Full text of DOI:10.1053/ajkd.2001.27754

Renal Hemodynamics in Space
Herbert J. Kramer, MD, Martina Heer, PhD, Massimo Cirillo, MD, and Natale G. De Santo, MD
●
Renal excretory function and hemodynamics are determined by the effective circulating plasma volume as well
as by the interplay of systemic and local vasoconstrictors and vasodilators. Microgravity results in a headward shift
of body fluid. Because the control conditions of astronauts were poorly defined in many studies, controversial
results have been obtained regarding diuresis and natriuresis as well as renal hemodynamic changes in response
to increased central blood volume, especially during the initial phase of space flight. Renal excretory function and
renal hemodynamics in microgravity are affected in a complex fashion, because during the initial phase of space
flight, variable mechanisms become operative to modulate the effects of increased central blood volume. They
include interactions between vasodilators (dopamine, atrial natriuretic peptide, and prostaglandins) and vasocon-
strictors (sympathetic nervous system and the renin-angiotensin system). The available data suggest a moderate
rise in glomerular filtration rate during the first 2 days after launch without a significant increase in effective renal
plasma flow. In contrast, too few data regarding the effects of space flight on renal function during the first 12 hours
after launch are available and are, in addition, partly contradictory. Thus, detailed and well-controlled studies are
required to shed more light on the role of the various factors besides microgravity that determine systemic and
renal hemodynamics and renal excretory function during the different stages of space flight.
©
2001 by the National Kidney Foundation, Inc.
INDEX WORDS: Space flight; glomerular filtration rate (GFR); renal plasma flow; diuresis; natriuresis.
ENAL HEMODYNAMICS is mainly deter-
mined by the effective circulating plasma
(GFR) independent of changes in renal plasma
R
flow (Table 1). It is likely that the lack of consis-
tency between past and recent data may reflect
differences in the degree of volume depletion of
the astronauts, who were instructed accurately to
maintain adequate fluid intake in missions on the
SLS Space Shuttle. It is known that the extracel-
lular volume depletion per se decreases renal
plasma flow and GFR. Therefore, in the presence
of the significant depletion of extracellular fluid
typical of space missions, the finding of normal
levels for renal plasma flow and GFR should be
interpreted as an activation of renal hemodynam-
ics.
volume together with neural and hormonal fac-
tors that regulate the balance between vasocon-
striction and vasodilation in the kidney. As early
as 1965 and 1966, during the Gemini 7 and
Cosmos 110 missions, microgravity was ob-
served to be associated with an acute loss of
body weight that was assumed to result from
increased urinary fluid and sodium loss. Because
many earlier studies compared only postflight
with preflight data without in-flight observations,
only limited data are available on body fluid
volume and renal hemodynamics during space
flights. Collections of blood and urine samples
and their preservation created problems, and
accurate matching of fluid intake with fluid out-
put during space flights was a major difficulty.
This review will describe changes in body fluid,
neurohormonal factors, and renal hemodynamics
during space flight to summarize the knowledge
on the mechanisms underlying changes in renal
function during space missions.
5
Leach et al reported a unique systematic
analysis of renal hemodynamics in space for 7
astronauts on 2 separate missions named SLS-1
5
and SLS-2, respectively. Leach et al showed
that the renal response to microgravity includes a
From the Renal Section, Medical Policlinic/Department
of Medicine, University of Bonn, Bonn, Germany; the DLR
Institute of Space Medicine, Cologne, Germany; the ESA
Topical Team for Kidney and Body Fluids; and First Chair
of Nephrology, Second University of Naples, Naples, Italy.
Received May 18, 2001; accepted in revised form July 5,
RENAL HEMODYNAMICS IN SPACE FLIGHTS
Although 400 astronauts have been in space,
very little data exist on renal hemodynamics
during space flights, and the existing data are
2
001.
