capacity in infants and children

Transcription

1 Archives of Disese in Childhood, 1974, 49, 654. DDAVP test for estimtion of renl concentrting cpcity in infnts nd children A. S. ARONSON nd N. W. SVENNINGSEN From the Deprtment of Peditrics, University Hospitl, Lund, Sweden Aronson, A. S., nd Svenningsen, N. W. (1974). Archives of Disese in Childhood, 49, 654. DDAVP test for estimtion of renl concentrting cpcity in infnts nd children. A new method for the estimtion of the renl cpcity to concentrte urine is described. Intrnsl dministrtion of DDAVP (1-demino-8-D-rginine vsopressin), synthetic nlogue of the ntidiuretic hormone, hs been used for the mesurement of urine concentrting performnce in 79 children nd 25 infnts. By comprtive studies of different doses of intrvenous nd intrnsl dministrtion of DDAVP, stndrd procedure hs been elborted with the intrnsl dministrtion of 2 jig in children nd 1,ug in infnts. The mximum urine osmollity vlues obtined with the DDAVP test re compred to those chieved with other renl concentrtion tests, i.e. dehydrtion test nd pitressin test. The present investigtion shows tht intrnsl dministrtion of DDAVP, with no or only moderte short-term fluid restriction, yields urine osmollity vlues comprble to those fter 22 hours of prolonged dehydrtion, nd higher thn those fter combined pitressin nd fluid deprivtion test. No side effects hve been observed with the procedure described. Different procedures for mesuring the urine concentrtion cpcity of the kidneys hve been widely used, e.g. prolonged dehydrtion tests (Edelmnn et l., 1967; Miles, Pton, nd de Wrdener, 1954; Polcek et l., 1965), pitressin tests (Jones nd de Wrdener, 1956; West, Treger, nd Kpln, 1955), or combined pitressin nd fluid deprivtion tests (Winberg, 1959). Higher urine osmollity is obtined fter prolonged dehydrtion thn fter pitressin dministrtion lone (Miles et l., 1954). However, the ddition of fluid deprivtion will reinforce the pitressin effect upon the urine concentrtion performnce (Winberg, 1959). DDAVP (1-demino-8-D-rginine vsopressin) is synthetic nlogue of the ntidiuretic hormone. It cn be given in doses producing mximum ntidiuretic effect without the disturbing side effects of pressor type (Anderson nd Arner, 1972; Aronson et l., 1973; Edwrds et l., 1973; Vvr et l., 1968). Furthermore, it cn be dministered by the intrnsl route. It ws therefore thought suitble for testing the renl concentrting cpcity (Aronson nd Svenningsen, 1973). Received 8 Februry Mteril A totl of 14 infnts nd children hve been studied. 25 infnts with birthweights rnging from 86 g to 449 g nd gesttionl ges from 27 to 43 weeks were studied t postntl ges of from 1 week to 3 months, nd 79 children t ges from 2 to 15 yers. They were inptients t the Deprtment of Peditrics in Lund, the infnts for vrious perintl disorders nd the children for control exmintions fter urinry trct infection or other kidney diseses. The following three urine concentrtion tests were compred: prolonged dehydrtion test, combined pitressin nd fluid deprivtion test, nd finlly the DDAVP test. The dehydrtion ws compred with the DDAVP test in children only, while the pitressin test ws compred with the DDAVP test in both children nd infnts. Methods Dehydrtion test. All fluid ws withheld for 22 hours strting t 1. p.m. nd ending the second dy t 11..m. Solid food ws llowed the whole time. Three to four urine specimens were collected between 6. nd 11..m. on the second dy. Pitressin test. Children were dehydrted for 18 hours nd infnts for 11 hours overnight. Pitressin 654

