original

Variability of creatinine excretion phenylketonuric and galactosemic children treated with anticonvulsant Jane

S. Lewis,3

Dr.P.H.,

Mary

ABSTRACT

300-500% significantly

Louise

Bunker,4

Creatinine

of more

the

per minute

24-hour variable

Sue S. Getts,

value for

excretion for

of normal, children, and drugs”2

M.A.,

and Ruth

Essien,

rates in individual

several

children

communications

children.

treated

with

voidings

Creatinine

M.A.

varied

as much

excretion

anticonvulsant

drugs

rates

than

for

as

were normal

children. Riboflavin-creatinine ratios determined on individual voidings were variable but adequate although total riboflavin was low. No time of day was found when creatinine excretion was representative of the 24-hour value. The creatinine height index when calculated from timed individual voidings during a 24-hour period varied for some children from 0.5 to more than 1.5 times published norms. Am. J. Clin. Nutr. 28: 3 10-315, 1975

Because creatinine excretion was believed to be constant for an individual it has been used as an index for urinary metabolites. However, recently several investigators found creatinine excretions of individuals were variable from one voiding to the next of adults (1-6), adolescents (7), and a few children (8, 9). Because 24-hour urine collections are difficult to obtain for children this study was made to determine if there is a time of day that a timed voiding is representative of the 24-hour creatinine excretion of a child so that it can be used for calculation of metabolite-creatinine ratios or creatinine height index.

individual

voidings

children. for the collection.

and

The subjects were S phenylketonuric, 7 galactosemic children, and 10 children receiving anticonvulsant drugs (dilantin combined with some other drug), all attending clinics at Childrens Hospital, Los Angeles, and 28 normal children, children of nutrition students

or

their

310

The American

Journal

of Clinical

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were

calculated

for

29

was calculated 24-hour urine

Findings

As

shown

in of

Table

variation

1

the

mean

of

the

children

of

the being

with

anticonvulsant drugs was signifi(P < 0.01) than the mean of the coefficients of variation of the normal children. Some children, as shown in Fig. 1, had creatinine per minute excretion rates for individual voidings that were 300-500% of the cantly

friends.

Urine, as spontaneously voided by each child during a 24-hour period, was timed, and each voiding preserved in separate brown bottles with 3 ml glacial acetic acid/i 00 ml urine, covered with toluene, and frozen until analyzed by alkaline picrate method for creatinine (10) and the Slater-Morell method for riboflavin (11). The creatinine excreted per minute for each voiding and the mean value of creatinine per minute in the

day

of variation each child’s

height index was calculated for all 50 using the creatinine values for normal children and Alvarado (13) and Clark et al. (14).

creatinine children of Viteri

treated

methods

the

Riboflavin in individual contiguous voidings of 6 children was determined and riboflavin-creatinine ratios were calculated and compared to the criteria of the Ten State Nutrition Survey (12). For each of 21 children the voidings were pooled and creatinine determined for the 24-hour period. The

coefficients

Subjects

for

The coefficient voidings in

higher

24-hour

made

value.

‘From California 2

in

Annual

3Professor, 4Graduate 28:

excretion

(which

APRIL

State

part

at

Meetings,

Home student. 1975,

rate

is the

the California 90032.

Presented

Nutrition

Nutrition

The

on rising

of the

University,

the

and

Economics

pp. 310-315.

of the

Los Angeles,

American

1972

voiding

last voiding

Institute

of

1973.

Department.

Printed

in U.S.A.

VARIABILITY

TABLE

OF

CREATININE

311

EXCRETION

1

Coefficient of variation” of creatinine per minute in timed voidings of normal, galactosemic and phenylketonuric children, and children being treated with anticonvulsant drugs

Sex Ages,

years

Mean

SD

N

M

F

14

8

6

2-10

27.2

±

15.7

7 8

S 7

2 1

3-9 4-10

34.6 54.3”

±

7.6 24.0

±

Range

% Normals PKUGalactosemicb Dilantin treated

SD of mean “Coefficient

of variation

Phenylketonuric

b

=

mean 1 phenylketonuric

males,

±

% 3-73 23-48 16-103

100.

