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hIongre1 female dogs of unknown age, weighing between I I and 15 kg, were
used. Prior to ligation of the ureter on 2-3 different days, renal clearances were done
under anesthesia to establish a base line. In one of these preligation clearances urine
was collected from each kidney either by cystoscoping and catheterizing the ureters
or exposing and catheterizing the right ureter and catheterizing the bladder to deter-
mine the function of the right and left kidneys.
After these base line values had been obtained, a dog was anesthetized with
Nembutal or chloralose. Through a right flank incision the right ureter was exposed
retropertoneally, divided close to the bladder, and tied with a heavy silk thread.
The ureter was then brought out through the muscle layers and was left in the
subcutaneous layer. The muscles were loosely closed and the skin approximated. In
eight dogs a biopsy was taken of the right kidney and in four cases of the left kidney.
Seven days later, under anesthesia, the end of the right ureter was identified and
3 Aureomycin was generously supplied by the Lederle Laboratories Division of the American
Cyanamid Company; terramycin was generously supplied by the Pfizer Co.; and Gantrisin was gener-
ously supplied by Hoffman-La Roche, Inc.
4 This instrument was developed by Fiske Associates, 44 Bromfield St., Boston, Mass.
TABLE I. CHANGE IN GLOMERULAR FILTRATION RATE DETERMINED ONE HOUR AFTER COMPLETE
URETERAL OBSTRUCTION FOR ONE WEEK IS RELEASED
-- __-____- _-.-
* Separate renal clearances from each kidney in 15 animals revealed the equality of the clear-
ances by the two kidneys. Ratio of the GFR of the right kidney to the left kidney was .98, ~t.065.
Ratio of ERPF of right to left was .96, zt.054. t 8/37 = 22. $67/37 = 18r.
(4-57 days), the function of each kidney stabilized. The clearances of the right kid-
ney stabilized at a level below the control level and those of the left kidney stabilized
above the control value. Thereafter, the ratio of GFR or ERPF of the right to the
left kidney did not change significantly over a period as long as 442 days.
Two days after release of the right ureter the control (left) kidney was removed
from two dogs. There was a striking difference in the rate and degree of improve-
ment in GFR and ERPF of the previously obstructed kidney in these two animals,
compared with the group of animals who did not have the control kidney removed.
Five and twelve days after removal of the control kidney, the GFR of the previously
obstructed kidney had increased to 70% and 90% of the control total of both kid-
neys prior to ligation. The ERPF followed a similar pattern. The GFR and ERPF
stabilized at levels well above the control value of the right kidney. These two dogs
were studied 12 and 22 months, respectively.
Table I shows the results of GFR measurements in IO dogs I hour after release
of the right ureter. The GFR of the obstructed kidney was reduced to an average of
9.9 ml/m2 BSA which constituted an average GFR of 25 % of the control value. The
reduction in filtration rate on the obstructed side was associated with an increase on
the control side. The filtration rate increased to 165% of control value. The ratio of
GFR right to left kidney (R/L) averaged o. 16.
Table 2 showsthe data on ERPF corresponding to the data on filtration rate
in table I. The average changesin ERPF correspondedvery closely to the changes
in GFR. An average ERPF of 27% of the control value on the obstructed side and a
167% increaseon the control side were noted. The ratio of ERPF R/L averaged
0.16.~
A. Results When Control Kidney Was Not Removed. Changesin GFR and
ERPF. Five of the ten dogs listed in table I were studied 49-442 days after the
right ureter was untied. The control kidney in this group was not removed. Table 3
5 There was a high coefficient of correlation c--*91) between GFR R/L and R./L on the
day the right ureter was untied.
TABLE 2. CHANGE IN EFFECTIVE RENAL PLASMA FLOW DETERMINED ONE HOUR AFTER COMPLETE
URETERAL OBSTRUCTION FOR ONE WEEK IS RELEASED
----- --_____- - - I-
Preligation Obstr. Kidney (Rt.) Normal Kidney (Lt.)
