Clinical Science and Molecular Medicine (1975) 49, 193-200.
Effect of proportional reduction of sodium intake on the
adaptive increase in glomerular filtration rate/nephron and
potassium and phosphate excretion in chronic renal failure
in the rat
C. H. ESPINEL
Virginia Commonwealth University, Medical College of Virginia,
Department of Medicine, Division of Nephrology, Richmond, Virginia, U.S.A.
(Received 3 February 1975)
potassium and phosphate per nephron are characteristics of chronicrenal failure(Platt, 1952; Schultze,
Shapiro & Bricker, 1969; Schultze,Taggart, Shapiro,
Pennell, Caglar & Bricker, 1971; Slatopolsky,
Robson, Elkan & Bricker, 1968). Sodium metabolism substantially affects renal functions : a large
amount of sodium given acutely to a subject with
normal renal function results in an increase in GFR")
and in potassium and phosphate excretion (HerreraAcosta, Andreucci, Rector & Seldin, 1972; Seldin,
Carter & Rector, 1971; Suki, Martinez-Maldonado,
Rouse & Terry, 1969), implying that the mechanisms
regulating GFR, and potassium and phosphate
excretion, depend on those regulating sodium
excretion. A normal dietary sodium seemingly may
provide the same physiological stimulus when given
to a subject with chronic renal failure. Dietary
sodium, if this dependency prevailed in chronic renal
failure, would impose limitations on the flexibility
of these mechanisms. Conversely, autonomous adaptation of each individual mechanism would permit
its regulation despite varying sodium intake.
The purpose of this study was to examine the relation between sodium excretion and the adaptations
in GFR/nephron, and potassium and phosphate
excretion in chronic renal failure. The experiments
were performed in rats in which chronic renal failure
was produced by sequential partial nephrectomies.
Examination of these adaptive mechanisms was
made over a period of 5 months at three successive
stages of renal failure. The adaptive increased
natriuresis was produced in the control group by
administration of a diet constant in sodium and
SY
1. The influence of dietary sodium intake on the
glomerular filtration rate (GFR/nephron) and
potassium and phosphate excretion was examined
at three stages of progressive chronic renal failure
produced in rats by sequential partial nephrectomies.
2. The adaptive increased sodium excretion per
nephron in the control group receiving a constant
sodium intake did not occur in the experimental
group that had a gradual reduction of dietary
sodium in direct proportion to the fall in GFR.
3. Despite the difference in sodium excretion,
the increase in GFR/nephron, the daily variation
in the amount of potassium and phosphate excreted,
the increase in potassium and phosphate excretion
per unit nephron, and the plasma potassium and
phosphate concentrations were the same in the two
groups.
4. The concept of 'autonomous adaptation' in
chronic renal failure is presented.
Key words : chronic renal failure, kaliuresis,
natriuresis, phosphaturia, salt intake.
Introduction
Increase in glomerular filtration rate per nephron
(GFR/nephron) and in the excretory rate of sodium,
( l ) Abbreviation: GFR, glomerular filtration rate.
Correspondence:Dr Carlos H. Espinel, Virginia Commonwealth University, Medical College of Virginia, Department
of Medicine, Division of Nephrology, Richmond, Virginia,
23298, U.S.A.
193
194
C. H. Espinel
prevented in the experimental group by gradual
reduction in dietary sodium in direct proportion to
the fall in GFR (Espinel & Bricker, 1973).
Methods
Experimental animals
Meticulous balance and clearance studies were
successfully completed on ten female SpragueDawley rats of the Holtman strain. The observation
period was prolonged sufficiently to allow for
adaptation to each stage of reduction of renal mass;
the duration, however, was limited by the degree of
renal failure. Chronic renal failure was produced
by stepwise partial nephrectomies in three stages.
The pre-operative period was designated stage I.
Stage IIA consisted of the removal of approximately
75% of the left kidney, comprising both upper and
lower poles, and the subsequent 30 days of observation. Stage IIB consisted of the removal of 75%
of the right kidney, with a similar surgical technique,
and an observation period of 90 days. Stage 111
consisted of the removal of the remnant right kidney
and a subsequent observation period of 30 days.
Studies were begun on the animals only when body
weight approached 200 g and, subsequently, changes
were recorded daily. Balance and clearance studies
were performed at each stage of decrease in renal
mass with techniques to be described below.
