and new recovery decided, therefore,...

A SURVEYOF THETWENTY-FOUR-HOURURIC ACID ANDUREACLEARANCESIN ECLAMPSIA AND SEVEREPREECLAMPSIA1

By ROYW. BONSNESAND H. J. STANDER(From the Department of Obstetrics and Gynecology, Cornell University Medical College, and

the New York Hospital, New York City)(Received for publication November 3, 1945)

The uric acid clearance in eclampsia (1) and insevere preeclampsia (2), has recently been shownto be decreased. Similarly, earlier work hadshown the urea clearance in this disease to be de-creased (3 to 6). More recently, kidney functiontests (clearance) performed with such foreign sub-stances as inulin, diodrast and phenol red (PSP)have uniformly shown a decreased glomerularfiltration rate as the outstanding alteration in kid-ney function found in .the late toxemias of preg-nancy by these techniques (7 to 9). One mightexpect, therefore, a general increase in the level

,of several blood constituents in the late toxemiasof pregnancy as a consequence of this decreasedglomerular filtration rate. Yet there are patientswho seem to have normal N.P.N. and urea val-ues with definite elevations in the uric acid levels.

Wedecided, therefore, to study further the uricacid and urea clearance in the late toxemias ofpregnancy in order to determine if there weresome cases which are classified clinically as eithereclampsia or severe pre-eclampsia which mighthave a normal kidney function with respect to onemetabolite, such as urea, and an abnormal or de-creased function with respect to another metabo-lite, such as uric acid. Wewished, further, to ob-tain as continuous a picture of the kidney functionas is possible so that the changing blood levels ofboth the uric acid and the urea might be correlatedwith the clearances obtained.

The short clearance periods usually employedwill yield exact information as to the kidney func-tion during the time (at best 1 to 2 hours) thetest is performed. Such data might justifiably beconsidered as a close approximation of the kidneyfunction for some hours preceding and followingthe test if it is assumed that the rate of change inthis parameter is rather slow. Now it is obviousclinically that in the toxemias of pregnancy kid-

1 This study was aided by a grant from the John andMary Markle Foundation.

ney function may change markedly from day today and in some instances from hour to hour.Under such circumstances the usual clearancetechnique will yield information which is repre-sentative of the kidney function only at one particu-lar moment.

Furthermore, if one is interested in obtaining acontinuous picture of kidney function during theacute phase of the disease and during the recoveryperiod, one might conceivably perform short pe-riod clearances daily during both the active phaseof the disease and the puerperium. However, inconsidering a survey study such a procedureseemed both impracticable and, from the point ofview of the welfare of the patient, definitely con-traindicated.

It was decided, therefore, to collect 24-hoururines and to calculate the clearances on this basis.The accuracy of such clearances as compared withthe short period clearances is probably reducedand these clearances may yield only figures whichare of the correct order of magnitude and not theexact values. In spite of the potential sources oferror which will be discussed below, the 24-hourclearances do yield information which may be ob-tained practically, as to the average 24-hour per-formance of the kidney and as to the relative rateof change in this function.

This report deals with the uric acid and ureaclearances obtained by this procedure during theyears 1942, 1943, and 1944, on 32 cases of latetoxemia of pregnancy (eclampsia and severe pre-eclampsia).

SUBJECTS AND METHODS

The data reported herein were obtained upon 3 casesof antepartum eclampsia, 2 cases of questionable post-partum eclampsia and 27 cases of severe pre-eclampsia.The pertinent obstetrical data relating to these cases aregiven in Table I. Only the uric acid clearances weredetermined on the first 7 cases. Both the uric acidand urea clearances were obtained on the remaining 25.The regimen upon which these patients were placed prob-

378

URIC ACID AND UREA CLEARANCESIN PREECLAMPSIA

TABLE I

Obstetrical histories of patients studied

casInitais History Ag Week Complica-no. Initials no. Age of preg- Parity tionno. N.Y.H. nancy I

1 M.P. 312860 27 34 1-1-1 SPE2 E.D. 308678 25 38 1-1-1 SPE3 C.C. 319565 29 39 1-1-1 SPE4 M.C. 328757 44 40 7-7-6 SPE5 M.B. 317370 20 29 1-1-1 SPE6 C.R. 318210 29 32 1-1-1 E7 H.R. 323208 21 32 1-1-1 E8 C.S. 331232 28 27 0-1-0 SPE9 J.U. 164200 24 34 2-2-1 SPE

