A Survey of the Twenty-Four-Hour Uric Acid and Urea Clearances in Eclampsia and Severe Preeclampsia

A SURVEY OF THE TWENTY-FOUR-HOUR URIC ACID AND UREA CLEARANCES IN ECLAMPSIA AND SEVERE PREECLAMPSIA

Roy W. Bonsnes, H. J. Stander

J Clin Invest. 1946;25(3):378-385. https://doi.org/10.1172/JCI101718.

Research Article

Find the latest version: https://jci.me/101718/pdf A SURVEY OF THE TWENTY-FOUR-HOUR URIC ACID AND UREA CLEARANCES IN ECLAMPSIA AND SEVERE PREECLAMPSIA1 By ROY W. BONSNES AND 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 in ney function may change markedly from day to severe preeclampsia (2), has recently been shown day and in some instances from hour to hour. to be decreased. Similarly, earlier work had Under such circumstances the usual clearance shown the urea clearance in this disease to be de- technique will yield information which is repre- creased (3 to 6). More recently, kidney function sentative of the kidney function only at one particu- tests (clearance) performed with such foreign sub- lar moment. stances as inulin, diodrast and phenol red (PSP) Furthermore, if one is interested in obtaining a have uniformly shown a decreased glomerular continuous picture of kidney function during the filtration rate as the outstanding alteration in kid- acute phase of the disease and during the recovery ney function found in .the late toxemias of preg- period, one might conceivably perform short pe- nancy by these techniques (7 to 9). One might riod clearances daily during both the active phase expect, therefore, a general increase in the level of the disease and the puerperium. However, in ,of several blood constituents in the late toxemias considering a survey study such a procedure of pregnancy as a consequence of this decreased seemed both impracticable and, from the point of glomerular filtration rate. Yet there are patients view of the welfare of the patient, definitely con- who seem to have normal N.P.N. and urea val- traindicated. ues with definite elevations in the uric acid levels. It was decided, therefore, to collect 24-hour We decided, therefore, to study further the uric urines and to calculate the clearances on this basis. acid and urea clearance in the late toxemias of The accuracy of such clearances as compared with pregnancy in order to determine if there were the short period clearances is probably reduced some cases which are classified clinically as either and these clearances may yield only figures which eclampsia or severe pre-eclampsia which might are of the correct order of magnitude and not the have a normal kidney function with respect to one exact values. In spite of the potential sources of metabolite, such as urea, and an abnormal or de- error which will be discussed below, the 24-hour creased function with respect to another metabo- clearances do yield information which may be ob- lite, such as uric acid. We wished, further, to obtained practically, as to the average 24-hour per- tain as continuous a picture of the kidney function formance of the kidney and as to the relative rate as is possible so that the changing blood levels of of change in this function. both the uric acid and the urea might be correlated This report deals with the uric acid and urea with the clearances obtained. clearances obtained by this procedure during the The short clearance periods usually employed years 1942, 1943, and 1944, on 32 cases of late will yield exact information as to the kidney func- toxemia of pregnancy (eclampsia and severe pre- tion during the time (at best 1 to 2 hours) the eclampsia). test is performed. Such data might justifiably be considered as a close approximation of the kidney SUBJECTS AND METHODS function for some hours preceding and following The data reported herein were obtained upon 3 cases the test if it is assumed that the rate of change in of antepartum eclampsia, 2 cases of questionable postpartum eclampsia and 27 cases of severe pre-eclampsia. this parameter is rather slow. Now it is obvious The pertinent obstetrical data relating to these cases are clinically that in the toxemias of pregnancy kid- given in Table I. Only the uric acid clearances were determined on the first 7 cases. Both the uric acid 1 This study was aided by a grant from the John and and urea clearances were obtained on the remaining 25. Mary Markle Foundation. The regimen upon which these patients were placed prob- 378 URIC ACID AND UREA CLEARANCES IN PREECLAMPSIA 379