Balance studies
The animals were divided in two groups. The
control group received a constant amount of dietary
sodium chloride throughout the three stages of
reduction in renal mass. The experimental group
(PRNa) received a proportional reduction in dietary
sodium chloride at each stage of decrease in renal
mass. A total of 23 ml of distilled water was
administered each day via gastric tube as the food
solvent. An additional amount was left in bottles
as drinking water and a careful record was made of
the intake.
Dietary sodium was administered in the following
doses: (1) control group, 2.50 mmol/day (0.75 mmol
with each morning and evening meal and 1 mmol at
separate noon feeding); (2) PRNa group, stage IIA
1.20 mmol/day, stage IIB 0.60 mmol/day, stage 111
0.45 mmol/day (except for rat no. 27, in which a
very low GFR of the left kidney at stage IIB indi-
cated 0.30 mmol of sodium/day). As in the control
animals, the dose of sodium chloride was divided into
three separate feedings. Sodium was decreased for
the PRNa group within the first 24 h after the designated removal of renal mass. Administration of
salt in proportion to GFR cannot be readily
extrapolated to the human on a body weight basis.
For example, the 250 mmol of sodium/200 g rat
with a GFR of 2.50 ml/min would be equivalent to
an unphysiological amount (approximately 800
mmol/day) in a 70 kg human.
The synthetic sodium-free diet (ICN Nutritional
Biochemicals Division, International and Nuclear
Corp., Cleveland, Ohio, U.S.A.), administered by
gastric tube, has the following composition (%):
casein, 20; corn oil, 8 ; dextran, 67; sodium-free salt
mixture, 4; supplementary vitamins. Each animal
received a total of 16 g of this diet daily. Each 8 g
was homogenized in 10 ml of solution of sodium
chloride in distilled water and given directly through
a gastric tube at morning and evening. The sodium,
potassium and phosphate contents of the diet were
measured frequently. Total daily potassium intake
was 1.60 mmol, and phosphate was 0.97 mmol.
Animals were kept in individual metabolic cages,
which were constructed with a funnel-shaped floor,
the aperture of which fitted tightly into the urinecollecting tube to prevent evaporation. In addition,
the funnel was covered by a metallic filter which
permitted separation of urine and faeces. The
animals were trained to permit facile gastric intubation and emptying of the bladder by gentle
abdominal massage upon completion of 24 h urine
collections. Urine collections were begun at 12.00
hours and finished after exactly 24 h. The urine was
collected under oil in uncontaminated tubes, with
thymol as a preservative. Urine volume and sodium,
potassium and phosphate concentrations were
measured each day for the 10 days preceding the
clearance studies.
Clearance studies
Clearance studies were performed on the unanaesthetized animal at the end of the balance
period. The preparation of the animal for these
procedures was accomplished in the manner described in detail by Shankel, Robson & Bricker
(1967). The rat was lightly anaesthetized with ether
for the insertion of arterial, venous and bladder
catheters. After the animal was placed on the
PRNa
Stage I11
Control
PRNa
Stage IIB
Control
PRNa
Stage IIA
Control
+SEM
Mean
+SEM
Mean
~ S E M
Mean
0.76
013
0.71
0.07
1.02
0.09
1-01
0.11
+SEM
1-83
0.06
1.87
0.06
Mean
~ S E M
Mean
~ S E M
Mean
Potassium
Phosphate
0.42
2.50
0.60
2.50
1*20
2-50
2.45
001
0.40
0.03
059
0.03
0.11
2.42
2.43
016
1.13
014
138.0
0.6
137.6
1 *o
137.6
0.8
138.0
03
137.0
1.1
138.0
0.7
1.60
1 *60
1-60
1.60
1.60
1.60
1.31
0.04
1.26
003
003
1*05
1.01
003
4.36
0.10
4.14
0.10
4-10
0.06
4.18
0.08
0.97
0.97
0.97
0.97
0.97
0.92
0.03
0.97
4.10
006
4.06
0.04
0.91
0.05
0.45
001
0.44
0.02
039
0.01
039
0.02
0.19
000
0.00
019
2.92
0-18
2.99
0.20
2.19
0.12
2.27
0-14
1.39
0.03
1.39
002
GFR
Intake
Intake
PNa
Intake
PK
Urine
Urine
PP
Urine
(ml/min) (mmol/day) (mmol/day) (mmol/l) (mmol/day) (mmol/day) (mmol/l) (mmol/day) (mmol/day) (mmol/l)
Sodium
TABU1. Sodium, potassium and phosphate balance and plasma concentrations in control and experimental groups at different stages of decrease in
glomerular filtration rate
PRNa, experimental group (n= 5 in control and experimental groups). PNa,PK, Pp= plasma concentrations for sodium, potassium and phosphate.