X

female,

1 galactosemic

male,

and

1 galactosemic

female.

cP

0

Or,

Cl,

4 puns

2

-

0.22

Or

-

0.13

10

#{128}

.1?,

pumns

0.96

Cr

Or0.60g

4.0

6..

2.0

2.0

1.0

1.0

1

ratios acceptable

0.21

0.23

ag 6

3.8

3.0

FIG. 2. Riboflavin-creatinine dotted line represents the Nutrition Survey (12).

3 ys..rs -

ug

S.

in contiguous riboflavin-creatinine

(12) in midmorning and midafternoon, and the only unacceptable ratios for them were in the early morning voidings (the last voiding in the 24-hour collection). These children had very low creatinine excretions which resulted in high vitamin-creatinine ratios. Figure 3 shows that for these children the highest rates of riboflavin excreted per minute did not occur with the highest rates of creatinine excreted or vice versa. If the timed voiding with the lowest creatinine per minute excretion had been used to calculate the creatinine height index, 27 of the 29 children would have had creatinine height indexes below 0.9, as shown in Fig. 4. If the highest creatinine rate had been used 21 of 29 children would have had creatinine height indexes above 1.0. Subjects DL, ML, JA, and DF had creatinine height indexes based on 24-hour collections that were 50% or less than published norms (13) yet they had individual voidings which if the creatinine were extrapolated to 24 hours would have given creatinine height indexes of 1.3-1.8.

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8,30..

7S5

voidings

a 24-hour period for 6 children. according to the criteria of the Ten

during

ratio

Only height normal Fig. 5. 0.8 but shown

7 out of 50 children had indexes that were equal to or values of Viteri and Alvarado The mean creatinine height the mean relative weight was in Table 2.

The State

creatinine above the (13). See index was normal as

Discussion As observed by other investigators (1-9) creatinine excretions of individuals were variable during a 24-hour period. Schizophrenics (15, 16) and mental patients during emotional changes (17) were observed to have greater changes in creatinine excretion just as the children being treated for seizures had more variable excretions. Variability in metabolite-creatinine ratios was also observed by Hegsted et al. (18), Kulkarni and Kilgore (9), and Clark et al. (7) who likewise found that riboflavin-creatinine and thiamin-creatinine ratios sometimes were acceptable

midafternoon or unacceptable

or

high

voidings in

in

the

midmorning

and

when they had been low the first voiding in the

VARIABILITY

OF

CREATININE

EXCRETION

313

Oj

CREATININE RIBOFLAVIN

‘.5

+---

0.10

0.0

ID

-

-

-

DP 0

I

7:30am

7:30pm

7:30am

z

O.5L&J

z z

I-, 4

w U

:00am

6:00pm

6.-OOc

m

I3X

1.5

I.0

0-I

(-I

Jp

8:OOum FIG. 24-hour

aoOpm

3. Riboflavin per minute period for 6 children.

and

800am creatinine

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per

minute

excretion

rates

in

contiguous

voidings

during

a

LEWIS

314

ET

morning. Thus at times when specimens are likely to be collected in the field vitamincreatinine ratios may be considered acceptable when the 24-hour value is unsatisfactory. Prinsloo et al. (19) also found normal vitamincreatinine ratios when N-methylnicotinamide and creatinine lagrous children.

excretions height

study

Viteri

and

low

for

creatinine values may not be representative for heights of this generation of American children. Viteri et al. (22) checked the creatinine height index values by using 3-hour specimens of normal Guatemalan children. If urine specimens

pel0

Creatinine

in this

were

AL.

were

indexes

for

normal

lower

than

the

Alvarado

(13)

who

000

children criteria of

based

NORMAL

X

DILANTIN TREATED GALACTOSEMIC-PKU VITERIS

-

NORMALS

(25)

900

their

normal values on creatinine values of Stearns et al. (20) and the heights of Stuart and Stevenson (21) obtained a generation ago. Possibly these

