ISOPTWPO Today

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ISOPTWPO Today

Dr.Shannon Walker ,NASA ASTRONAUT Dr. Shannon Walker began her professional career with the Rockwell Space Operations Company at the Johnson Space Center in 1987 as a robotics flight controller for the Space Shuttle Program. She worked several Space Shuttle missions as a flight controller in the Mission Control Center, including STS - 27, STS - 32, STS - 51, STS - 56, STS 60, STS - 61, and STS - 66. From 1990 to 1993, Dr. Walker took a leave of absence from the Johnson Space Center to attend graduate school, where her area of study was the solar wind interaction with the Venusian atmosphere. In 1995, she joined the NASA civil service and began working in the International Space Station (ISS) Program at the Johnson Space Center. Dr. Walker worked in the area of robotics integration, working with the ISS International Partners in the design and construction of the robotics hardware for the Space Station. In 1998 she joined the ISS Mission Evaluation Room (MER) as a manager for coordinating on-orbit problem resolution for the International Space Station. In 1999, Dr. Walker moved to Moscow, Russia to work with the Russian Space Agency and its contractors in the areas of avionics integration for the ISS as well as integrated problem solving for the ISS. She returned to Houston in 2000 after a year in Russia and became the technical lead for the ISS MER as well as the Deputy Manager of the On - Orbit Engineering Office. Prior to selection as an astronaut candidate, Dr. Walker was the Acting Manager of the On-Orbit Engineering Office.

Selected by NASA in May 2004, Walker completed Astronaut Candidate Training in February 2006. Her training included scientific and technical briefings, intensive instruction in Shuttle and International Space Station systems, physiological training, T-38 flight training, and water and wilderness survival training. Dr. Walker is qualified to fly aboard the Space Shuttle and the International Space Station. She has also completed qualification in the Extravehicular Activity (EVA) Skills program and the Canadian Space Agency Mobile Servicing System (MSS) Robotics Operator (MRO) course.

Dr. Walker launched and served as flight engineer (co-pilot) of Russian Soyuz spacecraft, TMA-19, on June 15, 2010 for a long duration mission aboard the International Space Station. She again served as a Flight Engineer during landing, which occurred November 25, 2010. The entire mission lasted 163 days, 161 of them aboard the Station.

I also want to encourage young people to think about what the future can be like if we work together to accomplish difficult goals, such as the exploration of space.–Dr.Walker — Image Credit: NASA/Johnson Space Center

ISOPTWPO Today

Kidney in Space Kidneys and the many hormone-secreting organs and glands (such as the adrenals, pituitary, and thyroid) are part of the body’s regulatory system.The kidneys control water balance and the removal of waste products and help regulate blood volume and pressure.Hormones are secreted throughout the body to control various functions, such as growth and blood pressure. These chemical messengers may initiate a response in one organ or may coordinate activities between systems.Kidneys and hormones keep the body in a stable state with the right amount of fluids and electrolytes (dissolved salts and minerals such as sodium, potassium, calcium, and phosphate). One of the main functions of the kidneys and hormones is to regulate blood volume. If sensors in the circulatory system detect too much or too little fluid, the brain and heart signal the glands and kidneys to secrete specific hormones that either reduce or increase body fluids In space, all features of water balance are generally diminished including oral hydration and skin evaporation.

Decreased water intake is often observed during spaceflights and could be attributed to space motion sickness and reduced sensation of thirst.Weightlessness decreases sweat losses during exercise as well as insensible skin losses.

Possible explanations could be a reduced convective air flow, the presence of persistent sweat film instead of sweat dripping, reduced energy requirements, and reduced need for thermoregulatory convective heat transfer.During the Spacelab Life Sciences-1 and 2 (SLS-1, SLS-2) missions, plasma volume was estimated to be reduced by 17 % in almost all astronauts enrolled from the first few days after flight until after landing. However, there was no indication of an early absolute fluid loss (in contrast to ground simulation models), since total body water did not differ from preflight values.

SLS - 1 investigations collect data early in flight when rapid changes are expected to occur in kidney function and hormone levels. Before this mission, scientists used groundbased simulations to develop hypotheses about what happens to the body during the first hours in space. Subjects immersed in water, confined to bed, or resting in a headdown position appear to have some of the same physiological changes as space travelers; all experience a rapid headward shift of fluids that initiates a complex set of reactions, including pressure increases in the blood vessels, enhanced renal blood flow, altered hormone secretion, increased excretion of fluids and electrolytes, and diminished thirst and water intake.

