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The Osmolality Adjustment in Urinalysis HERVEY B. ELKINS, Pii.D., LEONARD D. PAGNOTTO, and MAX RICHMOND, Boston, Mass. n as s es s in g exposure to or absorption of toxic balance. Below are shown the lead concentra I substances, urinalysis results are not con tions in the urine of a lead-poisoning patient sistent. For example, consecutive samples from who was put on forced fluids. the same worker may yield quite different find ings, and samples from several workers with similar exposure may have widely varying con tents of toxic element or metabolite. In indus trial hygiene literature, it is not infrequent to Condition Forced fluids .Test 1 Test 2 Fluids restricted Lead (mg./L.) 0.035 0.015 0.22 find statements to the effect that "there is no relationship between individual excretion and exposure" to a given substance.1 While the above is an extreme case, dilute urine samples are frequently obtained during routine procedures, and failure to compensate The general implication of such statements for this fact can lead to incongruous results; seems to be that urinalyses are inherently un Measurement of rate of excretion by collection reliable as indices of absorption of toxic sub of 24-hr. or other timed samples is the classical stances. While this may be true in some, if not method of correcting for variation in fluid bal in all cases, a number of other explanations of ance, but the practical difficulty of securing the reported variabilities of results are possible. reliable timed samples is a serious drawback to Contamination of the sample or loss of the sub this procedure. stance being sought (due to the decomposition An obvious alternative is to relate the amount of the urine sample) are frequent possibilities. of the substance to some component of the In addition, many of the methods--especially urine other than water. For example, in the those used in determining microgram and sub urine sulfate test for benzene exposure, the con microgram amounts of toxic metals--are quite centration of sulfate-conjugated phenols is re difficult, and in performing such analyses the lated to the concentration of sulfate. Experi best laboratories are not infallible. Even if the ence has shown that, in general, this compen above difficulties are overcome and our assump sates for variation in fluid balance, the urine tions regarding exposure are accurate, there are sulfate ratios of similarly exposed workers bc- other factors which can affect the results of the ing the same in dilute and concentrated urines.2 urinalyses in such a way as to produce incon Another component of urine which is some sistent findings. times used for this purpose is creatinine. When urinalysis results are expressed as parts Aside from the use of timed samples, the most per million, milligrams per liter, or in other common method of correcting for variation in units of concentration, they may be subject to fluid intake is the specific-gravity adjustment.2 great variation due to differences in water This may be considered as relating the concen tration of a single component to the total solid From the Massachusetts Division of Occupational Hy giene, Boston, Mass. Supported by Research Grant 5 ROl OH 00035 from the Division of Occupational Health, U. S. Public Health Content of the urine. Some studies have indi cated that values calculated with the specificgravity adjustment are more consistent than Service. Presented at the Annual Meeting of the American Con ference of Governmental Industrial Hygienists, Pittsburgh, Pa., May 17, 19GG. those from timed samples, even when the latter are collected with unusual care. Nevertheless, urinalysis results calculated according to the 528 N36925 DUP050312878 Vot. a No. 10 ^Qstober^l 966 ELKINS ET AL. 529 specific-gravity formula have also failed to be uniformly consistent. Consecutive samples from the same worker have shown considerable varia tion and samples from different workers with the same exposure have given even less con sistent results. While a number of factors may contribute to this variation (one of the most interesting suggestions being that of die pres ence of natural chelating agents, in the case of heavy metals), it seemed plausible to suppose that specific gravity was not die best possible measure of urine concentration for tiiis purpose. At the suggestion of Dr. Edward Radford a study was made of osmolality as a substitute for specific gravity in adjusting urinalysis re sults. Osmolality , What is osmolality? We have been unable to find the word in any dictionary, nor does it appear in any of several recent text books of physical chemistry. It is used in recent papers on renal physiology. A number of (properties of nonelectrolyte solutions (including vapor pressure, osmotic pressure, freezing point, and boiling point) de pend on the solvent's molality--that is, die num ber of moles of solute per 100d gm. of solvent (in our case, water). It is thus possible to determine the molality of a nonelectrolyte solu tion by measuring