fi’
5
az
196
C. H. Espinel
plastic restraining device, a period of 90-120 min
was allowed for complete recovery from the anaesthetic. In stage IIB, when each kidney was studied
separately, the right ureter was catheterized with a
silastic tube PE 10, which, fixed to the ureter by a
ligature, was conducted out of the abdomen through
a small ventral incision. Simultaneously, the urine
from the left kidney was collected from the bladder
via a silastic catheter (outside diameter 1.25 mm).
Glomerular filtration rate was measured with
carboxyZ-14C-labelled inulin. A priming dose of
1 pCi of [14C]inulin was followed by a sustaining
solution to provide counting rates at least ten times
greater than background in a 10 p1 sample of plasma.
The average value of a minimum of four clearances
of inulin of at least 30 min duration each was taken
as GFR. Plasma sodium, potassium and phosphate
were measured immediately before the clearance
studies in order to avoid possible variations resulting
from the inulin infusion.
The fractional excretion of sodium (FEN.), of
potassium (FEK), and of phosphate (FE,) were
calculated by computing the average 24 h sodium
excretion as UN.V, of potassium as UKV, and of
phosphate as UpV, and the filtered load from the
GFR and plasma sodium, potassium and phosphate
measured during the clearance study.
respectively. The PRNa group received 1.20 mmol/
day at stage IIA and excreted an average of 1.13
mmol/day. At stage IIB, this group received 0.60
mmol and excreted a mean value of 0.59 mmol/day.
At stage 111, this group received 0.45 mmol (except
rat no. 27) and excreted 0.40 mmol/day. Thus all
animals maintained external sodium balance with
close accuracy despite different dietary sodium intake
and progressive decrease in GFR. Plasma sodium
concentrations were normal for all animals. The
mean fractional excretion of sodium for the control
rats changed from 0.69 at stage IIA to 1.28 at stage
IIB and, finally, to 1.83 at stage 111. In the PRNa
group, the FEN. averaged 0.32, 0.31 and 0.29%
in the three stages of study. The prevention of
adaptive increased natriuresis in the PRNa group was
demonstrated by the consistency of external sodium
balance and constancy of FEN. despite progressive
decrease in G F R (Fig. 1). Potassium intake was
maintained constant at 1.60 mmol/day in both
groups. The 24 h urinary excretion rates were substantially less than the rate of intake in stage IIA,
averaging 0.91 and 0.92 for control rats and PRNa
group respectively. At stage IIB, they were 1.01
and 1.03 and increased to 1.31 and 1.26 at stage 111.
Thus the rate of potassium excretion varied with the
stage of study, but at each stage the mean values
Analysis
The electrolyte content of the diet was determined
in nitric acid extracts. Sodium and potassium were
measured with a flame photometer. Phosphate was
measured by the method of Gomori (1942) and by
the micro-method of Chen, Toribara & Warner
(1956). Radioactivity of [carboxyZ-14C]inulin was
counted in a liquid scintillation spectrometer.
Statistical significance was determined by Student’s
t-test.
0
Nointoke (mrnol/day )
Control PRNa
24
26
32
36
40
V
\
A 21
0 23
0 25
V
A
0 27 0
V 35 H
0
Results
Table 1 presents the results of GFR, sodium, potassium and phosphate measurements in both groups
at the three stages of decreased GFR. Sodium
excretion values represent the average of the daily
sodium excretion for the 10 days of balance study.
Sodium intake was maintained at 2.50 mmol/day
throughout the 5 months of observation in the
control group. The mean values of daily UN.V
were 2.43, 2.42 and 2.45 in stages IIA, IIB and I11
0
0.4
0.8
1.2
1-6
GFR (ml/min)
2-0
2-4
FIG. 1 . Adaptation in sodium excretion. Comparison of
fractional excretion of sodium with GFR for ten rats subjected to chronic renal failure. Control: constant dietary
sodium intake (mmol/day). Experimental (PRNa): proportionally reduced sodium intake (mmol/day).