Because few measurements have been made during the initial hours of missions, ground-based models have not been validated. For instance, samples collected every 24 hours during Skylab did not show expected increases in renal excretions of salt and urine, leading scientists to postulate that dehydration might be responsible for the fluid reductions; however, measurements may not have been taken soon enough to detect the increases. During SLS-1, samples are taken every time a crew member voids so that scientists can identify any early changes in fluid balance.

Fluid-Electrolyte Regulation During Space Flight (Exp. No. 192) developed by Dr. Carolyn S. Leach of the NASA Johnson Space Center,Houston, Texas, measures fluid shifts immediately from the onset of weightlessness and seeks to determine if the human renal and circulatory systems conform to hypotheses formulated in ground-based studies that simulate low - gravity.

The experiment identifies immediate and adaptive changes in kidney function, changes in water, salt, and mineral balances, shifts in body fluids from cells and tissues, and changes in hormone levels that affect the kidneys and circulation. Data from the experiment are correlated with data from the cardiovascular experiments to determine how the responses of the systems are related.

Crew members give urine and blood samples as soon as possible in flight and at specified intervals thereafter; the samples are stored and returned for analysis. Body mass is measured daily, and a log is kept of fluids and medications consumed by each crew member; the dietary log helps monitor ingestion of sodium, potassium, calcium, and protein.

Early in the flight, the subjects are injected with chemical tracers that are distributed in the blood. Renal clearance tests (which determine the amount of certain tracers released from a given volume of blood or plasma into the urine in a specified time) help scientists follow the fluid shift and spot changes in kidney function and water, salt, and mineral balances. These tests are done twice in flight by collecting blood samples at timed intervals after each subject has received a carefully measured dose of tracers.

To determine the amount and rate of body water loss, each subject drinks water containing a heavy isotope of oxygen; then urine samples are collected at timed intervals to measure losses of this water. By collecting blood samples at timed intervals after the water is drunk, scientists can measure plasma volume and extracellular fluid volume.

Sensitive assays of both blood plasma and urine collected during SLS-1 are performed after the mission to reveal changes in hormones, such as aldosterone, antidiuretic hormone, angiotensin I, prostaglandins, cortisol, and adrenocorticotropin, which regulate fluid and electrolyte levels in the body. Before and after flight, crew members participate in the same experiments, and simultaneous ground experiments are done with non-crew subjects to determine the changes resulting from space flight.

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Results from the SLS missions showed that increased diuresis and natriuresis were not responsible for the reduced plasma volume. It seems that the transfer of fluid from the intravascular to the intracellular and interstitial space is the principal adaptation mechanism to microgravity . This could be attributed to a reduced transverse G-stress and the absence of mechanical pressures on tissues and organs.

Renal response to oral water load (600 ml) was also assessed in 3 male cosmonauts on the MIR space station and in 14 healthy males on earth in simulated weightlessness by 6 degree head - down - tilt bed rest. Under simulated microgravity conditions, water load decreased serum osmolality and suppressed antidiuretic hormone (ADH) leading to diuresis. In space, this response was blunted and urine osmolality was less reduced Unexpected renal responses in space Urine output in astronauts following ingestion of an oral water load was low in space on the Russian space station Mir and less than during simulation by 6 degree head-down bed rest. This surprising observation shows that the effects of gravity and weightlessness on fluid volume regulation are not well understood and that the head - down bed - rest model does not simulate the effects of weightlessness on renal water handling.

Three healthy male astronauts (age 38 - 40 years, height 167 - 182 cm, weight 69 - 79 kg) were investigated at least 120 days before, on the 6th or 13th day during, and at least 120 days after flight on the Russian space station Mir. The protocol was repeated on flight days 60 and 107 in two of the crew members and, in addition, on flight days 138 and 164 in one. Two to four ground-based sessions were done with individuals supine for 5.5 h. The protocol was in compliance with the Declaration of Helsinki and approved by the European Space Agency Medical Board. Sodium intake was controlled for 3 days before each experiment with free access to fluid. Ambient conditions were the same on ground and in space (temperature 27 degree C [SD 2] and 27 degree C , humidity 54% and 52% , respectively, pressure 1 atm with 21% oxygen). After at least 7 h of sleep, and food and fluid deprivation, the individuals emptied their bladders and ingested bread, jam, and 200 mL of water. After 90 min, the bladder was emptied again and 600 mL of water was ingested within 10 min. Over the next 4 h, the bladder was emptied at intervals of 1 h or 2 h.

