Comparative Renal Function in Reptiles,

Birds, and Mammals

EldonJ. Braun, PhD

In this article, the regulation of the homeostasis of the

extracellular fluid is compared for reptiles, birds, and
mammals. The principle focus is on the role of the
kidneys in this process. Although the basic elements of
renal function are similar in the three classes, birds and
mammals are set apart from reptiles in that the kidneys
of these species have the ability to produce urines that
are hyperosmotic to plasma. Reptiles and birds are sat
apart from mammals by the fact that these t w o groups
excrete nitrogen as uric acid and not urea as do mammals. Reptiles and birds are further set apart from
mammals in that the kidneys of these t w o groups are
not the sole organs that function to regulate the composition of the extracellular fluid. In addition to having
functional salt glands, the lower gastrointestinal tracts
of reptiles and birds function in concert with the kidneys
in the maintenance of homeostasis. There is a much
greater range in body mass among mammals than in
the other t w o groups. This has necessitated that the
kidneys of mammals change size, shape, and internal
organization to be able to carry out their homeostatic
function. The kidneys of reptiles and birds do not follow
a similar pattern. It would appear that no one group has
the advantage over the other with respect to regulation
of the composition of the extracellular fluid because
representatives of all groups inhabit a broad range of
environments and ecological habitats.

Copyright9 1998by W. B, Saunders Company.

Key words: Reptiles, birds, Mammals, kidney, morphology, physiology

reptiles, birds, and mammals are all

A lthough
amniotes (have a similar pattern of embryonic development), the kidneys of these three
vertebrate groups achieve their goal of maintaining the homeostasis of the extracellular fluid
(ECF) in different ways. Although some of the
basic processes are similar, there are marked
differences in the extent and degree to which the
kidneys are involved in the regulation of the
composition of the ECF in each group. Before
From the Department of Physiology, Collegeof Medicine, University ofArizona, Tucson, AZ.
Address reprint requests to EldonJ. Braun, PhD, Department of
Physiology, College of Medicine, University of Arizona, Arizona
Health Science Ctr 4121, PO Box 245051, Tucson, AZ 85724.
Copyright9 1998 by W. B. Saunders Company.
1055-937X/98/0702-0002~8. 00/0

62

discussing the similarities and differences in

renal function, it would be wise to review the
gross anatomy of the kidneys, n e p h r o n structure,
and histology for the three groups. T h e kidneys
of mammals will be described first, followed by
those of birds and reptiles.

Gross Morphology of Kidneys

The mammalian kidney is most typically depicted as a unipapillate, bean-shaped organ. This
is true for the kidneys of small mammals (to a
body mass of about 5 kg).l-3 However, the external form and internal organization of the kidney
change as body mass increases and as animals
from different habitats are examined. In general,
as the body mass of mammals increases, the
internal organization o f the kidney changes. The
first change that is observed is a dividing of the
medullary region into subunits, although the
cortex remains undivided. This c o m p o u n d multirenculate kidney is seen in primates, including
humans, z-3 In some mammals the renal medulla
remains undivided, but its depth decreases and
its anterior-posterior length increases. This form
of the kidney is referred to as a crest kidney and
is typical of the kidneys of carnivores (large cats
and t h e dog family) and some artiodactylids
(camels, wildebeests). 1-3 As the body mass of
mammals increases further, the cortical tissue of
the kidneys also becomes subdivided. These
kidneys are called discrete multirenculate and
are the form observed in large mammals such as
the pinnipeds (seals) and cetaceans (whales). 1-3
Extreme examples of this kidney form are seen
in some of the large marine mammals, in which
the whole kidney is composed of a large n u m b e r
of individual units that, when sectioned midsagitally, resemble the kidneys of rodents in shape
and size. 2 Fig 1 depicts examples of the different
kidney types (shapes) f o u n d in mammals.
Why d o n ' t the kidneys of mammals retain the
rather simple shape of those seen in rodents (the
unipapillate kidney) and just b e c o m e larger to fit
the demands of maintaining the consistency of

Seminars in Avian and Exotic Pet Medicine, Vol 7, No 2 (April), 1998:pp 62-71

Renal Function

Figure 1. Schematic illustrations of the morphology

of the kidney types that occur in mammals. No
attempt has been made to draw the illustrations to an
appropriate scale. In total size, the (A) unipapillate
kidney is actually the smallest kidney and the (D)
discrete multirenculate is the largest kidney. (B) crest;
(C) compound multirenculate.
the ECF? After all, the unipapillate kidney has
b e e n suggested to be the most primitive kidney
form. 1 Part of the answer lies in the structure of
the nephrons. W h e n a relationship between
n e p h r o n length a n d body mass is developed a n d
plotted, it is observed that the total length of the
n e p h r o n s does n o t continue to increase as body
mass increases, a However, kidneys of elephants
and whales do not have extremely long n e p h r o n s
to m a t c h their body mass. These kidneys have a
large n u m b e r of small n e p h r o n s that are packaged in a different manner. However, the total
n u m b e r of n e p h r o n s in the kidneys of m a m m a l s
does scale allometrically with body mass. 4
W h a t limits the absolute length of the n e p h tons of m a m m a l s as body mass increases? Examination of the factors that d e t e r m i n e how m u c h
plasma water is separated f r o m the b l o o d a n d
crosses the filtration barrier reveals that two
p a r a m e t e r s function as the main determinates of
the process o f ultrafiltration. These are the
hydrostatic pressure put on the Mood by the
p u m p i n g action of the heart a n d the concentration of proteins in the blood. The hydrostatic
pressure forces fluid across the filtration barrier,
a n d the colloidal osmotic pressure exerted by
the plasma w o t e i n s opposes the filtration process. W h e n systemic blood pressure a n d plasma
protein c6ncentration are e x a m i n e d for a wide
range of body masses of mammals, it is seen that
these two p a r a m e t e r s do not scale allometrically
with b o d y mass. 4 Large m a m m a l s do n o t have

