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Studies on renal function after relief of complete unilateral ureteral obstruction of three months' duration in man
Studies on Renal Function After Relief of Complete Unilateral Ureteral Obstruction of Three Months’ Duration in Man
ORI
S. BETTER,
ALLEN
I.
SHAUL
G.
CHARLES
M.D.*
ARIEFF, MASSRY,
H.
Los Angeles,
the
Cedars-Sinai
Nephrology
Cedars-Sinai
worth
General
and and
of Medi-
Center, UCLA
WadsSchool
California.
by General
SerMedical
Department and
Los Angeles,
No.
Center,
Medical
Hospital
supported
Hypertension
Medical
Institute,
cine,
Medicine,
M.D.
California
From
Research
M.D.
MAXWELL,
vice,
Grant
M.D.$
R. KLEEMAN,
MORTON
was
M.D.?
This
Research
5-501-RR05468-08.
of
study
Support
Requests
for
reprints should be addressed to Dr. Shaul G. Massry. Cedars-Sinai Medical Center, Mount Sinai Hospital Divisions, 8720 Beverly Blvd., Los
Angeles,
California
90048.
Manuscript
received January 4, 1971; accepted January 25. 1971. *Visiting Scientist. Present address: Department ment
of
Hospital,
Nephrology, Haifa,
Rambam
Govern-
Israel.
tclinical Investigator, Veterans Administration. SEstablished Investigator, American Heart Association.
234
February
1973
The American
Journal
Individual renal functions were studied in a 24 year old woman following relief of a complete unilateral ureteral obstruction of three months’ duration. Function of the previously obstructed kidney was investigated over a period of six weeks and compared with that of the contralateral unobstructed kidney. Within one week after relief of obstruction, the creatinine clearance in the affected kidney increased from 2.6 to 10.2 ml/minute and remained essentially unchanged thereafter. In comparison to the contralateral kidney, fractional sodium excretion was moderately increased, maximal diluting ability was normal, generation of free water (corrected for glomerular filtration rate) was supranormal, and urinary excretion of phosphate was very low; the latter was presumably due to excessive tubular reabsorption of phosphate. The urinary pH was higher than that from the contralateral kidney and did not decrease normally after the ingestion of ammonium chloride. The excretion of titratable acid was low, partially due to low urinary phosphate excretion and high urinary pH. After 16 hours of water deprivation, the urine from the affected kidney remained hypotonic to the plasma. The natriuretic response to volume expansion, sodium retention after the administration of mineralocorticoids and the phosphaturic action of parathyroid hormone extract were normal as compared to the contralateral kidney. Despite the prolonged period of complete ureteral obstruction, the renal function attained by this kidney would probably have been adequate to support life were this kidney the only one available to the patient. Ligation of the ureter is an occasional complication of pelvic surgery. It has been reported in 11 per cent of operations for pelvic malignancy or uncontrolled uterine bleeding [l] and in 2 per cent of abdominal gynecologic surgery [2,3]. Several case reports described a return of renal function after the relief of ureteral occlusion. In many of these cases ureteral obstruction was due to a calculus, so that neither the duration nor the completeness of the obstruction could be estimated [4-61; fur-
of Medicine
Volume
54
RENAL
FUNCTION
thermore, the evidence for return of renal function in the affected kidney was based on roentgenographic studies, such as visualization on intrave-
CASE REPORT
Sinai
Hospital
uterine
days
prior
had a normal
to her
initial
(MSH).
The
by uterine
oxytocin.
An
both
patient
uneventful,
low grade
fever.
right
two
sure
was
nisms of
therapy
sterile
plored
via
ureter. the
with
was
days
good
tasis
time
blood
88/minute
was
treated
60
days
nonfunctioning
right
ferred
to MSH.
A retrograde
ization
of the
lumbar
vertebra,
(PAH)
rate
96/minute
and
temperature
the
nephrostomy
from
coli; After
gentamycin,
both
orga-
eight
days
the
urine
be-
was
ex-
ureter
A fibrous
band
compressed
over
a cysto-ureteral
good
surgery
in
and
body
right
were
function
the
the
(1
catheter.
was
discharged right
pyelogram. right
cm
and
of the splinted
patient
in the
size
the
incised,
anastomosed
intravenous
present
ureter
Calycec-
kidney,
which
difference
in
was
length)
to the left kidney.
ry patterns
of sodium,
magnesium;
of
and
the
with
accompanied
by a
these
studies
pressure
115,’
duration
was
17,’
between 99” and was 9,800/mm3 was normal.
sulfisoxazole
ride
of
specified,
after
kidney,
right
ureter
and
surgery the
patient
pyelogram only
to the
revealed
urine
was
showed level
a re-
visual-
of the
fifth
with no demonstrable right kidney. A showed normal up(Hgzo3 chlormerodrin)
by the left kidney
but none by the right
nephrostomy was original surgery. approximately in the pelvis. One inulin
of the right
week and kidney
kidney.
normal size with 40 ml of Very little hydronephrosis after the nephrostomy that of para-aminohippurate were
9.5
and
the
50 ml/minute,
with
neous
Davies
function
of with
tion
creatinine
otherwise
by Perkin model were
made
and
the
303.
both hour
from
normal
determined
the side.
in 2.0
(Precision);
determined
Elmer
the
by sponta-
photometer,
measured
in 24
directly
from
flame
chio-
Unless
side
were
In
to
osmometer
content
Laboratories magnesium
ammonium
utilizing
were
a cryoscopic
spectrophotometer, and
urine
osmolalities
potassium
minutes’
according
was collected
bladder
[8].
of 20
were
kidneys,
on the affected
sodium
and
[9].
studies
normal
ml samples
cium
short
and
urine
chlo-
technics
periods
The
Urine
ability;
para-aminohippurate
Wrong
voiding
strumentation
and
performed
and
calcium
diluting
of ammonium
standard
was
tube
and
and
load
clearance
performed.
renal
and
phosphate,
test
collections.
phorus
performed 98 days after the At operation, the right kid-
inulin
affected
of renal
the excreto-
injection, mineralocorticoid of saline solution.
of
were
loading
method the
(Gantri-
potassium,
measured three
rate;
concentrating
to an oral
clearances
the evaluation
filtration
ride, parathyroid extract administration and infusion were
respirations
the
responses
The
surgery
included
and glomerular
and
Plasma
pyelogram
was present. clearance of
pulse
splinted
performed
flow
(PAH)
and
with
The studies
the
pain
shift to the left; urinalysis
ney was of sterile urine
fever pres-
tissue
reduced compared
with
patient’s
of
to
after
the blood
scar
in the still
readmitted
and
after
ureter
time
with
function
was
slightly
to be readweeks
Escherichia
showed
demonstrated
re-
At this
urine
the
A nephrostogram
venous
Right patient’s
and
Adhesions
ureter. Eight
scan
four
to gentamycin.
laparotomy.
ureter
was
and
parenteral
MSH
However,
Hg,
the
sensitive
nephrostomy
scan
of
were
came
renal
of the right
lS/minute
Enterobacter
sine) for 14 days, and her fever gradually abated, but she continued to complain of right flank pain. An intra-
renal
mm
Cultures out
from
patient
respirations
101°F. grew
time.
tenderness.