10 B.S. 297718 23 36 1-2-1 SPE11 M.H. 334290 27 40 1-1-1 SPE12 H.P. 340692 27 37 1-1-1 SPE13 J.P. 343526 26 33 2-2-2 SPE14 R.O. 345159 31 33 1-1-1 SPE15 L.E. 345953 24 37 1-1-1 E16 M.C. 272867 37 36 2-3-3 SPE17 V.K. 347785 33 39 2-4-2 SPE18 J.N. 333272 28 30 0-2-0 SPE19 M.S. 366390 35 34 2-2-1 SPE20 V.V. 360393 33 35 2-2-2 SPE21 J.R. 376076 28 31 1-1-0 SPE22 J.O. 369460 27 29 0-1-0 SPE23 A.V. 348308 35 36 9-11-6 SPE24 S.M. 367203 33 37 2-2-2 SPE25 G.D. 373202 36 38 3-4-3 SPE26 B.B. 102727 41 38 4-4-4 SPE27 A.P. 384802 18 29 0-1-0 SPE28 A.M. 383855 25 35 1-3-1 SPE*29 M.L. 380679 39 38 1-1-1 SPE30 H.M. 375749 27 40 1-1-1 Tox.-Unc.31 M.S. 382530 21 38 1-1-1 PPE32 M.M. 279291 27 32 0-4-0 SPE

E = Eclampsia; SPE = Severe preeclampsia; PPE =Postpartum eclampsia; Tox.-Unc. = Toxemia, unclassified.

* Also had PPE.

ably does not modify the clearances except as discussedbelow.

The 24-hour urines were collected in the usual manner.However, it is not always possible to obtain complete 24-hour specimens under these conditions. Therefore, thecreatinine content of all the urines was determined andthe urine volumes were corrected subsequently to an ap-proximately constant creatinine excretion which seemedto be characteristic for the particular individual.

Blood specimens were obtained by venipuncture, gen-erally of the cubital vein.

Uric acid was determined in Wufiltrates of plasma andin suitably diluted specimens of urine by the 1933 Folinmethod (10) in the first part of the work, and later bythe 1922 Folin method (11) modified as previously de-scribed (12). If it was necessary to deproteinize theurine, the deproteinization was performed as described bySchaffer, et al. (2).

Urea was determined by the hypobromite manometricmethod of Van Slyke and Kugel (13).

Creatinine was first determined by the Folin method(14) and subsequently by the method described elsewhere(15).

The clearances were calculated in the usual way fromthe following data. The urine concentration of the sub-stance in question was obtained by an analysis of a suit-able aliquot of the 24-hour urine. The average plasmaconcentration was approximated by averaging the valueobtained in blood drawn at the beginning and at the endof the 24-hour period. In the less acutely ill patientsthese blood specimens were taken before breakfast; thoseacutely ill might have been receiving an infusion of 20per cent glucose in distilled water shortly before theblood was drawn. The urine flow was calculated bydividing the corrected urine volume in ml. by 1440 min-utes. At times, particularly during the post partum pe-riod when it was not necessary to obtain a blood specimendaily, the value for the days on which the blood was nottaken was determined by interpolation and subsequentaveraging as described above. All clearances are cor-rected to 1.73 sq. m. surface area.

RESULTS

The 24-hour uric acid clearances obtained inthis way during the active phase of the diseaseaveraged 6.4 ml. per minute, and during the post-partum or early puerperium period, 10.4 ml. perminute.2 The difference between these two aver-age values and the differences between these andthe average normal 24-hour uric acid clearance arestatistically significant.

Similarly, the 24-hour urea clearance during theactive phase of the disease averaged 42 ml. perminute, and during the recovery phase, 55 ml. perminute.2 Again the difference between these twoaverage values and the differences between theseand the average normal 24-hour urea clearance arestatistically significant.

The average postpartum clearances in the tox-emia group should not be expected to reach normalvalues when all the postpartum data are averaged,since the clearances do not reach normal valuesuntil the third to fourth postpartum day.

The normal 24-hour uric acid clearance is con-sidered to be about 12 ml. per minute. This figurehas been arrived at by averaging 39 separate 24-hour periods obtained at various times upon 7different patients who were being fed the usualhospital diet. There seems to be no appreciabledifference between pregnant and non-pregnantwomen.