2 DDA VP test for estimtion of renl concentrting cpcity in infnts nd children tnnte in oil ws dministered intrmusculrly 2 hours before strting fluid deprivtion. Two urine specimens were collected on the following dy t the end of the thirst period. The pitressin dose ws 2 ytg/kg. DDAVP test. Preliminry studies. Before the finl design of the DDAVP test (see below) hd been developed, some preliminry studies were performed in order to determine the optiml dose nd method of dministrtion. Grded doses of DDAVP were given intrnslly in 2 children nd 1 infnt. The wrd nurse dministered the DDAVP (1,Lg/ml or 4,ug/ml) with grded nsl tube (rhinyl). In 6 children nd 5 infnts the effect of DDAVP by the intrnsl route (2,ug in children nd 1 jug in infnts) ws compred with the effect of DDAVP dministered intrvenously (2,ug in children nd 5 zg/m2 in infnts). During these tests urine specimens Urine mosm/kg 1t 1 - o mosm/kg b _ 3 _ 2. 1 _ H2 ge: 6 yers 15 - I I I I pg DDAVP H2 1 11g /.*\;.. 2 pg9 were collected 1- or 2-hourly to obtin the mximl urine osmollity. Finl design. The children were not deprived of fluid nd were llowed to regulte their wter intke freely. In infnts the fluid intke ws restricted to 5% of the ordinry intke t the two mels fter dministrtion of DDAVP in order to void wter overlod. The doses, 1,ug for infnts nd 2 pg for children, were given t 7.3.m. by intrnsl route. After voiding t 8.3.m., urine specimens were collected from the children t 1.3.m. nd 12.3 p.m., nd strting 1 hour fter DDAVP-dministrtion three consecutive urine smples were collected from the infnts. Lbortory nlysis. The urine osmollity ws mesured cryoscopiclly with Fiske osmometer. Serum sodium ws determined with flme photometry. 1-5 \\ o ge: 5 p,1d... OF ~~~~~~~ I 7 1 t DDAVP in ge 6 yers I I I I, J DDAV P 3 weeks I I I Time FIG. 1().-Mximum urine osmollity vlues chieved with incresing doses of intrnslly dministered DDAVP ( ,ug) in 2 children. (b) DDA VP response curve fter incresing doses of intrnslly dministered DDA VP (5-1-2,ug) in n infnt. The pek vlue on ech curve shows the mximl urine osmollity obtined fter ech dose of DDAVP. 655

3 mosm/kg H2 15 _ c. 1~ O. -I L,'' Aronson nd Svenningsen,,, * /, /, *- / ( CHILDREN 5-15 yers *> mosm/kg H2 DEHYDRATION FIG. 2.-Correltion between mximum urine osmollity vlues fter 22 hours of dehydrtion nd 2,ug intrnslly dministered DDA VP, respectively, in 28 children. Results Comprison between different doses of DDAVP. In 2 children nd 1 infnt, incresing doses of DDAVP were dministered intrnslly, i.e. in children [ig nd in infnts 5-1-2,ug. The doses were given every second or third dy. As shown in Fig. l nd b, mximum urine osmollity vlues were chieved fter 2,ig in the children nd fter 1 V±g intrnslly in the infnt. After these titrtion studies n intrnsl DDAVP dose of 1 jig for infnts nd 2,ig for children ws chosen in the finl design of the DDAVP renl concentrtion performnce test. Comprison between intrvenous nd intrnsl DDAVP dministrtion. Intrnsl s compred to intrvenous dministrtion of DDAVP ws studied in 6 children ged 5 to 13 yers nd in 5 infnts ged 4 to 6 weeks. In the children the effect of 2,ig DDAVP intrnslly ws compred to tht of 2 Fig intrvenously. The men mximum osmollity obtined fter either wy of dministrtion ws 976 mosm/kg nd 142 mosm/kg, respectively. A similr study in the infnts fter dministrtion of 1,ug DDAVP intrnslly nd g/m2 intrvenously resulted in men mximum osmollity of 477 mosm/kg nd 521 mosm/kg, respectively. The differences observed were not significnt (P > -5, Student's 't'-test). Comprison between DDAVP test nd dehydrtion test. In 28 children the DDAVP test s well s the dehydrtion test were performed. The mximl urine osmollity obtined in these tests re plotted in Fig. 2. In 15 children the DDAVP test resulted in higher, nd in 13 children, in lower, mximum urine osmollity thn fter dehydrtion for 22 hours. There ws no sttisticl devition of the group vlues from the line of equlity (P> -5). Comprison between DDAVP test nd pitressin test. The mximum urine osmollity chieved fter the DDAVP test nd the pitressin test, respectively, ws compred in 51 children nd 25 infnts. As shown in Fig. 3 there ws mong children cler tendency to higher urine osmollity fter the DDAVP test thn fter the pitressin test.