120/75
regular,
Hgzo3
discharged
the
flank
an
re-anastomosis
at a later
was
the body temperature ranged The white blood cell count
take
was
be
performed ligated
after
minute; 101°F.
patient
not
Recovery
days
Hg,
The
rate
were
75 mm
with a slight
and right
time
ET AL.
by the kidney.
the nephrostomy
plasma
massive
was
arteries
flank
At this
pulse
de-
Mount
could
hemorrhage.
but
aching
delivery
laparotomy
of the
at
and the administration
hypogastric
control
had
after which
packing
emergency
inferior
generally’
day
full term
evaluation
developed
controlled and
woman
hemorrhage
subsequent
bladder
OBSTRUCTION-BETTER
METHODS
old white
94
which
for elective
when
of azotemia.
livery
patient
mitted the
at
no uptake
The
re-anastomosis of the obstructed ureter. The studies to be described were carried out over a six week period after placement of a nephrostomy tube in the obstructed kidney. The normal contralateral kidney served as a control and provided an opportunity to study renal function in man after the relief of ureteral obstruction in the
A 24 year
OF URETERAL
respectively, vealed
nous pyelogram [7] or estimation of function by radioisotope renogram [4]. There are no detailed studies on renal function in man following relief of a complete long-standing ureteral occlusion. Recently, we were presented with a case of complete unilateral obstruction of three months’ duration due to accidental occlusion at surgery. Because of the lack of information in the literature regarding the potential for recovery of renal function in such cases, nephrostomy was performed to enable us to evaluate the improvement in renal function, which if significant would justify elective
absence
AFTER RELIEF
by Inand
atomic Inorganic with
cal-
absorpphos-
the Techni-
con@ Autoanalyzer.@ RESULTS
The results of renal function studies of both the obstructed and the normal kidney are presented in Tables I, I I and I I I, and Figures 1 through 3. A
February 1973
The American Journal of Medicine
Volume 54
235
...
.., ...
Control day for Florinef
... 2 mg Florinef
Control period for saline infusion
B Neph
B Neph
B Neph
0* Neph*
Bt Nepht
B Neph
...
B Neph
g/3/70
g/6/70
g/7/70
9/a/70
9/a/70
g/21/70
g/22/70
10/7/70
min)
2.1 0.7
3.4 0.8
3.9 0.9
2.5 1.3
“IL
... ..,
... ...
... ...
... .
.. ...
. . ...
..
...
...
...
357* 50*
77.0* 9.4*
...
...
... ... ... ...
...
... ... ... ...
la.2 1.2
61.0 8.6
... ...
10.9 0.2
77.7 11.3 17.9 1.3
12.6 0.1
64.8 10.9
74.9 9.4
12.8 0.2
15.2 0.05
11.6 0.06
10.0 0.04
15.6 0.06
68.0 a.6
67.2 10.2
47.2 5.0
47.3 5.9
69.0 2.7
min)
... ...
...
...
...
...
0.216 0.188
.. ... ... ...
. . . . ...
C,
... ...
4.4 0.2
24.0 13.7 30.0 13.5
2.7 0.07
3.0 0.2
3.5 0.07
3.2 0.1
2.4 0.09
2.3 0.1
1.2 0.3
min)
$7
14.0 2.0
19.4 0.9
17.9 2.1
22.5 0.5
24.5 1.2
21.1 0.6
22.6 2.1
CQ X 100
$; (Ai,
CPAH CPAH min)
... .. ...
.. ... ...
min)
WI
GIN
Excretion from Both the Normal and Obstructed ChIg
... ...
5.8 1.7
3.4 0.6
4.6 1.7
5.1 0.7
4.7 1.2
5.2 1.8
4.9 2.3
1.9 9.9
X 100
. . ...
7.2 1.2
5.7 1.0
6.5 1.4
... ...
8.2 1.4
7.6 0.8
7.0 1.2
2.5 0.5
min)
19.6 4.1 28.1 a.3
0.4 0.9 1.3 2.4 4.6 4.3
34.9 12.7 125.1 28.8
12.2 11.2
.
53.8 15.1
113.9 24.5
99.2 15.2
7.4 a.8 9.6 13.0
417.8 65.3
10.1 13.2
...
42.9 4.8
1.1 1.8
72.2 12.3
19.8 2.7 20.1 3.9 26.0 4.5
0.9 1.0 1.1 1.9 0.6 1.3
25.3 2.3
31.4 3.6
16.1 16.6
1.5 2.3
99.0 la.7
39.2 2.5
14.8 19.9
0.2 1.09
UKV Ccr &es/ X 100 min)
CNa
21.4 4.0
(req/ min)
UNaV
3.6 la.0
Ccr X 100
c::(“2;
C.
Kidney
9.0
9.6
... 4.5
.. 1.0
...
3.9
. . ... ... ... .. ...
......
... 4.2
140 4.4
...
141 4.5
...
141 5.5
..
138 4.2
...
140 4.0
...
140 4.0
..
140 4.0
...
140 3;a
...
134
............
1.9
...
2.0
...
1.9
...
1.8
...
1.9
...
1.8
..
1.1
..
1.9
Na K (mEq/liter)
1.1
10.8
..
...
... 4.7
9.3
...
9.2
...
9.1
...
9.0
...
9.0
...
1.0
...
... 4.3
1.0
...
... 4.2
1.1
...
... 4.1 1.1
...
... 4.0
... 1.0
4.1
...
... 1.1
4.1 1.1
Mg
Blood Ca Cr P (mg/lOO ml)
=
NOTE: AlI urinary data obtained from 24 hour collections except when otherwise indicated. B = bladder, Neph = nephrostomy, UV = urine volume, C = clearance, IN calcium was 60 per inulin, P = phosphate, Cr = creatinine, Ca = calcium, Mg = magnesium, PTE = parathyroid extract, C Cnwas calculated assuming ultrafiltrable cent of Serum calcium, and CAI, was calculated assuming ultrafiltrable magnesium was 75 per cent of serum magnesium. * Each data Point is the average of three clearance periods each of 20 minutes duration. t Data are obtained from a clearance period of two hours’ duration.
...
+SfJO U PTE intramuscularly
Control day for PTE injection
Saline infusion
4.9* 1.2*
3.0 0.9
2.3 0.5
2.2 0.7
2.4 0.3
was placed
...
B Neph
Procedure
Nephrostomytube
Specimen
Summary of Data of Electrolyte
a/30/70
I
a/27/70
Date
TABLE
RENAL
TABLE II
Dilution and Concentration
AFTER RELIEF
OF URETERAL
POsm
UOsm (mOsm/kg
CL? (ml/min)
COSnl (ml/min)
(mosm/kg HzO)
HzO)
Dilution: After the oral ingestion of 20 ml of water per kilogram l/9/70
Normal Diseased
2/g/70
Normal Diseased
8.5 1.2
69.0 2.7
Concentration:
~______
~-
... ..
42 44
Effect of Oral Ammonium
Chloride
C. Date g/3/70 ____
Kidney
(ml/Zn)
Normal Diseased
766 265
7.25 1.01
10.5 37.4
.
.. ...
UOsm
=
.. ...
urinary
..
osmolality,
POsm
___ ____
Control
Exper.
Control
Exper.
NH4
32.3 1.6
89.4 6.5
2.8 0.8
37.3 1.4
189 114
4.9 5.7
TA = titratable acid, TA-!-lCO, = titratable of NH&I.
of the data of electrolyte excretion both kidneys appears in Table I. Glomerular Filtration Rate (GFR) and Renal ma Flow (RPF). During the first 24 hours placement of the nephrostomy tube, clearance (Cc,) was 2.7 ml/minute and within one week to 10.2 ml/minute; it essentially unchanged thereafter. lnulin
from Plasafter
creatinine increased remained clearance
(GIN) in the second postoperative week was ml/minute when creatinine clearance was
9.4 8.6
osmolality,
Per 100 ml Cc+
Control
Exper.
= plasma
Acidification NHa (req/min) _ _______
excretion, chloride, ingestion
x 100
C+,
body weight 1.29 0.19
290 290
clearance,
on Urinary
summary
24
277 277
CIi,”
CHJO (ml/min)
Urinary pH ____~ _~_
6.7 6.7
47.3 6.9
NOTE: NH, = urinary ammonium preceding ingestion of ammonium maximal values obtained following
ET AL.