Urine was collected in plastic bags, the exact time of voiding recorded, and urine volume measured by compressing the empty part of the bag and reading the volume of the filled part on a scale.Samples were frozen at 20 degree C. During the 2 h following the water loading, urine output did not increase significantly in space (mean 0.7 [SE 0.2] to 2.3 [0.8] mL/min, p>0.05, Figure 1). By contrast, urine output increased 7.2 (1.9) - fold on the ground from 0.7 (0.1) to 4.9 (1.1) mL/min (p < 0.05). After intake of the water load, urine osmolality decreased less in space (953 to 422 mOsm/kg, p>0.05) than on the ground (862 to 182 mOsm/kg, p < 0.05). The attenuated diuretic response was maintained during the repeated water loadings throughout flight. Contrary to expectations, the urinary excretion rate of norepinephrine was not lower in space (10 and 12 Âľ g over 6 h, respectively, in two individuals) than on the ground (9 and 9 Âľ g over 6 h).

Figure.1:Urine flow rate after an oral water load of 600 mL in space .Significant change (ANOVA, p<0.05) from Human Spaceflight Edition c International Space Agency (ISA)

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ISOPTWPO Today value before water load.

Exactly the same protocol was done in 14 healthy males (age 25 years, height 175 cm, weight 74 kg) during 10 - 19 days of simulated weightlessness by 6 degree head - down bed rest. Urine output during bed rest increased 5.6 (0.7)-fold from 0.7 (0.1) to 3.9 (0.4) mL/min (p<0.05) during the 2 h following intake of the water load (Figure 2).

This was similar to the 5.6 (1.0) - fold increase in the acute supine position, when the individuals had not been bed rested (1.1 [0.2] to 4.7 [0.4] mL/min, p < 0.05). In six individuals, water loadings were repeated twice up to 106 days of bed rest, which produced similar increases in urine output (5.2 [1.1] and 5.9 [2.3] - fold). Urine osmolalities were not affected by bed rest.

Figure 2:Urine flow rate following an oral water load of 600 mL during simulation of weightlessness by head - down bed rest Values are mean (SEM) of 14 males according to the same protocol as in space during acute horizontal supine conditions and on days 10 - 19 of 6 degree head - down bed rest. Significant increase (ANOVA, p<0.05) from value before the water load.

Results unexpectedly show that • Weightlessness attenuates urine output after an oral water load and that head - down bed rest is not a correct simulation model in this regard.

• Whether factors other than weightlessness caused the attenuation is doubtful, but it cannot be excluded that the claustrophobic and noisy environment on Mir had an effect.

• The individuals were probably not more dehydrated in flight than on the ground, because overnight fluid deprivation led to the same urine outputs and osmolalities during the 90 min before the water loadings.

• There were no systematic differences between sodium intake in space (162 mmol over 24 h) and on the ground (178 mmol over 24 h).

• The attenuated diuretic responsein space resembles a clinical state of intravascular volume depletion with activation of antidiuretic mechanisms.

Sodium handling can be estimated from oral sodium intake and urinary sodium excretion as long as little sweating occurs. Insensible losses are sodium free and fecal losses account for less than 2 % of total body sodium.

Data from the Skylab-3 mission as well as the SLS-1 and SLS-2 missions showed that the daily sodium retention during microgravity was considerably higher and led to a positive sodium balance.

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ISOPTWPO Today Add Salt? Astronauts’ Bones Say Please Don’t.

It has been known since the 1990s that the human body holds on to sodium, without the corresponding water retention, during long stays in space.

Salt intake was investigated in a series of studies, in ground-based simulations and in space, and it was found that not only is sodium retained (probably in the skin), but it also affects the acid balance of the body and bone metabolism.

So, high salt intake increases acidity in the body, which can accelerate bone loss.

The European Space Agency’s, or ESA’s, recent SOdium LOad in microgravity, or SOLO, study zoomed in on this question.

SOLO - SOdium LOading in Microgravity Objective SOdium LOading in Microgravity (SOLO) is a continuation of extensive research into the mechanisms of fluid and salt retention in the body during bed rest and spaceflights. It is a metabolically-controlled study. During long-term space missions astronauts will participate in two study phases, 5 days each. Subjects follow a diet of constant either low or normal sodium intake, fairly high fluid consumption and isocaloric nutrition.

Experiment specific goals and detailed objectives • To scrutinize the observation of a hormonal sodium retaining status and positive sodium balances without fluid retention during average sodium intake in further astronauts.

• To examine the effect of osmotically inactive sodium retention on calcium excretion, acid-base balance and bone resorption markers following a low, and average normal sodium intake in space and on Earth.

Microgravity leads to an activation of sodium retaining hormones even at normal sodium intake levels and causes positive sodium balances. Average and high sodium intake in microgravity exacerbates the rise in bone resorption in space.

