British Journal of Urology (1974), 46, 15-23

Experimental Ureteric Obstruction

DAVID OSBORN, JULIUS LEE and GRANT WILLIAMS

Charing Cross Hospital, London

It is now established that glomerular filtration continues after ureteric obstruction (Taylor andUllman, 1961; Salomon and Lanza, 1962; Selkurt, Deetjen and Brechtelsbauer, 1965). Tubularreabsorption continues in both proximal and distal parts of the nephron (Malvin, Wilde andSullivan, 1958). Renal blood flow increases initially (Selkurt, 1963; Harsing, Szanto and Bartha,1967; Wax, 1968; Navar and Baer, 1970; Carlson and Sparks, 1970; Suki et al., 1971; Hondaet al., 1971) but later declines (Murphy and Scott, 1966; Vaughan, Sorenson and Gillenwater,1968).

The normal resting proximal tubular pressure in the rat is raised during diuresis (Gottschalkand Mylle, 1957; Falchuk et al., 1971). Proximal tubular pressure is also raised following uretericobstruction and a further increment occurs during simultaneous ureteric obstruction and diuresis(Gottschalk and Mylle, 1956; Selkurt et al., 1965). Struthers (1969) found raised renal pelvicpressures during diuresis in the dog. Bretland (1972) in his review of the literature on uretericobstruction concluded that “actual pressure achieved seems to depend on the degree of diuresisand varies from 40 to 75 mm Hg in the dog”.

Nephron damage following ureteric obstruction has been shown to be proportional to thepressure applied (Selkurt, Brandfonbrener and Geller, 1952; Wax, 1968; Honda et al., 1971).This series of experiments was designed to examine whether hydration during ureteric obstruction,in the rat, would influence nephron recovery after a short (less than 2 hours) and long (6 hours)period of ureteric obstruction.

Method and Results

Short-term ObstructionIn the first series of experiments, hydrated and dehydrated groups of rats were studied. Thehydrated group of animals received an intravenous infusion of 0.3% NaCl at 5 ml/hr and theureter was obstructed for 75 minutes. The dehydrated group received a maintenance infusionof 0.8 ml/hr of O-3 “/;: NaCl. Ureteric obstruction was prolonged to 90 to 120 minutes in thisgroup as the initial rise of ureteric pressure was slow due to the dead space of the pressuretransducer relative to urine flow rate.

End ureteric pressures (Fig. I) of the diuretic series (8 rats) reached a steady level at 53 mm Hgwhereas in the antidiuretic series (9 rats) the pressure level was 27 mm Hg. These differences werehighly significant (P <O.OOl).

In the hydrated series (7), urine volumes (Fig. 2) in control periods prior to obstruction showedlittle difference between the control and the experimental kidney (P > 0.8).

After release of the obstruction in the hydrated group there was a prompt washout of urinefrom the renal pelvis and ureter. However, the urine flow rate continued at higher rates fromthe experimental kidney than from the control for 1 hour after release. Differences were significant(P ~0.05) during the period 10 to 40 minutes following release.

In the dehydrated series (5 rats) during the 30-minute control period prior to obstruction,experimental and control urine flow rates were similar (P>O.7) (Fig. 3). For 30 minutes after

Read at the 29th Annual Meeting of the British Association of Urological Surgeons in London, June 1973.1 5

16 BRITISH JOURNAL OF UROLOGY

release of obstruction the urine flow rate from the experimental kidney was greater than from thecontrol but the differences were significant for only 0 to 15 minutes following release (P ~0.05).

Ureteric pressure* - m m . Hg.

T

Fig. 1

1 4 0 -

130

I

Urine vol: !pl/min

120 Hydrated serier

" 20

Fig. 2

Time min

4 0 6 0 8 0 100

Time rn~n

In the hydrated series (7 rats) and the dehydrated series (5 rats) there was no significant differ-ence in osmolality between the urine of the experimental and the control kidneys prior to uretericobstruction.

In the hydrated series from 5 to 60 minutes (Fig. 4) after release of obstruction, the experimentalkidney urine was hypotonic compared to the control urine (P ~0.025). In’the dehydrated series

EXPERIMENTAL URETERIC OBSTRUCTION 17

urine osmolality was significantly less than in the control (P ~0.05) from 0 to 30 minutes only(Fig. 5).