its freezing point. However, if electrolytes are present--as diey are in urine and other body fluids--the depression of die freezing point and changes in other properties are greater than from an equal molal concen tration of nonionic solute. The term "osmolality" indicates the apparent molality of the solution, in terms of nonelectro lyte solute. It can be considered an index of the osmotic pressure, a property of great physio logical importance. For example, it is believed that under conditions of dehydration the degree to which urine can be concentrated is deter mined by its osmolality. The specific gravity per se is unimportant. For this reason measure ment of osmolality, rather than specific gravity, has been recommended in various kidney func tion tests, etc.4 As a practical test for measuring urine con centration, osmolality has both advantages and disadvantages in comparison with specific grav ity--a property easily and rapidly determined by a very simple device, the urinometer. Equally primitive methods of measuring freezing point are not sufficiently rapid or accu rate- for the purpose of measuring osmolality, and devices of some complexity and cost are commonly employed. We have used a Fiske osmometer,* containing a refrigerating unit and cooling system, and with a thermistor and Wheatstone bridge for accurate measurement of temperature. The device requires a 2-mL sample, and reads directly in terms of milliosmols per 1000 gm. of water. The data obtained by such a unit are more accurate than specific-gravity readings with a urinometer. For equally precise and rapid meas urements of specific gravity, more expensive in strumentation providing close temperature con trol would be needed. The usual urinometer method also requires a rather large volume of urine. Both specific gravity and osmolality are af fected in die same way by changes In the fluid balance, being increased by dehydration and decreased by water diuresis. A plot of average, osmolality against specific gravity (Fig. 1) shows a nearly linear relationship up to a spe cific gravity of about 1.027. Above this value, osmolality increases less rapidly dian specific .gravity. The most important components of urine un der normal conditions are urea and sodium chloride. The osmolalities of solutions of' these compounds are much higher, in comparison with their specific gravity, than are those found in the average urine sample (Fig. 1). This re flects the presence of Substances of higher mo-. Iecular weight, which contribute more to the density of the solution than to its osmotic pres sure. The mean specific gravity of urine samples from workers as found by Levine and Fahy8 is 1.024. At this specific gravity the average osmolality is about 0.9; at a specific gravity of about 1.027, an average osmolality of unity is reached. Our results are only in fair agreement with those published by others. In comparison with specific-gravity results, Jacobson et al* found markedly higher osmolalities in urine samples obtained from controls and patients than we found in workers. Holmes reported somewhat higher relative osmolalities in samples obtained from medical students, but lower values from patients with renal disease.5 Neither of these *Fisfcc Associates, Inc., Uxbridge, Muss. DUP050312879 530. OSMOLALITY IN URINALYSIS . Occupational Ta b l e 1. Co mp ar is o n or Os mo l a n d Ad j u s t ed .Vo l u me Ex c iu s t io n Surface area (*?. !.) 1.50 1.65 1.75 1.85 1.95 . 2.05 2.15 2.25 Osmols/24 hr. 0.60 0.68 0.77 0.78 0.85 0.88 0.99 1.00 Adjusted voi/24 hr. (.) 1 0.65 0.74 0.86 0.88 0.95 1.00 1.06 1.15 reports listed samples with specific gravities above 1.030, whereas our data include nearly 100 specimens with gravities between 1.031 and 1:042. The discrepancy between our results and those of Holmes appears to lie in the specificgravity measurements. For purposes of the spe cific-gravity adjustment,* it is important that the density of urine be related to that of water at the temperature of measurement, and our data are on this basis. Holmes' specific-gravity values appear to relate to water at 4 C.; i.e., they are essentially tire same as the density and would average about 0.003 units lower than ours for the same samples. For practical purposes we can consider drat liters X osmolality = osmols, and mg./(L. X osmolality) = mg./osmol. Below are shown data on 24-hr. and shorter timed samples, in terms of osmols per 24 hr., for individuals of different body size. Projected values refer to timed samples (6-12 hr.), calcu lated on a 24-hr. basis. Av. surface area (sfl. -ra.) 1.48 1.52 1.65 1.75 1.85 1.05 2.05 2.15 2.23 2.28 Osmoh/%4 hr. Actual Projected 0.61 -- 0.66 0.72 0.76 0.80 0.88 1.03 0.98 -- . -- 0.60 0.69 0.83 0.81 0.90 0.91 0.95 -- 1.03 The average excretion per 24 hr. varies from 0.6 osmols for very small men and women adjusted 0.02+ mg./L. X s g. of sample -- 1.000 . mg./Lg. Ta b l e 2. Le a d in " Dil u t e a n d Co n c e n t r a t e d : Ur in e Sa mp l e s Lead ftntnd Nature S. //. Wo. mg./osmol. mg./Lg. Dilute < 1.010 