Changes in Urine Parameters After Desert Exposure: Assessment

of Stone Risk in United States Marines Transiently Exposed to a

Desert Environment

James H. Masterson,* Victor J. Jourdain, Daniel A. Collard, Chong H. Choe,Matthew S. Christman, James O. L’Esperance and Brian K. Auge

From the Department of Urology, Naval Medical Center San Diego, San Diego (JHM, DAC, CHC, JOL) and 2nd Battalion, 4th MarineRegiment Battalion Surgeon, Camp Pendleton, Camp Pendleton (VJJ), California; Division of Urology, Children’s Hospital of Philadelphia,Philadelphia, Pennsylvania (MSC); and St. Luke’s Mountain States Urology, Boise, Idaho (BKA)

Purpose: Living in a desert environment has been associated with a higherincidence of kidney stone formation, likely because of concentrated urine output,higher production of vitamin D and genetic predisposition. We determined thechanges in urinary parameters after a group of United States Marines tempo-rarily transitioned from a temperate environment to a desert environment.Materials and Methods: A total of 50 Marines completed a questionnaire andperformed 3, 24-hour urine collections before mobilization to the desert, after 30days in the desert and 2 weeks after returning from the desert.Results: Daily urine output decreased 68% to 0.52 L despite marked increasedfluid intake (17 L per day). Total daily urinary excretion of calcium, uric acid,sodium, magnesium and potassium in the desert decreased by 70%, 41%, 53%,22% and 36%, respectively. Urinary pH decreased from 6.1 to 5.6 while in thedesert, and citrate and oxalate had minimal changes. After their return from thedesert, apart from a decrease of 22% in oxalate, there were no statisticallysignificant differences from baseline. While in the desert, relative supersatura-tion risks of uric acid and sodium urate were increased 153% and 56%, respec-tively. Brushite relative supersaturation decreased 24%. After their return therewas no statistical difference from baseline.Conclusions: Our findings suggest that the kidneys preserved water and elec-trolytes while the Marines were subjected to the desert environment. Despite thisconservation, relative saturations indicate increased risk of stones in healthymen exposed to a desert environment with rapid resolution upon return.

Abbreviations

and Acronyms

MRE � meals ready to eat

RS � relative supersaturation

Accepted for publication August 8, 2012.Study received institutional review board ap-

proval.The views expressed in this article are those

of the authors, and do not reflect the officialpolicy or position of the Department of the Navy,Department of Defense or the United States Gov-ernment.

* Correspondence: Department of Urology,Naval Medical Center, San Diego, 34800 Bob Wil-son Drive, San Diego, California 92124 (telephone:619–532-7200; e-mail: James.masterson@med.navy.mil).

See Editorial on page 16.

Key Words: urolithiasis, desert climate, military personnel

POPULATIONS residing in a desert envi-ronment have long been suspected tohave a propensity for the formation ofurinary stones. It was as early as1902 when Mr. F. R. S. Milton, anEnglish surgeon stationed in Cairo,Egypt noted a yearly average of 150stone admissions to the Kasr-el-AinyHospital.1 The lifetime risk of uroli-

thiasis is 10% to 15% in the developed

0022-5347/13/1891-0165/0THE JOURNAL OF UROLOGY®

© 2013 by AMERICAN UROLOGICAL ASSOCIATION EDUCATION AND RES

world but can be as high as 20% to25% in the Middle East.2 More re-cently this increased incidence ofstone disease was seen in militarypersonnel translocated to a desert en-vironment as described by Evans andCostabile in 2003 regarding Kuwaitand Iraq.3 One presumed cause of thisincreased stone propensity is diaphoresis

and increased urinary concentration.

http://dx.doi.org/10.1016/j.juro.2012.08.097Vol. 189, 165-170, January 2013

EARCH, INC. Printed in U.S.A.www.jurology.com 165

CHANGES IN URINE PARAMETERS AFTER DESERT EXPOSURE166

This has also been shown to be the case in manuallaborers exposed to extreme conditions, such as steelworkers.2

Sunlight exposure has been studied as a cause ofhypercalciuria. Several epidemiological studies in-volving lifeguards in Israel and English troops de-ploying to Bahrain have demonstrated this connec-tion. The mechanism is likely due to increasedsunlight related vitamin D production leading tosolar absorptive hypercalciuria.4,5

Genetic causes have been implicated, as demon-strated by Arab populations having a higher preva-lence of CA II genetic mutations and SoutheastAsian populations having a higher incidence of AE1genetic mutations. These mutations are both asso-ciated with renal tubular acidosis type 1, which is aknown risk factor for stone formation.6

In this study we assessed the effects of acuteenvironmental change on urinary parameters asso-ciated with the stone formation. We studied a groupof United States Marines mobilized from a temper-ate environment to a desert environment for amonthlong period of intense training. To our knowl-edge, a study of this nature has not been conducted.We hypothesized that this environmental transitionwould cause an increase in lithogenic factors in a24-hour urine profile.