63

extremely high blood pressures and protein

concentrations. W h e n all the factors involved in
the process of ultrafiltration in m a m m a l s are
considered, there are only a b o u t 10 m m H g
hydrostatic pressure to o v e r c o m e the frictional
resistance of the filtration barrier. Therefore, the
n e p h r o n length cannot increase as body mass
increases, because the resistance to flow along
the n e p h r o n s would increase a n d the pressure
put on the system by the h e a r t would be unable
to maintain flow along the n e p h r o n . The compromise is that larger m a m m a l s have an increased
n u m b e r of smaller nephrons. T h e increased
n u m b e r of n e p h r o n s necessitates that they be
packaged in a different m a n n e r to facilitate the
flow of tubule fluid (urine) to the ureter a n d on
to the bladder.
T h e lengths of the n e p h r o n s within the kidneys of m a m m a l s may vary f r o m species to
species and even within a given kidney, but they
are all c o m p o s e d of the same segments. A nephron begins with the renal corpuscle (capsula
glomeruli) that leads into the proximal convoluted tubule (PT-Fig 2). Based on function (transp o r t characteristics), the PT can be divided into
three segments: $1, $2, a n d $3. T h e PT leads to
the descending limb of the loop o f the n e p h r o n
(Ansa nephroni), which makes a hairpin turn at
varying depths of the renal medulla and forms
the ascending limb of H e n l e (ALH). T h e ALH
returns to the renal cortex a n d makes contact
with the renal corpuscle f r o m which the nephron originated. This point signals the beginning
of the distal convoluted tubule (DT). T h e DT
leads into the connecting tubule, which connects
the n e p h r o n to the cortical collecting duct
(CCD). The CCD descends straight to the renal
medulla, coalesces with o t h e r collecting ducts
(CDs), and finally terminates at the papillary tip.
T h e large ducts (collecting ducts) at the tip of
the papilla do n o t make a direct c o n n e c t i o n with
the ureter. T h e urine literally drips f r o m the
collecting ducts a n d is c o l l e c t e d by the renal
calyces, which coalesce to f o r m the renal pelvis,
which narrows to f o r m the ureter.
T h e lengths of the n e p h r o n s within a m a m m a lian kidney vary d e p e n d i n g on the location of
the renal corpuscle in the cortex. At the extremes, there are renal corpuscles located n e a r
the surface of the kidney, superficial cortical
nephrons, a n d renal corpuscles located at the
b o u n d a r y between the cortex a n d medulla,juxta-

EldonJ. Braun

64

N,~

J,:://::://::.2

~
~

Proximal
Tubule ,,

~ ]

Distal
Tubule

Intermediate
Segment or
Loop o f Henle
Collecting
Duet

Figure 2. IUustrations showing the different nephron

configurations that can be found in the kidneys of
reptiles, birds, and mammals. The nephrons are not
drawn to scale. (A) The nephrons in the kidneys of
reptiles have a rather long PT, a thin intermediate
segment, and a short DT. The DTs enter the CD at
right angles. (B) The loopless nephrons of bird
kidneys have a similar configuration to the nephrons
in reptilian kidneys, but are simpler in structure.
These nephrons have only a PT and D T and no
intermediate segment, but enter CDs at right angles as
do the nephrons in the kidneys of reptiles. These
loopless nephrons are very short, being'only 4 to 5 mm
in total length. (C) The looped nephrons of avian
kidneys are quite similar to the looped nephrons in
the kidneys of mammals. The major difference is that
they do not have a thin ascending segment to the loop
of the nephron. These nephrons are quite long (ca. 15
mm) with highly convoluted PT and DT. (D) Except
for some of the shortest superficial cortical nephrons,
the nephrons of mammal kidneys are longer than
those found in the other groups. The looped nephrons of the-avian and mammalian kidneys are arranged parallel to the CDs. This facilitates the operation of eountercurrent multiplier systems to allow the
production of urine that is more concentrated than
the plasma (hyperosmotic urine).