2 Cearances within normal limits during the activephase of the disease or definitely subnormal after the 4thpostpartum day as described below are not included inthese averages.

379

ROY W. BONSNESAND H. J. STANDER

TABLE IIAverage 24-hour and short period uric acid

and urea clearances

ToxemiasClearance . Normal

Antepartum Postpartum

24 hr. UAC 6.442.0 10.4±2.1 12.4±2.4

ml-m2* 1 'I5.8 4.8OfD

24 hr. UC 41.8± 13.7 54.7± 13.0 63.4 ±8.7

ml-mi 33.1 13.0

Short UAC 14.5±2.7 14.0±2.9

ml-m2 V.S.a'DShort UC 75±13 76±13ml-m2 V.S.

aD

UAC-Uric acid clearance. UC-Urea clearance.-am measure of the significance of the difference

between the two values to the right and left immediatelyabove. A numerical value greater than three is consideredhighly significant.

V.S. = very small, i.e., not significant.

The normal 24-hour urea clearance (29 periodson 6 different patients) averages 63 ml. per min-ute, with all clearances calculated as maximal clear-ances. (Complete numerical data are presentedin Table II).

To determine the relationship between theclearance and the blood value of uric acid and urea,the coefficients of correlation between these valueshave been calculated. None of the data has beenexcluded. As might be expected, a significant

negative correlation is found between the uric acidclearance and the plasma uric acid. (Numericaldata are presented in Table III.) Similarly, asignificant negative correlation is found betweenthe urea clearance and the blood urea nitrogen.Presumably, if the few cases cited below which areexceptions to the general rule were omitted fromthe calculations, even better correlations would beobtained. Further, there is a significant positivecorrelation between the urea clearance and theuric acid clearance. It seems, therefore, that theseoverall data may be taken to indicate a decreasedability on the part of the kidney to excrete ureaand uric acid. They also indicate a definite re-lationship between this kidney function and theblood levels of both uric acid and urea.

However, when the cases are considered indi-vidually certain exceptions to this general be-havior are found. The majority of the patientson which there are sufficient data (17 out of 25),have both low uric acid and urea clearances duringthe active phase of the disease. Both these clear-ances have become essentially normal by the thirdto fourth postpartum day. In some cases there isa slight decrease in the uric acid clearance follow-ing this initial rise, with a subsequent gradual risein the clearance to essentially normal values.Cases No. 12, 13, and 27 in Table IV are presentedas examples.

There were 4 cases (No. 9, 20, 21 and 22) inwhich the uric acid clearance remained low dur-ing the course of the disease and returned to nor-mal during the early puerperium, as those above.But the urea clearance seemed to remain withinnormal limits at all times. Case No. 9 is presented

BLE III

Numerical data from statistical evaluations of 24-hour clearances

x y Mx my N ex WY r t Equation

UAC PUA 8.16 6.61 408 3.29 1.57 -0.62 16.02 y = 9.03 - 0.03 xUC BUN 51.9 11.46 250 17.28 3.41 -0.56 10.63 y = 17.17 - 0.11 xUC UAC 51.9 7.9 250 17.28 3.21 +0.47 8.41 y = 3.42 + 0.87 xV UAC 1.23 8.16 408 0.65 3.53 +0.16 2.44 y = 7.09 + 0.87 xV UC 1.27 51.9 250 0.65 17.28 +0.28 4.60 y = 42.40 + 7.44 xV UC 1.11 50.4 222 0.42 27.27 +0.16 2.40 y = 38.91 + 10.38 x

UAC= Uric acid clearance PUA = Plasma uric acidBUN= Blood urea nitrogen V = Urine flow

Mx = Mean of x My = Mean of yay = Standard deviation of y r = coefficient of correlation

calculated as follows t = rt - X, *N-I2.

UC = Urea clearanceN = Number of clearancesax = Standard deviation of x

t = "t" value. An index of significance,

380


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as an example in Table IV. It will be noted thatin this case (and in the others) the blood urea

nitrogen remained well within normal limits fora pregnant woman at term.

There were two cases (No. 26 and 31) in whichthe uric acid clearance remained within normallimits at all times, but the urea clearance decreasedduring the puerperium. In both these cases theblood urea nitrogen was increasing while theplasma uric acid remained essentially constant or

decreased somewhat. Case No. 26 is presentedas an example in Table IV.