60

i

Vrine WI: ;LI /mins

55 Dehydrated experiment

5 0

10t

5 Control k,dney4’

- - - _-+

T/-~----~--

0 3 0 60 90 120 150 165 180 210 2 4 0

Fig. 3

400

350

300

150

100

0

Fig. 4

Urine asmolality- milliosm/litre

/ ( / ,2 0 4 0 6 0 60 100 120 140 160 170

1 COIWOIktdney

No significant difference was seen in inulin clearance after release of obstruction in the hydratedseries (4 rats).

Urinary sodium concentration (7 rats) was lower in the postobstructive kidney of the hydrated4611 - B

18

22%

2ooc

1750

1500

EE5 1250p5

1000

750

500

Fig. 5

IT- - 1-

30

f

I

90 120 150 165 180 210 240Time min

Urine osmolality-6 hours obstruction

Hydrated series

BRITISH JOURNAL OF UROLOGY

750

I

T T T 75 0 0 1 I L Experimental I

kidney250

t01 I I I I

6 1 5 30 45 60 75Ttme min

Fig. 6

series compared with the control. Urinary sodium excretion was, however, greater from theexperimental kidney although none of these findings was statistically significant.

6-hour ObstructionIn the second series of experiments, rats had 1 ureter tied during a light ether anaesthetic and theanimals were allowed to recover. One group was hydrated (10 rats) with a stomach load (5%body weight) of water and in the second dehydrated group (8 rats), water was withheld. In bothgroups, ureteric obstruction was released after 6 hours and nephron function then assessed.Measurements were made at 15minute intervals from 6 minutes after release of obstruction.

EXPERIMENTAL URETERIC OBSTRUCTION 1 9

Whilst no significant difference was seen between urine volume of experimental kidneys, urineosmolality from the experimental kidneys (Figs. 6 and 7) was significantly less than from thecontrol (P~0.01). The difference was greater in the dehydrated group owing to previous dehy-dration of the animal.

Glomerular filtration was measured by the clearance of inulin. The average control kidneyinulin clearance was 0.5 ml/min for both groups. Experimental kidney inulin clearance was

Urine osmolality- 6 hours obstruction

0 1 5 0 0E

? 1 2 5 0

TI

TI TIT I

Experimental

, I I I6 1 5 30 45 60 75

Ttme min

Fig. 7

0.12 to O-15 ml/min in the hydrated group (10 rats) and 0.3 to 0.35 ml/min in the dehydratedgroup (8 rats). The differences between the experimental kidney inulin clearances in the 2 groupsare expressed as a ratio of control kidney inulin clearances (Fig. 8). The ratio of control kidneyand experimental kidney inulin clearances are significantly greater for the hydrated series at15, 30 and 60 minute collections (P <0*05).

Sodium concentration alone showed no marked difference between the 2 groups. However,

when sodium excretion was related to the inulin clearance Sodium ExcretionG.F.R.

a sodium loss

was seen from the experimental kidney, which was greater in the hydrated series (Figs. 9 and 10).

20 BRITISH JOURNAL OF UROLOGY

Discussion

Urine osmolality proved a sensitive index of nephron damage after both short-term (less than 2hours) and 6-hour obstruction. This confirms osmolar changes described by Jaenike and Bray(1960), Kessler (1960), Selkurt (1963) and Finkle, Karg and Smith, (1968). Urine osmolalityshows greater nephron damage in the hydrated kidney after short-term obstruction compared

8

I

7-

6

Sodium excretion/G.F.R. - 6 hours obstruction

Dehydrated series

6 1 5 30 45 60 75

Time min

Fig. 9

Sodium excretion/G.F.R. - 6 hours obstruction

8-I

Hydrated ser ies

01 ! I I6 1 5 30 45 60 75

Ttme min

Fig. 10,.

to the dehydrated low-pressure group. The production of hypotonic urine and free water clearancein the postobstructive hydrated kidney makes washout of the corticomedullary gradient unlikelyto be the entire explanation. Urinary sodium excretion was greater in the postobstructive kidneyof the hydrated series despite the hypotonicity. This natriuresis combined with the natriuresis/G.F.R. seen in the 6-hour obstructed kidney suggests a proximal tubular damage with overloadof distal tubular capacity agreeing with Bercovitch ef al. (1971). Yarger, Aynedjian and Bank(1972), from micropuncture evidence, after 24 hours’ ligature in rats thought distal nephrondamage to be more important. However, of necessity, routine micropuncture only measuressuperficial nephrons and from loss of total G.F.R. the authors concluded there was greatestdamage in deep nephrons.