After 16 hours of water deprivation
. . ...
NOTE: UV = urine volume, Cc., = endogenous creatinine r&,0 = free water clearance. C r,q,,, = osmolal clearance, TABLE III
OBSTRUCTION-BETTER
of Urine
UV (ml/min)
Kidney
Date
FUNCTION
TA-HCOI (peq/min) ~.
NH4
TA
TA
76.6 24.6
2.4 4.6
Control = values obtained from a 24 hour urine collection acid minus bicarbonate excretion, Exper. = experimental:
ml/minute; the clearance of PAH (CPAH) was 50 ml/minute. The filtration fraction (CIN:CPAH) was 0.22 in the normal kidney and 0.19 in the diseased kidney. Concentration and Dilution of Urine (Table II). After 16 hours of water deprivation, serum osmolality was 290 mOsm/kg water, and the osmolality of the urine from the nephrostomy was 265 mOsm/kg water whereas the normal kidney concentrated
the urine
to 766 mOsm/kg
water.
An
7.0 -) Before
0
During U
Diseased
PTE
/
20
Normal
5.0 -
4 0
, 0600
~ Diseased
The phosphaturic response Figure 7. cular injection of 800 units of parathyroid
< 1
I
1200
1
I
1600
Hour Normal to the intramusextract.
Figure 2. Changes in urine pH after the oral tration of 0.1 g/kg body weight of ammonium between6and8AM.
February 1973
The American Journal of Medicine
adminischloride
Volume 54
237
RENAL
FUNCTION
AFTER RELIEF
-
400
-
-
m
200
-
During
............. ...**.*.*.* ....... ............. .*.*.*.*. .. .. .. .. s.... .............. ........... ........‘... .... .:.:.:.I. .......* .. .. .. .......‘. .:.:.:.:. ..*.*.*.a. .... .:.:.:.I. .*... .:.:.I.:. .*... ........ ..:.:.:.I. .... .....*.*.*. ..*.*.*. ...*.*... .:.:*:.:. :.:.:.:.: .a.*..... ......... .:.:.:.I. ....*. ... *.*.*...~ .......~’ *...*...* .....
E >,e ‘3
IOO-
0 l
dl
I.:.:.: .*,a.*. .a...*. ..::. ... :.I.:.:
Diseased
Normal
The response to the intravenous 3. 1 liter of normal saline solution.
Figure
OBSTRUCTION-BETTER
Volume Expansion
Before
300
OF URETERAL
infusion
of
oral water load of 20 ml/kg body weight was given between 7:00 and 8:00 AM, and the patient drank water equal to urine output thereafter. Urinary osmolality fell to very low levels on both sides (diseased kidney 44, and normal kidney 42 mOsm/kg water). During this test the free water clearance (CH~O) from the diseased kidney was 1.01 ml/minute and amounted to more than one third of the GFR (C~,o:Ccr X 100 = 37.4 per cent). This is a supranormal value when compared with the normal kidney which had a CH20:CCr X 100 of 10.5 per cent. Urinary Phosphate Excretion and Response to Parathyroid Extract Injection. Phosphate excretion was consistently low on the diseased side. The fraction of filtered phosphate excreted (C,:Ccr X 100) ranged between 0.5 to 2.1 under basal conditions. This was approximately one tenth to one twentieth of the simultaneous values from the normal kidney (14.0 to 24.5). A total of 800 units of parathyroid extract (Eli Lilly) was injected intramuscularly at 9 AM and 4 PM in two divided doses. The excretion of phosphate increased from both kidneys during the day of parathyroid administration as compared to the preceding control day. There was a sixfold increase in Cp:Ccr X 100 in the diseased kidney (from 2.0 to 13.7). However, even during the height of this phosphaturia the fractional excretion of phosphate from the affected kidney was only half of the
238
February 1973
The American Journal of Medicine
ET AL
value from the normal kidney (Figure 1). Fractional excretion of phosphate from the obstructed kidney increased spontaneously and reached a value of 13 per cent of filtered phosphate 48 days after ngphrostomy. Urinary Acidification (Table I II and Figure 2). Random urinary pH measurements from the nephrostomy ranged between 6.5 to 7.5 which was consistently higher than values from the normal kidney (pH 5.5 to 6.5). After the oral ammonium chloride load, urinary pH fell to 5.7 in the affected kidney and to 4.9 in the normal kidney. Ammonia excretion on the diseased side was normal considering the reduced renal mass and the higher urinary pH [9]. Titratable acid excretion of 1.4 peq/minute was low even when allowance is made for the reduced renal mass [lo]. Also the contribution of titratable acid excretion to net urinary hydrogen ion excretion was considerably lower on the affected side (NH4:TA = 4.06 on the affected side, compared to 2.4 on the normal side). The diminished titratable acid excretion in the affected side was due, at least in part, to the low excretory rates of phosphate. Sodium Excretion. Basal conditions: The fraction of filtered sodium excreted was consistently higher in the affected kidney (1 .O to 2.3 per cent) than in the normal kidney (0.2 to 1.5 per cent). Response to mineralocorticoid administration: After a control 24 hour urine collection, 2.0 mg of Florinef@ (fludrocortisone) was given orally, and a 24 hour urine was collected during the day the drug was administered. Fludrocortisone decreased the fractional excretion of sodium approximately by half in both kidneys. Response to infusion of saline solution: After three control clearance periods, each of 30 minutes’ duration, 1 liter or normal saline solution was infused over a period of one hour, and urine was collected for two hours after the infusion was completed. Sodium excretion increased approximately twofold (from 29 to 65 peq/minute) on the diseased side and more than threefold (from 125 to 417 peq/minute) on the normal side (Figure 3). However, at the height of sodium diuresis the fraction of filtered sodium excreted was 4.3 per cent in the affected kidney and 4.6 per cent in the normal kidney. Divalent cation excretion: Except for the first urine specimen obtained at the time of nephrostomy, the fraction of filtered calcium excreted was consistently greater in the normal kidney than in the diseased kidney. Since the values for the fractional excretion of calcium from the affected kid-
Volume 54
RENAL FUNCTION AFTER RELIEF OF URETERAL OBSTRUCTION-BETTER
ney were within the normal range (0.7 to 2.3 per cent), it appears that the excretion of calcium from the normal kidney was high, for unknown reasons. The fraction of filtered magnesium excreted was similar in the two kidneys. COMMENTS
Ureteral obstruction after pelvic surgery often is unrecognized. The usual complaint is flank pain which may be accompanied by fever; urinalysis is usually normal in complete unilateral ureteral obstruction. The diagnosis is established by intravenous pyelogram followed by retrograde pyelography. Renal scan using Hg203 chlormerodrin is useful in establishing the presence of obstruction within the first five days of the obstruction [ll 1. After discovery of an occluded ureter a course of action must be decided upon. The possibilities are (1) to leave the obstructed kidney in place, (2) to remove the obstructed kidney, and (3) to relieve the obstruction and reestablish urinary flow by appropriate means. Leaving the obstructed kidney in place involves the risk of infection, and occasionally hypertension which has been reported in association with unilateral ureteral obstruction [12]. Removal of the obstructed kidney may be justified if renal function does not improve after relief of the obstruction. Radioisotope studies alone are not adequate for such evaluation; our patient, for example, had no visualization of the affected kidney by Hg203 scan when GFR was 9.4 ml/minute. In experimental animals, improvement of renal function after relief of unilateral ureteral occlusion varies widely among different species [13-151; also different patterns of the return of renal function have been reported in the same species by different investigators [15-171. In dogs, rabbits and rats, there is essentially no return of renal function after stasis of over four weeks [13,14]. The exact length of time of complete ureteral occlusion after which a good return of renal function can be expected is not known. Although there have been several reports of return of renal function after ureteral occlusion for as long as one and a half years [S], complete obstruction has usually not been documented, and the evidence for’the return of renal function has been based on roentgenographic studies alone [4,5,18]. In only a few cases was GFR measured, and even in these instances only the total clearance from both kidneys was determined [7]. Based only on roentgenographic and isotopic studies, no improvement of renal function occurred after complete ureteral
obstruction “complete” obstruction
ET AL.