4 DDA VP test for estimtion of renl concentrting cpcity in infnts nd children mosm/kg H2O S * * *. I ~~P *~~ * * // Se CHILDREN yers n-56 + mosm/kg H2O PITRESSIN-test FIG. 3.-Correltion between mximum urine osmollity vlues during pitressin test nd DDA VP test, respectively; 56 comprtive mesurements performed in 51 children. The difference from the line of identity is significnt (P <1). Similr results were obtined in infnts, s shown in Fig. 4 (P < 1). Side effects of DDAVP. In the present investigtion no signs of pressor effects were observed with the DDAVP doses used. Neither were ny signs of overhydrtion seen in the children, ll regulting their wter intke freely. Serum sodium vlues, controlled in 31 children nd 13 infnts, did not fll below the norml rnge in ny cse; comprison between vlues obtined on the dy before nd on the dy of the DDAVP test t 1. p.m. showed no significnt difference (men serum sodium 14 nd 139 meq/l. in children, 136 nd 135 meq/l. in infnts, respectively; P > *5). Among the 25 infnts studied, trnsient wter intoxiction occurred in 1 infnt with congenitl hert defect. However, in this cse the fluid restriction fter DDAVP dministrtion hd ccidentlly been disregrded. In no other infnt were ny side effects observed. Discussion DDAVP for mesurement of urinry concentrtion cpcity. The effectiveness of 6 ) >L 1 1 _. A L x.a, m S 5 1.,t' 657 DDAVP, synthetic nlogue of the ntidiuretic hormone, hs previously been documented in dibetes insipidus in dults (Anderson nd Arner, 1972; Edwrds et l., 1973; Vvr et l., 1968) nd in children (Aronson et l., 1973; Kuli nd Lron, 1974). It hs severl dvntges over other ntidiuretic hormone preprtions, i.e. pitressin nd lysine vsopressin. This ws confirmed in the present investigtion where DDAVP hs been used for estimtion of the renl urine concentrting cpcity. First, in contrst to both pitressin nd lysine vsopressin, DDAVP hs-in clinicl relevnt doses-no pressor effects. Secondly, DDAVP hs long durtion (6-14 hours in dults) in comprison to lysine vsopressin. Thirdly, DDAVP cn be given intrnslly without discomfort to the ptient. The present results show tht intrnsl dministrtion of DDAVP is s effective s DDAVP given intrvenously. The optiml dose of DDAVP intrnslly ws found to be 1 [±g in infnts nd 2 jig in children: higher doses did not increse the mximl urine osmollity. The risk of overhydrtion with such potent ntidiuretic hormone nlogue s DDAVP must, of course, be borne in mind. In children, who re ble to regulte the wter intke themselves, this