EXPERIMENTAL URETERIC OBSTRUCTION 21

After 6 hours’ ureteric obstruction, inulin clearance was significantly reduced in the experi-mental kidney of the hydrated compared to the dehydrated group. During ureteric obstructionimportant changes to non-reabsorbed solutes and the usual filtration markers have been reported(Lorentz, Lassiter and Gottschalk, 1972). This explains the reduced residual filtration afterureteric obstruction in mannitol diuresis (Taylor and Ullman, 1961; Selkurt et al., 1965).

In no experiments were osmotic diuretics used. Loss of G.F.R. following 6-hour obstructionmay be due to each nephron filtering at a decreased rate, but previous evidence suggests adecreased nephron population (Malvin, Kutchai and Ostermann, 1964; Jaenike, 1972).

Increased ureteric end pressures and greater nephron damage in the hydrated series may bedue to higher renal plasma flow and G.F.R. in the volume-expanded rat causing greater load tothe occluded nephron: secondary to a fall of renal afferent arteriolar resistance (Brenner et al.,1972). Proximal tubular reabsorption may be decreased in the hydrated animal secondary to afall of peritubular capillary protein, and a rise of peritubular hydrostatic pressure (Brenner et al.,1969; Brenner et al., 1971; Brenner, Troy and Daugharty, 1972). The action of a natriuretichormone is also possible.

In hydration, A.D.H. secretion is minimal and thus distal nephron permeability is low.Interesting is the previous suggestion of minimal osmolar changes when A.D.H. was given duringobstruction (Kessler, 1960; Suki et al., 1971).

Finally, during hydration the escape route of either pyelolymphatic or pyelovenous shuntsmay be overloaded.

Relevance to human renal physiology may be questioned. In particular, G.F.R. and renalblood flow are constant in man during diuresis (Pitts, 1968). However, much of human renalphysiology is based on animal experimentation and it is possible that during ureteric obstructionthe human kidney resembles the phylogenetically simpler rat. In support of the experimentalwork is the increase of pain following diuresis during ureter obstruction in man (Weaver, 1968).It is suggested therefore that in clinical work possibly greater nephron damage during partial ortotal ureteric obstruction following hydration should be considered. It is accepted, however, thata policy of restricting fluids may require modification in patients with recurrent stone formationsecondary to high urinary concentration of inorganic compounds.

Conclusions

(i) Obstructed ureteric end pressures are significantly greater in hydrated rats.(ii) Release after less than 2 hours’ obstruction shows nephron recovery as shown by urine

osmolality to be greater in lower pressure dehydrated rats.(iii) Release after 6 hours of ureteric obstruction in rats showed:

(a) Urine osmolality was significantly decreased in both hydrated and dehydrated groups.(b) Inulin clearance of experimental kidney was lower in hydrated series.(c) Natriuresis/G.F.R. was greater in hydrated series.

(iv) In clinical work possibly greater nephron damage during partial or total ureteric obstruc-tion following hydration should be considered as well as concentrations of bacteria orinorganic compounds.

Summary

Renal function during and after release of a short period (less than 2 hours) and following releaseof a long period (6 hours) of total ureteric obstruction in the rat was studied in 2 series ofexperiments.

Ureteric end pressures were found to be significantly higher in diuretic compared to dehydratedrats in the short period series of experiments. In both series of experiments nephron recoveryfollowing release of ureteric obstruction was greater in dehydrated compared to hydrated rats.

22 BRlTISH JOURNAL OF UROLOGY

The reasons for the difference of results in hydrated compared to dehydrated rats and sitesof nephron damage are discussed.

Possible relevance to clinical work is also propounded.

References

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EXPERIMENTAL URETERIC OBSTRUCTION 23

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The Authors

David Osborn, MBBS, Research Fellow.Julius Lee, MD, DSc, FRCP, Professor of Endocrine Physiology.Grant Williams, MS, MSc, FRCS, Consultant Urologist.