Boo

0

0

600 z

0 500 (.2

0 401

x

300

x

0 20(

x 0

00

0 Jo

IOINAL

M%5LMJN$SJLSS duNN s 161108 AITO5VULSAII MUGS

CNILN5II

MC%CTIOUJPAL PSE5TIILTS.IIC 150 GALACTGSLNIC CN(LOINI

00

00

k.0)

FIG. normal,

5. Twenty-four-hour

phenylketonuric children being

and

treated

plotted

against height, creatinine excretions and

Alvarado

height

indexa children,

and and

mean relative weights’ children being treated

Creatinine

height

F

mean

All Normals

50 28

31 17

18 11

0.80 0.81

Dilantin treated Phenylketonuricgalactosemic”

10 12

9 6

1 6

0.79 0.79

creatinine excretion of and galactosemic children, with anticonvulsant drugs a curve representing normal height published by Viteri

of normal, galactosemic with anticonvulsant drugs

index

SD

±

Relative

range

height

index

weight

M

F

mean

SD

16 9

0.96 0.93

± ±

0.13 0.11

0.71-1.26 0.71-1.20

±

range

0.20-1.50 0.47-1.47

48 26

32 17

±

0.39

0.20-1.50

1

0.97

±

0.17

0.78-1.26

0.26

0.40-1.32

10 12

9

±

6

6

0.97

±

0.15

0.81

24-hour

creatinine

=

=

males,

N

0.27 0.22

±

creatinine

subject. 50th

Phenylketonuric

weight

±

subject’s

4

40

sex

M

24-hour

C

.20

(13).

sex N

b Relative

and for

11U

CM

2

Mean creatinine and phenylketonuric

#{176} Creatinine

‘0

HEBKI

FIG. 4. Creatinine height index based on 24-hour excretion (o) and range of values (I.-, -.j,) for creatinine height index calculated from - individual voidings during the same 24-hour period for normal, phenylketonuric and galactosemic children, and children being treated with anticonvulsant drugs.

TABLE

0

percentile

weight

1 phenylketonuric

of normal

children

same

height

and sex

weight for

subject’s

female,

Downloaded from https://academic.oup.com/ajcn/article-abstract/28/4/310/4716480 by University of Glasgow user on 26 April 2018

height

and

2 galactosemic

sex males,

and 5 galactosemic

females.

-1.14

VARIABILITY

were rates

collected midday creatinine might have been higher than

the

OF

CREATININE

modification determining

excretion 24-hour

rate.

Since a

creatinine

subject,

excretion

nor

depressed

is

at

it

a given

is not

constant

consistently

elevated

time

there

of day,

for

creatinine

excretion

said

that

rate.

creatinine

give

erroneous

not

be used

as a reference

that

24-hour

urine

reliable

results

estimates

We

used (6,

with that

standard

may

(24),

would

urinary

others 14.

it should give

metabolites

and more (19).

15.

El References 1. CURTIS, G., AND M. FOGEL. Creatinine excretion: diurnal variation and variability of whole and part-day measures. Psychosom. Res. 32: 337, 1970. 2. RUBIN, R. T. Urine creatinine excretion: variability and volume dependency during sleep deprivation. Psychosom. Med. 33: 539, 1971. 3.

PASTERNACK, nal variations

creatinine. 1971. 4.

S.

A., AND B. KUHLBACK. Diurof serum and urine creatine and Scand. J. Clin. Lab. Invest. 27: 1,

6. VESTERGAARD, P., AND R. LEVERETT. Constancy of urinary creatinine excretion. J. Lab. Clin. Med. 51: 211, 1958. 7. CLARKE, R. P., L. DE G. COSGROVE AND E. H. MORSE. Vitamin to creatinine ratios. Am. J. Clin. Nutr. 19: 335, 1966. 8. RAM, M. M., AND V. REDDY. Variability in urinary creatinine. Lancet 2: 674, 1970. 9.

KULKARNI, variations

Nutrition

16.

17.

M.,

AND

L.

KILGORE.

of hydroxyproline and creatinine tion in children. Am. J. Clin. Nutr. 26: 1973.

ODDS. normal women.

10.

Interdepartmental

11.