The hypothesis of an increased urine flow as the main cause for body mass decrease has been questioned in several recently flown missions. Data from the American SLS1/2 missions as well as the European Euromir ’94 and MIR 97 mission show that urine flow and total body fluid is unchanged when isocaloric energy intake is achieved.

However, in two astronauts during these missions the renin-angiotensin system was considerably activated while plasma ANP (Atrial Natriuretic Peptide) concentrations were decreased. Calculation of daily sodium balances during a 15 day experiment of the MIR 97 mission, by subtracting sodium excretion from sodium intake- showed an astonishing result: the astronaut retained on average 50 mmol sodium daily in space compared to balanced sodium in the control experiment.

PRELIMINARY RESULTS • Salt intake was investigated in a series of studies, in ground-based simulations and in space, and it was found that not only is sodium retained (probably in the skin), but it also binds to certain sugar-protein molecules and affects the acid balance of the body and bone metabolism.

• High salt intake increases acidity in the body, which can accelerate bone loss.

Renal function and hemodynamics During the first 2 days of spaceflight, the glomerular filtration rate (GFR) shows a moderate transient increase (initial phase) as demonstrated by the SLS missions.This elevation seemed to be independent of alterations in renal plasma flow, which remained stable. This phenomenon results in an increase in the filtration fraction until a new equilibrium is reached (adaptive phase).

The increased sodium reabsorption and the normal or slightly increased GFR indicate that changes in the tubular handling of sodium play a primary role. A low interstitial hydrostatic pressure in the kidney leads to an increase in filtration fraction (tubuloglomerular feedback) and sodium reabsorption. Low fluid intake and increased antidiuretic hormone (ADH) levels also enhance sodium reabsorption and maintain normal renal hemodynamics, despite the low plasma volume.

Early in-flight, ADH levels are expected to be very high since space motion sickness promotes ADH release from the posterior pituitary. During chronic adaptation, ADH levels were considerably elevated in proportion to the reduced

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ISOPTWPO Today plasma volume.

Since its original detection in the 80s, circulating atrial natriuretic peptide (ANP) has also been evaluated in different missions. ANP is released secondary to cardiac atrial stretching. In space, ANP exhibits a biphasic profile. Initially, it increases during the first 24 h in space contributing to increased vascular permeability and fluid extravasation. ANP is later reduced, so that, on day 7, its levels are 50 % lower, compared with the preflight levels. Similar results have been demonstrated for the cyclic GMP (c-GMP) which is ANPâ&#x20AC;&#x2122;s second messenger. Furthermore, plasma renin activity was found to be persistently elevated in astronauts from different missions, and this elevation was independent of flight day. Perhaps, the activation of sodium wasting mechanisms is one of the initial steps that promote sodium retention in space. The constantly activated renin-angiotensin-aldosterone system also indicates that the retained sodium is rapidly transferred to extravascular compartments.

Hypothesis Based on the GFR and ADH release, it seems that adaptation to microgravity occurs in a two - phase manner. It is, therefore,reasonable to accept the new hypothesis by Kirsch et al.[4] which includes an acute and a chronic phase of adaptation, the latter occurring several hours after arrival in microgravity.

In the acute phase, early inflight, the cephalad fluid shift results in an increased central blood volume. However, central venous pressure is decreased due to a significant reduction in mediastinal pressure in parallel with the loss of gravitational forces. Increased left atrial size, as confirmed in studies from parabolic flights, promotes the release of atrial natriuretic peptide as a vasodilator and mediator of vascular permeability.

Although it is rather speculative and unconfirmed, a functional decoupling of the kidney probably takes place with suppression of both diuresis and sodium excretion. Total body water and body weight remain stable. In combination with the exaggerated decrease in plasma volume, a rapid extravasation of fluid from the intravascular to the interstitium or intracellular space is a reasonable assumption.

During chronic adaptation, the substantial decrease in the effective blood volume seems to be the central event.

ANP levels are also diminished as a new steady state is reached after the acute adaptation. Compensatory mechanisms activated secondary to plasma volume deficit include renin-angiotensin-aldosterone system, ADH release, and sympathetic nervous system activation. Sodium is continuously retained and redistributed, but it is not followed by water. It appears that a new steady state tries to be the remedy for the decreased plasma volume.

Renin-Angiotensin Aldosterone System (RAAS)

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A possible explanation of the dissociated renal handling of sodium (retained) and water (no or little retention) and the decreased plasma volume could be attributed to the persistent hypercalciuria secondary to increased bone mineral loss in space.