Ratio of
Tpp&h T&2 ERPF R/L
ERPF TO Cont. Value ERPF yO Cont. Value
_-~-- .--
152 76 I4 28 87 114 . 16
294 I47 12 8 288 I97 l 04
206 103 34 33 I92 178 .18
180 90 56 63 124 I38 045
242 121 24 20 218 180 . IO
210 105 45 43 219 i 209 .21
234 117 90 8 161 145 -05
230 115 22 20 186 162 . I3
206 103 38 37 168 I63 023
258 I29 IO 8 222 181 904
shows the changesin GFR R/L (Right Kidney/Left Kidney) in these dogs. With
the exception of dog 4, the GFR R/L decreasedfrom the control average of .g8 to
.21 or less.Thereafter, the filtration rate of the right kidney improved and that of
the left (control) kidney decreased.The total of the right and left kidney GFR re-
mained essentially unchanged. Ultimately the fraction contributed by each kidney
became constant. This state of equilibrium or maximum recovery occurred in 4-57
days. Clearance studies after the ureter was untied were done every 7 days in four
of these dogs and every day in dog 13 until maximum recovery was reached. Thus,
no more than 7 days elapsedbetween the day of maximum recovery and the previous
test. The number of tests after maximum recovery ranged from 2-11. The average
of the GFR R/L ratio for these tests showed no significant change from the ratio
on the day maximum recovery was reached.
Table 4 showsthe change in ratio ERPF R/L subsequentto untying the ureter.
The data in this table were obtained simultaneously with data in table 2. It is evi-
dent that on the day maximum recovery is reached, the average ratio for ERPF
and GFR is not statistically different and that they stabilized at the sametime.
Fluctuation in TmPAHboth in the control periods and following release of the
ligated ureter were so variable no significant trends were observed.
As would be inferred from the equality of reduction of GFR and ERPF, the
filtration fraction of the right kidney, left kidney and total right and left was not
significantly different on any given day.
Results of acidiJicationand alkalinization studies. One meansof studying tubular
integrity was to find whether the ability to produce an acid or an alkaline urine on
the two sideswas equal. An ammonium chloride load was given to two animals after
the renal clearances had stabilized. The urine PH from the right kidney was 5.71
and 5.8, respectively, and from the left kidney 5.8 and 5.8; thus there was no appar-
ent difference in the ability of the previously ligated kidney to acidify the urine.
One of theseanimals wasgiven 5 gm of sodiumbicarbonate and the urine pH rose to a
maximum of 8.1 on the right side and 8.3 on the left side?
6 The fact that the PH'S are equal on each side does not of course mean the ability of both
kidneys to transfer I3 ions into the urine is equal, but rather the intensity of acidification as measured
by the PH is equal.
TABLE 3. CHANGE IN RATIO OF GFR OF RIGHT TO LEFT KIDNEY IN RELATION TO TIME AFTER
RELEASE OF THE OBSTRUCTED KIDNEY
--
Ratio GFR No. Days After Ratio GFR Interval Between No. Tests Av. Ratio No. Pays Dog
R/L on day Untying Before R/L on Day Max. Recovery After Max. GF’.Cef/L StudlFd After
Rb IJi’,e;& Maket;gz;ery Makef;;;;ery and Previous Recovery Unbg~e~lght
n Test Tests
I . I2 I3 043 7 3 -44 49
4 -53 7 -55 7 5 l 38 244
6 .08 29 .58 7 .62 57
x2 -09 57 -55 7 i l ss 442
I3 . 21 4 42 2 II -47 153
Maximum recovery is the day that the fraction contributed by each kidney became constant.
Resultsof stady of ability to concentrate and dilute urine. Another meansof assess-
ing renal function was to compare the concentrating and diluting ability on the two
sides. Following water deprivation of 24-48 hours urine specimenswere collected
and total solute concentrations determined. The ability to produce a dilute urine was
not impaired. However, the results indicated a significant impairment in concentrat-
ing ability of the previously ligated kidney. The results are shown in table 5.
B. Results When Control Kidney Was Removed. Changes in GFR arzd ERPF.
The control (left) kidney of two dogs (3 and ro> was removed 2 days after untying
the right ureter. The control GFR values for these dogsare in table I. In dog 3, the
GFR of the previously obstructed kidney was found to be reduced from a control
value of 40 ml-10 ml on the day the right ureter was untied. Five days after removal
of the control (left) kidney, the GFR of the right kidney had increasedfrom IO ml
to 56 ml. Thus the GFR (right kidney) which had been 25% of the control value on
the day of releaseof the ureter had increased to 160% of the control value 7 days
later. The average of the 16 subsequentclearancesdone over a 22 month period was
68 ml (I 70% of the control value). In dog IO, the GFR of the right kidney increased
from 3.5 ml on the day the right ureter wasreleasedto 31 ml 5 days after left nephrec-
tomy. Twelve days after nephrectomy the GFR was 63 ml (r80% of the control
value of the right kidney). The average of the next five clearancesperformed in the
following II months averaged 73 ml (208% of the control value).
