URIC ACID EXCRETION.*

BY ALFRED E. KOEHLER.

(FTOWZ the Department of Physiological Chemistry, University of Wisconsin, Madison.)

(Received for publication, April 17, 1924.)

The excretion of uric acid has been one of the perplexing problems of the physiological chemist for many years and until recently the views and data relating to its elimination have been as vague and varied as those related to the metabolism of this nitrogenous end-product.

It is not the purpose of this paper to add another discussion to the already voluminous literature on this subject, but merely to present some data obtained in an attempt to contribute to the solving of another problem; namely, a method to determine renal insufficiency with a greater accuracy.

The statement that the present renal function tests are in- adequate needs no elaboration. Indeed, nothing demonstrates this better than the number of present methods advocated and the continuous search for new ones. Some clinicians use one method, some another, none relying on any one. Many use the data obtained from several tests together with the results of blood analysis and clinical findings to form an opinion concerning renal damage or functional insticiency, and then a positive statement can only be made after extensive damage has been done. It is usually believed that the reason for this is found

*This work was begun early in 1922 at the University of Wisconsin, but the greater portion of it, especially on the clinical material, was done in the Department of Medicine, University of Minnesota, during the summer of 1922. The author wishes to express his gratitude to Dr. George E. Fahr, whose kindness and help made the work possible. The results herewith published were not presented earlier because of the hope to continue the study with a much larger number and a greater variety of patients, but this not having been possible, they are now presented for the value they may have for other workers.

721

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722 Uric Acid Excretion

in the large margin of safety of the normal kidney, thus one kidney can usually be removed without embarrassing the renal activity.

At the time this work was undertaken the opinion was prev- alent that uric acid was one of the first substances to be re- tained in the blood in renal damage. It was thus believed that by overloading the kidney with uric acid, forcing all the renal tissue into activity, and then measuring the excretion of uric acid, a method might be obtained which would not only show slight degrees of renal insufficiency but would show quantitative changes as well. More recently the study of a large series of cases, renal and otherwise, by many different workers, has shown that high uric acid values in the blood may be completely independent of kidney pathology and in nephritis there may be a high retention of other nitrogenous constituents with substantially normal uric acid levels (Fdin (1)) Feinblatt (2)).

It is altogether reasonable to assume that a substance suitable to measure excretory insufficiency on the part of the kidney should be one that is normally eliminated by that organ. The second requisite that such a substance should fulfill is failure of destruction in the body, in other words, the substance must be quantitatively recoverable after a given amount is administered. If a part of it is destroyed a variable error is introduced into the method which may completely invalidate the results obtained. The low results that the phenolsulfonephthalein method gives at times without demonstrable renal involvement is undoubtedly due to this factor. Uric acid seemed to be a substance, not easily eliminated by the kidney, a normal product of metabolism and eliminated without destruction. The view that uric acid is not destroyed is conveyed by our modern text-books and is based largely upon the findings of Wiechowski (3) who showed in 1909 that when uric acid is injected subcutaneously nearly all of it reappears in the urine and upon the experiments of Schitten- helm (4) who demonstrated that uric acid is not destroyed when it is incubated with extracts of organs at body temperature. The findings of Wiechowski are especially interesting from our standpoint. He injected 1 gm. of uric acid as the sodium salt subcutaneously and recovered 82 to 85 per cent in from 1 to 3 days. More recently, however, results have been obtained

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A. E. Koehler 723

that question these findings. In 1920 Burger (5) injected uric acid intravenously dissolved in 0.1 N NaOH or in 1 per cent pipcrazine in amounts of 0.5 gm. He recovered various amounts in the urine in the 24 hours following, ranging from 17.6 to 52.2 per cent. The added recovery on the following days raised these percentages but slightly. During the same year Griesbach (6) failed to recover a considerable percentage of uric acid injected intravenously in six out of seven cases. In one case he recovered more than injected. These authors from their results concluded uricolysis. After the work of this paper was started in 1922, the results of Thannhauser and Weinschenk (7) were published. These authors recovered from 25 to 93 per cent of the uric acid injected intravenously in 1 gm. amounts as the monosodium salt. They found that in the normals there was practically no increased elimination after 24 hours after injection while in individuals with gout the elimination was prolonged over 4 or 5 days. In one of their gout cases only 15 per cent of the injected amount was elim- inated during the 1st day which gradually rose to 81.9 per cent on the 4th day. These experimenters also found that the uric acid level in edematous tissue fluids rose quite slowly after in- travenous injection, 8 hours elapsing before equilibrium took place.