of seven and a half months [18], and return of function is probable if the is of less than three weeks’ duration
[41. The data in our patient demonstrate that only limited recovery of kidney function can be expected in man after complete ureteral occlusion of three months’ duration. GFR was 2.7 ml/minute at the time of nephrostomy and increased to about 10 ml/minute. Several abnormalities in renal function have been described after the relief of obstructive uropathy. Among these are low GFR [19], osmotic diuresis due to retained solutes [19,20], impaired sodium reabsorption located most probably in the proximal tubule [20,21], nephrogenic diabetes insipidus [22] and defects in urinary acidification [22,23]. Most of these abnormalities were observed in our patient. Osmotic diuresis did not occur since the presence of the contralateral normal kidney prevented the retention of nitrogenous solutes. The obstructed kidney in our patient was unable to concentrate the urine to isotonicity even after 16 hours of dehydration, suggesting a state of renal refractoriness to the action of antidiuretic hormone. However, the diluting ability was intact, and indeed supranormal values of C~,o/lO0 ml GFR were observed. A similar phenomenon was previously reported by Suki et al. [24] in chronic urinary tract obstruction in dogs: these investigators suggested that decreased tubular back-diffusion of fluid secondary to both diminished medullary hypertonicity and relative impermeability of the distal tubules and collecting ducts to water may underlie this phenomenon. Abnormality in the renal handling of sodium was noted in the obstructed kidney of our patient. A slightly greater fraction of filtered sodium was excreted from the affected kidney as compared with the normal side. This observation indicates a mild impairment in tubular reabsorption of sodium. This abnormality was not due to failure of the renal tubule to respond to mineralocorticoid since the administration of fludrocortisone decreased fractional excretion of sodium in both kidneys. Bricker et al. [19] and Massry et al. [21] reported similar observations on the effect of mineralocorticoids on sodium diuresis which followed the relief of short-term urinary tract obstruction. Despite the prolonged obstruction on our present case, the affected kidney responded satisfactorily to volume expansion as well. An unusual but consistent finding in our study
February 1973
The American Journal of Medicine
Volume 54
239
RENAL FUNCTION AFTER RELIEF OF URETERAL OBSTRUCTION-BETTER
was the strikingly low urinary excretion of phosphate from the obstructed kidney. This was most probably due to excessive tubular reabsorption of phosphate (TRP). Theoretically, an enhanced TRP could be due to a fall in filtered load of phosphate per nephron secondary to glomerular hypoperfusion, or to refractoriness of the tubule to the phosphaturic action of parathyroid hormone, or to both. An intrinsic change in the tubular reabsorptive capacity for phosphate secondary to obstruction should also be considered. Refractoriness to parathyroid hormone seems remote since the administration of parathyroid extract produced marked phosphaturia on the unaffected side. Several features of the function of the obstructed kidney are consistent with hypoperfusion per nephron; among these are the lower filtration fraction and the lower fractional excretion of calcium and phosphate. However, the excretory patterns of sodium, magnesium and free water do not support this assumption. Finally, the possibility that prolonged obstruction can induce selective changes in the renal handling of phosphate cannot be excluded. Although defects in urinary acidification have
ET AL
been described [22,23] in obstructive uropathy, little has been published regarding the constituents of hydrogen ion excretion in such patients. In six of the seven cases of obstructive uropathy studied by Berlyne [23], the urine could not be acidified but ammonia production during acid loading was normal; titratable acid was measured directly in two patients and was found to be low in one [23]. In our patient the affected kidney could not normally lower urinary pH, and titratable acid excretion was low during an acid load. The low titratable acid excretion was at least in part due to the relatively high urine pH and the diminished urinary excretion of phosphate. If this abnormality in renal handling of phosphate occurs in chronic obstructive uropathy, it could presumably aggravate the acidosis seen occasionally in these patients. ACKNOWLEDGMENT We are indebted to Dr. Harold Holland for allowing us to study this patient. We thank Mrs. Gloria Bailin and Mrs. Miriam Bick for their technical help and Miss Catherine Weckesser for her secretarial assistance.
REFERENCES 1. 2.
7.
8.
9. IO.
11.
12. 13.
240
Wertheim E: Zur frage der Radikaloperation beim Uteruskrebs. Arch Gynak 61: 627, 1900. Harrow BR: Ureteral injuries recognized after gynecologic operations. Surg Gynec Obstet 127: 1267, 1968. Freda VC. Tacchi D: Ureteral injury discovered after pelvic surgery. Amer J Obstet Gynec 83: 406, 1962. Earlam RJ: Recovery of renal function after prolonged ureteric obstruction. Brit J Urol 39: 58, 1967. Graham JB: Recovery of kidney after ureteral obstruction. JAMA 181: 993, 1962. Papaioannou AN, Brunschwig A: Return of function of a kidney not visualized on intravenous pyelogram for 1 l/2 years. Arch Surg 90: 367, 1965. Lewis HY, Pierce JM: Return of function after relief of complete ureteral obstruction of 69 days’ duration. J Urol 88: 377, 1962. Smith HW, Goldring W, Chasis H: The measurement of the tubular excretory mass, effective blood flow, and filtration rate in the normal human kidney. J Clin Invest, 17: 263, 1938. Wrong 0, Davies HEF: Excretion of acid in renal disease. Quart J Med 28: 259,1959. Better OS, Chaimowitz C, Alroy CG, Sisman I: Spontaneous remission of the defect in urinary acidification following cadaver kidney homotransplantation. Lancet 1: 110, 1970. Johnston GS, Murphy GP: The effect of acute and chronic ureteral occlusion upon renal handling of Amer J Roentgen 98: 163. Hg 203 chlormerodrin. 1966. Garrett J, Polse SL, Morrow JW: Ureteral obstruction and hypertension. Amer J Med 49: 271, 1970. Beer E: Experimental study of the effects of ureteral
February
1973
The American
Journal of Medicine
14.
15. 16.
17.
18.
19.
20.
21
22. 23. 24.
Volume 54
obstruction on kidney function and structure. Amer J Uro18: 171. 1912. Pridgen WR, Woodhead DM, Younger RK: Alterations in renal function produced by ureteral obstruction. JAMA 178: 563, 1961. Fylling P: Restitution of rat kidney after temporary ureteral ligation. J Urol 78: 337, 1957. Murphy GP, Scott WW: The renal hemodynamic response to acute and chronic ureteral occlusions. J Urol 95: 636, 1966. Vaughan ED Jr, Sorenson EJ, Gillenwater JY: The renal hemodynamic response to chronic unilateral complete ureteral occlusion. Invest Urol 8: 78, 1970. Brunschwig A, Barber HRK, Roberts S: Return of renal function after varying periods of ureteral occlusion. JAMA 188: 125, 1964. Bricker NS, Shwayri El, Reardan JB, Kellog D, Merrill JP, Holmes JH: An abnormality in renal function resulting from urinary tract obstruction. Amer J Med 23: 554, 1957 Muldowney FP, Duffy GJ, Kelly DG. Duff FA. Harrington C. Freahey R: Sodium diuresis after relief of obstructive uropathy. New Eng J Med 274: 1294, 1966. Massry SG, Schainuck LI, Goldsmith C, Schreiner GE: Studies on the mechanism of diuresis after relief of urinary tract obstruction. Ann Intern Med 66: 149. 1967. Early LE: Extreme polyuria in obstructive uropathy. New Eno J Med 255: 600, 1956. Berlyne GM: Distal tubular function in chronic hydronephrosis. Quart J Med 30: 339, 1961. Suki W, Eknoyan G, Rector FC, Seldin DW: Patterns of nephron perfusion in acute and chronic hydronephrosis. J Clin Invest 45: 122, 1966.