medullary nephrons. With some exceptions, the

superficial cortical n e p h r o n s t e n d to be considerably shorter than the j u x t a m e d u l l a r y nephrons.
This structural difference may have a functional
correlate in the overall renal processing of sodium and water.
T h e kidneys of birds have some anatomical
features in c o m m o n with the kidneys of b o t h
m a m m a l s and reptiles. A stylized avian kidney is
depicted in Fig 3. Whereas all the n e p h r o n s
within the kidneys of m a m m a l s have a loop of
the n e p h r o n , only a small p e r c e n t a g e of those in
avian kidneys have loops of the n e p h r o n . The
majority (70% to 90%) of n e p h r o n s have no
loops and m o r e closely resemble those f o u n d in
the kidneys of reptiles. 5 All the n e p h r o n s within
the kidneys of reptiles lack the loop of the
n e p h r o n (Fig 2).5 T h e gross organization of the
avian kidney, as depicted in Fig 3, does not
change as dramatically with b o d y mass as does
that of mammals. T h e same p a t t e r n of organization appears to be retained as body mass increases. If a parallel were to be drawn with the
m a m m a l i a n kidney, the avian kidney probably
m o s t closely resembles in internal organization
the c o m p o u n d multirenculate kidney. Although
the cortical region of avian kidneys is m o r e
divided than that of the c o m p o u n d multirenculate kidney, it is less divided than the discrete
multirenculate kidney o f mammals.
A n o t h e r m a j o r difference between avian and
m a m m a l i a n kidneys relates to the termination of
the collecting duct systems. As n o t e d previously
for the kidneys of mammals, the collecting ducts
terminate at the papillary tip in rather large
openings. This discontinuity does not exist in the
collecting duct system of the avian kidney. T h e
e n d of each medullary cone is f o r m e d by one
large collecting duct. Several of these large
collecting ducts m e r g e to f o r m a p r i m a r y ureteral branch, and several of these p r i m a r y ureteral branches unite to f o r m the ureter that runs
on the ventral surface of the kidney. T h e e n d
result is that within the avian kidney (and the
reptilian kidney), there is a continuous system of
ducts f r o m the smallest loopless n e p h r o n on the
surface of the kidney to the entrance of the
ureters into the cloaca.
T h e kidneys of birds also differ f r o m those of
m a m m a l s in the degree of morphological heterogeneity that is observed in the populations of
n e p h r o n s that make up these kidneys (Figs 2 and

65

Renal Function

VEIN
DUCT
I(EFFERENT)
'LY
NEPHRON

NEPHRON

Figure 3. An illustration
showing th e internal organization of the avian kidney.
The whole kidney is shown
at the lower left with two
successive enlargements to
show the fine detail of the
kidney. (Reprinted with permission. 24)
3). T h e r e is a m u c h greater e x t r e m e in n e p h r o n
structure in the avian kidney than the m a m m a lian kidney. All the n e p h r o n s of m a m m a l i a n
kidneys have loops of the n e p h r o n , whereas only
10% to 30% of,the n e p h r o n s in avian kidneys
have loops of the n e p h r o n . These loops, vase
recta, a n d collecting ducts f o r m the m e d u l l a r y
cones o f the avian kidney (Fig 3). D e p e n d i n g on
the species, the remaining 70% to 90% of the
n e p h r o n s in avian kidneys do n o t have a loop of
the n e p h r o n . These are small n e p h r o n s that fold
over themselves four times a n d their connection
to collecting ducts is at right angles. This anatomical a r r a n g e m e n t does not permit these n e p h rons a n d their collecting ducts to func Lion as a
c o u n t e r c u r r e n t multiplier system. This means
that the tubule fluid (urine) elaborated by these
n e p h r o n s cannot be m o r e c o n c e n t r a t e d than the
plasma. This organization o f the avian renal
cortex is similar to the general organization of all
the n e p h r o n s in the kidneys of reptiles. T h e
functional result is the same for reptilian kidneys: a urine m o r e concentrated than the plasma
c a n n o t be produced. In the avian kidney, the
collecting ducts that drain the loopless n e p h r o n s
e n t e r the medullary cones and m e r g e with the
collecting ducts that drain the l o o p e d n e p h r o n s .
Thus, these collecting ducts deliver a large
a m o u n t of dilute to isosmotic fluid to the count e r c u r r e n t multiplier system that operates in the
medullary cones. This may limit the capacity of
the avian kidney to concentrate the urine.

)HRON

Reptiles as a g r o u p of vertebrates display an

e x t r e m e variation in body f o r m f r o m the legless
Ophidians (snakes) to the tetrapod forms (Lacertilia-lizards, Crocodilia-alligators a n d crocodiles,
and Chelonia-turtles a n d tortoises), a n d this
affects the gross shape o f the kidneys. Those of
the tetrapod reptiles are all somewhat similar in
shape (oval, flattened, compact), In keeping
with their body form, the kidneys of ophidians
are long, narrow, rod-shaped structures. 5 U n d e r
an external capsule, the kidneys of all reptiles
show a very distinct s e g m e n t a t i o n into lobules.
These tend to be wedge-shaped and fit in a
c o m p l e m e n t a r y m a n n e r with each n e i g h b o r i n g
lobule along the long axis of the kidney. T h e
collecting ducts, which are oriented at right
angles to the long axis of the kidney, originate on
the dorsolateral surface of each lobule. They
t e n d to r e m a i n on the surface as they wrap
a r o u n d the lateral margin of the lobule a n d pass
ventrally to enter the ureter, which lies on the
ventral-medial surface of the kidney. 5 This gross
organization of the reptilian kidney is very different f r o m that of b o t h birds and mammals.
T h e r e is a definite p a t t e r n in which the
n e p h r o n s of reptilian kidneys are organized (Fig
2). T h e individual n e p h r o n s in each lobule are
oriented at right angles to the long axis of the
kidney and enter the collecting ducts at right
angles. The renal corpuscles lie in a circular
pattern near the m i d p o r t i o n of each lobule. In
the tetrapod reptiles, there are two rows of renal