MATERIALS AND METHODS

After obtaining institutional review board approval, 50United States Marines were recruited as volunteers froman Infantry Battalion of 1,000 men. The battalion, sta-tioned in San Diego, was due to conduct a 1-month exer-cise in the Mojave Desert during the month of July. Froma 98-man company 50 were enrolled. Exclusions werebased solely on funding and the consent process, and noton past medical history. A baseline 24-hour urine collec-tion called Baseline was performed immediately beforedeployment, and a second urine collection called Desertwas performed after the Marines were in the desert be-tween 3 and 4 weeks. A third collection called Return wasperformed 2 weeks after the completion of the exercise.The 24-hour urine collection measured volume, pH, andexcreted calcium, oxalate, uric acid, citrate, sodium, cre-atinine, phosphorus, magnesium and potassium. We usedUroRisk® kits for all collection analysis. The relative su-persaturation risks for sodium urate, brushite and cal-cium oxalate were also measured. Before the exercise theMarines lived in air-conditioned barracks near the coast-line in a temperate climate. During the deployment theywere required to abstain from coffee, alcohol and weightlifting supplements. Hydration was encouraged but no setvolume was given. The Marines were issued MREs 3 timesper day with a daily 20 oz electrolyte beverage (table 1).They also had ready access to water which was not forti-fied with minerals or electrolytes.

The Marines simulated a combat environment and of-

ten wore full battle dress, which consists of body armor,

helmets, full-length sleeves and pants, and combat boots.They were encouraged to cover exposed skin with sun-block.

Information was collected on each volunteer’s personalmedical history, diet and fluid intake in the desert, as wellas family medical history of stones. Weather informationfor the desert and southern California was recorded aswell.7

Statistical analysis was performed using QuickCalcs(GraphPad®). Simple statistics were used to calculate pa-tient demographics, and 2-tailed paired t tests were usedto compare individual test results, calculate p values anddetermine 95% CIs with � � 0.05. Statistical significancewas set at p �0.05.

RESULTS

A total of 50 male United States infantry Marineswere recruited into the study and completed theinitial baseline 24-hour urine collection. Median agewas 19 years (range 19 to 25) and median weightwas 77.3 kg (range 63.6 to 101.4). Of the subjects92% (46 of 50) completed the second 24-hour urinecollection. Two subjects were medically evacuatedfor nonheat related injuries and 2 did not provide asample. The third urine collection was submitted by72% (36 of 50) of the Marines. The remainder did notprovide a sample because they had immediately de-ployed overseas after returning from the desert. Thestudy questionnaires were completed by 68% (34 of50) with the remainder not returning the question-naire before deployment. A family history of kidneystones in a first-degree relative was identified by 6%(2 of 34). No subjects were taking medications. OneMarine had a diagnosis of hypertension, and 1 had ahistory of heat exhaustion as well as a family historyof kidney stones.

The average high temperature before deploying tothe desert was 78F with 77% humidity. In the desertthe average high was 106F with 29% humidity.After returning to base the average high was 73F

Table 1. Oral intake

Av Amount (range)

Water 17 (12–21) LEnergy 2,645 kcalProtein 64 gmCarbohydrate 381 gmFat 1.5 gmVitamin D4 3.5 mcgCalcium 700 mgPhosphorus 490 mgSodium 3,785–5,185 mgPotassium 2,240 mg

The Marines consumed a large quantity of water and a balanced diet slightlyheavy with sodium while in the desert. These amounts do not reflect salt packetsincluded in MREs.

with 78% humidity.7 The Marines reported wearing

CHANGES IN URINE PARAMETERS AFTER DESERT EXPOSURE 167

full gear with long sleeves and sweating continu-ously throughout the exercise. Of the 1,000-manbattalion 3 were diagnosed in the field with symp-tomatic kidney stones during the monthlong exer-cise and were medically evacuated. These 3 Marineswere not study participants.

Table 1 shows oral intake while in the desert,calculated with the known nutritional value ofMREs and a 20 oz electrolyte beverage containingcitrate.8 The total volume was obtained by askingthe Marines how much water they drank (3 L perportable water pack).

