Peggy A. Whitson

The potential role of salt abuse on the risk for kidney stone formation

The kidney stone-forming risk of a high sodium diet was evaluated by assessing the effect of such a diet on the crystallization of stone-forming salts in urine. Fourteen normal subjects participated in 2 phases of study of 10 days duration each, comprising a low sodium phase (basal metabolic diet containing 50 mmol. sodium per day) and a high sodium phase (basal diet plus 250 mmol. sodium chloride per day). The high sodium intake significantly increased urinary sodium (34 +/- 12 to 267 +/- 56 mmol. per day), calcium (2.73 +/- 1.03 to 3.93 +/- 1.51 mmol. per day) and pH (5.79 +/- 0.44 to 6.15 +/- 0.25), and significantly decreased urinary citrate (3.14 +/- 1.19 to 2.52 +/- 0.83 mmol. per day). Arterialized venous blood bicarbonate and total serum carbon dioxide concentrations decreased significantly during the high sodium diet, whereas serum chloride concentration increased. However, no change in arterialized venous pH was detected. Thus, a high sodium intake not only increased calcium excretion, but also increased urinary pH and decreased citrate excretion. The latter effects are probably due to sodium-induced bicarbonaturia and a significant decrease in serum bicarbonate concentration, respectively. Commensurate with these changes, the urinary saturation of calcium phosphate (brushite) and monosodium urate increased, and the inhibitor activity against calcium oxalate crystallization (formation product) decreased. The net effect of a high sodium diet was an increased propensity for the crystallization of calcium salts in urine.

FAST at MACH 20: Clinical ultrasound aboard the International Space Station

BACKGROUND Focused assessment with sonography for trauma (FAST) examination has been proved accurate for diagnosing trauma when performed by nonradiologist physicians. Recent reports have suggested that nonphysicians also may be able to perform the FAST examination reliably. A multipurpose ultrasound system is installed on the International Space Station as a component of the Human Research Facility. Nonphysician crew members aboard the International Space Station receive modest training in hardware operation, sonographic techniques, and remotely guided scanning. This report documents the first FAST examination conducted in space, as part of the sustained effort to maintain the highest possible level of available medical care during long-duration space flight. METHODS An International Space Station crew member with minimal sonography training was remotely guided through a FAST examination by an ultrasound imaging expert from Mission Control Center using private real-time two-way audio and a private space-to-ground video downlink (7.5 frames/second). There was a 2-second satellite delay for both video and audio. To facilitate the real-time telemedical ultrasound examination, identical reference cards showing topologic reference points and hardware controls were available to both the crew member and the ground-based expert. RESULTS A FAST examination, including four standard abdominal windows, was completed in approximately 5.5 minutes. Following commands from the Mission Control Center-based expert, the crew member acquired all target images without difficulty. The anatomic content and fidelity of the ultrasound video were excellent and would allow clinical decision making. CONCLUSIONS It is possible to conduct a remotely guided FAST examination with excellent clinical results and speed, even with a significantly reduced video frame rate and a 2-second communication latency. A wider application of trauma ultrasound applications for remote medicine on earth appears to be possible and warranted.

Renal stone risk assessment during Space Shuttle flights

PURPOSE The metabolic and environmental factors influencing renal stone formation before, during, and after Space Shuttle flights were assessed. We established the contributing roles of dietary factors in relationship to the urinary risk factors associated with renal stone formation. MATERIALS AND METHODS 24-hr. urine samples were collected prior to, during space flight, and following landing. Urinary and dietary factors associated with renal stone formation were analyzed and the relative urinary supersaturation of calcium oxalate, calcium phosphate (brushite), sodium urate, struvite and uric acid were calculated. RESULTS Urinary composition changed during flight to favor the crystallization of calcium-forming salts. Factors that contributed to increased potential for stone formation during space flight were significant reductions in urinary pH and increases in urinary calcium. Urinary output and citrate, a potent inhibitor of calcium-containing stones, were slightly reduced during space flight. Dietary intakes were significantly reduced for a number of variables, including fluid, energy, protein, potassium, phosphorus and magnesium. CONCLUSIONS This is the first in-flight characterization of the renal stone forming potential in astronauts. With the examination of urinary components and nutritional factors, it was possible to determine the factors that contributed to increased risk or protected from risk. In spite of the protective components, the negative contributions to renal stone risk predominated and resulted in a urinary environment that favored the supersaturation of stone-forming salts. Dietary and pharmacologic therapies need to be assessed to minimize the potential for renal stone formation in astronauts during/after space flight.