ORI
S. BETTER,
ALLEN
I.
SHAUL
G.
CHARLES
M.D.*
ARIEFF, MASSRY,
H.
Los Angeles,
the
Cedars-Sinai
Nephrology
Cedars-Sinai
worth
General
and and
of Medi-
Center, UCLA
WadsSchool
California.
by General
SerMedical
Department and
Los Angeles,
No.
Center,
Medical
Hospital
supported
Hypertension
Medical
Institute,
cine,
Medicine,
M.D.
California
From
Research
M.D.
MAXWELL,
vice,
Grant
M.D.$
R. KLEEMAN,
MORTON
was
M.D.?
This
Research
5-501-RR05468-08.
of
study
Support
Requests
for
reprints should be addressed to Dr. Shaul G. Massry. Cedars-Sinai Medical Center, Mount Sinai Hospital Divisions, 8720 Beverly Blvd., Los
Angeles,
California
90048.
Manuscript
received January 4, 1971; accepted January 25. 1971. *Visiting Scientist. Present address: Department ment
of
Hospital,
Nephrology, Haifa,
Rambam
Govern-
Israel.
tclinical Investigator, Veterans Administration. SEstablished Investigator, American Heart Association.
234
February
1973
The American
Journal
Individual renal functions were studied in a 24 year old woman following relief of a complete unilateral ureteral obstruction of three months’ duration. Function of the previously obstructed kidney was investigated over a period of six weeks and compared with that of the contralateral unobstructed kidney. Within one week after relief of obstruction, the creatinine clearance in the affected kidney increased from 2.6 to 10.2 ml/minute and remained essentially unchanged thereafter. In comparison to the contralateral kidney, fractional sodium excretion was moderately increased, maximal diluting ability was normal, generation of free water (corrected for glomerular filtration rate) was supranormal, and urinary excretion of phosphate was very low; the latter was presumably due to excessive tubular reabsorption of phosphate. The urinary pH was higher than that from the contralateral kidney and did not decrease normally after the ingestion of ammonium chloride. The excretion of titratable acid was low, partially due to low urinary phosphate excretion and high urinary pH. After 16 hours of water deprivation, the urine from the affected kidney remained hypotonic to the plasma. The natriuretic response to volume expansion, sodium retention after the administration of mineralocorticoids and the phosphaturic action of parathyroid hormone extract were normal as compared to the contralateral kidney. Despite the prolonged period of complete ureteral obstruction, the renal function attained by this kidney would probably have been adequate to support life were this kidney the only one available to the patient. Ligation of the ureter is an occasional complication of pelvic surgery. It has been reported in 11 per cent of operations for pelvic malignancy or uncontrolled uterine bleeding [l] and in 2 per cent of abdominal gynecologic surgery [2,3]. Several case reports described a return of renal function after the relief of ureteral occlusion. In many of these cases ureteral obstruction was due to a calculus, so that neither the duration nor the completeness of the obstruction could be estimated [4-61; fur-
of Medicine
Volume
54
RENAL
FUNCTION
thermore, the evidence for return of renal function in the affected kidney was based on roentgenographic studies, such as visualization on intrave-
CASE REPORT
Sinai
Hospital
uterine
days
prior
had a normal
to her
initial
(MSH).
The
by uterine
oxytocin.
An
both
patient
uneventful,
low grade
fever.
right
two
sure
was
nisms of
therapy
sterile
plored
via
ureter. the
with
was
days
good
tasis
time
blood
88/minute
was
treated
60
days
nonfunctioning
right
ferred
to MSH.
A retrograde
ization
of the
lumbar
vertebra,
(PAH)
rate
96/minute
and
temperature
the
nephrostomy
from
coli; After
gentamycin,
both
orga-
eight
days
the
urine
be-
was
ex-
ureter
A fibrous
band
compressed
over
a cysto-ureteral
good
surgery
in
and
body
right
were
function
the
the
(1
catheter.
was
discharged right
pyelogram. right
cm
and
of the splinted
patient
in the
size
the
incised,
anastomosed
intravenous
present
ureter
Calycec-
kidney,
which
difference
in
was
length)
to the left kidney.
ry patterns
of sodium,
magnesium;
of
and
the
with
accompanied
by a
these
studies
pressure
115,’
duration
was
17,’
between 99” and was 9,800/mm3 was normal.
sulfisoxazole
ride
of
specified,
after
kidney,
right
ureter
and
surgery the
patient
pyelogram only
to the
revealed
urine
was
showed level
a re-
visual-
of the
fifth
with no demonstrable right kidney. A showed normal up(Hgzo3 chlormerodrin)
by the left kidney
but none by the right
nephrostomy was original surgery. approximately in the pelvis. One inulin
of the right
week and kidney
kidney.
normal size with 40 ml of Very little hydronephrosis after the nephrostomy that of para-aminohippurate were
9.5
and
the
50 ml/minute,
with
neous
Davies
function
of with
tion
creatinine
otherwise
by Perkin model were
made
and
the
303.
both hour
from
normal
determined
the side.
in 2.0
(Precision);
determined
Elmer
the
by sponta-
photometer,
measured
in 24
directly
from
flame
chio-
Unless
side
were
In
to
osmometer
content
Laboratories magnesium
ammonium
utilizing
were
a cryoscopic
spectrophotometer, and
urine
osmolalities
potassium
minutes’
according
was collected
bladder
[8].
of 20
were
kidneys,
on the affected
sodium
and
[9].
studies
normal
ml samples
cium
short
and
urine
chlo-
technics
periods
The
Urine
ability;
para-aminohippurate
Wrong
voiding
strumentation
and
performed
and
calcium
diluting
of ammonium
standard
was
tube
and
and
load
clearance
performed.
renal
and
phosphate,
test
collections.
phorus
performed 98 days after the At operation, the right kid-
inulin
affected
of renal
the excreto-
injection, mineralocorticoid of saline solution.
of
were
loading
method the
(Gantri-
potassium,
measured three
rate;
concentrating
to an oral
clearances
the evaluation
filtration
ride, parathyroid extract administration and infusion were
respirations
the
responses
The
surgery
included
and glomerular
and
Plasma
pyelogram
was present. clearance of
pulse
splinted
performed
flow
(PAH)
and
with
The studies
the
pain
shift to the left; urinalysis
ney was of sterile urine
fever pres-
tissue
reduced compared
with
patient’s
of
to
after
the blood
scar
in the still
readmitted
and
after
ureter
time
with
function
was
slightly
to be readweeks
Escherichia
showed
demonstrated
re-
At this
urine
the
A nephrostogram
venous
Right patient’s
and
Adhesions
ureter. Eight
scan
four
to gentamycin.
laparotomy.
ureter
was
and
parenteral
MSH
However,
Hg,
the
sensitive
nephrostomy
scan
of
were
came
renal
of the right
lS/minute
Enterobacter
sine) for 14 days, and her fever gradually abated, but she continued to complain of right flank pain. An intra-
renal
mm
Cultures out
from
patient
respirations
101°F. grew
time.
tenderness.
