Renal Stone Risk During Spaceflight: Assessment and Countermeasure Validation (Renal Stone) - 04.20.16
The Renal Stone experiment collects urine samples from crewmembers and tests a possible countermeasure for preventing kidney stone formation. Science Results for Everyone
It is not easy to empty your bladder in space. As if that were not enough, crew members face an increased risk of developing kidney stones, due to decreased urine output, urine acidity, and increased calcium excretion (a result of bone loss). Therapy options for this debilitating condition are severely limited in spacecraft, making prevention the best approach. This investigation tested whether potassium citrate (K-Cit) pill supplements could help. Results suggest that these supplements may decrease the risk for developing three types of kidney stones (calcium oxalate, uric acid, and brushite) both during and immediately after missions. Experiment Details
OpNom: Renal Stone
Peggy A. Whitson, Ph.D., Johnson Space Center, Houston, TX, United States
Robert A. Pietrzyk, M.S, Wyle Science-Technology and Engineering Group, Houston, TX, United States
Clarence F. Sams, Ph.D., Johnson Space Center, Houston, TX, United States
Jeffrey A. Jones, M.D., Baylor College of Medicine, Houston, TX, United States
NASA Johnson Space Center, Human Research Program, Houston, TX, United States
Sponsoring Space Agency
National Aeronautics and Space Administration (NASA)
Human Exploration and Operations Mission Directorate (HEOMD)
ISS Expedition Duration 1
August 2001 - December 2002; November 2002 - May 2003; October 2003 - April 2004; April 2005 - April 2007
Previous ISS Missions
Similar studies were conducted on Shuttle, including STS-107 (Columbia), which was lost in 2003. Renal Stone has been performed on ISS for Expeditions 3-6, 8 and 11-13.
- Bone loss that is known to occur in space significantly increases the amount of calcium in the urine which can lead to the formation of renal (kidney) stones.
- Renal stone formation could have severe health consequences for crewmembers and negatively impact mission success.
- This experiment tests the performance of potassium citrate, a proven therapy to minimize calcium containing renal stone development on Earth, as a countermeasure to reduce the risk of renal stone formation in space.
ISS Science Challenge Student Reflection
ISS Science Challenge Selected Project
I chose Renal Stone Risk During Spaceflight: Assessment and Countermeasure Validation (Renal Stone) experiment because one of my closest family members recently had a kidney stone which had to be surgically removed. So the overall topic interested me to learn more about it. From this experiment, I learned: How the data was collected and analyzed to study about the stone formation in crew members during and after space flight; Astronauts are at greater risk of formation of stones like calcium oxalate, calcium phosphate, and uric acid during space missions because the urine becomes concentrated due to decreased urine output and pH and also higher excretion of calcium; Crewmembers ingested with K-cit had very good decrease in CAOX and uric-acid. Overall, it was a great learning experience!
-Adarsh, Grade 9, American High School, Fremont, California
The loss of calcium from bone combined with decreased fluid intake in flight increases the probability for kidney stone formation during and after flight. Development of a kidney (or renal) stone in an astronaut can have serious consequences since it cannot be treated in flight as it would be on the ground. To better understand the risks to astronaut on long duration spaceflights, quantification of renal stone formation potential and recovery is required. This experiment studied the potential development of renal stones in space crews and the efficacy of a pharmaceutical countermeasure.
Potassium citrate (K-cit) is a proven ground-based treatment for patients suffering from renal stones. In this study, from three days before launch and continuing through 14 days after landing each crewmember ingested either two K-cit tablets or two placebos daily. Urine samples were collected during 24-hour periods at three points during the crewmembers’ mission, once at the beginning, midway point, and at the end. In addition to taking pills and collecting urine samples, crewmembers maintained handwritten logs of their daily food and fluid intake, exercise, and medication during the time of the urine collections. These log books acted as a backup to the barcode reader records that are part of the inventory management system with which crews typically record food intake and medication.
Ultimately, these data will not only help long-duration space flight crews but also will aid those on Earth in understanding how renal stones form in otherwise healthy persons. This should also provide insight into stone-forming diseases on Earth.
Human exposure to microgravity results in a number of physiological changes. Among these are changes in renal function, fluid redistribution, bone loss, and muscle atrophy, all of which contribute to an altered urinary environment and the potential for renal stone formation during and immediately after flight. In-flight changes previously observed include decreased urine volume and urinary citrate and increased urinary concentrations of calcium and sodium. The formation of renal stones could have severe health consequences for crewmembers and negatively impact the success of the mission. This study will provide a better understanding of the risk factors associated with renal stone development during and after flight, as well as test the efficacy of potassium citrate as a countermeasure to reduce this risk.
Understanding how the disease may form in otherwise healthy crewmembers under varying environmental conditions will also provide insight into stone forming diseases on Earth.
All operational requirements are centered on crew participation. Each crew member will be assigned a pallet containing the pills and UCKs. They will use the Inventory Management System Barcode Reader to record their samples, food intake (food packets are marked with barcodes), and medication.
The samples will be returned to Earth and sent to the principal investigator (PI) for analysis. The PI will study the urine chemistry of the crew members to determine each individual's risk of renal stone formation, and compare the urine chemistry based on the crew member's medication and daily activities to determine what factors may have caused increases and decreases in stone-forming chemicals. The study will measure the total volume of urine voided by each crew member and the levels of chemicals associated with stones: calcium, oxalate, sodium, sulfate, phosphorus, magnesium, potassium, creatinine, uric acid, as well as pH balance.