ADH translocates aquaporine-2 water (AQP-2) channels to the luminal surface of the collecting duct and in a later stage increases its renal expression, thus promoting water reabsorption.Hypercalciuria has been shown to promote AQP-2 proteolysis and decrease water reabsorption. In addition, the calcium sensitive receptor (CaSR) is expressed in the renal tubules and its activation by high urine calcium may contribute to blunted water reabsorption.

In view of these important findings, renal responses to microgravity appear to be similar to those in patients with heart failure (sodium retention, edema, low blood volume, increased sympathetic activity).

FMPT/L-1, endocrine and metabolic changes of payload specialist: Modification of fluid-regulating hormones by stress reaction From preliminary studies on adaptation to microgravity environment, the following results were obtained: • The cephalad fluid shift causes elevation of central venous pressure, and release of Antidiuretic Hormone (ADH), resulted in re-absorption of water in the kidney, and increase of the amount of urine.

• Renin-Angiotensin-Aldosterone System is suppressed by increase of circulatory blood, while release of Atrial Natriuretic Peptide (ANP) increases.

• Suppression of aldosterone and ANP release causes diuresis, and reliefs plethora. In actual flight, stress may affect fluid and electrolytes metabolism.

To confirm these results, urine and blood was analyzed from the payload specialist, Dr. Mori, to determine hormone and electrolytes concentration before, after and during space flight. In the early stage of the flight, cephalad fluid shift was observed but transient increase of urine was not confirmed. After sixth day, cortisol excretion was increased remarkably, which suggests heavy stress. ADH and aldosterone excretion was also increased in the later stage of the flight. These results support those of preliminary studies that stress may modify fluid metabolism. Adrenocortical hormones released by stress may exacerbate bone and muscular atrophy[5].

Albuminuria In the terrestrial environment, daily urinary albumin excretion (UAE) depends on a variety of factors including the glomerular load of albumin, the glomerular filtration rate, glomerular permselectivity and the reabsorption of albumin in the proximal tubule. Data from space are somewhat controversial.

Low urinary albumin excretion in astronauts during space missions Urinary albumin, as an index of proteinuria, and other variables were analyzed in 4 astronauts during space missions onboard the MIR station and on the ground (control). Mission duration before first urine collection in the four astronauts was 4, 26, 26, and 106 days, respectively.

On the ground, data were collected 2 months before mission in two astronauts, 6 months after in the other astronauts. A total of twenty-two 24-hour urine collections were obtained in space (n per astronaut = 1-14) and on the ground (n per astronaut = 2-12). Urinary albumin was measured by radioimmunoassay. For each astronaut, mean of data in space and on the ground was defined as individual average.

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ISOPTWPO Today The individual averages of 24 h urinary albumin were lower in space than on the ground in all astronauts; the difference was significant (mean +/- SD, space and on the ground = 3.41 +/- 0.56 and 4.70 +/- 1.20 mg/24 h, p = 0.017). Dietary protein intake and 24-hour urinary urea were not significantly different between space and on the ground.

Urinary albumin excretion is low during space mission compared to data on the ground before or after mission. Low urinary albumin excretion could be another effect of exposure to weightlessness (microgravity).

Acute urinary retention Urinary retention is the inability to completely empty the bladder. It has been reported during space flight on several occasions, usually occurring in the first 48 hours of flight, as part of the Space Adaptation Syndrome (SAS). Causes of urinary retention in the early phases of flight include altered baseline physiology seen with exposure to microgravity, anticholinergic side effects of medications that are taken to combat space motion sickness, and other contributing factors. SAS-related urinary retention may impact health on orbit by causing discomfort and increasing the risk of urinary tract infection (UTI). Treatment including urethral catheterization has been performed on orbit.

To date, only two astronauts have been reported to have transient urinary retention in spaceflights.

Although acute urinary retention (AUR) is not commonly thought of as a life-threatening condition, its presentation in orbit can lead to a number of medical complications that could compromise a space mission. A middle-aged astronaut who developed urinary retention during two spaceflights.

On the first mission of note, the astronaut initially took standard doses of promethazine and scopolamine before launch, and developed AUR immediately after entering orbit. For the first 3 d, the astronaut underwent intermittent catheterizations with a single balloon-tipped catheter. Due to the lack of iodine solution on board and the need for the astronaut to complete certain duties without interruption, the catheter was left in place for a total of 4 d.

Although the ability to void returned after day 7, a bout of AUR reemerged on day 10, 1 d before landing. On return to Earth, a cystometrogram was unremarkable. During the astronautâ&#x20AC;&#x2122;s next mission, AUR again recurred for the first 24 h of microgravity exposure, and the astronaut was subsequently able to void spontaneously while in space.