It was deemed advisable to continue the study of elimination of uric acid under high blood levels using the more accurate methods of uric acid estimation developed during the last few years in this country.

Methods.

The uric acid was determined in the blood, urine, and the solution to be injected according to the method of Benedict and Franke (8), using the arsenophosphotungstic acid color reagent. The regular Folin-Wu method of blood precipitation was modified according to the method of Pucher (9) who showed that the original technique gave only a 75 per cent recovery of added uric acid in blood and that heating before filtering gave a 93 per cent recovery.

The uric acid used was a preparation of Merck’s and was precipitated twice with dilute HCl from a solution of the uric

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724 Uric Acid Excretion

acid in 0.1 N NaOH. After thorough washing by suspension in distilled water the uric acid was dried over H&SO4 in a vacuum desiccator.

For intravenous injection the monolithium urate was formed by interaction of uric acid with the proper amount of Li&Oa. This solution was made isotonic with glucose. The following propor- tions were used.

Uric acid............................................. l.OOgm. Li,COs............................................... 0.28 “ Glucose.............................................. 1.35 “ Waterupto......................................... 100.00 cc.

This solution was made up just before use with sterile distilled water, boiled for exactly 2 minutes, the lost water added, and injected when cooled to body temperature. The reaction of the solution was approximately pH 7.4. The uric acid content was determined calorimetrically on a portion and the amount injected based upon this estimation. Approximately 12 mg. of uric acid were injected per kilo of body weight.

The subjects were placed on a controlled amount of food in- take during observation based upon their usual diet for that period. An attempt was made to control the water intake so as to to be about 2,000 cc., but this was not always successful in the hospital wards. Upon the day of the test the morning meal was omitted and the injection or ingestion of the uric acid was started about 9.00 a.m. after a blood sample was taken. The injections were made by the gravity method in the vein of the forearm at the rate of about 10 cc. per minute. The subject received one glass of water at the end of the injection and one 2 hours after when an- other blood sample was taken. Urine samples were taken for the 24 hours before, 1 hour after, at the end of 3 hours, and 24 hours after. Toluene was added as a perservative and the urine kept in an ice chest.

RESULTS.

The effect that ingested uric acid has on the blood level has never been clearly demonstrated and it was thought advisable to ascertain whether this would be a method of raising the blood uric acid and so adapt itself to our problem. Only a few pre-

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A. E. Koehler 725

liminary attempts on normals were made, the results of which are shown in Table I. NaHCOs was given in a few instances to insure solution of the uric acid in the intestine. The results show that t.he increments of increase were small if not insignificant. Only in one case was the increase appreciable and that was only with a massive dose during thorough alkalization. The results of the

TABLE I.

Ingestion of Uric Acid.

Uric acid per 100 cc. blood.

Excretion of uric acid in urine.

j d 2

-3

6 2 E :: pj % d ”

i$.g i r:

p1 N P 2’ 5 3

;: ---

m7. n&7. WI. cc. mg. VW.

M. G. B., male, 22, age 4.004.100.10 24 hrs. before. 1,640 241 396 weight 64.4 kg. 5 gm. 24 “ after. 1,550 255 405 uric acid suspended 2nd 24 hrs. after. 1,520 276 420 in water.

__-- M. G. B., male. 10 gm. 3.994.15 0.25 24 hrs. before. 1,590 195 310

uric acid + 20 gm. 24 “ after. 2,000 199 398 NaHCOa. 2nd 24 hrs. after. 1,650 252 420

_-__ ~--

A. E. K., male, 25, age 3.60 3.70 0.10 24 hrs. before. 1,750 206 360 weight 67.3 kg. 10 gm. 24 “ after. 1,980 207 410 uric acid + 10 gm. 2nd 24 hrs. after. 1,500 266 490 NaHCOa.

--- -~--

A. E. K., male. 15 gm. 3.80 4.700.90 24 hrs. before. 1,580 206 325 uric acid + 10 gm. 24 “ after. 2,100 295 620 NaHCOs. 10 gm. 2nd 24 hrs. after. 1,650 267 433 NaHCOs 1 hr. before and 10 1 hr. after. gm.

urinary output were similar in nature. This method of attempting to increase the blood level of uric acid was therefore not adaptable to our problem and further studies were not made.