66

Eldon J. Braun

corpuscles n e a r the center of each lobule o f the

kidney. In the ophidian kidneys, the n e p h r o n is
gently folded on itself such that it traverses the
c o m p l e t e thickness of the lobule three times. 5 In
the tetrapod reptiles, the n e p h r o n s a p p e a r to
have a similar folding pattern, but each n e p h r o n
traverses only half the thickness of a kidney
lobule. 6
A comparison of the structural organization
of the n e p h r o n s f r o m the kidneys o f the three
classes of vertebrates is presented in Fig 2. A
typical n e p h r o n f r o m a reptilian kidney starts
with the renal corpuscle, which is c o n n e c t e d by a
thin, ciliated neck s e g m e n t to the proximal
tubule. This is followed by a narrow, ciliated
i n t e r m e d i a t e segment. This is followed by the
distal tubule, which leads to the collecting duct.
This pattern of organization is not followed in
either the avian or m a m m a l i a n kidneys. As mentioned previously, the population of n e p h r o n s in
the avian kidney is morphologically very heterogeneous, m u c h m o r e so t h a n is observed in
either the reptilian or m a m m a l i a n kidneys. T h e
small n e p h r o n s on the surface o f the avian
kidney have just proximal a n d distal tubules and
lack a neck and intermediate segment. These
n e p h r o n s are stucturally very simple, with the
tubule folded on itself three times. At the o t h e r
extreme, some of the n e p h r o n s of the avian
kidney have almost all the segments typically
f o u n d in the n e p h r o n s of m a m m a l i a n kidneys.
These are (in sequence) the renal corpuscle,
proximal tubule, loop of the n e p h r o n , and distal
tubule.
T h e structure of the n e p h r o n s of the avian
kidney has not b e e n e x a m i n e d in t h e s a m e detail
as has the structure of the n e p h r o n s o f the
m a m m a l i a n kidney, except perhaps for the loop
of the n e p h r o n and collecting ducts. 7 For example, it is not known whether the avian proximal tubule can be divided into three functional
segments as has b e e n d o n e for mammals. With
respect to the loops of the n e p h r o n , the organization of these tubule segments is different in
birds. For the long-looped n e p h r o n s in the
m a m m a l i a n kidney, there is a thin ascending
segment. T h e l o o p e d n e p h r o n s in the avian
kidney do not have this segment. 7 For all l o o p e d
n e p h r o n s in avian kidneys, the epithelium thickens before the hairpin loop is f o r m e d such that
there is a thick descending s e g m e n t to the loop
of the n e p h r o n . 7

Urine Concentration
T h e differences between birds and m a m m a l s
in structure of the loops of the n e p h r o n and in
the medullary regions is expressed in the function of this region of the kidney for the two
groups. In mammals, the osmotic gradient that
extends f r o m the cortical-medullary b o u n d a r y to
the tip of the medullary region is primarily m a d e
of two solutes, sodium chloride and urea. In
birds, this gradient is m a d e of o n l y sodium
chloride. T h e p r i m a r y function of the renal
medulla is to modulate the osmotic potential of
the urine d e p e n d i n g o n the n e e d to either rid
the body of excess water or to conserve body
water. T h e ability to conserve body water by
p r o d u c i n g urine m o r e c o n c e n t r a t e d than the
body fluid (plasma) is m u c h greater in m a m m a l s
than in birds (Table 1). Birds at best can generate urine-to-plasma ( U / P ) osmolar ratios of about
2.0 to 2.5, whereas some m a m m a l s can generate
U / P ratios as high as 25 to 30.
For several reasons, caution must be used
w h e n c o m p a r i n g birds and m a m m a l s with respect to U / P osmolar ratios. First, the plasma
osmolality of birds tends to be m o r e labile than
that of mammals. H u m a n s a n d some standard
laboratory animals (rats, rabbits) have plasma
osmolalities a b o u t 300 m O s m / k g H 2 0 that
Table 1. Urine to Plasma Osmolar Ratios for
Selected Birds and Mammals
Birds

U/Po,m

Mammal~

Domestic Fowl
Senegal dove
Savannah Sparrow
Budgerigar
Singing Honeyeater
King quail
House finch
Zebra finch
Stubble quail