And finally there were 2 cases (No. 23 and 28)in which the uric acid clearance was low duringthe active phase of the disease and remained lowduring the puerperium. In one of these the urea

clearance was nearly normal but in the other itwas. definitely low. This last patient exhibitedclinical signs and symptoms of "late postpartumeclampsia" and will be described in detail in an-

other publication. Case No. 23 is presented as an

example in Table IV.If the fetal heart is lost these changes take place

exactly as if the uterus has been emptied. Thesubsequent delivery of the dead fetus does not alterthe clearances which remain normal. Case No.22 is presented as an example in Table IV. In thisand another instance (Case No. 21) the urea clear-ance remained within normal limits, but in twoother cases which were not followed daily untilthe dead fetus had been delivered (Cases No. 8and 22) both the uric acid and urea clearanceswere low and improved following the loss of thefetal heart as in the majority of the other cases

cited above.Ordinary short period uric acid and urea clear-

ances were obtained on the majority of thesecases during the early puerperium (5 to 15 dayspostpartum). These, data are presented in TableV. In every instance they confirm the data ob-tained by the 24-hour clearances. It will be seen

that the uric acid and urea clearances are withinnormal limits in most of the cases. The average

of the uric acid clearances (excluding the two lowvalues in parentheses) is 14.5 ml. per minute.This value is practically identical with the valuepreviously reported by us for clinically normalwomenduring the early puerperium (12).

The urea clearances (again excluding those val-ues in parentheses) average 75 ml. per minute.

TABLE V

Short period uric acid and urea clearances-postpartum

Case Days UAC uno. postpartum

mi. per min. ml. per min.7 8 10.1 568 8* 13.3 749 7 16.2 75

12 12 16.0 8513 7 16.1 8214 8 (113)15 7 11.7 8816 9 16.8 8517 5 8418 6 7419 5 6620 6 13.4 (113)21 6 14.5 7822 8 10.4 8623 7 (6.6) 6624 12 13.6 (113)25 9 19.2 9926 9 13.5 (44)27 15 10.0 6328 6** (7.6) 5729 6 14.3 5331 15 18.7 82

* Days following the loss of the fetal heart** One day before convulsions.

Again this is about the same value as that ob-tained on clinically normal women (12).

It will be noted that the aberrant low uric acidclearances were obtained upon the patients whoalso had low 24-hour clearances and the low ureaclearances similarly upon that one patient who ex-hibited low 24-hour clearances.

The three high urea clearances (113 ml. permin.) cannot be explained.

The only really low urea clearance was obtainedon one of the two cases which exhibited a decreas-ing clearance during the early puerperium with anormal uric acid clearance. Since the other simi-lar case had normal clearances for both uric acidand urea fifteen days postpartum, one could sup-pose that the same would occur in this case, too,if another clearance had been obtained.

It appears, therefore, that in general the uricacid and urea clearances are low during the activephase of the disease, and that both these clearancesreturn to normal in the early puerperium. Sincethere is a good correlation between these clear-ances and the blood levels of uric acid and urea,it is probable that a large portion of the increasesin blood level of both uric acid and urea in severepreeclampsia and in eclampsia is due to a de-creased kidney excretory function. Certain cases

382


do appear, however, which are classified clinicallyas severe preeclampsia, which are distinct excep-tions to this general behavior.

DISCUSSION

Before any attempt is made to interpret andevaluate the above data, a defense of some of themore obvious criticisms of this type of procedureshould be made. Since a day by day picture of thekidney function with respect to uric acid and ureaduring both the active and the recovery phase ofthe disease was wanted, the procedure whichseemed to be the best compromise was chosen-the use of 24-hour periods. But it has already beenpointed out that it is nearly impossible to obtaincomplete collections of 24-hour urines during theactive phase of the disease. And it is just as im-practical to conduct the regular short periodclearances each day upon such patients. Wewereforced to assume, therefore, that the creatininecontent of the urine could be used as a guide tothe accuracy of the collection of the 24-hour urine.

There is evidence in the literature which justi-fies our making this assumption. Smith (16) hasshown that the creatinine excretion is essentiallynormal in severe preeclampsia. Our own ex-periments tend to confirm these observations forwe have had some few cases in which the collec-tions were adequate as judged by the constancyand the total amount of creatinine excreted. Evenif the amount of creatinine excreted daily in se-were preeclampsia is constant and normal, it doesnot justify our correcting incomplete specimens tothe correct 24-hour volume unless it is known thatthe rate of excretion of creatinine is constant overthe whole 24-hour period. Though it is so in thenormal, it may not be so in these cases, but thevariations are probably not sufficiently large tointroduce large errors. A more serious error isprobably introduced into the uric acid clearanceby this correction since it is known that there isa diurnal variation in the excretion of uric acid.