Table II shows the changes in normal individuals in the blood level and urinary output after intravenous injection of uric acid. The subjects were medical students normal in every

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TABL

E II.

Intra

veno

us

Inje

ctio

n of

Uric

Ac

id

in

Nor

mal

s.

R.

G.

II.,

mal

e,

age

30,

weig

ht

71.7

kg.

935

mg.

uric

ac

id

in-

ject

ed.

E. C

. R

I., fe

mal

e,

age

24,w

eigh

t 59

.0 k

g.

770

mg.

ur

ic ac

id

inje

cted

.

RI.

G.

B.,

mal

e,

age

22, w

eigh

t 64

.4

kg.

841

mg.

ur

ic ac

id

inje

cted

.

A. E

. I<

., m

ale,

ag

e 25

, we

ight

67

.3

kg.

1,00

0 m

g.

uric

acid

in

ject

ed.

- Ur

ic ac

id pe

r W

I cc

. blo

od.

Befor

e.

mo.

W

I.

4.05

5.

65

3.87

5.

60

3.64

6.

55

2.91

4.10

-

2 hr

s. af

ter.

5.66

1.

56

xfd-

ence

.

m7.

1.60

1.73

Excre

tion

of uri

c ac

id in

urine

. z

24 h

rs.

befo

re.

24

“ “

24

“ af

ter.

2nd

24 h

rs.

afte

r. 3r

d 24

“

“

24 h

rs.

befo

re.

24

” ”

24

“ af

ter.

2nd

24 h

rs.

afte

r. 3r

d 24

“

“

24 h

rs.

befo

re.

1 hr

af

ter.

2 hr

s.

“ 1s

t. 21

“

“ 3r

d.

2nd

24 h

rs.

afte

r. To

tal

1st

24 h

rs.

24 h

rs.

befo

re.

1 hr

. af

ter.

2 hr

s.

“ 1s

t. 21

“

“ 3r

d.

2nd

24 h

rs.

afte

r. To

tal

1st

24 h

rs.

Vol-

ume.

I I

Liter

. To

tal.

--- cc

. m

7.

’ I

m7.

1,70

0 18

2 31

0 1,

630

197

325

1,81

0 48

6 88

0 1,

720

205

345

1,00

0 22

5 36

0 __

-- 1,

310

281

368

1,46

0 26

7 38

8 1,

390

661

919

1,2S

O

293

375

1,43

0 25

2 36

0 __

-~

1,50

0 21

3 32

O.t

223

334

74.t

196

410

80.1

1,

260

517

652.

f 1,

470

211

31o.

t 1,

679

807.

f ---

1,80

0 20

0 36

O.f

200

343

68.l

210

336

70.!

1,44

0 I,7

201

471

679.

t 23

8’

411.

t 1,

850

I I

818.

( - 1 5 3 I 1 I i 6 5 )I 3:

3

Per

hr.

m0.

12.9

13

.5

36.7

14

.3

15.0

15.3

16

.1

38.3

15

.6

15.5

13.3

74

.6

40.2

31

.0

12.9

15.0

68

.6

35.8

32

.3

17.1

Reco

very.

m7.

570

531

487

458

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A. E. Koehler 727

respect. They were up and around doing their usual work except that they rested in a recumbent position for the 2 hours following injection. 1 hey differ in this respect from t,he subjects in the following observations who were all confined to their beds through- out the period. The rise in the blood uric acid level at the end of 2 hours was about 2 mg., although there was no great uniformity. Practically all the uric acid that could be recovcrcd from the urine was eliminated during the first 24 hours following injection, there being no definite increase over normal the second 24 hours. Small changes that did occur after 24 hours fall within the error of day to day variation. The recovery ranged from 45.8 to 69 per cent. Kone of these subjects had any discomfort or showed any symptoms that might have been attributable to the injected uric acid.

Table III shows the results obtained in a similar observation on a series of patients who did not have demonstrable renal disturbances. The results are similar except that the per- centage recovery is somcwhat lower and the variation greater. This may merely be due to the fact that a much larger number of subjects were studied.