120/75
regular,
Hgzo3
discharged
the
flank
an
re-anastomosis
at a later
was
the body temperature ranged The white blood cell count
take
was
be
performed ligated
after
minute; 101°F.
patient
not
Recovery
days
Hg,
The
rate
were
75 mm
with a slight
and right
time
ET AL.
by the kidney.
the nephrostomy
plasma
massive
was
arteries
flank
At this
pulse
de-
Mount
could
hemorrhage.
but
aching
delivery
laparotomy
of the
at
and the administration
hypogastric
control
had
after which
packing
emergency
inferior
generally’
day
full term
evaluation
developed
controlled and
woman
hemorrhage
subsequent
bladder
OBSTRUCTION-BETTER
METHODS
old white
94
which
for elective
when
of azotemia.
livery
patient
mitted the
at
no uptake
The
re-anastomosis of the obstructed ureter. The studies to be described were carried out over a six week period after placement of a nephrostomy tube in the obstructed kidney. The normal contralateral kidney served as a control and provided an opportunity to study renal function in man after the relief of ureteral obstruction in the
A 24 year
OF URETERAL
respectively, vealed
nous pyelogram [7] or estimation of function by radioisotope renogram [4]. There are no detailed studies on renal function in man following relief of a complete long-standing ureteral occlusion. Recently, we were presented with a case of complete unilateral obstruction of three months’ duration due to accidental occlusion at surgery. Because of the lack of information in the literature regarding the potential for recovery of renal function in such cases, nephrostomy was performed to enable us to evaluate the improvement in renal function, which if significant would justify elective
absence
AFTER RELIEF
by Inand
atomic Inorganic with
cal-
absorpphos-
the Techni-
con@ Autoanalyzer.@ RESULTS
The results of renal function studies of both the obstructed and the normal kidney are presented in Tables I, I I and I I I, and Figures 1 through 3. A
February 1973
The American Journal of Medicine
Volume 54
235
...
.., ...
Control day for Florinef
... 2 mg Florinef
Control period for saline infusion
B Neph
B Neph
B Neph
0* Neph*
Bt Nepht
B Neph
...
B Neph
g/3/70
g/6/70
g/7/70
9/a/70
9/a/70
g/21/70
g/22/70
10/7/70
min)
2.1 0.7
3.4 0.8
3.9 0.9
2.5 1.3
“IL
... ..,
... ...
... ...
... .
.. ...
. . ...
..
...
...
...
357* 50*
77.0* 9.4*
...
...
... ... ... ...
...
... ... ... ...
la.2 1.2
61.0 8.6
... ...
10.9 0.2
77.7 11.3 17.9 1.3
12.6 0.1
64.8 10.9
74.9 9.4
12.8 0.2
15.2 0.05
11.6 0.06
10.0 0.04
15.6 0.06
68.0 a.6
67.2 10.2
47.2 5.0
47.3 5.9
69.0 2.7
min)
... ...
...
...
...
...
0.216 0.188
.. ... ... ...
. . . . ...
C,
... ...
4.4 0.2
24.0 13.7 30.0 13.5
2.7 0.07
3.0 0.2
3.5 0.07
3.2 0.1
2.4 0.09
2.3 0.1
1.2 0.3
min)
$7
14.0 2.0
19.4 0.9
17.9 2.1
22.5 0.5
24.5 1.2
21.1 0.6
22.6 2.1
CQ X 100
$; (Ai,
CPAH CPAH min)
... .. ...
.. ... ...
min)
WI
GIN
Excretion from Both the Normal and Obstructed ChIg
... ...
5.8 1.7
3.4 0.6
4.6 1.7
5.1 0.7
4.7 1.2
5.2 1.8
4.9 2.3
1.9 9.9
X 100
. . ...
7.2 1.2
5.7 1.0
6.5 1.4
... ...
8.2 1.4
7.6 0.8
7.0 1.2
2.5 0.5
min)
19.6 4.1 28.1 a.3
0.4 0.9 1.3 2.4 4.6 4.3
34.9 12.7 125.1 28.8
12.2 11.2
.
53.8 15.1
113.9 24.5
99.2 15.2
7.4 a.8 9.6 13.0
417.8 65.3
10.1 13.2
...
42.9 4.8
1.1 1.8
72.2 12.3
19.8 2.7 20.1 3.9 26.0 4.5
0.9 1.0 1.1 1.9 0.6 1.3
25.3 2.3
31.4 3.6
16.1 16.6
1.5 2.3
99.0 la.7
39.2 2.5
14.8 19.9
0.2 1.09
UKV Ccr &es/ X 100 min)
CNa
21.4 4.0
(req/ min)
UNaV
3.6 la.0
Ccr X 100
c::(“2;
C.
Kidney
9.0
9.6
... 4.5
.. 1.0
...
3.9
. . ... ... ... .. ...
......
... 4.2
140 4.4
...
141 4.5
...
141 5.5
..
138 4.2
...
140 4.0
...
140 4.0
..
140 4.0
...
140 3;a
...
134
............
1.9
...
2.0
...
1.9
...
1.8
...
1.9
...
1.8
..
1.1
..
1.9
Na K (mEq/liter)
1.1
10.8
..
...
... 4.7
9.3
...
9.2
...
9.1
...
9.0
...
9.0
...
1.0
...
... 4.3
1.0
...
... 4.2
1.1
...
... 4.1 1.1
...
... 4.0
... 1.0
4.1
...
... 1.1
4.1 1.1
Mg
Blood Ca Cr P (mg/lOO ml)
=
NOTE: AlI urinary data obtained from 24 hour collections except when otherwise indicated. B = bladder, Neph = nephrostomy, UV = urine volume, C = clearance, IN calcium was 60 per inulin, P = phosphate, Cr = creatinine, Ca = calcium, Mg = magnesium, PTE = parathyroid extract, C Cnwas calculated assuming ultrafiltrable cent of Serum calcium, and CAI, was calculated assuming ultrafiltrable magnesium was 75 per cent of serum magnesium. * Each data Point is the average of three clearance periods each of 20 minutes duration. t Data are obtained from a clearance period of two hours’ duration.
...
+SfJO U PTE intramuscularly
Control day for PTE injection
Saline infusion
4.9* 1.2*
3.0 0.9
2.3 0.5
2.2 0.7
2.4 0.3
was placed
...
B Neph
Procedure
Nephrostomytube
Specimen
Summary of Data of Electrolyte
a/30/70
I
a/27/70
Date
TABLE
RENAL
TABLE II
Dilution and Concentration
AFTER RELIEF
OF URETERAL
POsm
UOsm (mOsm/kg
CL? (ml/min)
COSnl (ml/min)
(mosm/kg HzO)
HzO)
Dilution: After the oral ingestion of 20 ml of water per kilogram l/9/70
Normal Diseased
2/g/70
Normal Diseased
8.5 1.2
69.0 2.7
Concentration:
~______
~-
... ..
42 44
Effect of Oral Ammonium
Chloride
C. Date g/3/70 ____
Kidney
(ml/Zn)
Normal Diseased
766 265
7.25 1.01
10.5 37.4
.
.. ...
UOsm
=
.. ...
urinary
..
osmolality,
POsm
___ ____
Control
Exper.
Control
Exper.
NH4
32.3 1.6
89.4 6.5
2.8 0.8
37.3 1.4
189 114
4.9 5.7
TA = titratable acid, TA-!-lCO, = titratable of NH&I.
of the data of electrolyte excretion both kidneys appears in Table I. Glomerular Filtration Rate (GFR) and Renal ma Flow (RPF). During the first 24 hours placement of the nephrostomy tube, clearance (Cc,) was 2.7 ml/minute and within one week to 10.2 ml/minute; it essentially unchanged thereafter. lnulin
from Plasafter
creatinine increased remained clearance
(GIN) in the second postoperative week was ml/minute when creatinine clearance was
9.4 8.6
osmolality,
Per 100 ml Cc+
Control
Exper.
= plasma
Acidification NHa (req/min) _ _______
excretion, chloride, ingestion
x 100
C+,
body weight 1.29 0.19
290 290
clearance,
on Urinary
summary
24
277 277
CIi,”
CHJO (ml/min)
Urinary pH ____~ _~_
6.7 6.7
47.3 6.9
NOTE: NH, = urinary ammonium preceding ingestion of ammonium maximal values obtained following
ET AL.