This report details the presentation of this astronaut, the precautions that were taken for space travel subsequent to the initial episode of AUR, and the possible reasons why space travel can predispose astronauts to urinary retention while in orbit.

The four major causes of AURâ&#x20AC;&#x201C;obstructive, pharmacologic, psychogenic, and neurogenic-are discussed, with an emphasis on how these may have played a role in this case.

Pharmacologic causes of an acute inability to void in space include scopolamine, an anticholinergic medication commonly used for space motion sickness or space adaptation syndrome (SMS/SAS) prevention that can inhibit detrusor muscle contraction, or promethazine, an antihistaminic/anticholinergic agent which may trigger retention due to its ability to competitively block muscarinic receptors.

Furthermore, although less likely, loss of the gravitational force that aids micturition could have been a contributing factor. Numerous precautions are taken to prevent AUR. Medications that can prevent SMS/ SAS, like ondansetron, with little or no side effects such as urinary retention, can be used instead. Keeping records of voiding frequencies plus a sonographic evaluation of postvoid residual volumes may prove helpful in the preflight screening. Routine urodynamics may prove helpful in preventing unexpected medical conditions in those with abnormalities on screening tests.

Renal Stone Formation The formation of renal stones poses an in-flight health risk of high severity, not only because of the impact of renal colic on human performance, but also because of complications that could possibly require crew evacuation such as hematuria, infection, and hydronephrosis.

Renal stones come in different types, and the formation of a specific stone-type depends upon the presence of particular risk factors.

1) The most common renal stone, and a main component in stones of mixed composition, is calcium oxalate. This

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ISOPTWPO Today type may occur as multiple stones or may recur, can induce pain with both passage and obstruction, and is commonly caused by treatable metabolic disorders of hypercalciuria.

2) Similar to calcium oxalate stones, uric acid stones induce the same adverse effects but differ with their rarer occurrence (only 5% of renal stones). Uric acid stones are also translucent and, unlike the other stones, cannot be distinguished by radiographs.

3) Struvite stones are generated by infections of urease-containing microorganisms that are capable of hydrolyzing the urea in urine to carbon dioxide and ammonia. When urine pH exceeds 7.2, struvite stones may form, and the resulting obstruction can fill the renal collection system and erode into the renal tissue. Treatment is by surgical removal unless stone size is <2 cm where lithotripsy can be applied to fragment the stone.

4)Unlike other renal stones, cystine stones have a single etiology - hereditary cystinuria - where stone formation begins in childhood and can grow large enough to fill the renal collection system.

5) Finally, brushite is the name for a calcium phosphate stone, the formation of which is promoted by high urine pH and supersaturation of urine with the calcium phosphate salt. Just as on Earth, it is more cost effective to prevent stone formation during a spaceflight mission than it is to treat a crewmember (Parks, 1996). Thus, understanding the etiology for the formation of specific stone types and identifying which stones are more likely to be formed during spaceflight missions will direct the application of appropriate countermeasures for nephrolithiasis.

Furthermore, renal stones have been documented in astronauts after return to earth and in one cosmonaut during flight. Biochemical analysis of urine specimens provided indications of hypercalciuria and hyperuricemia, reduced urine volumes, and increased urine saturation of calcium oxalate and calcium phosphate.

A major contributor to the risk for renal stone formation is bone atrophy with increased turnover of the bone minerals. Dietary and fluid intakes also play major roles in the risk because of the influence on urine pH (more acidic) and volume (lower).

Specific assessments in Skylab crewmembers indicated that calcium excretion increased early in flight (by 10 days) and almost exceeded the upper threshold for normal excretion (i.e., 300 mg/day in males) in some crewmembers during Skylab missions. Other crewmember data documented reduced intake of fluid and reduced intake of potassium, phosphorus and magnesium in the diet.

The results from an investigation of eleven astronauts and cosmonauts who flew on the Mir space station provided evidence of the risk for stone formation during long duration missions.Retrospective analysis of urinary data from U.S. Space Shuttle crewmembers was conducted in 24-hour urine specimens that were collected 10 days pre-launch Human Spaceflight Edition c International Space Agency (ISA)

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ISOPTWPO Today (approx L-10 day) and immediately post-landing. Analysis consisted of urine characteristics associated with renal stone formation and relative supersaturation of stone-forming constituents.

It was first reported that an increased risk of calcium oxalate and uric acid stone formation was evident immediately after spaceflight concurrent with the hypercalciuria and hypocitraturia quantified after return (Whitson et al., 1993). Further investigation, which included analysis of urine collected during flight, revealed that many of the contributing factors to renal stone formation during spaceflight were related to nutrition, urinary pH and volume output (Whitson et al., 1997).