Table IV shows the results on subjects where definite renal insufficiency could be demonstrated. Although the number of cases is altogether too small upon which to base any definite con- clusions, the results show a definite retention of uric acid. This is evident in most cases, not only by a very definite retention as shown by the blood level at t,hc cd of 2 hours, but also by the delayed elimination extending over 24 hours. Case 1 is an interesting example of marked retention of uric acid although the initial blood level was normal. T\;o renal insufficiency was shown by the phenolsulfoncphthalein test, or by the blood chemis- try. Case 2 is one t,hat probably showed no renal pathology, but showed an insufhciency by t,hc uric acid test due to cardiac dccom- pensation. Case 3, one of essential hypertension (blood pressure 21O/lciO), showed dcfinitc retention, but whether t,his was due to an arteriosclerotic kidney or to functional changes is difhcult to tell. Here there were other positive findings of insufficiency. Cases 3 and 4 were of patients with chronic nephritis, one of these, Case 3 with marked edema, and the other without edema, yet the uric acid elimination was approximately the same in both.

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TABL

E 11

1.

Intra

veno

us

Inje

ctio

n of

Ur

ic Ac

id

in

Dise

ases

Ot

her

than

Re

nal.

Case

1.

D.

P.,

fem

ale,

ag

e 17

, we

ight

37

.2 k

g.

486

mg.

ur

ic ac

id

inje

cted

. Ne

uras

then

ia

Case

2.

V.

P.

, m

ale,

ag

e 50

, we

ight

48

.9 k

g.

639

mg.

ur

ic ac

id

inje

cted

. As

thm

a.

Case

3.

C.

B.,

fem

ale,

ag

e 28

, we

ight

56

.6 k

g.

739

mg.

ur

ic ac

id

inje

cted

. O

ptic

neu-

rit

is,

brai

n tu

mor

.

Case

4.

J.

H

., m

ale,

ag

e 13

, we

ight

37

.2

kg.

1,00

0 m

g.

uric

acid

in

ject

ed

(26.

9 m

g.

per

kg.).

As

thm

a.

I -- -- _

_

-

w7.

3.64

3.11

3.66

3.03

m7.

6.36

5.00

5.40

6.00

Diffe

r en

ee.

- m

.

2.72

1.89

1.74

2.69

--

Excre

tion

of uric

acid

in uri

ne.

24 h

rs.

befo

re.

1 hr

. af

ter.

2 hr

s.

“ 1s

t. 21

“

“ 3r

d.

24

“ “

; tot

al.

24 h

rs.

befo

re.

1 hr

. af

ter.

2 hr

s.

“ 1s

t. 21

“

“ 3r

d.

24

“ “

; tot

al.

24 h

rs.

befo

re.

1 hr

. af

ter.

2 hr

s.

“ 1s

t. 21

“

“ 3r

d.

24

“ “

; tota

l.

24 h

rs.

befo

re.

1 hr

. af

ter.

2 hr

s.

“ 1s

t. 21

“

“ 3r

d.

24

“ “

; tot

al.

- I -I-

-- cc.

mo.

m

o.

m0.

620

222

137

5.7

120

332

40

40.0

48

0 12

5 60

30

.0

860

176

141

6.7

1,46

0 24

0 ---

- 1,33

0 16

6 21

1 8.

8 22

0 25

0 55

55

.0

120

246

29

14.7

l,o

oO

286

286

13.6

1,

340

370

830

310

257

10.0

22

0 25

6 56

56

.0

165

352

58

29.0

1,

210

361

437

20.8

1,

595

551

---- 94

0 18

2 17

1 7.

1 18

57

7 14

14

.0

260

473

130

65.0

1,

550

320

496

23.6

1,

828

639

w.

104

- 159

294

168

-

per

cent

39.9

46.8

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Case

5.

S.

B.,

mal

e,

age

47,

weig

ht

70.5

kg.

914

mg.

uric

ac

id

inje

cted

. G

astri

c ul

cer,

gout

.

Case

6.

M.

G.,

mal

e,

age

36,

weig

ht

59.9

kg.

78

2 m

g. u

ric

acid

in

ject

ed.

Gas

tric

ulce

r.

Case

7.

A. J

. B.

, m

ale,

ag

e 47

, we

ight

85

.3 k

g. 1

,115

mg.

uric

ac

id

inje

cted

. Sy

philis

of

th

e ce

ntra

l ne

rvou

s sy

stem

.

Case

8.

R

. B.

, m

ale,

ag

e 29

, we

ight

54

.4 k

g.

715

mg.

ur

ic ac

id

inje

cted

. Ch

roni

c ga

s-

tritis

.

Case

9.

D.

H.,

fem

ale,

ag

e 15

, we

ight

30

.8 k

g.