Address reprint requests to Herbert J. Kramer, MD, Pro-
1
-4
fessor of Medicine and Nephrology, Med. Univ. Poliklinik,
Wilhelmstr. 35-37, 53111 Bonn, Germany. E-mail:
hkramer@uni-bonn.de
inconsistent. In the old missions, no change or
a transient decrease in creatinine clearance was
reported (Table 1). In contrast, Spacelab Life
Sciences (SLS) missions indicated an early and
transient increase in glomerular filtration rate
©
0
2001 by the National Kidney Foundation, Inc.
272-6386/01/3803-0035$35.00/0
doi:10.1053/ajkd.2001.27754
American Journal of Kidney Diseases, Vol 38, No 3 (September), 2001: pp 675-678
675

676
KRAMER ET AL
Table 1. Renal Hemodynamics in Astronauts During Space Missions: GFR as Measured by Creatinine (Gemini 7,
Apollo 17, and Skylab Missions) or Inulin Clearance (SLS Space Shuttle) and Renal Plasma Flow (RPF) as
Measured by Paraminohippuric Acid Clearance
GFR (mL/min)
ERPF (mL/min)
C
creat
C
inulin
C
PAH
Gemini 7 (n ϭ 2)
No change
—
—
Apollo 17 (n ϭ 12)
Skylab missions (n ϭ 9)
SLS Space Shuttle (n ϭ 5 to 7)
In-flight day 1: decrease then preflight values
Generally elevated
Preflight: 97 Ϯ 19
—
—
—
—
145 Ϯ 34
660 Ϯ 198
day 1: 109 Ϯ 29
day 1, 2: 107 Ϯ 27
day 8: 102 Ϯ 11
170 Ϯ 48*
174 Ϯ 46*
663 Ϯ 357
770 Ϯ 304
NOTE. Data from Smith et al, Leach et al, and Grigor’yev et al3,4 are shown as the mean Ϯ standard deviation (SD).
1
2,5
*SD; P Ͻ 0.05.
transient increase in the filtration fraction, when
measured as creatinine clearance, plasma inulin
disappearance, or plasma urea concentration (Fig
assume that the changes in urine volume and
secretion of antidiuretic hormone must have been
different on the 2 missions. This problem is
relevant to the interpretation of the entire set of
1
). Data on creatinine clearance and on fluid
5
balance are difficult to interpret in the study by
renal data in the paper of Leach et al. Recent
5
Leach et al. For creatinine, it is well known that,
studies suggest, in fact, that changes in the level
of hydration affect several aspects of renal func-
due to creatinine secretion from the renal tu-
bules, creatinine clearance is 10% to 30% higher
than inulin clearance in healthy individuals and
patients with renal diseases. In contrast, in the
6
tion, including renal hemodynamics. That the
glomerular hyperfiltration described by Leach et
5
al started on the day of the reduction in fluid
5
paper by Leach et al, creatinine clearance was
intake and urine volume supports the possibility
that the 2 effects were linked.
about 20% lower than inulin clearance also after
correction of inulin data for the 20% to 30%
overestimate due to single-injection technique.
The unusual difference between creatinine and
inulin data could not be due to technical prob-
lems during measurements in space, because
creatinine clearance was lower than inulin clear-
ance even on the ground. The authors did not
discuss whether the discrepancy reflected an er-
ror in the measurement of creatinine clearance or
other factors. The intake of fluids during pre-
flight days was very high (ie, Ͼ3,000 mL/d in the
Future studies are needed to investigate
changes in renal hemodynamics during space
flight and to assess whether they are dependent
on fluid balance. The experimental model based
on water immersion has long been considered to
represent renal function in space. This, however,
does not seem to be the case. During water
immersion, GFR is stable and renal plasma flow
7
is increased, hence filtration fraction is low. The
opposite trend is reported during space flight:
GFR is stable or increased and renal plasma flow
is stable, hence the filtration fraction tends to be
increased. The same contrast is reported for renal
handling of water and sodium, a function linked
to renal hemodynamics. Renal reabsorption of
water and sodium is low during water immersion
4
astronauts on mission SLS-1 and Ͼ4,500 mL/d
in the 3 astronauts on mission SLS-2). During
the first day in space, fluid intake went down in
all astronauts. However, the decrease was substan-
tially different between the missions: Ϫ70% for
mission SLS-1 versus Ϫ20% for mission SLS-2.