1.5
1.7
1.7
2.3
2.4

Long-nosed bat
Nutria
Mountain beaver
Pig
Hereford cow

1.8
2.4
2.8
2.6

Blue whale
Bottle nose dolphin
Weddell seal
Dog
Cat
Cottontail
Merriam's kangaroo
rat
House mouse
Desert pocket mouse
Australian hopping

U/Po~m

1.1
2.5
2.7
3.6
3.9
4.5
6.1
6.8
8.7
10.8
11.0
21.2
23.3
28.6
31.2

mouse

NOTE. The U/Posm values for mammals were computed

using data from Beuchat3 and assuming a plasma osmolality
of 300 mOsm for all the species listed.
Data for birds are from BraunY5

Renal Function

change little with water deprivation. O n the

contrary, the plasma osmolality of birds tends to
increase with water deprivation, which prevents
the calculated U / P ..... ratio f r o m increasing.
Second, the f o r m in which nitrogen is excreted
by birds (uric acid) contributes very little to the
pool of osmotically active solutes in the urine.
T h e similarities in renal function a m o n g this
g r o u p of vertebrates are in the processes of
g l o m e r u l a r filtration, reabsorption o f solutes
and fluid, and the secretion of solutes by the
renal tubules. T h e f u n d a m e n t a l m e c h a n i s m s
underlying these functions are similar, but their
m a g n i t u d e differs.

Blood Supply
T h e b l o o d supply to the kidneys differs a m o n g
these three vertebrates. Typically, each m a m m a l
kidney is supplied with blood by one renal artery
that branches f r o m the abdominal aorta, a n d
each avian kidney is supplied with b l o o d by three
renal arteris. T h e kidneys of reptiles are supplied
by multiple arteries; the n u m b e r depends on the
size or body mass of the animal. In addition to
b e i n g supplied with arterial blood, reptilian a n d
avian kidneys receive a venous blood supply by
way o f functional renal portal systems. This latter
b l o o d supply facilitates secretion of substances
by the renal tubules.

Nitrogen Excretion
In animals, the metabolic pathways that lead
to the p r o d u c t i o n of nitrogen c o m p o u n d s start
with the degradation of a m i n o acids, which
d e p e n d s on the degradation of protein. A m m o nia is the simplest f o r m by which to excrete the
nitrogen p r o d u c e d by the metabolism of a m i n o
acids. However, this molecule is very toxic to the
central n e r v o u s system a n d requires large
a m o u n t s of water for its rapid removal f r o m an
organism. As animals m o v e d f r o m aquatic envir o n m e n t s to terrestrial habitats where water was
less abundant, different forms of nitrogen excretion evolved. In reptiles and birds, the principle
f o r m of nitrogen excretion that evolved was uric
acid. This f o r m of nitrogen excretion is conside r e d very efficient with respect to the a m o u n t of
water required for its excretion because of its
very low aqueous solubility (0.386 m m o l / L for
the acid form, but the salts o f uric acid have

67

slightly higher solubilities). Because the majority

of the uric acid in reptilian and avian urine is not
in solution, but exists as a colloidal suspension, it
does not contribute to the osmolality of the
urine. This suspension is m a d e up of small
spherical structures, which r a n g e in d i a m e t e r
f r o m 0.5 to 15 pm, and rather large amounts of
protein, s,9 T h e spheres are c o m p o s e d of a b o u t
65% uric acid. 1~ These are n o t crystals and the
uric acid is not in a crystalline f o r m within the
spheres, but the uric acid is chemically b o u n d to
a matrix protein that f o r m s the spheres.9
T h e urine of reptiles a n d birds contains rather
large amounts of protein, at least when the urine
of these two forms is c o m p a r e d with that of
mammals. Although I a m not aware of measurements on the urine of reptiles, avian urine
contains an average of 5 m g / m L of protein. 1~
T h e urine of m a m m a l s is relatively free of protein. Thus, reptiles and birds m a y not require as
m u c h water to excrete nitrogen as m a m m a l s do,
b u t they require large a m o u n t s of protein to
maintain uric acid in colloidal suspension to
prevent the uric acid f r o m precipitating f r o m
solution. This has to be taken into account when
considering the efficacy o f uric acid as a nitrogen
excretory product.
Mammals excrete nitrogen as urea, a comp o u n d 40,000 times m o r e soluble in water than
uric acid. Because of this solubility, it does
require water for its excretion. A small portion of
the u r e a is retained in the renal medulla, where
it plays an i m p o r t a n t role as a c o m p o n e n t of the
intramedullary solute gradient. This gradient is
necessary for the p r o d u c t i o n of urine that is
hyperosmotic to plasma, which can conserve
water when an animal is deprived of water.
Which f o r m of nitrogen excretion is m o r e
efficient? Uric acid requires protein for its excretion and u r e a requires water for its excretion,
b o t h of which can "cost" animals in terms of
energy and survival. For reptiles and birds, the
protein in ureteral urine is n o t excreted (lost to
the animal) because the urine is m o v e d f r o m the
cloaca into the rectum by a reverse peristalsis. 11
In the rectum (lower gastrointestinal tract), the
protein of the urine is d e g r a d e d and the peptides and a m i n o acids are absorbed and recycled. 12 U r e a is highly soluble in water a n d does
n o t require large a m o u n t s of water for its excretion ( c o m p a r e d with a m m o n i a ) . Therefore, b o t h

EldonJ. Braun

68

forms of nitrogen excretion are efficient for the

purposes they serve in the different animals.