403

mg.

ur

ic ac

id

inje

cted

. H

yper

ten-

sio

n.

Bloo

d pr

essu

re

206/

14

3,

left

vent

ricul

ar

hype

r- tro

phy.

5.24

9.

08

3.84

3.14

4.

96

1.82

3.62

6.

23

2.61

4.00

4.16

5.

52

1.36

5.56

1.

56

24 h

rs.

befo

re.

1 hr

. af

ter.

2 hr

s.

“ 1s

t. 21

“

“ 3r

d.

24

“ “

; tot

al.

24 h

rs.

befo

re.

1 hr

. af

ter.

2 hr

s.

“ 1s

t. 21

“

“ 3r

d.

24

“ “

; tot

al.

24 h

rs.

befo

re.

1 hr

. af

ter.

2 hr

s.

“ 1s

t. 21

“

“ 3r

d.

24

“ “

; tot

al.

24 h

rs.

befo

re.

1 hr

. af

ter.

2 hr

s.

“ 1s

t. 21

“

“ 3r

d.

24

“ “

; tot

al.

24 h

rs.

befo

re.

1 hr

. af

ter.

2 hr

s.

“ 1s

t. 21

“

“ 3r

d.

24

“ “

; tot

al.

650

240

156

6.5

190

272

52

52.0

11

0 30

5 34

17

.0

530

357

189

9.0

830

264

---- 70

0 16

3 11

4 4.

7 18

0 24

4 44

44

.0

150

143

22

11.0

48

0 44

8 21

5 10

.2

810

381

----

1,85

0 94

17

3 7.

2 50

0 30

0 15

0 15

0.0

460

213

98

49.0

1,

100

315

347

16.5

2,

060

595

---- 45

0 14

3 64

2.

7 15

0 23

0 35

35

.0

10

150

2 1.

0 50

0 44

4 22

2 10

.6

660

258

__--~

1,

020

190

194

8.1

170

167

28

28.4

60

20

5 12

6.

1 1,

000

264

264

12.6

1,

230

304

108

267

422

194

111

27.5

11.9

34.3

37.8

27.0

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TABL

E Ill-

COTK

hded

.

Case

10.

H

. R

., m

ale,

ag

e 35

, we

ight

63

.4 k

g. 8

28 m

g. u

ric

acid

in

ject

ed.

Gas

tric

neur

osis.

Case

11

. A.

A.

, m

ale,

ag

e 49

, we

ight

93

kg.

1,

215

mg.

ur

ic ac

id

inje

cted

.. G

astri

c ul

cer.

Case

12.

T.

R

., m

ale,

ag

e 49

, we

ight

63

.5 k

g. 8

30 m

g. u

ric

acid

in

ject

ed.

Mul

tiple

ne

uritis

(a

lcoho

lic?)

.

-

-

ml.

4.00

4.54

4.50

WI.

6.86

6.35

6.00

-

Diffe

r-

w7.

2.86

1.80

1.50

Excr

etion

of

ur

ic ac

id in

wine

.

24 h

rs.

befo

re.

1 hr

. af

ter.

2 hr

s.

“ 1s

t. 21

“

“ 3r

d.

24

“ “

; tot

al.

24 h

rs.

befo

re.

1 hr

. af

ter.

2 hr

s.

“ 1s

t. 21

(‘

“ 3r

d.

24

“ “

; tot

al.

24 h

rs.

befo

re.

1 hr

. af

ter.

2 hr

s.

“ 1s

t. 21

“

“ 3r

d.

24

“ “

; tot

al.

- I j&

1 Lit

er.

1 To

tal.

1 Per

hr

.

---- cc

. 7x

7.

m7.

m

7.

2,00

0 73

14

7 6.

1 23

0 23

0 53

, 53

.0

200

400

50

25.0

1,

770

3 53

7 25

.6

2,10

0 64

0 ~-

-- 880

166

156

6.5

100

390

39

39.0

85

32

0 27

13

.5

970

380

369

17.5

1,

155

435

----

1,84

0 13

6 25

1 1o

.s

170

261

44

44.0

90

23

4 21

10

.5

2,92

0 19

3 $3

4 26

.9

3,18

0 I

I 63

0’

m7.