TABLE I The clearances were calculated in the usual way from Obstetrical histories of patients studied the 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 plasma casInitais History Ag Week Complica- concentration was no.no.Initials no. Age of preg- Parity tion approximated by averaging the value N.Y.H. nancy I obtained in blood drawn at the beginning and at the end 1 M.P. 312860 27 34 1-1-1 SPE of the 24-hour period. In the less acutely ill patients 2 E.D. 308678 25 38 1-1-1 SPE these blood specimens were taken before breakfast; those 3 C.C. 319565 29 39 1-1-1 SPE acutely ill might have been receiving an infusion of 20 4 M.C. 328757 44 40 7-7-6 SPE 5 M.B. 317370 20 29 1-1-1 SPE per cent glucose in distilled water shortly before the 6 C.R. 318210 29 32 1-1-1 E blood was drawn. The urine flow was calculated by 7 H.R. 323208 21 32 1-1-1 E dividing the corrected urine volume in ml. by 1440 min- 8 C.S. 331232 28 27 0-1-0 SPE utes. At the 9 J.U. 164200 24 34 2-2-1 SPE times, particularly during post partum pe- 10 B.S. 297718 23 36 1-2-1 SPE riod when it was not necessary to obtain a blood specimen 11 M.H. 334290 27 40 1-1-1 SPE daily, the value for the days on which the blood was not 12 H.P. 340692 27 37 1-1-1 SPE taken was determined by interpolation and subsequent 13 J.P. 343526 26 33 2-2-2 SPE as All 14 R.O. 345159 31 33 1-1-1 SPE averaging described above. clearances are cor- 15 L.E. 345953 24 37 1-1-1 E rected to 1.73 sq. m. surface area. 16 M.C. 272867 37 36 2-3-3 SPE 17 V.K. 347785 33 39 2-4-2 SPE 18 J.N. 333272 28 30 0-2-0 SPE RESULTS 19 M.S. 366390 35 34 2-2-1 SPE 20 V.V. 360393 33 35 2-2-2 SPE The 24-hour uric acid clearances obtained in 21 J.R. 376076 28 31 1-1-0 SPE this way during the active phase of the disease 22 J.O. 369460 27 29 0-1-0 SPE 23 A.V. 348308 35 36 9-11-6 SPE averaged 6.4 ml. per minute, and during the post- 24 S.M. 367203 33 37 2-2-2 SPE partum or early puerperium period, 10.4 ml. per 25 G.D. 373202 36 38 3-4-3 SPE 26 B.B. 102727 41 38 4-4-4 SPE minute.2 The difference between these two aver- 27 A.P. 384802 18 29 0-1-0 SPE age values and the differences between these and 28 A.M. 383855 25 35 1-3-1 SPE* 29 M.L. 380679 39 38 1-1-1 SPE the average normal 24-hour uric acid clearance are 30 H.M. 375749 27 40 1-1-1 Tox.-Unc. statistically significant. 31 M.S. 382530 21 38 1-1-1 PPE 32 M.M. 279291 27 32 0-4-0 SPE Similarly, the 24-hour urea clearance during the active phase of the disease averaged 42 ml. per E = Eclampsia; SPE = Severe preeclampsia; PPE = minute, and during the recovery phase, 55 ml. per Postpartum eclampsia; Tox.-Unc. = Toxemia, unclassified. * Also had PPE. minute.2 Again the difference between these two average values and the differences between these ably does not modify the clearances except as discussed and the average normal 24-hour urea clearance are below. statistically significant. The 24-hour urines were collected in the usual manner. The average postpartum clearances in the tox- However, it is not always possible to obtain complete 24- emia hour specimens under these conditions. Therefore, the group should not be expected to reach normal creatinine content of all the urines was determined and values when all the postpartum data are averaged, the urine volumes were corrected subsequently to an ap- since the clearances do not reach normal values proximately constant creatinine excretion which seemed until the third to fourth postpartum day. to be characteristic for the particular individual. The normal 24-hour uric acid clearance is con- Blood specimens were obtained by venipuncture, gen- erally of the cubital vein. sidered to be about 12 ml. per minute. This figure Uric acid was determined in Wu filtrates of plasma and has been arrived at by averaging 39 separate 24- in suitably diluted specimens of urine by the 1933 Folin hour periods obtained at various times upon 7 method (10) in the first part of the work, and later by different patients who were being fed the usual the 1922 Folin method (11) modified as previously de- hospital diet. There seems to be no appreciable scribed (12). If it was necessary to deproteinize the and urine, the deproteinization was performed as described by difference between pregnant non-pregnant Schaffer, et al. (2). women. Urea was determined by the hypobromite manometric method of Van Slyke and Kugel (13). 2 Cearances within normal limits during the active Creatinine was first determined by the Folin method phase of the disease or definitely subnormal after the 4th (14) and subsequently by the method described elsewhere postpartum day as described below are not included in (15). these averages. 380 ROY W. BONSNES AND H. J. STANDER