All urine collections with a 24-hour creatininegreater than 38.3 mg/kg or less than 13.5 mg/kg perday were excluded from analysis. These limits wereobtained from the 1976 study by Greenblatt et al onthe range of creatinine clearance in young men.9

This resulted in an adequate collection for 98% (49 of50) of first collections, 74% (34 of 46) of second col-lections and 50% (18 of 36) of third collections. Noneof the desert collections was noted to have uric acidcrystals. The laboratory noted uric acid crystals inthe specimen in 1 baseline collection and 1 returncollection.

Table 2 shows the median results from each col-lection with interquartile ranges. For statisticalcomparison 33 subjects had adequate first and sec-ond collections, and 18 subjects had adequate firstand third collections. A paired t test was used tocompare the first and second collections as well asfirst and third collections (table 3). The figure is agraphic presentation of the results in table 3. Per-cent changes in desert collection and return collec-tion urinary parameters are compared to the base-line collection.

Notable findings were the decrease in severalurine parameters from the baseline collection whilein the desert, including total volume 68%, uric acid

Table 2. 24-Hour urine parameters

Median Baseline Collection (IQR)

Total vol (L/day) 1.36 (1.11–2.06)Creatinine (mg/day) 1,941 (1,541–2,160)Calcium (mg/day) 191 (147–231)Oxalate (mg/day) 33 (27–37)Uric acid (mg/day) 625 (471–788)Citrate (mg/day) 349 (252–528)pH 6.1 (5.8–6.4)Sodium (mEq/day) 156 (132–193)Phosphorus (mg/day) 1,161 (893–1,452)Magnesium (mg/day) 135 (104–164)Potassium (mEq/day) 43 (34–61)Sodium urate RS 2.7 (1.6–5.7)Calcium oxalate RS 1.9 (1.1–2.4)Brushite RS 2.2 (1.6–2.9)Uric acid RS 1.3 (0.6–2.6)

Median 24-hour urine volume in the desert was 0.47 L. The body appeared to co

appeared to decrease in the desert from 6.1 to 5.6. Surprisingly citrate and oxalate wer

41%, sodium 55%, magnesium 22% and potassium34%. Statistical significance was attained in allthese parameters and no urine parameters had anincrease from baseline.

The other findings noted were that average pHdecreased from 6.1 to 5.6, which was statisticallysignificant. In addition, oxalate and citrate re-mained relatively unaffected. The RS risk of stonedisease changed with increases in sodium urate of56%, calcium oxalate 14%, uric acid 150%, and adecrease in brushite of 24%. The RS for uric acid,sodium urate and brushite reached statistical signif-icance.

After returning from the desert, all values re-mained decreased from the baseline collection withstatistical significance reached only in oxalate. Totalvolume was decreased by 8%, calcium by 16%, ox-alate 22%, uric acid 21%, citrate 29%, sodium 18%,phosphorus 21%, magnesium 13% and potassium23%. Average pH had changed from 6.2 before de-parture to 6.0 upon return, but this was not statis-tically significant.

Other notable findings from the return collectionwere that oxalate urinary excretion had decreasedslightly while in the desert (8%), which was notstatistically significant. It decreased even moreafter returning (22%), which was statistically sig-nificant. RS risks did not show statistically signif-icant changes.

DISCUSSION

The total urinary volume was surprisingly low whilein the desert. The Marines drank an average of 17 Lwater not fortified with electrolytes per day. Thisextreme difference between oral fluid intake andurinary output can only be explained by sweatingand insensible losses. Previous physiological studies

Median Desert Collection (IQR) Median Return Collection (IQR)

0.47 (0.38–0.58) 0.96 (0.70–1.36)1,580 (1,426–2,226) 1,567 (1,341–1,893)

52 (26–76) 150 (121–203)32 (21–39) 24 (19–37)

377 (206–470) 459 (324–699)336 (250–480) 313 (174–413)

5.6 (5.5–5.9) 6.0 (5.6–6.4)69 (36–94) 130 (81–175)

1,078 (783–1,324) 892 (663–1,176)111 (78–123) 100 (74–153)

29 (21–40) 40 (29–46)5.1 (1.7–7.9) 3.9 (1.9–5.6)2.2 (1.6–2.8) 2.0 (1.6–2.4)1.7 (0.8–2.8) 2.2 (1.3–3.4)4.5 (3.0–6.9) 1.8 (1.0–3.7)

calcium, uric acid, sodium and potassium while in the desert. The urine pH also

nserve e relatively unchanged.