Renal Stone is designed as a double-blind study. Each crew member will be assigned a blister packet of pills, but they will not know if their personal packet contains potassium citrate or placebos. Two pills are taken at dinner time. In addition to taking pills and collecting urine samples, the crew will maintain handwritten logs of their daily food and fluid intake, exercise, and medication. The log books will act as backup to the Barcode Reader records.
Decadal Survey Recommendations
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The Renal Stone investigation contained two sequential sampling groups in its single-trial, two-phase design. Phase 1 of the study sampled 12 male astronauts and cosmonauts during NASA-Mir spaceflights during 129 to 208-day missions and served as a control group with no treatment. Phase 2 collected data from 18 ISS crewmembers in a double-blind study that included control, and treatment with potassium citrate (K-Cit) pill supplements during 93 to 215-day missions from ISS Expeditions 3-14. Urine samples were collected and analyzed before, during, and after mission, as was dietary information from crewmembers to document urine chemistry and mineral-nutrient throughput. As a safety measure, all phase 2 participants were K-Cit-tolerance tested before launch, and none showed any adverse reactions.
Renal stones come in the forms of calcium stones (calcium oxalate (CAOX) and calcium phosphate (Brushite)), uric acid stones, and struvite stones (ammonium magnesium phosphate), with the CAOX type being the most common. Astronauts are at an increased risk for developing calcium oxalate, calcium phosphate and uric acid stones during space missions when crew’s urine typically becomes supersaturated with the chemical species of these stone-forming salts as a result of decreased urine output and pH and increased calcium excretion. Potassium citrate is known to bind with calcium to impede the growth of calcium-containing crystals, which can become kidney stones. The Renal Stone study quantifies the effectiveness of K-Cit in lowering the elevated risk factors for renal stone formation during space missions, and shows significant decrease in CAOX and uric-acid superstaturation risks in crewmembers ingesting K-Cit versus the control groups. K-Cit also increases urinary pH without elevating the risk for forming brushite stones, and appears to be well tolerated over the entire course of the study. Results from this investigation suggest that supplementation with potassium citrate may decrease the risk of renal stone formation during and immediately after space exploration missions.
Renal stones can be extremely debilitating and medical therapy options, widely available on Earth, are severely limited during long-duration space exploration, hence prevention is the most logical and cost-effective approach. The Renal Stone study, while collecting valuable scientific data, stresses the importance of maintaining a balance between pharmacological safety and effectiveness in conducting medical research involving crew members. Related results are expected from an ISS investigation in progress with bisphosphonates for mitigating bone loss, and a bed rest clinical ground study prescribing potassium magnesium citrate for reducing the risk of renal stone formation (Whitson 2009).
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Whitson PA, Pietrzyk RA, Jones JA, Nelman-Gonzalez MA, Hudson EK, Sams CF. Effect of Potassium Citrate Therapy on the Risk of Renal Stone Formation During Spaceflight. Journal of Urology. 2009; 182: 2490-2496. DOI: 10.1016/j.juro.2009.07.010.
Ground Based Results Publications
Whitson PA, Pietrzyk RA, Morukov BV, Sams CF. The risk of renal stone formation during and after long duration space flight. Nephron. 2001; 89(3): 264-270.
Whitson PA, Pietrzyk RA, Sams CF. Space flight and the risk of renal stones. Journal of Gravitational Physiology. 1999; 6(1): P87-P88.
Hoyer JR, Pietrzyk RA, Whitson PA. Effects of microgravity on urinary osteopontin. Journal of the American Society of Nephrology. 1999; 10(Suppl 14): S389-S393.
Drinnan NR, Begougne de Juniac A. The effects of microgravity on the urological system: a review. Journal of Clinical Urology. 2013 November; 6(6): 391-394. DOI: 10.1177/2051415813500955.
Jones JA, Jennings R, Pietrzyk RA, Ciftcioglu N, Stepaniak P. Genitourinary issues during spaceflight: a review. Inrenational Journal of Impotence Research. 2005; 17: S64-S67.
Pietrzyk RA, Jones JA, Sams CF, Whitson PA. Renal Stone Formation Among Astronauts. Aviation, Space, and Environmental Medicine. 2007; 78(4 Suppl): A9-A13.
Pietrzyk RA, Feiveson AH, Whitson PA. Mathematical model to estimate risk of calcium-containing renal stones. Mineral and Electrolyte Metabolism. 1999; 25(3): 199-203.
NASA Fact Sheet
Renal Stone Urine Collection Kits containing the Urine Collection Devices, Urine Collection Bags and Syringes. Image courtesy of NASA, Johnson Space Center.
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The micrograph shows calcium oxalate crystals in urine. These small crystals can develop to form renal stones. Image courtesy of NASA, Marshall Flight Space Center.
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NASA Image: JSC2005E32573 - ESA astronauts, Leopold Eyharts (left) and Thomas Reiter (right) during Renal Stone training at Johnson Space Center. Renal Stone hardware displayed is the potassium citrate/placebo palle and the Renal Stone and urine collection hardware.
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NASA Image: ISS011E13481 - Renal Stone hardware on board ISS during Increment 11.
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NASA Image: ISS011E13490 - ISS Expedition 11 Science Officer John Phillips with Renal Stone Hardware on board ISS.
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NASA Image: ISS011E13500 - ISS Commander Sergei Krikalev with Renal Stone Hardware during ISS Expedition 11.
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NASA Image: ISS013E56052 - ISS Expedition 13 Flight Engineer, Thomas Reiter, on board ISS processes samples for the Renal Stone investigation.
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