On the other hand, severe preeclampsia is notan all-or-none phenomenon, since clinically thereare actually degrees of severity of severe pre-eclampsia. So it is possible that the creatinineexcretion is not constant in all cases. Some ofour recent data show this to be definitely true.For example, the creatinine excretion during shortclearance periods on a patient with "fulminating"

severe preeclampsia was approximately 80 to 90per cent of normal, with a urea clearance of 40 percent of normal.

In general, however, any error due to correctingthe urine volume to constant creatinine excretiontends to reduce the differnce between the clearancevalue obtained during the active phase of the di-sease and that observed during the recovery phase,or that observed in normal women.

Secondly, many of these patients have received,at various times, infusions of 20 per cent glucosein distilled water. Wehave observed recently, inqualitative agreement with Talbot (17) and con-trary to our previous observations made followinga single injection of 50 ml. of 50 per cent glucose,that the continuous infusion of hypertonic glu-cose may increase the excretion of uric acid. Theseobservations are published in detail in the follow-ing paper (18).

However, any increase in the uric acid clearancedue to the presence of glucose will again tend tominimize the difference between the antepartumand the postpartum or normal uric acid clearances.

Thirdly, the fluid intake of these patients islimited. The urine flows can therefore be ex-pected to be low. Our overall data indicate, how-ever, that the low clearances are not due to thelow flows only, since low clearances have been ob-served in many cases in spite of relatively highurine flows. Moreover, the coefficient of correla-tion between the urine flow and the uric acid clear-ance (all the data) and the urine flow and the ureaclearance (both all the data and for flows of 2.00ml. and less) are low and of the same order ofmagnitude. It would appear, therefore, that theeffect of the urine flow upon the clearances wouldbe of about the same order of magnitude in bothinstances (for numerical data see Table III).

And lastly, it is not known how far the dietin these cases affects the uric acid clearance. Wedo know that the cases of mild preeclampsia whichare receiving the same diet as those cases of se-vere preeclampsia do not exhibit these markedchanges in uric acid clearance.

In spite of these potential sources of error thedata have been of definite value. They show thatwide variations in the clearances of these sub-stances may occur. And in spite of the potentialsources of error the agreement which has been ob-tained between the 24-hour clearances and the

383


short period clearances when these have both beenperformed on the same day, have in general beenmuch better than has been expected, during boththe active phase of the disease and the puerperium.

The data presented, even if not composed of ex-act values, are suggestive of the actual changeswhich occur in the kidney function. One is forced,therefore to the tentative conclusion that the hy-perurecemia of eclampsia is due in part to a de-creased excretion of uric acid by the kidney. Toconclude that these changes in clearance provethe hyperuricemia of eclampsia to be only due tokidney dysfunction requires the assumption bemade that the rate at which uric acid is produced(or destroyed or utilized) remains constant.There are no data at hand at the present timeto justify such an assumption. Therefore, theinverse relationship which is seen to exist be-tween the uric acid clearance and the plasmauric acid level may be taken only as presumptiveevidence which indicates that a decrease in kidneyfunction is one of the factors operating towardthe maintenance of a hyperuricemia. However,the significant positive correlation between theuric acid clearance and-the urea clearance, and thesignificant negative correlation between the ureaclearance and the blood urea nitrogen, tend to offeradditional evidence to support the contention thata part of the elevation seen in both the blood uricacid and in the blood urea is due to a decrease inkidney function.

In terms of the present day concept of kidneyfunction, this decrease in uric acid and urea clear-ance which is observed in the majority of cases canprobably be ascribed to a decrease in the glomeru-lar filtration rate. The maintenance of a normalrate of creatinine excretion can be attributed to anincreased tubular secretory activity. Such an in-terpretation is in complete accord with the ob-servations made previously by other methods inthis and in other laboratories (7 to 9).

