This viewgraph presentation describes the risks of renal stone formation in manned space flight. The contents include: 1) Risk; 2) Evidence; 3) Nephrolithiasis -A Multifactorial Disease; 4) Symptoms/signs; 5) Urolithiasis and Stone Passage; 6) Study Objectives; 7) Subjects; 8) Methods; 9) Investigation Results; 10) Potassium Citrate; 11) Calcium Balance; 12) Case Study; 13) Significant Findings; 14) Risk Mitigation Strategies and Recommended Actions; and 15) Future Potential

Jones, Jeffery A.

Pietrzyk, Robert A.

Sams, Clarence F.

Smith, Scott M.

Whitson, Peggy A.

NASA Technical Reports Server

Bone 
demineralization
Underlying 
medical
disease
RENAL STONE RISK DURING SPACEFLIGHT:
ASSESSMENT AND COUNTERMEASURE VALIDATION
PRINCIPAL INVESTIGATOR:  Peggy A. Whitson, Ph.D., CB/NASA/JSC
CO-INVESTIGATORS:
Robert A. Pietrzyk, M.S., SK/Wyle
Clarence F. Sams, Ph.D, SK/NASA/JSC
Jeffery A. Jones, M.D., SD/NASA/JSC
Scott M. Smith, Ph.D., SK/NASA/JSC
SCIENCE TEAM:
Ed K. Hudson, Ph.D., SK/JES Tech
Mayra Nelman-Gonzalez, SK/Wyle
https://ntrs.nasa.gov/search.jsp?R=20090006694 2019-08-30T06:11:04+00:00Z
Risk
• Mission risk and Impacts:
 Potential risk condition exists during the pre-, in- and postflight 
phases
 Risk to crewmember for both acute and chronic health effects
 Potential for significant impact to mission operational objectives
• Early termination of mission
• Significant impact to affected crewmember’s performance
• Significant impact to other crewmembers for medical care 
and treatment of affected crewmember
EVIDENCE
 As of 2008, 15 symptomatic urinary 
calculi have been experienced by 13 
U.S. astronauts (Pietryzk, et al, 2006; 
Jones et al, 2008)
Multiple stone events among 
cosmonauts reported by Russian 
medical investigators 
 One in-flight episode nearly causing 
a mission termination but was resolved 
by spontaneous stone passage
RENAL STONE 
FORMATION
Urine supersaturation
of stone-forming
salts
Bone 
loss
Low fluid 
intake
Excess
calcium
excretion
Low urine
volume
Low urinary
pH
Decreased
urinary
citrate
Nutrition Renal stone
history
Underlying 
medical
disease
High
calcium
intake
High
sodium
intake
High
protein
intake
NEPHROLITHIASIS – A MULTIFACTORIAL DISEASE
SYMPTOMS/SIGNS
• Severe / agonizing pain in the flank (back just below the 
ribs spreading around to the front of the abdomen) often 
extending into the groin area.
• Usually nausea and often vomiting
• Fever chills and sepsis, if infection is present
• Gross or microscopic blood in the urine
• Progression if not treated, hydronephrosis, renal 
shutdown
Urolithiasis and Stone Passage
Stone Size Chance of 
Spontaneous 
Passage
Time to Pass 
Stone
Require 
surgical 
intervention
<2 mm >85% 4.5-8 days 5%
<5 mm 78-80 7 – 14.5 days 17%
5-7 mm 20-50%
(35% avg)
5.5-22 days 50%
>7 mm < 10% 
(8% avg)
53 days - never >80%
Stones 3 mm in size can cause transient or complete obstruction 
Recurrence approx 5-10%/year up to 75% at 20 years
STUDY OBJECTIVES
 Quantitate the pre-, in- and postflight risk of renal stone formation 
associated with space flight.
 Determine the efficacy of potassium citrate as a countermeasure 
in reducing the in-flight and postflight for renal stone formation.
 Evaluate dietary impact on the urinary biochemistry.
SUBJECTS
Placebo Group: n = 18
NASA-Mir missions   12 male subjects, mission duration  129 - 208 days
ISS missions               6 male subjects, mission duration 93 - 175 days 
KCIT Group: n = 12 
ISS missions 11 male/1 female subjects, mission duration 93 - 175 days 
 24-hour urines collected pre-, in-, and post-flight
 Food, fluid, exercise, and medications monitored before and
during the urine collection period
 Two potassium citrate (KCIT) pills, 10 mEq/pill, ingested daily
(with the last meal of the day) from L-3 days to R+14 days