In table 2, the controlvalues for ERPF of dog 3 and IO are shown. After left
nephrectomy, the changesin ERPF were similar to the changesin GFR. In dog 3,
the ERPF of the right kidney on the day the right kidney was untied was 31 ml.
This increased to 163 ml 5 days after nephrectomy (158% of the control value).
Twelve days after nephrectomy the ERPF was 215 ml. The average of the next 13
clearances,covering a period of 20 months, was 204 ml (198% of the control value).
The ERPF of dog IO followed the samepattern. It stabilized at an average of
I 71 ml (146 % of the control value).
Results of acidi&ation and alkalinization studies. Ammonium chloride was given
to these two animals after the clearanceshad stabilized. The urine PH of the right
kidney was 5.6 (dog 3) and 5. I (dog I-O). The administration of 5 gm of sodium bicar-
bonate increasedthe urine PH to 7.7 (dog 3) and 8.3 (dog IO). Neither the ability to
acidify nor alkalinize urine seemedto be affected in these kidneys.
Results of sttidy of ability to concentrate and dihte urine. The ability of the right
I .16 I3 7 3 940 49
4 l 45 7 7 5 -36 244
6 . IO 29 .62 57
I2 . I3 57 77 ii -57 442
I3 . 23 4 2 II 944 153
Av. . 21 l 48
kidney in this group to concentrate urine was impaired to the same extent as in the
obstructed kidney in the group without contralateral nephrectomy. The ability to
dilute urine was unaffected in both groups. See table 5.
Elevation of urea retention after removal of the normal (left) kidney. The plasma
NPN was not elevated after ligation of the right ureter for 7 days. However, the
removal of the normal (left) kidney causedthe NPN to rise as high as 173 mg % in
dog 3 and I 22 mg % in dog IO. Table 6 showsthe increaseand subsequentfall in
NPN value in dog 3. The GFR on the 4th day after nephrectomy was 56 ml (70% of
the control value of both kidneys) and it remained at this level. One would expect
that the NPN would be promptly restored to a normal value by a filtration rate of
this magnitude. However, the NPN did not return to a normal value for 34 days after
nephrectomy. Removal of a normal kidney in the presenceof another normal kidney
doesnot causea similar protracted elevation of NPN. Apparently the tubules of the
previously ligated kidney must have been damaged and an abnormal amount of
urea diffused back into the circulation. Ultimately, the tubules recovered and the
NPN returned to and remained at a normal level without an increasein GFR or
change in protein intake.
C. Histological Changes Caused by Ureteral Obstruction of Seven Days’ Dura-
tion. The effect of ureteral ligation on the microscopicappearanceof the kidney was
not marked. In order to obtain sectionsthrough the entire parenchyma of obstructed
kidneys, the right ureter of seven dogswas ligated for I week and then the dogs were
killed. The sectionswere examined by Dr. Wilbur Thomas.7In the obstructed kidney
there was a mild to moderate dilatation of scattered convoluted tubules. The collect-
ing tubules showed very slight uniform dilatation. The control kidney was not
remarkable.
Small biopsieswere taken from the right kidney in 8 and from the left kidney in
4 animals of the IO dogs listed in table I. These biopsiesall revealed normal kidney
histology. Biopsies of the right kidney after untying the ureter were taken in only
two animals. No changeswere noted.
Microscopic sections were made of the previously ligated kidneys of five dogs
295-22 months after the ureter had been untied. In all of these kidneys, areas of
acute and chronic inflammation just beneath the pelvic mucosawere noted. A rare
I2 360 70 75
361 1380 1965 70
369 1710 2800 60
379 960 2050 50
I.? 160 66 47
162 540 2 700 20
165 390 1216 32
I4 80 1275 2500 51
81 130 I32
3 33 1100
360 1100
362 75
IO 485 1335
500 1100
495 80
area of acute or chronic pyelonephritis was noted in the kidney cortex of three of
these animals.