Microgravity induces prostaglandin E2 and interleukin-6 production in normal rat osteoblasts: role in bone demineralization

It has been suggested that microgravity alters bone metabolism. Evidence for this phenomenon includes the negative calcium balance and decreased bone density in astronauts, as well as, inhibition of bone formation in rats flown for 2 to 3 weeks. However, the specific mechanisms that modulate these changes in microgravity are unknown. The purpose of this study was to clarify the mechanism of microgravity-induced bone demineralization using normal rat osteoblasts obtained from femur marrow cultures. The osteoblasts were cultured for 5 days during a Shuttle-Spacelab flight (STS-65). After collection of the culture medium, the cellular DNA and RNA were fixed on board. Enzyme-immunoassay of the culture medium for prostaglandin E2 (PGE2) indicated that microgravity induced a 4.5- to 136-fold increase in flight samples as compared to the ground control cultures. This increase of PGE2 production was consistent with a 3.3- to 9.5-fold elevation of inducible prostaglandin G/H synthase-2 (PGHS-2) mRNA, quantitated by reverse transcription-polymerase chain reaction (RT-PCR). The mRNA induction for the constitutive isozyme PGHS-1 was less than that for PGHS-2. The interleukin-6 (IL-6) mRNA was also increased (6.4- to 9.3-fold) in microgravity as compared to the ground controls. Since PGE2 and IL-6 are both known to play a role in osteoclast formation and bone resorption, these data provide molecular mechanisms that contribute to our understanding of microgravity-induced alterations in the bone resorption process.

The risk of renal stone formation during and after long duration space flight

Background: The formation of a renal stone during space flight may have serious negative effects on the health of the crewmember and the success of the mission. Urinary biochemical factors and the influence of dietary factors associated with renal stone development were assessed during long duration Mir Space Station missions. Methods: Twenty-four-hour urine samples were collected prior to, during and following long duration space flight. The relative urinary supersaturation of calcium oxalate, calcium phosphate (brushite), sodium urate, struvite and uric acid were determined. Results: Changes in the urinary biochemistry of crewmembers during long duration spaceflight demonstrated increases in the supersaturation of the stone-forming salts. In-flight hypercalciuria was evident in a number of individual crewmembers and 24-hour dietary fluid intake and urine volume were significantly lower. During flight, there was a significant increase in brushite supersaturation. Conclusions: These data suggest acute effects of space flight and postflight changes in the urinary biochemistry favoring increased crystallization in the urine. The effects of dietary intake, especially fluid intake, may have a significant impact on the potential for renal stone formation. Efforts are now underway to assess the efficacy of a countermeasure to mitigate the increased risk.

Alterations in Renal Stone Risk Factors after Space Flight

Exposure to the microgravity environment of space produces a number of physiological changes of metabolic and environmental origin that could increase the potential for renal stone formation. Metabolic, environmental and physicochemical factors that influence renal stone risk potential were examined in 24-hour urine samples from astronauts 10 days before launch and on landing day to provide an immediate postflight assessment of these factors. In addition, comparisons were made between male and female crewmembers, and between crewmembers on missions of less than 6 days and those on 6 to 10-day missions. Results suggest that immediately after space flight the risk of calcium oxalate and uric acid stone formation is increased as a result of metabolic (hypercalciuria, hypocitraturia, pH) and environmental (lower urine volume) derangements, some of which could reflect residual effects of having been exposed to microgravity.