Response to Water Deprivation

For mammals, the kidneys are the Sole organs
that function to regulate the composition o f the
extracellular fluid. Water can be lost t h r o u g h
o t h e r routes (skin, lungs, gastrointestinal [GI]
system), but only through the kidneys is the loss
regulated for the purpose o f maintaining the
consistency of the extracellular fluid. T h e kidneys of m a m m a l s respond to water deprivation
by extracting m o r e water f r o m the fluid within
the renal tubules and r e t u r n i n g this fluid to the
plasma. This occurs in the m e d u l l a r y region of
the kidney, where the collecting ducts change
their permeability to water in response to the
antidiuretic h o r m o n e . In the case o f mammals,
this is arginine vasopressin, which is released
f r o m the posterior pituitary gland. T h e antidiuretic h o r m o n e causes the insertion of water
channels into the luminal m e m b r a n e o f the
collecting duct cells. These channels allow the
passage of water f r o m the l u m e n t o the medullary interstitium, where it is picked u p by capillaries. T h e water moves out of the collecting ducts
on osmotic gradient, that is, the medullary interstitium has a higher osmotic potential then the
tubule lumen. T h e hypertonicity of the medullary interstitium is g e n e r a t e d by the countercurr e n t multiplier system. Urine concentrating abilities of m a m m a l s range f r o m the long-nosed bat
and nutria that at best can p r o d u c e isosmotic
urines when water deprived, to some of the small
desert rodents of the southwestern United States
and Australia that can p r o d u c e urineS that are 25
to 30 times m o r e c o n c e n t r a t e d t h a n plasma. ~
T h e response of birds to water dePrivation is a
bit m o r e complicated, as the kidne~es are n o t the
sole organs that can function to regulate the
composition of the extracellular fluid. In all
birds, the urine enters the terminal portion of
the GI tract (the cloaca), because birds do n o t
have a u r i n a r y bladder in which to store this fluid
until it can be conveniently voided. This automatically involves the lower GI tract in the regulation
of the composition of the extracellular fluid. In
addition, m a n y birds have functional nasal or salt
glands that play a major role in n o r m a l water
balance and how these birds r e s p o n d to the
stress of water deprivation. Thus, in this g r o u p of

vertebrates, the kidneys function in concert with

at least two o t h e r organs in the regulation of
fluid and electrolyte balance.
For birds with and without salt glands, the
urine enters the cloaca a n d is m o v e d by reverse
peristalsis into the rectum. 11 In general, fluid
moves across the epithelium of the lower GI tract
in an isosmotic fashion. T h a t is, large osmotic
gradients c a n n o t be m a i n t a i n e d across this tissue, and water flow follows the transport of
solutes. For this reason, the urine entering the
r e c t u m should n o t be highly concentrated. T h e
avian kidney, like that o f m a m m a l s , can p r o d u c e
a urine that is m o r e c o n c e n t r a t e d than the
plasma. As n o t e d previously, some m a m m a l i a n
kidneys have a remarkable capacity for this
function. However, the capacity of the avian
kidney to concentrate urine is rather limited, in
that at a m a x i m u m the urine can be two to
two-and-one-half times m o r e c o n c e n t r a t e d than
the plasma. For reasons j u s t m e n t i o n e d , this is as
it should be. In response to water deprivation,
the osmolality of the urine tends not to increase
a great deal. U n d e r m o s t circumstances, the
urine is isosmotic or only slightly hyperosmotic
(ca. 100 m O s m higher than plasma), a n d there is
evidence that if the urine b e c o m e s too concentrated, it will not be refluxed into the rectum, la
This is s u p p o r t e d by e x p e r i m e n t a l evidence that
the epithelium of the r e c t u m stops absorbing
water when the gradient across it reaches 100
m O s m . t~ In general, birds without salt glands
r e s p o n d to water deprivation by slowly allowing
the plasma osmolality to increase as the urine
osmolality increases such that a favorable osmotic gradient is m a i n t a i n e d across the epithelium of the rectum.
Some birds and reptiles use functional nasal
salt glands to excrete excess salt c o n s u m e d as a
n o r m a l part of the diet when the kidneys are
incapable of excreting these ions. As m i g h t be
expected, the response of birds with functional
salt glands to water deprivation is somewhat
different than that of birds that lack these organs. U n d e r circumstances of n o r m a l hydration,
the salt glands may not p r o d u c e large amounts of
fluid, with the kidneys a n d lower GI tract doing
m o s t of the work. W h e n stressed (water deprived
or salt loaded), the plasma a n d urine osmolality
will increase, a n d w h e n the urine osmolality
reaches a b o u t 400 to 450 m O s m / k g water, the
kidneys begin to decrease the a m o u n t of urine