Autonomous adaptation: chronic renal failure
for both groups were virtually identical. Plasma
potassium concentrations were normal for all
animals at all stages of decrease in GFR. Fractional
excretion of potassium averaged 8.7, 18.3 and 33.5
in the control group at the stages IIA, IIB and 111,
and 10.2, 18.0 and 32.5 in the PRNa rats. Therefore
the absolute and fractional excretion rates of potassium were the same in the presence and the absence
of increased natriuresis (Fig. 2). The intake of
phosphate was maintained constant at 0.97 mmol/day
in both groups at each stage of study. The 24 h
excretion rates for phosphate varied with the stage of
study, but at each stage the mean values for both
30E
20
197
groups were identical. The values averaged approximately 0.19 mmol/day for both groups at stage IIA
and increased to 0.39 mmol/day in stage IIB and to
0.45 mmol/day at stage 111. For both groups of
animals there was a progressive increase in plasma
phosphate concentration from stage IIA to stage 111.
At stage IIA the plasma phosphate concentration
averaged approximately 1.39mmol/l, and at stage 111,
2.90 mmol/l. A similar increase in FEp was observed
in both groups from stage IIA to stage I11 (Fig. 2).
The daily weight gained (g/day) averaged for the
control group 1.15 f 0.04, 0.75 k 0.04and 0.43 k 0.1 1
at stages IIA, IIB and I11 respectively; for the PRNa
group, the weight gains were 1.18 fO.01, 0.71 f0.05
and 0.40 k 0.03 at stages IIA, IIB and I11 respectively.
Thus the proportional reduction of sodium intake
had no influence on growth rate.
To examine the effect of proportional reduction of
sodium on the degree of compensatory increase in
GFR, a comparison was made of the values for the
left kidney before and after removal of the remnant
right kidney. For this purpose, as previously indicated, clearance studies were performed individually
on each kidney at stage IIB. The absolute values are
shownin Fig. 3. GFR increased by 1 2 6 ~ 13.9%
s ~ ~
in the control animals and 118 ~ S E M12.6% in the
PRNa group. Thus the adaptive change in GFR
lm
. .
.....
.....
.....
.....
.....
.....
.....
.....
1.25-
.....
.....
.....
.....
.....
....
1.00 -
-Z
._ 0.75-
-5a
T
E
I
&
hn,
.....
IIB
0 .5 0 -
0.25 -
IlA
Stages
FIG. 2. Comparison of excretory adaptation of sodium,
potassium and phosphate. Control (open columns): constant
dietary sodium intake. Experimental (PRNa) (dotted
columns): proportionally reduced sodium intake. Mean
v a l u e s k ~are
~ ~shown for all observations in both groups
of animals (n= 5 in each group). Details of stages IIA, IIB
and 111 are given in the text.
Stage I I B
Stagem
FIG.3. GFR of the left kidney mass before and after removal
of the contralateral kidney mass (from stage IIB to stage 111;
for details see the text). GFR in all animals ( 0 ,control group;
A , experimental; n=5 in each group) was reassessed at 35
or 36 day intervals.
198
C. H. Espinel
followed the same direction and degree in both
groups of animals.
Discussion
It is remarkable that chronically uraemic patients
may survive despite virtually total destruction of the
nephron population. The surviving nephrons must,
therefore, fulfil metabolic and excretory functions in
the presence of unrestricted dietary solute intake.
Consequently, preservation of life presupposes the
development of certain adaptive mechanisms whose
success is reflected in the maintenance of plasma
ionic values and increased rate of ionic excretion
per unit nephron. The experiments to be discussed
subsequently demonstrate that the adaptive increase
in GFRInephron, and potassium excretion and
phosphate excretion, are autonomous from the
adaptive increase in sodium excretion per nephron
in chronic renal failure.
Adaptation of GFR
An adaptive increment in GFR per nephron in the
residual nephrons of the chronically uraemic kidney
has long been known (Platt, 1952). The mechanism of
this adaptation, however, has not been established.
In the present study, the influenceof adaptive changes
in sodium excretion on this response was examined.
For this purpose, two separate assessments of GFR
were made. The first was the absolute value of GFR
at each stage of reduction in renal mass. The wide
range of values observed among the individual
animals, probably reflecting lack of uniformity in
surgical technique, however, did not permit definitive
evaluation of these results. The second assessment
obviated variations in surgical technique. It consisted
in the comparison of changes in GFR in the same
nephron population before and after removal of the
contralateral kidney mass. The results of observations
made at intervals of exactly 5 weeks disclosed no
association between the compensatory increases in
GFR and the degree of natriuresis (Fig. 3).