In addition, biochemical analysis of urine specimens obtained during longer Shuttle missions provided a temporal reflection of the risk indicating that the increased risk for renal stone formation occurs rapidly during spaceflight, continues throughout the mission, and persists following landing (Whitson et al., 1999). In-flight evidence from Space Shuttle missions associated the urinary supersaturations and decreased urine excretion with reduced fluid intake, and that increasing the volume of urine output effectively reduced the risk factor (that is, urine supersaturations) (Whitson et al., 2001a).

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(Preflight renal stone risk) and (Postflight renal stone risk) profiles display the relative risks of stone formation in a representative crew member of a Space Shuttle flight.

Note that the increased postflight risk for stone formation (Postflight) corresponded 1) with a larger excretion of calcium and a reduction in pH (metabolic factors) 2) with a reduction in total urine volume and increased levels of sulfate (hydration and dietary factors) 3) with greater urine saturation for stoneforming salts (sodium urate, calcium oxalate, brushite, and uric acid stones).

Representative preflight renal stone risk profile determined in a single crew member before a shortduration flight (i.e., Space Shuttle). BLUE bars represent decreased risk, RED bars represent increased risk.

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Representative postflight renal stone risk profile determined in the same crewmember immediately following a shortduration flight (i.e., Space Shuttle).Blue bars represent decreased risk, red bars represent increased risk.

Until 2007, 14 renal stone episodes have been documented in 12 US astronauts (10 men, 2 women) with 9 stone events occurring in 7 crew members postflight. Multiple stone events among Russian cosmonauts have also been observed. One in-flight episode endangered a flight but was relieved by spontaneous stone passage.Of the renal stones recovered from astronauts, 4 stones were of calcium oxalate, 1 stone was of uric acid, 1 stone was of mixed components, and 9 were of unknown composition.

The results from an investigation of eleven astronauts and cosmonauts who flew on the Mir space station provided evidence of the risk for stone formation during long duration missions (Whitson et al., 2001). Data from missions ranging from 129 to 208 days suggested spaceflight and the return to Earth have acute effects on the urinary biochemistry that may favor increased crystallization in the urine.

Changes previously observed during short duration Shuttle flights included a rapid increase in the supersaturation of the stone-forming salts in the urine early during the flight that continued through landing day. However, the stoneforming potential in the urine was different during and after spaceflight. During flight, an increased risk occurred for both calcium oxalate and calcium phosphate stones. Immediately after flight, however, the risk was greater for calcium oxalate and uric acid stone development, which could be attributed to low urine volumes and decreased urinary pH. In these long-duration crewmembers, there was a 47% decrease in urine volume early during the missions (< flight day 30) and a 39% lower urine output late in the mission (> mission day 60). Urinary calcium levels during the preflight period ranged from 159 mg/day to 316 mg/day, and during flight the range was 129 mg/day to 435 mg/day.

During flight, 7 of the 11 crewmembers demonstrated higher in-flight urinary calcium values as compared to their respective preflight levels, and 5 of these 11 crewmembers exhibited calcium excretion greater than 250 mg/day. Data from these long duration missions suggested a similar trend, as with short duration misHuman Spaceflight Edition c International Space Agency (ISA)

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ISOPTWPO Today sions, showing increased risk for calcium phosphate stone formation occurring early in-flight.

These data suggested that the early phase (< 30 days) of spaceflight may generate conditions in which the risk of stone formation was greater than during the later phases of the mission. These data were consistent with the short duration Shuttle data in which both calcium oxalate and calcium phosphate risk increased.

A flight experiment (96-E057) performed during long duration missions ("Renal stone risk during spaceflight: Assessment and Countermeasure Evaluation" with PI: P. Whitson) will provide data from crewmembers of International Space Station (ISS) missions. The aim of the experiment was to evaluate the in-flight efficacy of potassium citrate as a mitigator of the formation of renal stones (particularly composed of calcium salts) during long-duration spaceflight.

Potassium citrate is a known therapy for the formation of calcium oxalate, calcium phosphate, and uric acid containing stones, because of the formation of the soluble calcium citrate complex; risk factors are also alleviated by the alkalization of urine and by the reduction of physiological acid/base ratio as induced by potassium and the metabolism of citrate to carbonate. This double-blind study required crewmember subjects on Expeditions 3-6, 8, and 11-14 to consume two tablets (placebo or 20 mEq potassium citrate) with the last meal of the day every day from L-3 to R+14 days (3 days pre-launch to 14 days after return). Twenty-four hour urine specimens were collected three times during flight: early (< 35 days into flight), middle (between 36-120 days into flight), and late mission (within 30 days of undocking).