439

279

379

45.7

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A. E. Koehler 731

Table V shows a series of cases where no renal insufhciency could be demonstrated, but where there was a question of possible functional impairment. Of this series Case 3 is interesting as a re- petition of Case 1,Table IV, after the acute nephritis had apparently cleared up. Here the blood retention was 2.80 after the nephritis as compared with 6.36 during the acute stage and an elimination recovery of 48.4 per cent after as compared with 21.6 per cent for 24 hours during the attack. Case 4, a prceclamptic toxemia, showed a retention that pointed definitely to at least functional impairment of the kidney.

DISCUSSION.

Other workers who have injected uric acid intravenously and thus obtained higher blood levels have not dwelt upon the question of whether or not symptomatic effects were produced. Very probably if such effects were observed they would have been men- tioned. The first one of our subjects who received intravenous uric acid, 15 mg. per kilo of body weight, as the monolithium urate in distilled water, complained of a headache, had a slight fever, and was nauseated. This solution was not isotonic and it was considered a possibility that the reaction was due to hcmolysis, so in all other injections the solution was made isotonic wit’h glucose. There were no mom symptomatic effects. It is diffi- cult to say whether tonicit’y was a factor here or not or whether the one case was merely accidental. However, it might be in- teresting to point out the recent observation of Rowntree (10) that distilled water slowly injected intravenously killed a rabbit within 10 minutes after receiving 25 cc.

The results on the recovery of the injected uric acid agree with those of Biirgcr (5), Griesbach (G), and Thannhauser and Weinschenk (7) and warrant the conclusion that considerable uricolysis goes on in the human body. This statement can only be made on the provisional basis that part of the uric acid is not eliminated through other channels as by means of sweat or feces. Negative evidence upon the latter would not mean very much inasmuch as bacterial decomposition probably takes place. Although traces of uric acid have been fcund in the sweat, it has always been assumed that the amount eliminated in this way is insignificant.

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Case

1.

0.

H

., m

ale,

ag

e 11

, we

ight

41

.0 k

g.

535

mg.

uric

ac

id

inje

cted

. Ac

ute

ne-

phrit

is.

Albu

min

++

+,

phen

olsu

lfone

phth

alei

n 60

pe

r ce

nt

1st h

r.,

urea

N

15.

9,

purin

e-fre

e di

et.

Case

2.

I. W

., fe

mal

e,

age

36,

weig

ht

52.2

kg.

68

4 m

g. u

ric

acid

in

ject

ed.

Early

ca

rdia

c de

com

pens

atio

n,

albu

min

++

+,

phen

olsu

lfone

ph-

thal

ein

76 p

er

cent

1s

t. hr

.: ur

ea

N 1

4.

Case

3.

E. G

., fe

mal

e,

age

GO

, we

ight

63

kg

. 82

0 m

g.

uric

acid

in

ject

ed.

Esse

ntia

l hy

- pe

rtens

ion.

Al

bum

in

+,

phen

olsu

lfone

phth

alei

n fo

r 2

hrs.

3O

per

cent

, ur

ea

N 2

2.4,

ur

ea

I< 4

.3 (

Van

Slyk

e).

TABL

E IV

.

Intra

veno

us

Inje

ctio

n of

Uric

Ac

id

in

Rena

l D

iseas

e.

Uric

acid

per

100

cc.

blood

. I

Excr

etion

of

ur

ic ac

id in

urine

.

3efo

re

m7.

2.60

3.51

3.75

- . I

--

mg.

m

3.

5.96

6.

36

8.24

4.

73

6.52

2.

77

I 3iffe

r *II

ce.

-

24 h

rs.

befo

re.

1 hr

. af

ter.

2 hr

s.

“ 1s

t. 21

“

“ 3r

d.

24

“ “

; tot

al.

24 h

rs.

befo

re.

1 hr

. af

ter.

2 hr

s.

“ 1s

t. 21

“

“ 3r

d.

24

“ “

; tot

al.

24 h

rs.

befo

re.

1 hr

. af

ter.

2 hr

s.

“ 1s

t. 21

“

“ 3r

d.

24

“ “_

; to

tal.

- - _ _- “‘-

1

Liter

. 1

Tota

l. 1 P

er

hr

“Ill%

l,o@

J 12

5 12

5 5.

2 95

25

8 24

24

.0

120

227

25

12.5

1,

015

181

191

9.0

1,23

0 24

1

910

300

350

1,67

0 19

4 32

4 15

.4

1,42

0 43

3

---- 80

0 15

8 12

6 8.

0

1,21

0’

179

216

10.3

1,

690

325

116

259

200

24.3

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Case

4.

C.