Clinical and Biochemical Presentation of Gouty Diathesis: Comparison of Uric Acid Versus Pure Calcium Stone Formation

PURPOSE We compared gouty diathesis with uric acid versus calcium stones. MATERIALS AND METHODS We retrospectively reviewed clinical and laboratory data from 95 gouty diathesis patients (28 with uric acid and 67 with calcium stones) and 99 normal subjects. RESULTS Of the gouty diathesis patients gouty arthritis was present in 21% of those with uric acid and 12% of those with calcium stones. Hyperuricemia developed in 43% of those with uric acid and 27% of those with calcium stones, and 2% of controls. Urinary pH was independent of the net gastrointestinal absorption of alkali in the gouty diathesis groups. Urinary pH and citrate increased after potassium citrate treatment. CONCLUSIONS The characteristic features of primary gout were present in both gouty diathesis groups and both are responsive to treatment.

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

PURPOSE Exposure to microgravity affects human physiology and results in changes in urinary chemical composition during and after spaceflight, favoring an increased risk of renal stones. We assessed the efficacy of potassium citrate to decrease the stone risk during and after spaceflight. MATERIALS AND METHODS The study was done in 30 long duration spaceflight crew members to the space stations Mir and International Space Station. Before, during and after spaceflight 24-hour urine samples were collected to assess the renal stone risk. Potassium citrate (20 mEq) was ingested daily by International Space Station crew members in a double-blind, placebo controlled study. Mir crew members performed the identical protocol but did not ingest medication. RESULTS Potassium citrate treated crew members had decreased urinary calcium excretion and maintained the calcium oxalate supersaturation risk at preflight levels compared to that in controls. Increased urinary pH in the treatment group decreased the risk of uric acid stones. CONCLUSIONS Results from this investigation suggest that supplementation with potassium citrate may decrease the risk of renal stone formation during and immediately after spaceflight.

Quantification of urinary uric acid in the presence of thymol and thimerosal by high-performance liquid chromatography

A high-performance liquid chromatographic method was developed as an alternative to automated enzymatic analysis of uric acid in human urine preserved with thymol and/or thimerosal. Uric acid (tR = 10 min) and creatinine (tR = 5 min) were separated and quantified during isocratic elution (0.025 M acetate buffer, pH 4.5) from a mu Bondapak C18 column. The uric-acid peak was identified chemically by incubating urine samples with uricase. The thymol/thimerosal peak appeared at 31 min during the washing step and did not interfere with the analysis. We validated the high-performance liquid chromatographic method for linearity, precision and accuracy, and the results were found to be excellent.

Inhibition of HSP70 and a Collagen‐Specific Molecular Chaperone (HSP47) Expression in Rat Osteoblasts by Microgravity

Abstract: Rat osteoblasts were cultured aboard a space shuttle for 4 or 5 days. Cells were exposed to 1α, 25 dihydroxyvitamin D3 during the last 20 h and then solubilized by guanidine solution. The mRNA levels for molecular chaperones were analyzed by semi‐quantitative RT‐PCR. ELISA was used to quantify TGF‐β1 in the conditioned medium. The HSP70 mRNA levels in the flight cultures were almost completely suppressed, as compared to the ground (1 ×g) controls. The inducible HSP70 is known as the major heat shock protein that prevents stress‐induced apoptosis. The mean mRNA levels for the constitutive HSC73 in the flight cultures were reduced to 69%, ∼ 60% of the ground controls. HSC73 is reported to prevent the pathological state that is induced by disruption of microtubule network. The mean HSP47 mRNA levels in the flight cultures were decreased to 50% and 19% of the ground controls on the 4th and 5th days. Concomitantly, the concentration of TGF‐β1 in the conditioned medium of the flight cultures was reduced to 37% and 19% of the ground controls on the 4th and 5th days. HSP47 is the collagen‐specific molecular chaperone that controls collagen processing and quality and is regulated by TGF‐β1. Microgravity differentially modulated the expression of molecular chaperones in osteoblasts, which might be involved in induction and/or prevention of osteopenia in space.