Renal Function

produced. At this point, the salt glands begin to

secrete larger amounts of concentrated fluid
(the primary solute being sodium chloride in
most birds). The decreased function of the
kidneys is regulated by the h o r m o n e arginine
vasotocin (AVT), and salt gland function is initiated by the parasympathetic (choiinergic) nervous system. The corticosteroids and the horm o n e s prolactin and AVT play permissive roles
in salt gland function. 14
T h e pattern of response to water deprivation
in reptiles is similar to that of birds because of
similar anatomical characteristics, but with some
major differences. For reptiles, like birds, the
kidney is not the sole organ that functions in the
regulation of fluid and electrolyte balance. As in
birds, the urine enters the lower GI tract. Many
reptiles also have functional salt glands. A number of reptiles have urinary bladders, but this
organ serves a very different function than for
mammals. To a large extent in mammals, the
bladder serves purely a storage function. For
reptiles, the bladder also serves a storage function, but this storage is to conserve water so it can
be reabsorbed and used in periods of stress, ie, it
functions more as a canteen for these animals.
Reptiles are also set apart from mammals and
birds in that their kidneys can not produce urine
that is m o r e concentrated than the plasma. At
best, the urine of reptiles is isosmotic with
plasma. Thus, they do not have this avenue
through which to conserve water. Reptiles are
also like birds in that most of them excrete
nitrogen in the form of uric acid, which allows
for the conservation of water. Moreover, reptiles
r e s p o n d to water deprivation by allowing the
plasma and urine osmolalities to increase in
parallel, as is the case for birds. However, the
increases are more accentuated in reptiles. As is
the case with birds, a n u m b e r of reptiles (many
lizards, turtles, tortoises, and some snakes) have
functional salt glands. The t y p e of secretion
p r o d u c e d by these glands depends on the diet of
the animal. In most cases, the secretion is rich in
sodium chloride, but some herbivorous animals
primarily secrete potassium chloride. 15

Endocrine Aspects of Renal Function

T h e kidneys of vertebrates play a p r o m i n e n t
role in the regulation of the composition of the
ECF through the processes of filtration, selective

69

reabsorption, and secretion. Closely associated

with this role is the endocrine function of the
kidney, as the kidney produces several h o r m o n e s
that function either directly within the kidney or
indirectly (outside of the kidney) in the regulation of the composition o f the ECE A m o n g the
h o r m o n e s p r o d u c e d by the kidney are renin,
urodilatin, dopamine, kallikrein, prostaglandins,
erythropoeitin, and a form of vitamin D (1,25dihydroxycholecatciferol). Brief descriptions of
the action of each of these h o r m o n e s on the
kidney or other target organs follow.
Renin activity probably first appeared in the
bony fishes and has been conserved through the
aminoates, which means the renin-angiotensin
system is present in reptiles, birds, and mammals. However, the presence of a juxtaglomerular apparatus (JGA) as exists in the kidneys of
mammals is questionable for reptiles and is
present in birds, but without the morphological
clarity that is present in mammals. For reptiles,
the distal tubule returns to the parent renal
corpuscle, but there appears to be no specialized
region of macula dense cells. For the avian
kidney, the JGA is well-developed for only the
looped nephrons. The renin-angiotensin system
functions primarily to regulate sodium balance,
either through stimulating the release of aldosterone (which regulates sodium absorption by the
DT and CD) from the adrenal cortex, or by
affecting the a m o u n t of filtrate f o r m e d by controlling the resistance of the afferent and efferent
glomerular arterioles. 16
Urodilatin is a m e m b e r of the atrial natriuretic peptide (ANP) family that is p r o d u c e d
and secreted within the kidney and does not
circulate in the systemic plasma. This 32-aminoacid peptide differs by only four residues from
ANR 17 It is p r o d u c e d by the cells of the DT and
inhibits sodium transport by the cells of the CDs.
Thus, its action can be defined as being paracrine (produced by one cell and acting on
neighboring cells). The stimulus for its release is
an excess of sodium in the body. At this point in
time, this h o r m o n e has only b e e n isolated from
the kidneys of mammals. However, as members
of the ANP family have b e e n isolated in both
birds and reptiles, it should not be too surprising
if urodilatin is f o u n d in the kidneys of these two
groups. 18
Dopamine is p r o d u c e d within the kidney and
acts as an intrarenal natriuretic hormone.19 As

