiles completed on Shuttle crewmembers (n = 323) indicated substantial changes from preflight levels and from normal non-stone formers. With the previous in-flight history (n = 6) of some of the known urinary analytes that influence renal stone formation, we expect an increase in calcium-containing stones (both calcium oxalate and calcium phosphate stones), and sodium-containing stones (sodium urate). It is predicted that the increased risk observed during space flight can be minimized and beneficial changes in the urinary chemistry can be accomplished with the use of potassium citrate. Renal stone disease affects approximately 12% of the human population on Earth with recurrence rates of renal stones reaching 75% in untreated individuals. Morbidity is high and related health costs have been estimated to exceed two billion dollars a year. Understanding how the disease may form in otherwise healthy crewmembers under varying environmental conditions may lead to additional clues as to how crystals form in the urine and develop into renal stones.

Task Progress & Bibliography Information FY2004 
Task Progress: E-057: Renal Stone Risk During Spaceflight: Assessment and Countermeasure Validation

Principle Investigator: Peggy A. Whitson, Ph.D. NASA Johnson Space Center Houston, Texas 77058 Telephone: 281-244-8950 Fax: 281-244-8873 E-mail: peggy.whitson1@jsc.nasa.gov

Co-Investigators/Science Team: Charles Y.C. Pak, M.D. University of Texas Health Sciences Center Dallas, Texas 75235

Robert A. Pietrzyk, M.S. Enterprise Advisory Services, Inc. Houston, TX 77058

Jeffrey A. Jones, M.D. NASA Johnson Space Center Houston, Texas 77058 Clarence F. Sams. Ph.D. NASA Johnson Space Center Houston, Texas 77058

1. PURPOSE: Previous data have demonstrated that human exposure to the microgravity environment of space flight increases the risk of renal stone development during and immediately after space flight. Post-flight changes to the urinary chemical composition increase the risk of uric acid and calcium oxalate stone formation while in-flight assessment has shown a greater risk of calcium oxalate, calcium phosphate and sodium urate stones. Potassium citrate, a proven Earth-based therapy to minimize calcium-containing renal stone development, will be evaluated during space flight as a countermeasure to reduce the risk of renal stone formation. In this study, the renal stone-forming potential of humans will be assessed as a function of mission duration and it will be determined how long after space flight the increased risk exists. 2. BACKGROUND: As of October, 2001, there have been fourteen U.S. crewmembers that have developed renal stones. The Russian Space Program has reported three renal stone events and one in-flight episode of renal stone formation among cosmonauts. Exposure to the microgravity environment results in many metabolic and physiological changes to humans. Body fluid volumes, electrolyte levels, and bone and muscle undergo changes as the human body adapts to the weightless environment. Changes in the urinary biochemistry occurred as early as flight day 3-4 in the short duration crewmembers. Significant decreases were observed both in fluid intake and urinary output. During and following short duration Shuttle missions, significant changes were observed in the urinary pH, calcium, potassium and uric acid levels. During short duration missions, the risk of calcium oxalate stone formation increased early in the flight continued a elevated levels throught the flight and remained in the increased risk range on landing day. The risk returned to pre-flight levels one week following landing. The pre-flight calcium phosphate risk was significantly increased early in flight and remained significantly elevated throughout the remainder of the mission (Whitson et al., 1993, 1997). Results from the long duration Shuttle-Mir missions followed a similar trend. Most long duration crewmembers demonstrated increased urinary calcium levels despite lower dietary calcium intake. Fluid intake and urine volumes were significantly lower during the flight than during the pre-flight. The calcium oxalate risk was increased relative to the pre-flight levels during the early in-flight period and continued in the elevated risk range for the remainder of the space flight and through two weeks post-flight. Calcium phosphate risk for these long duration crewmembers increased during flight and remained in the increase risk range throughout the flight and following landing (Whitson et al., 2001). The complexity, expense and visibility of the human space program require that every effort be made to protect the health of the crewmembers and ensure the success of the mission. Results from our investigations clearly indicate that exposure to the microgravity environment of space significantly increases the risk of renal stone formation. These studies have indicated specific avenues for development of countermeasures for the increase renal stone risk observed during and following space flight. Increased hydration and implementation of pharmacological countermeasures should largely mitigate the in-flight risk of renal stones. Maintaining the health and well-being of crewmembers during space flight requires a means of minimizing potential detrimental health effects of microgravity. The formation of a renal stone during flight obviously has severe consequences for the affected crewmember as well as the success of the mission. The studies planned in this investigation will not only provide a better understanding of the stone-forming risk crewmembers experience during and after space flight, but will take tht enext ste to test the efficacy of potassium citrate as a countermeasures to reduce this risk. Based on the known increased risk crewmembers experience, it is imperative that countermeasure to reduce or alleviate this risk are developed and tested. Whitson, P.A. Pietrzyk, R.A. Pak, C.Y.C. Cintron, N.M. Alteration in renal stone risk factors after spae flight. J Urol 150: 803-807, 1993. Whitson, P.A. Pietrzyk, R.A. Pac, C.Y.C. Renal stone risk factors after space flight. J Urol 158: 2305-2310, 1997. Whitson, PA, Pietrzyk, RA, Morokov, B and Sams, CF. The risk of renal stone formation during long duration space flight Nephron. 89:264-270, 2001.