R.,

mal

e,

age

53,

weig

ht

62.0

kg.

82

1 m

g.

uric

acid

in

ject

ed.

Chro

nic

neph

ritis

with

ed

ema.

Al

- bu

min

+

+ +

+,

urea

N

74.

6,

purin

e-fre

e di

et.

Case

5.

T.

M.,

mal

e,

age

43,

weig

ht

60.0

kg.

78

4 m

g.

uric

acid

in

ject

ed.

Chro

nic

neph

ritis

with

out

edem

a.

Albu

min

+

+ +,

ph

enol

- su

lfone

phth

alei

n fo

r 2

hrs.

50

pe

r ce

nt,

urea

N

30

, pu

rine-

free

diet

.

24 h

rs.

befo

re

1,77

0 15

0 16

5 6.

9 1

hr.

afte

r. 11

0 35

5 39

39

.0

2 hr

s.

“ 1s

t. 21

0 15

9 34

17

.0

21

“ “

3rd.

1,

400

227

318

15.2

24

“

“ ; t

otal

. 1,

720

390

225

36.5

24 h

rs.

befo

re.

1 hr

. af

ter.

2 hr

s.

“ 1s

t. 21

“

“ 3r

d.

24

“ “

; tot

al.

2nd

24 h

rs.

afte

r. 3r

d 24

“

“

-__-

- 1,

500

103

156

6.5

180

142

26

26.0

19

0 17

0 32

16

.0

1,37

0 16

5 24

2 11

.5

1,74

0 29

9 1,

650

14.5

23

9 10

.0

1,48

0 11

2 16

6 6.

9

143 83

10

Tota

l.....

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

23

6

.?

18.3

.F

10

.6

1.3

R

8 -r 30

.2

g

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TABL

E V.

Intra

veno

us

Inje

ctio

n ( ?

f Uric

Ac

id

in

Que

stio

nabl

e Re

nal

Dise

ase.

- I

Excre

tion

of uri

c ac

id in

urine

.

- Re

cove

ry.

2 3e

fore.

m:.

3.71

2 hr

s. af

ter.

Mfer-

:IX

e. /

zzk.

/ Lit

er.

1 To

tal.

1 Per

hr.

-___--

-

nk?. 25

8

465

255

249

.I.

255

mc7.

4.88

4.10

w?.

1.17

cc.

7w.

m7.

WT.

570

188

107

4.5

200

253

51

51.0

31

01

268

83

41.5

1,

500:

15

4 23

1 11

.0

2,01

0 36

5 __

__

-~

-

2,37

0 17

0 40

3 16

.9

630

194

124

124.

0 45

0 21

2 95

47

.7

1,37

0 47

3 64

8 30

.9

2,45

0 86

8

1,24

0 18

1 22

5 10

.1

150’

20

4 31

31

.0

120

322

39

19.0

1,

240

330

410

17.1

1,

510

480,

1,70

0 11

8 14

4 6.

0 49

0’

220,

10

8 54

.0

210

310’

65

32

.5

24

hrs.

befo

re

1 hr

. af

ter.

2 hr

s. “

1st.

21

“ “

3rd.

24

“

“ ;

tota

l.

24

hrs.

befo

re.

1 hr

. af

ter.

2 hi

s.

“ 1s

t. 21

“

“ 3r

d.

24

“ “

; tot

al.

24

hrs.

befo

re.

1 hr

. af

ter.

2 hr

s. (‘

1st.

21

“ “

3rd.

24

“

“ ;

tota

l.

24

hrs.

befo

re.

1 hr

. af

ter.

2 hr

s. “

1st.

21

(‘ “

3rd.

24

“

“ ;

tota

l.

24

hrs.

befo

l’e.

1 hr

. af

ter.

2 hr

s. “

1st.

21

“ “

3rd.

24

“

“ ;

tota

l.

Case

1.

T.

M

., m

ale,

age

28,

weigh

t 54

. 4

kg.

710

mg.

ur

ic ac

id

inje

cted

. M

itral

and

aorti

c in

suffi

cienc

y wa

s de

- co

mpe

nsat

ed

wk.

befo

re.

Case

2.

A.

B.

, fe

male

, ag

e 50

, we

ight

57.7

kg

. 75

0 m

g.

uric

acid

in

ject

ed.

Polyu

ria,

noctu

ria.

Urea

N

18.6

, blo

od

suga

r 70

m

g.

Case

3.

0.

H.