After 16 hours of water deprivation
. . ...
NOTE: UV = urine volume, Cc., = endogenous creatinine r&,0 = free water clearance. C r,q,,, = osmolal clearance, TABLE III
OBSTRUCTION-BETTER
of Urine
UV (ml/min)
Kidney
Date
FUNCTION
TA-HCOI (peq/min) ~.
NH4
TA
TA
76.6 24.6
2.4 4.6
Control = values obtained from a 24 hour urine collection acid minus bicarbonate excretion, Exper. = experimental:
ml/minute; the clearance of PAH (CPAH) was 50 ml/minute. The filtration fraction (CIN:CPAH) was 0.22 in the normal kidney and 0.19 in the diseased kidney. Concentration and Dilution of Urine (Table II). After 16 hours of water deprivation, serum osmolality was 290 mOsm/kg water, and the osmolality of the urine from the nephrostomy was 265 mOsm/kg water whereas the normal kidney concentrated
the urine
to 766 mOsm/kg
water.
An
7.0 -) Before
0
During U
Diseased
PTE
/
20
Normal
5.0 -
4 0
, 0600
~ Diseased
The phosphaturic response Figure 7. cular injection of 800 units of parathyroid
< 1
I
1200
1
I
1600
Hour Normal to the intramusextract.
Figure 2. Changes in urine pH after the oral tration of 0.1 g/kg body weight of ammonium between6and8AM.
February 1973
The American Journal of Medicine
adminischloride
Volume 54
237
RENAL
FUNCTION
AFTER RELIEF
-
400
-
-
m
200
-
During
............. ...**.*.*.* ....... ............. .*.*.*.*. .. .. .. .. s.... .............. ........... ........‘... .... .:.:.:.I. .......* .. .. .. .......‘. .:.:.:.:. ..*.*.*.a. .... .:.:.:.I. .*... .:.:.I.:. .*... ........ ..:.:.:.I. .... .....*.*.*. ..*.*.*. ...*.*... .:.:*:.:. :.:.:.:.: .a.*..... ......... .:.:.:.I. ....*. ... *.*.*...~ .......~’ *...*...* .....
E >,e ‘3
IOO-
0 l
dl
I.:.:.: .*,a.*. .a...*. ..::. ... :.I.:.:
Diseased
Normal
The response to the intravenous 3. 1 liter of normal saline solution.
Figure
OBSTRUCTION-BETTER
Volume Expansion
Before
300
OF URETERAL
infusion
of
oral water load of 20 ml/kg body weight was given between 7:00 and 8:00 AM, and the patient drank water equal to urine output thereafter. Urinary osmolality fell to very low levels on both sides (diseased kidney 44, and normal kidney 42 mOsm/kg water). During this test the free water clearance (CH~O) from the diseased kidney was 1.01 ml/minute and amounted to more than one third of the GFR (C~,o:Ccr X 100 = 37.4 per cent). This is a supranormal value when compared with the normal kidney which had a CH20:CCr X 100 of 10.5 per cent. Urinary Phosphate Excretion and Response to Parathyroid Extract Injection. Phosphate excretion was consistently low on the diseased side. The fraction of filtered phosphate excreted (C,:Ccr X 100) ranged between 0.5 to 2.1 under basal conditions. This was approximately one tenth to one twentieth of the simultaneous values from the normal kidney (14.0 to 24.5). A total of 800 units of parathyroid extract (Eli Lilly) was injected intramuscularly at 9 AM and 4 PM in two divided doses. The excretion of phosphate increased from both kidneys during the day of parathyroid administration as compared to the preceding control day. There was a sixfold increase in Cp:Ccr X 100 in the diseased kidney (from 2.0 to 13.7). However, even during the height of this phosphaturia the fractional excretion of phosphate from the affected kidney was only half of the
238
February 1973
The American Journal of Medicine
ET AL
value from the normal kidney (Figure 1). Fractional excretion of phosphate from the obstructed kidney increased spontaneously and reached a value of 13 per cent of filtered phosphate 48 days after ngphrostomy. Urinary Acidification (Table I II and Figure 2). Random urinary pH measurements from the nephrostomy ranged between 6.5 to 7.5 which was consistently higher than values from the normal kidney (pH 5.5 to 6.5). After the oral ammonium chloride load, urinary pH fell to 5.7 in the affected kidney and to 4.9 in the normal kidney. Ammonia excretion on the diseased side was normal considering the reduced renal mass and the higher urinary pH [9]. Titratable acid excretion of 1.4 peq/minute was low even when allowance is made for the reduced renal mass [lo]. Also the contribution of titratable acid excretion to net urinary hydrogen ion excretion was considerably lower on the affected side (NH4:TA = 4.06 on the affected side, compared to 2.4 on the normal side). The diminished titratable acid excretion in the affected side was due, at least in part, to the low excretory rates of phosphate. Sodium Excretion. Basal conditions: The fraction of filtered sodium excreted was consistently higher in the affected kidney (1 .O to 2.3 per cent) than in the normal kidney (0.2 to 1.5 per cent). Response to mineralocorticoid administration: After a control 24 hour urine collection, 2.0 mg of Florinef@ (fludrocortisone) was given orally, and a 24 hour urine was collected during the day the drug was administered. Fludrocortisone decreased the fractional excretion of sodium approximately by half in both kidneys. Response to infusion of saline solution: After three control clearance periods, each of 30 minutes’ duration, 1 liter or normal saline solution was infused over a period of one hour, and urine was collected for two hours after the infusion was completed. Sodium excretion increased approximately twofold (from 29 to 65 peq/minute) on the diseased side and more than threefold (from 125 to 417 peq/minute) on the normal side (Figure 3). However, at the height of sodium diuresis the fraction of filtered sodium excreted was 4.3 per cent in the affected kidney and 4.6 per cent in the normal kidney. Divalent cation excretion: Except for the first urine specimen obtained at the time of nephrostomy, the fraction of filtered calcium excreted was consistently greater in the normal kidney than in the diseased kidney. Since the values for the fractional excretion of calcium from the affected kid-
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ney were within the normal range (0.7 to 2.3 per cent), it appears that the excretion of calcium from the normal kidney was high, for unknown reasons. The fraction of filtered magnesium excreted was similar in the two kidneys. COMMENTS
Ureteral obstruction after pelvic surgery often is unrecognized. The usual complaint is flank pain which may be accompanied by fever; urinalysis is usually normal in complete unilateral ureteral obstruction. The diagnosis is established by intravenous pyelogram followed by retrograde pyelography. Renal scan using Hg203 chlormerodrin is useful in establishing the presence of obstruction within the first five days of the obstruction [ll 1. After discovery of an occluded ureter a course of action must be decided upon. The possibilities are (1) to leave the obstructed kidney in place, (2) to remove the obstructed kidney, and (3) to relieve the obstruction and reestablish urinary flow by appropriate means. Leaving the obstructed kidney in place involves the risk of infection, and occasionally hypertension which has been reported in association with unilateral ureteral obstruction [12]. Removal of the obstructed kidney may be justified if renal function does not improve after relief of the obstruction. Radioisotope studies alone are not adequate for such evaluation; our patient, for example, had no visualization of the affected kidney by Hg203 scan when GFR was 9.4 ml/minute. In experimental animals, improvement of renal function after relief of unilateral ureteral occlusion varies widely among different species [13-151; also different patterns of the return of renal function have been reported in the same species by different investigators [15-171. In dogs, rabbits and rats, there is essentially no return of renal function after stasis of over four weeks [13,14]. The exact length of time of complete ureteral occlusion after which a good return of renal function can be expected is not known. Although there have been several reports of return of renal function after ureteral occlusion for as long as one and a half years [S], complete obstruction has usually not been documented, and the evidence for’the return of renal function has been based on roentgenographic studies alone [4,5,18]. In only a few cases was GFR measured, and even in these instances only the total clearance from both kidneys was determined [7]. Based only on roentgenographic and isotopic studies, no improvement of renal function occurred after complete ureteral
obstruction “complete” obstruction
ET AL.