Data on renal function were not separately given
for missions SLS-1 and SLS-2. The analyses for
all 7 astronauts indicated that a 40% reduction in
urine volume and a 4-fold increase in secretion
of antidiuretic hormone occurred on the first day
of the space mission. It seems reasonable to
8
and high during space missions. Therefore, a
comparative analysis suggests that the model
based on water immersion may not represent
renal function in space but may reflect changes
opposite to those occurring in the kidney during
space missions.
The association reported in space missions

REPORT SYNOPSIS
677
Fig 1. Mean values for se-
lected indices of fluid ho-
meostasis and renal func-
tion in
7 astronauts on
ground (preflight) and in
space during the first 8 days
of the SLS-1 and SLS-2 mis-
sions as calculated from data
5
reported by Leach et al.
Only data on fluid intake
were reported separately for
mission SLS-1 (n ؍ 4 astro-
nauts) and mission SLS-2
(n ؍ 3 astronauts). Abbrevia-
tions: ADH, antidiuretic hor-
mone; BUN, blood urea
nitrogen; GFR, glomerular fil-
tration rate as measured by
plasma inulin disappear-
ance; RPF, renal plasma flow
as measured by plasma p-
aminohippurate disappear-
ance.
between high sodium reabsorption and normal-
high glomerular filtration suggests that changes
in the tubular handling of sodium might have a
primary role. The alternative possibility of a
primary tendency toward high values for glomer-
ular filtration appears to be unlikely, because it
should be followed by a reduction in tubular
sodium reabsorption via glomerulotubular feed-
back. In this light, further research should be
performed on the mechanisms responsible for
the increase in tubular sodium reabsorption dur-
ing space missions. Sodium-retaining mecha-
nisms such as activation of renin-angiotensin-
aldosterone system and increased adrenergic
outflow may be involved.
The role of 2 other factors has so far been
neglected. The first of these is space-induced
changes in fluid intake and antidiuretic hormone
(ADH) secretion. On the basis of experimental
observations in animals and humans, it has been
proposed that the combination of changes in fluid
intake and ADH secretion might affect not only the
process of urine concentration (hence, urine vol-
9
ume) but also renal hemodynamics and sodium

678
KRAMER ET AL
1
0
reabsorption. According to this hypothesis, a low
fluid intake followed by an increase in ADH secre-
tion would cause anADH-dependent stimulation of
sodium reabsorption in the collecting duct. The
altered sodium balance then could stimulate renal
hemodynamics via glomerulotubular feedback.
Theoretically, these changes could maintain renal
hemodynamics in the normal range during space
missions despite the presence of low plasma volume.
A second important factor might be a change in
the gradient of hydrostatic pressure (⌬P) across the
glomerular filter. Changes in this gradient affect the
process of glomerular filtration and would be fol-
lowed by parallel changes in the filtration frac-
gate the effects of increased central blood volume.
This may explain the equivocal findings of sys-
temic and renal hemodynamics during the first 1 to
2 days after launch. In the second adaptive phase,
renal hemodynamics will reach a new equilibrium
that may not differ from conditions observed dur-
ing head-out water immersion. Accurate studies are
required to shed more light on the role of various
factors that, besides microgravity, influence sys-
temic and renal hemodynamics during the different
stages of space flight.
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11
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maintained by a high ⌬P due to a low hydrostatic
pressure in the Bowman capsule; at tubular level,
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Microgravity during space flight affects renal
excretory function and renal hemodynamics in a
complex, 2-phase fashion that contrasts with data
obtained during head-out water immersion and
head-down tilt—conditions in which a headward
shift of body fluid occurs. During the initial phase
of space flight, variable neural and hormonal mecha-
nisms may become operative to modulate and miti-
1
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ϩ
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