• Double-blind study design except for last 3 ISS subjects
 Biochemical analysis of urine samples for urinary 
factors associated with stone formation
 Dietary analysis completed to assess 
environmental influences on the urinary 
biochemistry
METHODS
INVESTIGATION
RESULTS
The majority of oral citrate is metabolized in the liver to bicarbonate, 
each citrate ion producing three bicarbonate ions.
Potassium Citrate
HCO3
pH
U-Citrate U-Calcium
Renal Stone
Effects on renal physiology
65-90% of filtered citrate is reabsorbed
10-35% of citrate is excreted into the urine
Effects of dosage used (20 mEq/d)
expected urinary increase of 130-140 mg/d
expected rise in urinary pH of 0.2 – 0.3 unitsUrinary Supersaturation
KCIT dosage of 20 mEq/d selected based on;
 results from Shuttle and NASA-Mir missions
 minimize any potential for in-flight GI upset 
(wax matrix/ slow release prep)
 minimize the potential to exaggerate the risk
for CaP stones (higher pH 7.25-7.5)
 minimize impact to crew time
D
IE
TA
RY
 F
LU
ID
 IN
TA
K
E 
 (l
/d
)
0
1
2
3
4
5
PLACEBO
KCIT
*
*
*
* *
U
R
IN
AR
Y 
TO
TA
L 
VO
LU
M
E 
(l/
d)
0.0
0.5
1.0
1.5
2.0
2.5
3.0
3.5
PLACEBO
KCIT
FLUID 
BALANCE
Fluid intake during flight
Low urine volumes (< 2L/d)
Similar fluid intake and total urine
volumes between groups
U
R
IN
A
RY
 p
H
5.0
5.5
6.0
6.5
7.0
7.5
PLACEBO
KCIT   
* *
*
* *
Effect of Potassium Citrate on Urinary pH
Urinary pH in
KCIT crewmembers, 
but not too high
U
R
IC
 A
C
ID
 S
U
PE
R
SA
TU
R
AT
IO
N
0
1
2
3
4
5
PLACEBO 
KCIT
Risk of uric acid stone
formation in KCIT 
crewmembers
Uric Acid Stones
Image from Mission Pharmacal
Effect of Potassium Citrate on Uric Acid Supersaturation
U
R
IN
AR
Y 
C
AL
C
IU
M
  (
m
g/
d)
0
100
200
300
400
PLACEBO
KCIT  
* *
*
D
IE
TA
RY
 C
AL
C
IU
M
  (
m
g/
d)
0
500
1000
1500
2000
PLACEBO 
KCIT 
CALCIUM
BALANCE
Dietary Ca intake below 
recommended levels
Urinary Ca excretion in KCIT
crewmembers
IN
-F
LI
G
H
T 
C
AL
C
IU
M
 O
XA
LA
TE
SU
PE
R
SA
TU
R
AT
IO
N
 (l
og
)
KCIT SUBJECTS
PREFLIGHT CALCIUM OXALATE
SUPERSATURATION (log)
-0.2 0.0 0.2 0.4 0.6 0.8 1.0 1.2 1.4
-0.5
0.0
0.5
1.0
1.5
2.0
2.5
PREFLIGHT CALCIUM OXALATE
SUPERSATURATION (log)
PLACEBO SUBJECTS
-0.2 0.0 0.2 0.4 0.6 0.8 1.0 1.2 1.4
-0.5
0.0
0.5
1.0
1.5
2.0
2.5
IN
-F
LI
G
H
T 
C
AL
C
IU
M
 O
XA
LA
TE
SU
PE
R
SA
TU
R
AT
IO
N
 (l
og
)
Comparison of in-flight risk to 
individual’s preflight risk
KCIT subjects maintained calcium
oxalate risk at preflight levels
C
Risk of Calcium Oxalate
Stone Formation
CASE STUDY
U
R
IN
AR
Y 
C
IT
R
AT
E 
 (m
g/
d)
0
500
1000
1500
2000
MIR
ISS
U
R
IN
AR
Y 
C
AL
C
IU
M
  (
m
g/
d)
0
100
200
300
400
500
MIR
ISS 
MIR IN-FLIGHT
HYPERCALCIURIA
CREWMEMBER PARTICPATED 
IN BOTH MIR AND ISS MISSIONS
MIR – No Treatment
ISS - KCIT
IN-FLIGHT CALCIUM EXCRETION 
DURING KCIT INGESTION
CASE STUDY
U
R
IN
AR
Y 
TO
TA
L 
VO
LU
M
E 
 (l
/d
)
0.0
0.5
1.0
1.5
2.0
2.5
3.0
MIR 
ISS
U
R
IN
AR
Y 
pH
5.0
5.5
6.0
6.5
7.0
7.5
MIR
ISS
Low urine volume during 
both missions
In-flight urinary pH during 
KCIT ingestion
CASE STUDY
U
R
IC
 A
C
ID
SU
PE
R
SA
TU
R
AT
IO
N
0
1
2
3
4
5
6
7
MIR
ISS
C
AL
C
IU
M
 O
XA
LA
TE
SU
PE
R
SA
TU
R
AT
IO
N
0
1
2
3
4
5
6
MIR 
ISS 
Decreased urinary supersaturation
during KCIT ingestion
Supersaturation values >2.0
indicate greater risk for
stone formation
 KCIT treated subjects exhibited decreased urinary calcium
excretion.
 KCIT subjects maintained the levels of calcium oxalate
supersaturation risk at their preflight levels.
 Increased urinary pH levels in KCIT treated subjects reduced the
risk of uric acid stones.
 Individual crewmember response may play a role in renal stone
susceptibility and efficacy of countermeasures.
SIGNIFICANT FINDINGS
Risk Mitigation Strategies 
and 
Recommended Actions
Recommendations
URINARY TOTAL VOLUME (l/d)
0 1 2 3 4 5
0
2
4
6
8
10
12
C
AL
C
IU
M
 O
XA
LA
TE
 