4. PROTOCOL:

Twenty-four urines will be collected before, during and after flight. Food, fluid, exercise and medications will be monitored 24 hours prior to and during the 24-hour urine collection in order to assess any environmental influences other than microgravity. Two 10 mEq potassium citrate tablets (total dose 20 mEq) will be ingested daily with the evening meal during the single preflight potassium citrate BDC evaluation session, all days during flight, and following landing through R+14. The following list of urinary biomedical parameters will be measured: total volume, pH, calcium, phosphorus, potassium magnesium, citrate, oxalate, sulfate, uric acid, sodium, creatinine, calcium oxalate, calcium phosphate (brushite), sodium urate, struvite and uric acid saturation. In addition, from the dietary records, the following data will be obtained: fluid intake, kilocalories, dietary calcium, oxalate, sodium, potassium, magnesium and phosphorus.

Preflight and postflight hardware for this investigation will consist of potassium citrate and placebo tablets, urine collection bottles, diet log book, chill pack and cooler. Flight hardware will consist of the urine collection devices, urine storage tubes, urine containment bag, potassium citrate kit, urine storage tube rack and the IMS bar code reader

Crewmembers will collect a 24-hour urine and maintain a 48-hour diet record during three preflight baseline data collection (BDC) session. The last BDC will be in collaboration with the required MedOps requirements for all crewmembers to minimize the demands on crew time. For long duration ISS missions, 24 hour urine collections and 48 hour dietary monitoring will be performed early (< FD 30), mid-mission (> FD30 < FD100) and late (within 30 days of landing). During flight two potassium citrate (20 mEq) or placebo tablets will be taken daily with the last meal of the day. Postflight urine and dietary monitoring will be performed at approximately R+0-2, R+7 and R+14 days.

5. PROGRESS REPORT

Pre-, in- and postflight sessions have been completed for the crewmembers participating in this study during the ISS Expedition 6 mission. Sample and data analysis have been completed and crew science debriefs were presented to the crewmembers.

This study is currently completing the analysis of samples collected during the pre, in- and postflight sessions for crewmembers participating in this study during the ISS Expedition 8 mission. Sample and data analysis is currently underway.

The Renal Stone Study is currently going through the process of pre-positioning for ISS Expedition 11. Preflight baseline data collections sessions will be completed in February, 2005 for the ISS Expedition 11crews.

FUTURE PLANS JULY 2004– OCTOBER, 2005

The study will continue with finalizing the samples and data analysis of the ISS Expedition 8 mission. In addition, crew science debriefs will be completed once all the data is obtained.

The investigation is under the process of being manifested for the ISS Expedition 11mission. The activities planned include pre-flight dietary and urinary assessments, in-flight sessions and postflight dietary records and urinary assessments.

7. PUBLICATIONS

1. Whitson, PA, Pietrzyk, RA, and Sams, CF Urine Volume and its effects on renal stone risk in astronauts. Aviation, Space and Environmental Medicine. 72(4) 368-372, April, 2001. 2. Whitson, PA, Pietrzyk, RA, Morokov, B and Sams, CF. The risk of renal stone formation during long duration space flight Nephron. 89:264-270, 2001. 3. Whitson, PA, Pietrzyk, RA, Jones, JA and Sams, CF. Renal Stone Risk Assessment During Spaceflight: Assessment and Countermeasure Validation. American Institute of Aeronautics and Astronautics International Space Station Utilization – 2001. October 15-18, 2001. Cape Canaveral, Florida. 4. Pietrzyk, RA, Whitson, PA, Jones, JA and Sams, CF. Overview of Renal Stones and Space Flight. 14th Annual Humans in Space Symposium. May 18-23, 2003, Baniff, Alberta, Canada.

Bibliography Type: Description: (Last Updated: 04/28/2010)  Show Cumulative Bibliography Listing
 
 None in FY 2004