CHANGES IN URINE PARAMETERS AFTER DESERT EXPOSURE168

showed the maximum amount of sweat humans canproduce is 3 L per hour but the average maximumamount is 1.4 L per hour.10

Our patients demonstrated decreased urinary ex-cretion of potassium, calcium, sodium and magne-sium while in the desert. This is likely a physiolog-ical response to electrolyte loss during sweating inthe extreme heat. Indeed, in subjects undergoing asweat test in which they lost approximately 2% of

Table 3. Paired t-test comparisons

Change from Baseline to DesertCollection (95% CI)/% (in 25)

Total vol (L/day) �1.10 (�1.38 to �0.83)/�68Creatinine (mg/day) �107 (�361 to 146)/�6Calcium (mg/day) �140 (�171 to �110)/�70Oxalate (mg/day) �1.6 (�7.6 to 4.3)/�5Uric acid (mg/day) �253 (�347 to �159)/�41Citrate (mg/day) �36 (�103 to 31)/�9pH* �0.38 (�0.57 to 0.18)Sodium (mEq/day) �88 (�115 to �61)/�55Phosphorus (mg/day) �48 (�247 to 151)/�4Magnesium (mg/day) �30 (�53 to �9)/�22Potassium (mEq/day) �18 (�27 to �8)/�36Sodium urate RS 2.1 (0.3 to 3.9)/56Calcium oxalate RS 0.3 (�0.2 to 0.7)/14Brushite RS �0.6 (�1.1 to �0.01)/�24Uric acid RS 2.9 (1.3 to 3.9)/153

A paired t test shows reduced total volume, calcium, uric acid, sodium, magnessignificantly difference from the baseline measurement was decreased oxalate exof 0.06. The RS of sodium urate and uric acid increased, but brushite decreased ibetween the baseline and return collections.* A percentage value was not given to change in pH because pH is a logarithmifrom the baseline to the desert value.

-100%-75%-50%-25%

0%25%50%75%

100%125%150%175%200%225%

Percent change inbaseline

Collec�on in desert

Body reduced excretion of total volume, calcium, uric acid, wateoxalate had statistically significant decrease with citrate trendinincreased in desert with decrease in brushite. After returningformation. pH had statistically significant decrease from 6.1 t

statistically significant when going from baseline to return.

their body weight, several electrolytes were cap-tured in the sweat of each patient including 190 mgpotassium, 50 mg calcium, 1,170 mg sodium and1,600 mg chloride.11

Interestingly in 1975 Parry and Lister reportedincreased calciuria in a patient population that de-ployed to a desert environment.5 In a study on life-guards in Israel Better also reported increased cal-ciuria.4 Nevertheless, our patient population had a

ValueChange from Baseline to Return

Collection (95% CI)/% (in 18) p Value

0.01 �0.13 (�0.98 to 0.13)/�8 0.130.40 �271 (�618 to 74)/�14 0.120.01 �31 (�97 to 35)/�16 0.350.58 �8 (�15 to �1)/�22 0.030.01 �148 (�319 to 22)/�21 0.860.28 �130 (�263 to 5)/�29 0.060.01 �0.16 (�0.47 to 0.16) 0.320.01 �32 (�85 to �21)/�18 0.220.63 �260 (�527 to 8)/�21 0.060.01 �18 (�59 to 22)/�13 0.360.01 �12 (�25 to 1)/�23 0.070.02 �0.3 (�2.5 to 2.0)/�6 0.800.21 0.2 (�0.4 to 0.8)/9 0.550.04 0.1 (�1.1 to 0.9)/�4 0.830.01 �0.4 (�0.7 to 1.6)/22 0.45

potassium while in the desert. Two weeks after returning the only statisticallyand citrate was trending toward a statistically significant decrease with a p valuesert with statistical significance. No statistical difference was noted in RS values

value. However, a statistically significant decrease in pH was noted when going

e parameters from 95% CI bars

2 weeks a�er return from the desert

ium, magnesium and potassium in desert. After returning, onlyard decreased amount. RS for sodium urate and uric acid wastatistically significant change was noted in RS for any stoneoing from baseline to desert collections. This value was not