Concentrated > 1.029 26 10 0.19 0.26 0.22 0.18 (weight, about 120 lb.) to about 1 osmol for men over 6 ft. and weighing over 200 lb. This means that the value "mg./osmol" will usually be greater than "mg./24 hr." except when the subject is a very big man. A similar relationship was found for total solids excretion, as measured by the specific gravity adjustment. In Table 1 daily specific-gravity adjusted vol umes (Lg)*' are compared with osmols per day for the different size groups. "Actual" and "Projected" values are combined for the pur poses of tills comparison. In general, excretion calculated as liters ad justed to 1.024 specific gravity exceeded that calculated as osmols by about 10%. In individual . cases "osmols/day" frequently equalled and oc casionally exceeded slightly "adjusted volume (liters.)/day."' This means that the term "mg./osmol" will on the average exceed "mg./Lg." by about 10%. A marked difference exists between dilute and concentrated samples, however, as shown in Table 2. Adjusted for osmolality the average values are slightly lower in dilute samples and signifi cantly higher in concentrated urines than are the specific-gravity adjusted values. In indi vidual cases the differences may be much great er. In Table 3, listing findings in lead workers, a number of samples of high specific gravity Adjusted volume = actual volume X DUP050312880 voi. a No. lb October 1966 ELKINS ET AL. 531 Ta b l e 3., Sa mp l e s o f Hig h Sp ec if ic Gr a v it y Lead found Av. for co- No. S. a. mg./osmol. ang./Lg. (mg.'Lj!.) 1 1.033 0.39 0.31 0.30 2 1.034 i: 0.24 0.17 0.30 3 1.034 i 0.45 0.30 0.30 . 4 1.035 l.v , , 0.16 0.13 0.14 5 1.036' 0.10 0.05 0.07 6 1.038; 0.16 0.09 0.18 7 1.040 i 0.09 0.04 0.17 are shown, together with the values adjusted both to osmolality and specific gravity. The averages for the co-worlcers (employes in the same work area and with occupations similar to those of the subject worker) are given for pur poses of comparison. In all cases the osmolality adjustment yields a higher result, sometimes more than twice the specific gravity value. Several of the urine samples of high specific gravity gave a positive test for sugar, and in all such cases the osmolality was relatively low. It seems highly probable that in such cases the specific-gravity adjustment gives too low a value. Whether the osmolality adjustment gives a result that can be substituted directly for the specific-gravity value is open to question, but it appears to be a logical procedure. Comparison of die consistency of results cal culated by both specific-gravity and osmolality adjustments yielded no clear-cut conclusions. Samples analyzed for lead and trichloracetic acid seemed slightly more consistent when the specific-gravity adjustment was used than when calculated bn the basis of osmolality, while the reverse was true for samples analyzed for mer cury phenol and hippuric acid. In determining osmolality it is desirable that the sample be reasonably fresli and that no acids be added. The osmolality is greatly in creased by small amounts of strong acids, such as are sometimes added to keep heavy metals in. solution when the sample cannot be re-, frigerated. .. Summary For the purpose of adjusting urinalysis re sults, a study was made of urine osmolality as a substitute for, or supplement to, specific gravity. The data indicate that, while osmolality has certain theoretical advantages, essentially the same results are obtained as with specific gravity--except in die case of extremely dilute c>r very concentrated samples, or samples con taining sugar or large amounts of other sub stances of high molecular weight. Department of Labor ir Industries . 286 Congress St. Boston, Mass. References 1. Mo s k o w it z, S. Exposure to mercury in industry. Monthly Reo N Y Div Indttstr Hyg Safety Stand ards 29:17 (May), 1950. 2. Massachusetts Division of Occupational Hygiene, Boston. Unpublished data. 3. Le v in e, L., and Fa h y , J. P. Evaluation of urinary lead determinations. I. The significance of the spe cific gravity. J Ind Hyg Toxicol 27:217 (October), 1945. 4. Jac o bs o n , M. H., Le v y , S. E., Ka u f ma n , R.. M., Ga l l in e k , W. E., and Do n n e l l y , O. W. Urine osmolality: A definitive test of renal function. Arch Intern Med (Chicago) 110:83 (July), 1962.- 5. Ho l mes , J. H. Measurement of Osmolality in Serum, Urine and Other Biologic Fluids by the Freezing Point Determination." In Manual of the Workshop on Urinalysis and Renal Function Studies., American Society of Clinical Pathology, Chicago, 1962. 6. El k in s , H. B., and Pa g n o t t o , L. D. Is the 24Hour Urine Sample a Fallacy? Amer Ind Hyg Assoc J 26:456 (September-October), 1965. PREVALENCE OF TUBERCULOSIS About three million deaths are attributed to tuberculosis annually and some fifteen million people living in newly emerging nations are capable of trans mitting tuberculosis according to a report of the 18th International Tuberculosis Congress held in Munich during October, 1965. Detroit Med News 57:7, Feb. 7, 1966. DUP050312881