Unrestricted salt intake in chronic renal failure
imposes upon the surviving nephrons an increased
responsibility for sodium excretion. Our experiments
demonstrate that relieving the surviving nephrons of
this responsibility does not modify this adaptation,
suggesting that factors other than sodium excretion
alone are the stimuli essential for this adaptation.
Adaptation of sodium excretion
The animals receiving a constant intake of salt
maintained external sodium balance at all stages of
decrease in GFR. Moreover, there was an inverse
relationship noted between the number of functioning nephrons and the rate of sodium excretion per
unit nephron. These animals therefore follow the
characteristic physiological behaviour well described
in experimental animals and in man (Schultze et al.,
1969; Slatopolsky, Elkan, Weerts & Bricker, 1968).
Conversely, increased natriuresis per nephron was
prevented in the experimental group of animals
whose salt intake was reduced proportionally to the
decrease in renal mass and to the concomitant
decrease in GFR (Fig. 1). Although acute reduction
in salt intake in chronically uraemic patients
frequently results in negative sodium balance, the
gradual proportional reduction of salt intake in
the chronically uraemic rats was not followed by
this complication. These data corroborate the
concept that sodium excretion in chronic renal
failure is a reflection of the vitality of the control
system regulating sodium balance. The physiological
implications of the prevention of natriuresis are
currently under investigation in this laboratory
(Espinel, 1974, 1975a, b). Similar manipulation of
dietary phosphate has resulted in prevention of adaptive increased phosphaturia per nephron in experimental uraemia (Slatopolsky, Caglar, Gradowska,
Canterbury, Reiss & Bricker, 1972).
Adaptation of potassium excretion
In chronic uraemia, there is an increase in the
rate of potassium excretion per unit nephron. In
the dog it has been demonstrated that aldosterone
concentrations and rate of sodium excretion are not
the sole factors responsible for this adaptation
(Schultze et al., 1971). Nor in the present study was
the direction of this response affected by changes in
the rate of sodium excretion (Fig. 2).
In this study the presence of the potassium control
system was investigated in young rats maintained on
constant dietary potassium intake throughout
progressive losses of nephron population and various
quantities of sodium intake. In health, the primary
objective of this control system is the maintenance
of potassium homeostasis, which is accomplished
by maintaining potassium balance and plasma
concentration within a range which optimally
Autonomous adaptation: chronic renal failure
serves biological responsibilities. In these
experiments, urinary potassium, representing the
surplus after fulfilment of these responsibilities was
closely comparable for all animals at each increment
in body weight. Moreover, plasma potassium
concentrations were maintained within a normal
range despite progressive decrease in GFR. These
characteristics therefore suggest the presence of
this control system operating autonomously from
thesodium control systemthroughout the progression
of chronic renal failure.
Adaptation of phosphate excretion
In chronic uraemia there is also an increase in the
rate of phosphate excreted per unit nephron
(Slatopolsky et al., 1968). It has recently been suggested that factors other than parathyroid hormone
activity might contribute to the reduced tubular
phosphate reabsorption (Popovtzer, Pinggera, Hutt,
Robinette, Halgrimson & Starzl, 1972). In normal
subjects it has been shown that acute sodium loads
result in a decrease in the rate, not only of sodium,
but also of phosphate reabsorption (Suki et al.,
1969). It might therefore be assumed that a similar
association exists between the adaptive natriuresis
and phosphaturia of chronic renal failure. In the
present study, however, in which phosphate intake
was maintained constant, the quantities of phosphate
excreted were not influenced by the pattern of sodium
excretion. Moreover, as the total nephron population
decreased, a similar increase in the plasma phosphate
concentration was observed in both groups of animals. It follows therefore that in the adaptation to
chronic renal failure the factors concerned with the
maintenance of phosphate homeostasis must operate
autonomously from those regulating sodium excretion.
One further observation should be discussed: the
increment in the absolute amounts of potassium and
phosphate excretion in both groups of animals at
the final stage of renal failure. At this stage, the
animals’ weights had increased by approximately
50% and the rate of weight gain had decreased
substantially. Thus it is possible that this observation
reflects changes in absorption and utilization of
potassium and phosphate related to growth and
body weight.