of seven and a half months [18], and return of function is probable if the is of less than three weeks’ duration
[41. The data in our patient demonstrate that only limited recovery of kidney function can be expected in man after complete ureteral occlusion of three months’ duration. GFR was 2.7 ml/minute at the time of nephrostomy and increased to about 10 ml/minute. Several abnormalities in renal function have been described after the relief of obstructive uropathy. Among these are low GFR [19], osmotic diuresis due to retained solutes [19,20], impaired sodium reabsorption located most probably in the proximal tubule [20,21], nephrogenic diabetes insipidus [22] and defects in urinary acidification [22,23]. Most of these abnormalities were observed in our patient. Osmotic diuresis did not occur since the presence of the contralateral normal kidney prevented the retention of nitrogenous solutes. The obstructed kidney in our patient was unable to concentrate the urine to isotonicity even after 16 hours of dehydration, suggesting a state of renal refractoriness to the action of antidiuretic hormone. However, the diluting ability was intact, and indeed supranormal values of C~,o/lO0 ml GFR were observed. A similar phenomenon was previously reported by Suki et al. [24] in chronic urinary tract obstruction in dogs: these investigators suggested that decreased tubular back-diffusion of fluid secondary to both diminished medullary hypertonicity and relative impermeability of the distal tubules and collecting ducts to water may underlie this phenomenon. Abnormality in the renal handling of sodium was noted in the obstructed kidney of our patient. A slightly greater fraction of filtered sodium was excreted from the affected kidney as compared with the normal side. This observation indicates a mild impairment in tubular reabsorption of sodium. This abnormality was not due to failure of the renal tubule to respond to mineralocorticoid since the administration of fludrocortisone decreased fractional excretion of sodium in both kidneys. Bricker et al. [19] and Massry et al. [21] reported similar observations on the effect of mineralocorticoids on sodium diuresis which followed the relief of short-term urinary tract obstruction. Despite the prolonged obstruction on our present case, the affected kidney responded satisfactorily to volume expansion as well. An unusual but consistent finding in our study
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was the strikingly low urinary excretion of phosphate from the obstructed kidney. This was most probably due to excessive tubular reabsorption of phosphate (TRP). Theoretically, an enhanced TRP could be due to a fall in filtered load of phosphate per nephron secondary to glomerular hypoperfusion, or to refractoriness of the tubule to the phosphaturic action of parathyroid hormone, or to both. An intrinsic change in the tubular reabsorptive capacity for phosphate secondary to obstruction should also be considered. Refractoriness to parathyroid hormone seems remote since the administration of parathyroid extract produced marked phosphaturia on the unaffected side. Several features of the function of the obstructed kidney are consistent with hypoperfusion per nephron; among these are the lower filtration fraction and the lower fractional excretion of calcium and phosphate. However, the excretory patterns of sodium, magnesium and free water do not support this assumption. Finally, the possibility that prolonged obstruction can induce selective changes in the renal handling of phosphate cannot be excluded. Although defects in urinary acidification have
ET AL
been described [22,23] in obstructive uropathy, little has been published regarding the constituents of hydrogen ion excretion in such patients. In six of the seven cases of obstructive uropathy studied by Berlyne [23], the urine could not be acidified but ammonia production during acid loading was normal; titratable acid was measured directly in two patients and was found to be low in one [23]. In our patient the affected kidney could not normally lower urinary pH, and titratable acid excretion was low during an acid load. The low titratable acid excretion was at least in part due to the relatively high urine pH and the diminished urinary excretion of phosphate. If this abnormality in renal handling of phosphate occurs in chronic obstructive uropathy, it could presumably aggravate the acidosis seen occasionally in these patients. ACKNOWLEDGMENT We are indebted to Dr. Harold Holland for allowing us to study this patient. We thank Mrs. Gloria Bailin and Mrs. Miriam Bick for their technical help and Miss Catherine Weckesser for her secretarial assistance.
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Wertheim E: Zur frage der Radikaloperation beim Uteruskrebs. Arch Gynak 61: 627, 1900. Harrow BR: Ureteral injuries recognized after gynecologic operations. Surg Gynec Obstet 127: 1267, 1968. Freda VC. Tacchi D: Ureteral injury discovered after pelvic surgery. Amer J Obstet Gynec 83: 406, 1962. Earlam RJ: Recovery of renal function after prolonged ureteric obstruction. Brit J Urol 39: 58, 1967. Graham JB: Recovery of kidney after ureteral obstruction. JAMA 181: 993, 1962. Papaioannou AN, Brunschwig A: Return of function of a kidney not visualized on intravenous pyelogram for 1 l/2 years. Arch Surg 90: 367, 1965. Lewis HY, Pierce JM: Return of function after relief of complete ureteral obstruction of 69 days’ duration. J Urol 88: 377, 1962. Smith HW, Goldring W, Chasis H: The measurement of the tubular excretory mass, effective blood flow, and filtration rate in the normal human kidney. J Clin Invest, 17: 263, 1938. Wrong 0, Davies HEF: Excretion of acid in renal disease. Quart J Med 28: 259,1959. Better OS, Chaimowitz C, Alroy CG, Sisman I: Spontaneous remission of the defect in urinary acidification following cadaver kidney homotransplantation. Lancet 1: 110, 1970. Johnston GS, Murphy GP: The effect of acute and chronic ureteral occlusion upon renal handling of Amer J Roentgen 98: 163. Hg 203 chlormerodrin. 1966. Garrett J, Polse SL, Morrow JW: Ureteral obstruction and hypertension. Amer J Med 49: 271, 1970. Beer E: Experimental study of the effects of ureteral
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obstruction on kidney function and structure. Amer J Uro18: 171. 1912. Pridgen WR, Woodhead DM, Younger RK: Alterations in renal function produced by ureteral obstruction. JAMA 178: 563, 1961. Fylling P: Restitution of rat kidney after temporary ureteral ligation. J Urol 78: 337, 1957. Murphy GP, Scott WW: The renal hemodynamic response to acute and chronic ureteral occlusions. J Urol 95: 636, 1966. Vaughan ED Jr, Sorenson EJ, Gillenwater JY: The renal hemodynamic response to chronic unilateral complete ureteral occlusion. Invest Urol 8: 78, 1970. Brunschwig A, Barber HRK, Roberts S: Return of renal function after varying periods of ureteral occlusion. JAMA 188: 125, 1964. Bricker NS, Shwayri El, Reardan JB, Kellog D, Merrill JP, Holmes JH: An abnormality in renal function resulting from urinary tract obstruction. Amer J Med 23: 554, 1957 Muldowney FP, Duffy GJ, Kelly DG. Duff FA. Harrington C. Freahey R: Sodium diuresis after relief of obstructive uropathy. New Eng J Med 274: 1294, 1966. Massry SG, Schainuck LI, Goldsmith C, Schreiner GE: Studies on the mechanism of diuresis after relief of urinary tract obstruction. Ann Intern Med 66: 149. 1967. Early LE: Extreme polyuria in obstructive uropathy. New Eno J Med 255: 600, 1956. Berlyne GM: Distal tubular function in chronic hydronephrosis. Quart J Med 30: 339, 1961. Suki W, Eknoyan G, Rector FC, Seldin DW: Patterns of nephron perfusion in acute and chronic hydronephrosis. J Clin Invest 45: 122, 1966.