Whether there is or is not a decrease in theglomerular filtration rate in those cases in whichthere is a decreased uric acid clearance and a nor-mal urea clearance, or vice versa, cannot be de-termined from these data. Regardless of this par-ticular point, one must postulate that wide fluc-tuations in the tubular reabsorption rate occur inthese instances if one is to ascribe the observedphenomena to alterations in kidney function. The

answer to this question can be had by determiiingthe glomerular filtration in patients who exhibitthese contrasts. Weare now collecting such data.A few preliminary experiments already performedindicate that deviations from normal tubular ac-tivity do occur in certain cases of severe pre-eclampsia.

SUMMARYANDCONCLUSIONS

The 24-hour uric acid clearance has been deter-mined daily in 32 obstetrical patients with eithereclampsia or severe preeclampsia as a complica-tion during the course of the disease and during re-covery from the disease. The 24-hour urea clear-ance has also been determined in 23 of these cases.The uric acid and urea clearances were found tobe subnormal during the active phase of the di-sease and to return to nearly normal values by thethird to fourth postpartum day in the majority ofcases (15 out of 23). However, certain exceptionsto this general behavior were found. Four patientsshowed subnormal uric acid clearances during thedisease, which improved during the early puer-perium as above. But the urea clearances re-mained normal throughout the period that thesepatients were under observation. Two patientsshowed apparently normal uric acid clearances andurea clearances during the antepartum, but de-creasing urea with normal uric acid clearancesduring the early puerperium. And finally, twoothers had subnormal uric acid clearances -duringboth the antepartum and the early puerperium.In one of these cases the urea clearance was a lownormal while in another it was definitely sub-normal. Short period uric acid and urea clear-ances had become normal in the majority of casesin the early puerperium. Those cases in whichthe short period clearances were not normal werethe same as those few which .exhibited abnormal24-hour uric acid clearances. The sources of errorand the possible interpretations of these data arediscussed.

It is concluded that there may be a hyperuri-cemia or a hyperuremia, or both, in eclampsia andsevere preeclampsia, and that these elevationsmay be due largely to an altered kidney function.A decrease in the glomerular filtration rate mayserve to explain the phenomena in the majority ofcases. However, some of the exceptional casescan be explained only by postulating a change in

384


the rate of tubular reabsorption of uric acid andurea. The possibility also exists that some ofthese changes may be due to alterations in the me-tabolism of these substances.

Wewish to express our thanks to the many membersof the house and nursing staffs whose cooperation hasmade this study possible. Many of the analyses wereperformed by Miss Hertha H. Taussky, M.S., some ofthe urea analyses by Mr. Nelson Osterberg, and thedrudgery of the statistical analyses by Mrs. Eleanor M.Brew.

BIBLIOGRAPHY

1. Nayar, A. S. M., Eclampsia. A clinical and bio-chemical study. II. Biochemical investigation ofeclampsia. J. Obst. and Gynaec. Brit. Emp., 1940,47, 404.

2. Schaffer, N. K., Dill, L. V., and Cadden, J. F., Uricacid clearance in normal pregnancy and preeclamp-sia. J. Clin. Invest., 1943, 22, 201.

3. Stander, H. J., Ashton, P., and Cadden, J. F., Thevalue of the various kidney function tests in thedifferentiation of the toxemias of pregnancy. Am.J. Obst. and Gynec., 1932, 23, 461.

4. Cadden, J. F., and McLane, C. M., Study of variouskidney function tests in relation to toxemias ofpregnancy. Surg., Gynec. and Obst., 1934, 59, 177.

5. Dieckmann, W. J., Renal function in toxemias ofpregnancy. Am. J. Obst. and Gynec., 1935, 29,472.

6. Brown, D. B., The value of the urea clearance testin pregnancy. J. Obst. and Gynaec. Brit. Emp.,1938, 45, 786.

7. Corcoran, A. C., and Page, I. H., Renal function inlate toxemia of pregnancy. Am. J. M. Sc., 1941,201, 385.

8. Wellen, I., Welsh, C. A., Taylor, H. C., Jr., andRosenthal, A., The filtration rate, effective renalblood flow, tubular excretory mass and phenol redclearance in specific toxemia of pregnancy. J.Chin. Invest., 1942, 21, 63.

9. Dill, L. V., Isenhour, C. E., Cadden, J. F., andSchaffer, N. K., Glomerular filtration and renalblood flow in the toxemias of pregnancy. Am. J.Obst. and Gynec., 1942, 43, 32.

10. Folin, O., Standardized methods for the determinationof uric acid in unlaked blood and in urine. J. Biol.Chem., 1933, 101, 111.

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