D. Changes in Capacity of the Kidney Pelvis After Release of the Ureteral Ob-
struction. There is a wide variation in the degree of hydronephrosis resulting from 7
days of complete ureteral obstruction. The amount of pelvic fluid was determined
accurately in eight of the dogs listed in table I and in nine others. The amount of
fluid varied between II and 35 ml. The average capacity was 16 ml. In seven dogs,
the pelvic capacity was determined daily by introducing a catheter via the ureteros-
tomy. In six of these animals, the capacity became I ml or less in 7-35 days. The pel-
vis of one dog (IO) contracted from a volume of 20 ml to IO ml and remained at the
lower level for 12 months. There was no evidence that this amount of residual urine
in the pelvis caused a reduction of function over the ~a-month period she was studied.
E. Elevation of Ureteral Pressure. The ureteral pressure after I week of ob-
struction was determined, using a water manometer, in seven dogs who were then
killed. The average pressure was 23.7 cm (range 16-30 cm).
F. Nature of the Pelvic Fluid Found at the Time of Release of the Ureteral Ob-
struction. Total solute concentration of the pelvic @id. In the above group of seven
animals, the average total solute concentration on the day the ureter was untied was
378 mOs/l. (range 338-465 mOs). This value does not differ appreciably from the
osmotic pressure of normal dogs’ serum, circa 310 mOs/l.
Bacteriological studies. Cultures of the pelvic fluid of eight dogs were taken after
7 days of ureteral obstruction. There was no growth in any of these. However, after
the ureter was sutured to the skin the urine on the right side promptly became in-
fected, despite the daily administration of p--IOO mg of aureomycin or terramycin.
There was a brief period of negative cultures when the pelvic capacity had decreased
to I ml or less, followed again by the presence of bacteria (B. proteus, B. coli or B.
pyocaneus) which persisted in small numbers.
TABLE 7. VARIATION IN DEPRESSION OF GFR AND ERPF ON THE DAY THE URETERAL OBSTRUCTION
WAS RELEASED AND VARIATION IN DEGREE OF SUBSEQUENT INCREASE IN GFR AND ERPF
---- ---- --
Av. 31 68 37 I
34 I 66 32
* 60 - 22 = 38.
d) weight of the right kidney (average 52 gm, range 42.5-73 gm). There was no ap-
parent correlation between the weight of the kidney, pelvic capacity, ureteral pres-
sure or total solute concentration.
A possible explanation for the variations noted above depends upon the degree
of interference with the blood supply caused by the pelvic distention. In the dog, the
main renal artery divides into a ventral and dorsal branch. The pelvis of the kidney
lies within the ‘Y’ formed by this division. When the kidney pelvis distends, the ven-
tral and dorsal branches are elongated and narrowed? A similar stretching and nar-
rowing of the smaller vessels, such as the interlobar and arcuate arteries, occurs as
the intrarenal portion of the pelvis enlarges. If the physical state of the arterial wall
is able to resist this stretching and narrowing, a more adequate blood supply would
be maintained. A less likely factor is the interference in circulation caused by the ob-
struction of the renal vein as the pelvis distends. This obstruction is quickly com-
pensated for by development of a collateral circulation via the cort.ical-capsular
system. As noted above, the GFR and ERPF of the right kidney of dogs I, 4 and 13
showed a greater degree of function on the day the ureter was released and reached
the point of maximum recovery earlier than dogs 6 and 12. It seems reasonable to
believe that the circulation of the obstructed kidneys in dogs I, 4 and 13 was more
adequately maintained during the obstruction and thus the better nourished nephrons
were able to function more efficiently and recover more promptly. Possibly these
three animals were younger and their kidneys were less susceptible to ischemia.
If the higher percentage of function (GFR and ERPF) retained by the right
kidney on the day of release in dogs I, 4 and 13 is explained on the basis of a more
adequate blood supply during the period of obstruction, one might assume that these
8 The changes in the renal arteries were easily demonstrated by aortograms using 70% urokon.
kidneys, which also reached the point of maximum recovery earlier than dogs6 and
12, would ultimately recover a greater degreeof function. Table 7 showsthat such
was not the case. On the day maximum recovery was noted, the GFR and ERPF
were found to be 60-74% and 55-73%, respectively.