70

EldonJ. Braun

with u r o d i l a t i n , t h e e v i d e n c e f o r this is t h e l a r g e
a m o u n t o f d o p a m i n e in t h e u r i n e t h a t is o u t o f
p r o p o r t i o n with t h e a m o u n t o f n o r a d r e n a l i n e o r
a d r e n a l i n e . D o p a m i n e e x e r t s is effects o n t h e
v a s c u l a t u r e a n d d i r e c t l y o n t h e r e n a l tubules. It
causes a d i l a t a t i o n o f t h e a r t e r i a l v a s c u l a t u r e ,
w h i c h i n c r e a s e s b l o o d flow a n d l e a d s to a d i u r e sis a n d natriuresis. T h e effect o n t h e p r o x i m a l
r e n a l t u b u l e s is to slow t h e r a t e o f ATP hydrolysis,
w h i c h l e a d s to a d e c r e a s e in s o d i u m r e a b s o r p t i o n a n d s u b s e q u e n t l y c o n t r i b u t e s to t h e d i u r e s i s
a n d natriuresis. T h e s e effects have b e e n des c r i b e d f o r t h e m a m m a l i a n kidney, b u t little
c o m p a r a t i v e w o r k has b e e n d o n e in this area.
T h e k a l l i k r e i n system consists o f a low m o l e c u lar w e i g h t s u b s t r a t e ( k i n i n o g e n ) a n d a f a m i l y o f
s e r i n e p r o t e a s e s (kallikreins) t h a t cleave t h e
k i n i n o g e n s to p r o d u c e t h e active e n d p r o d u c t ,
b r a d y k i n i n . 2~ B r a d y k i n i n p e r f o r m s a w i d e r a n g e
of functions, including the regulation of blood
flow a n d t h e t r a n s e p i t h e l i a l t r a n s p o r t o f w a t e r
a n d electrulytes. T h e k i n i n s ( b r a d y k i n i n ) h a v e a
v e r y s h o r t half-life ( < 3 0 sec), s u g g e s t i n g t h a t
t h e y act m o r e as p a r a c r i n e s t h a n as classical
h o r m o n e s . B e c a u s e o f this, c i r c u l a t i n g levels o f
t h e k i n i n s d o n o t r e f l e c t activity o f t h e k i n i n s at
tissues levels. W i t h i n t h e kidney, k i n i n o g e n is
p r o d u c e d in t h e early s e g m e n t s o f t h e c o l l e c t i n g
ducts (connecting tubule) and the targets of
b r a d y k i n i n a r e t h e cortical a n d m e d u l l a r y collecti n g ducts. T h e m a i n a c t i o n o f b r a d y k i n i n is to
cause a loss o f s o d i u m ( n a t r i u r e s i s ) . T h i s is
t h o u g h t to c o u n t e r - b a l a n c e t h e effect o f t h e
r e n i n - a n g i o t e n s i n system, w h i c h f u n c t i o n s to retain s o d i u m . A l t h o u g h this system is well s t u d i e d
in m a m m a l s ( m a n a n d rat), t h e r e a r e few i f a n y
c o m p a r a t i v e d a t a in t h e l i t e r a t u r e . T h e p r e s e n c e
o f this system has b e e n i d e n t i f i e d in fish (Black
Sea bass),21 t h e A f r i c a n lungfish, 22 a n d a m p h i b ians ( S o u t h e r n frog).21 T h u s , it is likely t h a t t h e
system is p r e s e n t in r e p t i l e s a n d birds.
T h e kidneys p r o d u c e a r a t h e r l a r g e n u m b e r
o f p r o s t a g l a n d i n s such as PGE2, PGE2~, PGD2,
t h r o m b o x a n e A2 a n d prostacyclin. 23 I n t h e cortex, t h e e n d o t h e l i a l cells o f t h e a r t e r i e s a n d
a r t e r i o l e s p r o d u c e t h e p r o s t a g l a n d i n s (PGs),
a n d i n t h e m e d u l l a it is p r i m a r i l y t h e i n t e r s t i t i a l
cells a n d t h e cells o f t h e c o l l e c t i n g d u c t s t h a t
p r o d u c e t h e s e c o m p o u n d s . T h e PGs w i t h i n t h e
k i d n e y f u n c t i o n p r i m a r i l y as m o d u l a t o r s o f t h e
activities o f o t h e r h o r m o n e s (or h o r m o n e systems) a n d o f t h e n e r v o u s system to c a u s e t h e loss

o f s o d i u m f r o m t h e body. F o r e x a m p l e , t h e
r e n i n - a n g i o t e n s i n system causes c o n s t r i c t i o n o f
t h e a f f e r e n t a r t e r i o l e s , w h i c h w o u l d t e n d to
r e d u c e t h e loss o f s o d i u m . B u t t h e r e n i n a n g i o t e n s i n system also s t i m u l a t e s t h e r e l e a s e o f
PGs, w h i c h cause d i l a t i o n o f t h e a r t e r i o l e s . Thus,
t h e two systems c o u n t e r - b a l a n c e e a c h other. T h e
s a m e is t r u e o f t h e a c t i o n o f a n t i d i u r e t i c horm o n e ( A D H ) , w h i c h l e a d s to t h e c o n s e r v a t i o n o f
water. However, A D H causes t h e r e l e a s e o f PGs,
w h i c h f e e d b a c k a n d , to a d e g r e e , i n h i b i t t h e
a c t i o n o f A D H o n t h e c o l l e c t i n g d u c t cells.
Virtually all this i n f o r m a t i o n c o m e s f r o m e x p e r i m e n t s o n rats a n d s o m e f r o m h u m a n tests. It is
k n o w n t h a t P G s a r e p r o d u c e d in t h e k i d n e y s o f
r e p t i l e s a n d birds, b u t v e r y little is k n o w n a b o u t
h o w this c o m p l e x h o r m o n e system f u n c t i o n s in
these groups.

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