National Defense (ICNND). Manual for Nutrition Surveys. Bethesda: National Institutes of Health. 1963, p. 135, p. 246. SLATER, E. C., AND D. B. MORELL. A

Committee

on

Nutrition

Downloaded from https://academic.oup.com/ajcn/article-abstract/28/4/310/4716480 by University of Glasgow user on 26 April 2018

Education

Survey

Atlanta,Ga.:

and

method of materials. Welfare.

1968-1970, Center

Ten BioControl,

IV.

for Disease

The variability of creatinine subjects, mental patients

excretion and pregnant

Chin. Chim. Acta 26: 567, 1969. D. M., S. N. GERSHOFF,

18. HEGSTED,

19.

20.

21.

AND

D.

H.

JOLLY.

22.

23.

for

24.

M.

Variation

in

F. in

riboflavin excretion. J. Nutr. 60: 581, 1956. PRINSLOO, J. G., J. P. DU PLESSIS, H. KRUGER, D. J. DE LANGE AND L. S. DE VILLIERS. Protein nutrition status in childhood pellagra. Evaluation of nicotinic acid status and creatinine excretion. Am. J. Clin. Nutr. 21: 98, 1968. STEARNS, G., K. J. NEWMAN, J. G. McKINLEY AND P. C. JEANS. The protein requirements of children from one to ten years of age. Ann. N. Y. Acad. Sci. 69: 857, 1958. STUART,

H.

C.,

AND

S.

S.

Physical growth and development. of Pediatrics (6th ed.), edited by

Diurnal

excre1069,

fluorimetric in biological 1946.

DHEW Pub!. No. (HSM) 72-8132, 1972, p. 224. VITERI, F. D., AND J. ALVARADO. The creatinine height index: its use in the estimation of the degree of protein depletion and repletion in protein calorie malnourished children. Pediatrics 46: 696, 1970. CLARK, L. C., H. L. THOMPSON, F. I. BECK AND W. JACOBSON. Excretion of creatine and creatinine by children. Am. J. Diseases Children 81: 774, 1951. SVED, S., A. PERALES AND J. P. HOULE. Urinary creatinine in drug excretion studies in chronic schizophrenics. Brit. J. Psychiatry 120: 219, 1972. PSCHEIDT, G. R., H. H. BERLET, J. SPAIDE AND H. E. HIMWICH. Variations of urinary creatinine and its correlation to excretion of indole metabolites in mental patients. Clin. Chim. Acta 13: 228, 1966. CHATTAWAY, F. W., R. P. HULLIN AND F. C.

TRULSON

PLOUGH, I. C., AND C. F. CONSOLAZIO. The use of casual urine specimens in evaluation of thiamine, riboflavin and N’ -methylinicotinamide. J. Nutr. 69: 365, 1959. LIS, A. S., D. I. McLAUGHLIN, R. K. McLAUGHLIN AND K. F. DE HACKBEIL. The function of creatinine: nocturnal-diurnal variation. Physiol. Chem. Physics 4: 70, 1972.

of the riboflavin

chemical.

13.

315

Biochem. J. 40: 644, U.S. Dept. Health,

State

or

as an index

7, 23),

collections of

agree

12.

is no

period during the day that a urine specimen can be assumed to be representative of the 24-hour

who

EXCRETION

Philadelphia: VITERI,

Saunders, 1954, E., J. ALVARADO

STEVENSON.

In: Textbook

W. p. 10-66.

E.

Nelson.

F. AND G. A. 0. ALLEYNE. Reply to Drs. Mendez and Buskirk. Am. J. Clin. Nutr. 24: 385, 1971. POLLACK, H. Creatinine excretion as an index for estimating urinary excretion of micronutrients or their metabolic end products. Am. J. Chin. Nutr. 23: 865, 1970. PATERSON, N. Relative constancy of 24 hour urine volume and 24 hour creatinine output. Clin. Chim. Acta 18: 57, 1967.

Variability of creatinine excretion of normal, phenylketonuric and galactosemic children, and children treated with anticonvulsant drugs.

Creatinine per minute excretion rates in individual voidings varied as much as 300-500 percent of the 24-hour value for several children. Creatinine e...
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