Apparently the left kidney during the week of right ureteral obstruction became
accustomedto a certain load previously carried by the right kidney. It hasbeennoted
in dogs 3 and I o that, when the left kidney has been removed after releaseof the
right ureter, the GFR and ERPF of the right kidney promptly increasedto values
significantly higher than the preligation control values. The previously obstructed
kidney in dogs in table 7 probably also were capable of complete recovery.
Thus, it is a curious but unexplained observation that the right kidney even when
followed 442 days doesnot recover its preligation value, and the left kidney continues
to bear the brunt of the excretory load. However, the increaseof function of the right
kidney to a level above the control value following removal of the left clearly indi-
cates the inherent capacity of the right kidney to increaseits function. The presence
of a supernormal left kidney actually appears to exert an inhibition on the function
of the right kidney!
The failure of the right kidney to concentrate urine as well as the control kidney
is evidence of damagesuffered by someportion of the tubules. The ability to acidify
and alkalinize urine is maintained. Thus, these functions of the distal tubule are not
impaired. The failure to concentrate urine is causedby damage either to the distal
tubule or the collecting tubules.
SUMMARY
The effects of complete ureteral obstruction for 7 days on renal function and the
degreeand rate of improvement which followed releaseof the obstruction have been
evaluated by renal clearance methods in dogs. One hour afler releaseof the right
ureter, the GFR and ERPF of the previously obstructed kidney were found to be 25 %
and 27%, respectively of the preligation control value, and the GFR and ERPF of
the control (left) kidney were found to be increasedto 165% and 167%, respectively
of the control value. The variations in degreeof depressionof function and the time
of and degree of maximum recovery suggestthat the degree of damage causedby
ureteral obstruction for I week varies. Subsequently, the GFR and ERPF of the
kidney improved and the clearancesof the control (left) kidney decreased.Ulti-
mately, the fraction contributed by each kidney became constant. Maximum re-
covery occurred in 4-57 days. Thereafter, the ratios GFR and ERPF, Right Kidney/
Left Kidney remained essentially unchanged. In one dog clearanceswere determined
at intervals for 442 days after the ureteral obstruction was released.
The control (left) kidney of two dogswas removed 2 days after the right ureter
was releasedto determine the pattern of recovery that the right kidney would show
when it had to do the work of both kidneys. Under this circumstance, the GFR and
ERPF of the right kidney improved more promptly and to a greater degree than
occurred in the presenceof the control kidney. Fluctuations in the TmPARin the
control periods and following releaseof the ligated ureter were sovariable no signifi-
cant trends were observed. The ability of the previously obstructed kidney both in
9 Hinman (5) thought that a damaged right kidney, in the presence of a stronger left kidney,
would show progressive disuse atrophy. Joelson et al, (II) demonstrated the inaccuracy of this theory.
Observations on dog confirmed those of Joelson. The ratio of GFR and ERPF of the right to the
12
left kidney did not change significantly over a period of 442 days.
the absence and presence of the control kidney to concentrate urine was impaired.
The ability to dilute urine was not impaired. The ability of the right kidney to
produce either an alkaline or an acid urine was not reduced.
The author wishes to express his indebtedness to Miss Claire Mauretti for her valuable techni-
cal assistance.
REFERENCES
I. HINMAN, F. J. Ural. 3: 147, 1919.
2. SUZAKI, T. Jena, 1912, quoted in Hinman (I), p. 149.
3. KEITH, N. M. AND R. R. SNOWDEN. Arch. ht. Med. XV: 239, 1915.
4. JOHNSON, R. A. J. Exper. Med. 28: 193, 1918.
5. HINMAN, F. Arch. Sztrg. 12: 1105, 1926.
6. TADDEI, G. AYCJI. ital. urol. 19: 229, 1942.
7. ROLF, D., A. SURTSKIN AND H. L. WHITE. Proc. sot. Exper. Biol. & Med. 72: 351, 1949.
8. BONSNES, R. W. AND H. H. TAUSSK~. J. Biol. Clzem. I#: 581, 1945.
9. GOLDRING, W. AND H. CHASSIS. The Commonwealth Fund. New York: Oxford, 1944.
IO. RHOADS, C. P., A. S. ALVING, A. HILLER AND D. D. VAN SLYKE. Am. J. Physiol. 109: 329, 1934.
II. JOELSON, J., C. BECK AND A. MORITZ. Arch. Surg. 19: 673, 1929.