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CHANGES IN URINE PARAMETERS AFTER DESERT EXPOSURE 169

decrease in calcium excretion, which may be due tophysiological conservation or perhaps to the limitedsunlight exposure. Requiring the men to wear fullcombat gear and sunscreen may have significantlylimited their effective sunlight exposure. This con-cept is especially true for this population as they livein a very sunny climate at baseline and are outsidefor several hours daily. In this regard our study mayrepresent a unique and paradoxical example of sun-light exposure deprivation, despite the fact that thesubjects deployed to a desert climate. This can becorroborated with studies of women in the MiddleEast. Hovsepian et al reported on vitamin D defi-ciency among adults in Isfahan, Iran,12 and Groen etal reported on osteomalacia among the Bedouin ofthe Negev.13 Laboratory studies showed that womenhad decreased levels of vitamin D with a subgrouphaving decreased serum calcium which was attrib-uted to their legal requirement to wear long sleevesand a veil. In a study of volunteers prevented fromsunlight exposure the lack of sunlight caused a de-creased amount of calcium in as little as 2 weeks.14

Urinary output of uric acid decreased drasticallyin the desert. We believe that this is not due tocrystal precipitation because no desert specimenwas reported as having crystals. The only 2 speci-mens with crystals in the study were from the base-line and return collections. Interestingly, humans,along with phylogenetically unrelated animals, haveincreased serum uric acid because of the dysfunctionof the gene that produces uricase. Excess uric acid iscurrently being studied as a free radical scavengerthat humans possess possibly to protect their largerand more complex brains.15 If uric acid is not only awaste product, but is a necessary component of hu-man physiology, this may explain why uric acid wasconserved in the extreme heat of the desert with theprevention of its excretion in urine. However, al-though uric acid was conserved, the uric acid stoneRS increased 2.4 times that of baseline, likely be-cause the even more pronounced decreased urinarywater output caused a supersaturation of the uricacid that remained.

Oxalate levels were even more decreased afterreturning from the desert where the difference wasstatistically significant. We suspect that this findingmay be diet related. In the desert the men had acontrolled diet, but before deployment and after re-turning the diet was uncontrolled. Further studiesmay investigate this anomaly by controlling dietbefore and after desert exposure.

Citrate levels had a nonstatistically significantdecrease in the desert, but decreased by 29% onreturn with a p value approaching significance at0.06. This anomaly may also be related to dietchanges after return and may serve as a point of

intervention. Our population had a controlled diet in

the desert only, but Marines deployed to desert ar-eas overseas often have access to cafeteria style foodwith a wide range of selection. Future studies mayinvestigate urine parameters of a population de-ployed to the desert and exposed to a broader rangeof food selection.

During the exercise 3 of 1,000 men were diag-nosed with kidney stones by flank pain in the pres-ence of hematuria. This number can roughly be ex-trapolated to a 3.6% incidence per year, which iseven higher than the annual incidence of 2% forpeople living in the desert compared to the 0.1% to0.3% annual incidence rates for the general popula-tion.16 Despite the reduced urinary excretion of uricacid, calcium and sodium, the RS risk of sodium urate,calcium oxalate and uric acid increased, with statisti-cal significance noted for sodium urate and uric acid.Despite physiological mineral conservation, the urinecontinued to be supersaturated because of the evenmore pronounced water conservation.

Several limitations of this study must be acknowl-edged. The subject population included only healthyyoung men, but no women, children or older sub-jects. In addition, none of the patients had previ-ously been diagnosed with a stone. Our subject pop-ulation was extremely physically active during themidday in the intense heat of the desert, which maybe different from populations living or transferringto the desert.

Total creatinine was problematic because of theuncertainty of the effect that the deployment wouldhave on creatinine excretion. Despite strict instruc-tions, some of the collections may have been over-collected or under-collected. We obtained our creat-inine limits of 13.5 to 38.3 mg/kg per day from aprospective study on creatinine excretion performedin 1976.9 In that study Greenblatt et al performed54 to 97, 24-hour urine collections from healthyyoung men with a noted range of 13.5 to 38.3 mg/kgper day and a coefficient of variation of 14.4.9 Withthis broad range of creatinine excretion we mayhave included inadequate or over-collected samplesin our analysis.

Further studies need to be performed with abroader section of the population including knownstone formers and women. Further studies shouldalso include subjects who are not undergoing ex-treme physical exertion when deployed to the desert.This setup will more accurately portray the effect ofthe desert environment on a group simply translo-cating to a desert environment.

CONCLUSIONS

Significant and somewhat unexpected acute changesin the 24-hour urine profile were seen in a group of

deployed Marines who transitioned from a temper-

CHANGES IN URINE PARAMETERS AFTER DESERT EXPOSURE170

ate to a desert environment. There was a globalreduction in total volume, calcium, uric acid, mag-nesium and potassium amounts. The RS risk of

stone formation was significantly increased for uric

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