TABLE II negative correlation is found between the uric acid Average 24-hour and short period uric acid clearance and the plasma uric acid. (Numerical and urea clearances data are presented in Table III.) Similarly, a Toxemias significant negative correlation is found between Clearance . Normal the urea clearance and the blood urea nitrogen. Antepartum Postpartum Presumably, if the few cases cited below which are 24 hr. UAC 6.442.0 10.4±2.1 12.4±2.4 exceptions to the general rule were omitted from ml-m2* 1 'I5.8 4.8 the calculations, even better correlations would be OfD obtained. Further, there is a significant positive 24 hr. UC 41.8± 13.7 54.7± 13.0 63.4 ±8.7 correlation between the urea clearance and the ml-mi uric acid clearance. It seems, therefore, that these 33.1 13.0 overall data may be taken to indicate a decreased ability on the part of the kidney to excrete urea Short UAC 14.5±2.7 14.0±2.9 and uric acid. They also indicate a definite re- ml-m2 V.S. lationship between this kidney function and the a'D blood levels of both uric acid and urea. Short UC 75±13 76±13 However, when the cases are considered indi- ml-m2 V.S. vidually certain exceptions to this general be- aD havior are found. The majority of the patients UAC-Uric acid clearance. UC-Urea clearance. on which there are sufficient data (17 out of 25), m-a measure of the significance of the difference have both low uric acid and urea clearances during between the two values to the right and left immediately the active phase of the disease. Both these clear- above. A numerical value greater than three is considered ances have become essentially normal by the third highly significant. V.S. = very small, i.e., not significant. to fourth postpartum day. In some cases there is a slight decrease in the uric acid clearance follow- The normal 24-hour urea clearance (29 periods ing this initial rise, with a subsequent gradual rise on 6 different patients) averages 63 ml. per min- in the clearance to essentially normal values. ute, with all clearances calculated as maximal clear- Cases No. 12, 13, and 27 in Table IV are presented ances. (Complete numerical data are presented as examples. in Table II). There were 4 cases (No. 9, 20, 21 and 22) in To determine the relationship between the which the uric acid clearance remained low dur- clearance and the blood value of uric acid and urea, ing the course of the disease and returned to nor- the coefficients of correlation between these values mal during the early puerperium, as those above. have been calculated. None of the data has been But the urea clearance seemed to remain within excluded. As might be expected, a significant normal 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 x UC BUN 51.9 11.46 250 17.28 3.41 -0.56 10.63 y = 17.17 - 0.11 x UC UAC 51.9 7.9 250 17.28 3.21 +0.47 8.41 y = 3.42 + 0.87 x V UAC 1.23 8.16 408 0.65 3.53 +0.16 2.44 y = 7.09 + 0.87 x V UC 1.27 51.9 250 0.65 17.28 +0.28 4.60 y = 42.40 + 7.44 x V 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 acid UC = Urea clearance BUN = Blood urea nitrogen V = Urine flow N = Number of clearances Mx = Mean of x My = Mean of y ax = Standard deviation of x ay = Standard deviation of y r = coefficient of correlation t = "t" value. An index of significance, calculated as follows t = rt- X, *N-I2. URIC ACID AND UREA CLEARANCES IN PREECLAMPSIA 381

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