The concept of ‘autonomous adaptation’ in
chronic renal failure is presented. The mechanisms
regulating GFR, potassium and phosphate excretion
199
adapt autonomously from those regulating sodium
excretion. The maintenance of homeostasis in the
presence of varying quantities of solute intake
presupposes the existence of individual control
systems for the regulation of each ion’s excretion.
Acknowledgments
The author is most grateful to Dr Neal S. Bricker,
who provided the facilities in which these studies
were initiated. The technical assistance of Jeanne
Fielding Lord and Rosalie Cornelius is acknowledged. This research was supported in part by
NIH training grant no. 2T12-HE05684.
References
CmN, P.S., TORIBARA,
T.Y. & WARNER,
H. (1956) Microdetermination of phosphorus. Analytical Chemistry, 28,
1756-1758.
ESPINEL.C.H. (1974) On the mechanism of natriuresis in
chronic uremia. Clinical Research, 22, 74A.
E~PINEL,
C.H. (1975a) Prevention of arterial hypertension in
experimental chronic renal failure. Clinical Research, 23,
35A.
ESPINEL,C.H. (1975b) The influence of salt intake on the
metabolic acidosis of chronic renal failure. Journal of
Clinical Investigation (in press).
ESPINEL,
C.H. &BRICKER,
N.S.(1973) Prevention of increased
natriuresis per nephron in the uremic rat. Clinical Research,
21, 75.
GOMORI,G. (1942) A modification of the colorimetric
phosphorus determination for use with the photoelectric
colorimeter. Journal of Laboratory and Clinical Medicine,
27,955-960.
HERRERA-ACOSTA,
J., ANDREUCCI,
V.E., ReCTOR, F.C.,
JR & SELDIN,D.W. (1972) Effect of expansion of extracellular volume on single-nephron filtration rates in the
rat. American Journal of Physiology, 222, 938-944.
PLATT, R. (1952) Structural and functional adaptation in
renal failure. British Medical Journal, i, 1313-1317.
POPOVTZER,M.M., PINGGERA,
W., H m , M., ROBINETTE,
J., HALORIMSON,
G. & STARZL,T.E. (1972) Serum parathyroid hormone levels and renal handling of phosphorus
in patients with chronic renal disease. Journal of Clinical
Endocrinology and Metabolism, 35, 213-218.
SCHULTZE,
R.G., SHAPIRO,
H.S. & BRICKER,
N.S. (1969)
Studies on the control of sodium excretion in experimental
uremia. Journal of Clinical Investigation, 48,869-877
SCHULTZE,
R.G., TAGGART,
D.D., SHAPIRO,
H., PENNELL,
J.P.,
CAOLAR.
S. & BRICKER,
N.S.(1971) On the adaptation in
potassium excretion associated with nephron reduction in
the dog. Journal of Clinical Inuestigation, 50, 1061-1068.
SELDIN,D.W., CARTER, N.W. & RECTOR, F.C., JR (1971)
Diseases of the Kidney, 2nd edn, vol. 1, p. 225. Ed. Strauss,
M.D. & Welt, L.G. Little, Brown & Co., Boston, Massachusetts.
SHANKEL,S.W., ROBSON,A.M. & BRICKER,
N.S. (1967)
On the mechanism of the splay in the glucose titration
curve in advanced experimental renal disease in the rat.
Journal of Clinical Investigation, 46, 164-172.
SLATOPOLSKY,
E., CAGLAR,
S., GRADOWSKA,
L., CANTERBURY.
J., REISS,E. & BRICKER,
N.S. (1972) On the prevention
200
C. H . Espinel
of secondary hyperparathyroidism in experimental chronic
renal disease using ‘proportional reduction’ of dietary
phosphorus intake. Kidney International, 2,147-151.
SLATOPOLSKY,
E., ELKAN,LO., WEERTS,
C. & BRICKER,
N.S.
(1968) Studies on the characteristics of the control system
governing sodium excretion in uremic man. Journal of
Clinical Investigation, 47, 521-530.
SLATOPOLSKY,
E., ROBSON,
A.M., ELKAN,I. & BRICKER,
N.S.
(1968) Control of phosphate excretion in uremic man.
Journal of Clinical Investigation, 41, 1865-1 874.
SUKI, W.N., MARTINEZ-MALDONADO,
M., ROUSE,D. &
TERRY,A. (1969) Effect of expansion of extracellular
fluid volume on renal phosphate handling. Journal of
Clinical Investigation, 48, 1888-1 894.