All diet, fluid, exercise and medications were logged for 48 hours before and during the urine collection time to assess the potential impact from environmental factors. Urinary saturation levels were analyzed.

In addition to evaluating the efficacy of potassium citrate to minimize the risk of stone formation, the results of this experiment described the renal stone forming potential in crewmembers as a function of time in space as well as the stone forming potential during the postflight period.

RESULTS: • The majority of renal stones are composed of calcium containing salts. The risk of calcium oxalate stone formation as determined by the urinary supersaturation of calcium oxalate was observed to be lower in the potassium citrate treated group. The decreased risk was evident during the in-flight and immediate postflight assessment sessions. The risk of calcium phosphate (brushite) risk followed the same trend observed with the risk of calcium oxalate stone formation.

• The effect of fluid intake and urinary output on the supersaturation of the urine and the potential risk of stone formation. Regarding the correlation between 24-hr urinary volume and the risk of calcium oxalate stone development, data indicate an inverse relationship between urine volume and risk of calcium oxalate stone formation.

• Approval for elimination of the double blind requirement was received from NASA in December, 2005. As a result, the participating crewmembers ingested only potassium citrate as a countermeasure to the risk of renal stone formation. Data from all the ISS missions were combined for a detailed analysis involving statistical analysis and evaluation of the pharmacologic countermeasure to reduce the risk of stone formation.

• 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. Results from this investigation suggest that supplementation with potassium citrate may decrease the risk of renal stone formation during and immediately after spaceflight.

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ISOPTWPO Today Reference: 1." Norsk P, Christensen NJ, Bie P, Gabrielsen A, Heer M, Drummer C ", Unexpected renal responses in space,doi:10.1016/S01406736(00)03135-4 2.Spacelab Life Sciences 1,NASA-NP-120 3.SOLO - SOdium LOading in Microgravity,EXPERIMENT RECORD No 9112,ERASMUS EXPERIMENT ARCHIVE,ESA 4.Kirsch KA, Rocker L, Gauer OH, Krause R, Leach C, Wicke HJ, Landry R (1984) Venous pressure in man during weightlessness. Science 225:218-219 5.http://airex.tksc.jaxa.jp/pl/dr/AA0008883080 6.Gregoriev AI, Morukov BV, Voroblev DV (1994) Water and electrolyte studies during long-term missions onboard the space stations SALYUT and MIR. Clin Invest 72(3):169-189 7.Cirillo M, De Santo NG, Heer M, Norsk P, Elmann- Larsen B, Bellini L, Stellato D, Drummer C (2002) Urinary albumin in space missions. J Gravit Physiol 9(1):P193-P194 8.Cirillo M, De Santo NG, Heer M et al (2003) Low urinary albumin excretion in astronauts during space missions.

Nephron Physiol93:102-105 9.Whitson PA, Pietrzyk RA, Pak CY, Cintron NM. 1993. Alternations in renal stone risk factors after spaceflight. J Urol.

150(3):803-807 10.Whitson PA, Pietrzyk RA, Pak CY. 1997. Renal stone risk assessment during Space Shuttle flights. J Urol. 158(6):23052310.

11.Whitson PA, Pietrzyk RA, Sams CF. 1999. Space flight and the risk of renal stones. J Gravit Physiol. 6(1):P87-88.

12.Whitson PA, Pietrzyk RA, Morukov BV, Sams CF. 2001. The risk of renal stone formation during and after long duration spaceflight. Nephron. 89(3):264-270.

13.Whitson PA, Pietrzyk RA, Sams CF. 2001a. Urine volume and its effects on renal stone risk in astronauts. Aviat Space Env Med.72:368-372.

14.Pietrzyk RA, Jones JA, Sams CF, Whitson PA (2007) Renal stone formation among astronauts. Aviat Space Environ Med 78(4, Suppl):A9-A13 15.Risk of Renal Stone Formation,HRP-47060,NASA 16.The kidney in space,DOI 10.1007/s11255-012-0289-7

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ISOPTWPO The ISOPTWPO is International Space Flight & Operations - Personnel Recruitment, Training, Welfare, Protocol Programs Office (International Space Academy). It is a division of the ISA organization.

Mr. Martin Cabaniss is director and Mr. Abhishek Kumar Sinha is Assistant Director of ISOPTWPO. Ad Astra ! To The Stars! In Peace For All Mankind !

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