SU
PE
R
SA
TU
R
AT
IO
N
URINARY TOTAL VOLUME  (l/d)
0 1 2 3 4 5
U
R
IC
 A
C
ID
SU
PE
R
SA
TU
R
AT
IO
N
0
1
2
3
4
5
6
7
 Encourage increased fluid intake to increase urine volume
Recommendations
 Use of Potassium Citrate
• urinary inhibitor of calcium-containing stones, binds with
calcium reducing the amount of calcium available to form CAOX
• inhibits crystal growth,  aggregation  and nucleation
• alkalinizes urine and decrease urinary calcium excretion
• supported by Space Medicine
• in Transition to Medical Practice process for operational use
 Assess dietary influences
• decrease protein, sodium and oxalate intake
• maintain calcium intake to recommended levels
 Perform urinary risk assessments
• identify crewmembers who are at any elevated risk
• provides an education program to help humans remain
healthy during space exploration
FUTURE POTENTIAL
(URINARY CALCIUM * URINARY OXALATE)/ 
URINARY TOTAL VOLUME
0 5000 10000 15000 20000 25000
C
AL
C
IU
M
 O
XA
LA
TE
SU
PE
R
SA
TU
R
AT
IO
N
0
2
4
6
8
10
12
Potential In-Flight Prediction of Stone Risk
Capability to measure urine volume provided with the installation of the
UMS on Flight 20A and the addition of the in-line calcium sensor for 
real-time data collection
Development of an oxalate sensor would be required to optimize real-time risk
Urine Monitoring System (UMS)
“ I'd rather give birth to an elephant than go through this”.
“ Like being hit with a two-by-four” .
“ Like being shot with an arrow”.  
“ Pain came on suddenly and did not pass until doctors hopped me up on pain 
meds. I've had  my gall bladder removed and nearly severed my thumb but I 
never in my life felt pain like this.  Would wish it upon no one!! 
“  I have had my leg crushed by a car backing over it and that has nothing 
compared to the pain  of a kidney stone”  !!!!
PATIENT COMMENTS: 
Characterizing the symptoms
ACKNOWLEDGEMEMTS
 All the astronauts and cosmonauts who participated in this study
 Mission Pharmacal, San Antonio, TX. for kindly providing both the
potassium citrate and placebo drugs (Space Act Agreement)
 Mineral Metabolism Lab, Center for Mineral Metabolism & GCRC, UT
Southwestern Med.Ctr. Dallas, TX
 NASA Johnson Space Center Clinical Laboratory
 NASA Johnson Space Center Nutritional Biochemistry Laboratory
 ISSMP Science and Flight Hardware support teams


Renal Stone Risk During Spaceflight: Assessment and Countermeasure Validation

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