, m

ale,

age

11,

weigh

t 40

.4

kg.

528

mg.

ur

ic ac

id

inje

cted

. Ap

pare

nt

re-

cove

ry fro

m

acut

e ne

phrit

is.

see

Case

1,

re

nal

dise

ase.

Case

4.

I,.

H.

, fe

male

, ag

e 23

, we

ight

55.2

kg

. 72

1 m

g.

uric

acid

in

ject

ed.

Pree

clam

ptic

toxe

mia,

al

bum

in

+ +

+,

blood

pr

essu

re

200,

‘120.

Case

5.

K.

J.

, fe

male

, ag

e 34

, we

ight

54.4

kg

. 71

0 m

g.

uric

acid

in

ject

ed.

Pest

pa

rturi-

tio

n,

hype

rtens

ion,

phen

ol-

sulfo

neph

thal

cin32

pe

r ce

nt

1st

hr.,

urea

N

12.1

, blo

od

pres

sure

18

0/12

0.

1.10

3.68

6.

48

2.80

3.64

7.

32

3.78

3.16

4.

88

1.72

2,47

0

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A. E. Koehler 735

Since uric acid cannot be quantitatively recovered from the urine and since the percentage recovery varies, it introduces an unknown error in its use as a measure of renal insufficiency. In spite of this objection our results show that the intravenous use of uric acid may be helpful in certain renal cases when other tests are negative. It perhaps is unnecessary to say that only a very extensive study of a large number of cases will determine the value of such a test. That much is still to be known about uric acid elimination before we can intelligently discuss its re- tention or destruction was recently demonstrated by .Lennox (11) when he showed a marked increase of the uric acid level in the blood without comparable increase in elimination upon prolonged starva- tion. He points out that this may possibly be due to renal in- volvement although other signs of such a complication were lack- ing. He cites that the increase of blood uric acid may be the first sign of nephritis. His suggestion that the hyperuricacidemia reported in cases of cancer, hypertension, thermic fever, and methyl poisoning may be due to a resulting nephritis certainly is atenable one.

Several recent attempts to localize the elimination of various substances in different parts of the excretory mechanism of the kidney are interesting in this connection and may explain the retention of certain substances in certain cases of nephritis, while in other cases the same substances may be normal and others retained. O’Connor and Conway (12) believe, after studying the localization of excretion, that uric acid is excreted in the lower part of the second convoluted tubule. It is possible that a special study of various substances in regard to retention may offer more definite knowledge as to where the pathology, if localized, exists in renal damage.

CONCLUSIONS.

1. A preliminary investigation showed that uric acid ingested by mouth did not appreciably raise the blood uric acid level or increase itsexcretion in the urine.

2. Only about one-half of the uric acid injected intravenously can be recovered in the urine. The amount recoverable varies with different individuals. Uricolysis is assumed.

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Uric Acid Excretion

3. The amount of uric acid retained in the blood 2 hours after injection and the rapidity of its elimination in the urine may be of value in determining renal insufficiency.

4. Variability of destruction and errors in metabolism, as gout, must be taken into consideration in the interpretation of reten- tion of injected uric acid.

BIBLIOGRAPHY.

1. Folin, O., The Harvey Lectures, 1919-20, xv, 109. 2. Feinblatt, H. M., Arch. Int. Med., 1923, xxxi, 758. 3. Wiechowski, W., Arch. exp. Path. U. Parmakol., 1909, lx, 185. 4. Schittenhelm, A., 2. physi’oZ. Chem., 1905, xiv, 161. 5. Biirger, M., Arch. exp. Path. u. Pharmakol., 1920, lxixvii, 392. 6. Griesbach, W., Biochem. Z., 1920, ci, 172. 7. Thannhauser, S. J., and Weinschenk, M., Deutsch. Arch. klin. Med.,

1922, cxxxix, 100. 8. Benedict, S. R., and Franke, E., J. Biol. Chem., 1922, lii, 387. 9. Pucher, G. W., J. Biol. Chem., 1922, lii, 329.

10. Rowntree, L. G., Arch. Int. Med., 1923, xxxii, 170. 11. Lennox, W. G., J. Am. Med. Assn., 1924, lxxxii, 602. 12. O’Connor, J. M., and Conway, E. J., J. Physiol., 1922, lvi, 190.

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Alfred E. KoehlerURIC ACID EXCRETION

1924, 60:721-736.J. Biol. Chem. 

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