5 658.S, Aronson nd Svenningsen mosm/kg H2 INFANTS 1 week-3 months A 75-25, o I k '9 9/ / * / PITRESSIN-test n-34 * mosm/kg H2 FIG. 4.-Correltion between mximum urine osmollity vlues during pitressin test nd DDA VP test, respectively; 34 comprtive mesurements performed in 25 infnts. problem does not seem relevnt. In fct there ws in no cse ny lowering of the serum sodium. In smll infnts, however, there is definite risk of wter intoxiction s observed in single cse in the present study. Yet, by restricting in bottle-fed infnts the fluid intke to hlf the ordinry mount, the ntidiuretic effect of DDAVP ws pproximtely mtched s judged by n unchnged body weight. In this wy prdoxicl decrese of urine osmollity, known to develop in some cses during progressive dehydrtion (Miles et l., 1954; Winberg, 1959; Hinkle, Edwrds, nd Wolf, 1951; Miles, De Wrdener, nd McSwiney, 1952), could lso be voided. DDAVP compred to other renl concentrtdon tests. The prolonged dehydrtion test is widely ccepted technique for mesuring the renl concentrtion cpcity. 22 hours of dehydrtion hs been shown to give resonbly ccurte mesurement of the mximum urine osmollity (Miles et l., 1954). Thus, fter 22 hours the verge urine osmollity is 97% of the mximum z S urine osmollity obtined fter 26 hours of dehydrtion. As shown in the present investigtion, the urine osmollity fter intrnslly dministered DDAVP rises to vlues of the sme order s fter 22 hours of prolonged dehydrtion. Yet, the DDAVP test hs obvious dvntges in comprison to dehydrtion tests. In infnts only short period of moderte fluid restriction is necessry, nd children cn be tested without ny dehydrtion t ll. Furthermore, urine hs to be collected only for few hours. In comprison to the pitressin test the DDAVP test lso seems dvntgeous, since there is no need for rel fluid deprivtion s in the pitressin test (West et l., 1955; Winberg, 1959) in order to obtin ner mximum levels of urine osmollity. The intrnsl dministrtion of DDAVP is lso preferble to the often pinful intrmusculr dministrtion of pitressin tnnte in oil. Furthermore, the risk of sensitiztion, which hs been described with the use of pitressin (Osvth et l., 197; Roth et l., 1966), is voided. Finlly, the mximum urine osmollity obtined in both infnts

6 DDA VP test for estimtion of renl concentrting cpcity in infnts nd children 659 nd children is generlly higher fter the DDAVP test thn fter the pitressin test (Fig. 3 nd 4). Consequently, the DDAVP test seems to be relible nd fesible method in infnts nd children for mesuring the renl concentrting cpcity. We thnk Dr. Jn Mulder t Ferring AB, Mlm6, Sweden, for the supply of DDAVP, nd Miss Mrgreth Hknson for ssistnce. REFERENcEs Anderson, K. E., nd Arner, B. (1972). Effects of DDAVP, synthetic nlogue of vsopressin, in ptients with crnil dibetes insipidus. Act Medic Scndinvic, 192, 21. Aronson, A. S., Anderson, K. E., Bergstrnd, C. G., nd Mulder, J. L. (1973). Tretment of dibetes insipidus in children with DDAVP, synthetic nlogue of vsopressin. Act Peditric Scndinvic, 62, 133. Aronson, A. S., nd Svenningsen, N. W. (1973). A new synthetic vsopressin derivte, DDAVP, in the evlution of renl concentrtion cpcity. Proceedings of the Europen Society of Peditric Endocrinology, 12th Annul Meeting, Bergen, June 1973, p. 46. Edelmnn, C. M., Jr., Brnett, H. L., Strk, H., Boichis, H., nd Rodriguez Sorino, J. (1967). A stndrdized test of renl concentrting cpcity in children. Americn Journl of Diseses in Children, 114, 639. Edwrds, C. R. W., Kitu, M. J., Chrd, T., nd Besser, G. M. (1973). Vsopressin nlogue, DDAVP, in dibetes insipidus; clinicl nd lbortory studies. British Medicl Journl, 3, 375. Hinkle, L. E., Jr., Edwrds, C. J., nd Wolf, S. (1951). Occurrence of diuresis in humns in stressful situtions nd its possible reltion to the diuresis of erly strvtion. Journl of Clinicl Investigtion, 3, 89. Jones, R. V. H., nd de Wrdener, H. E. (1956). Urine concentrtion fter fluid deprivtion or pitressin tnnte in oil. British Medicl journl, 1, 271. Kuli, R., nd Lron, Z. (1974). A vsopressin nlogue in tretment of dibetes insipidus. Archives ofdisese in Childhood, 49, 483. Miles, B. E., de Wrdener, H. E., nd McSwiney, R. R. (1952). Renl function during emotionl diuresis. Americn journl of Medicine, 12, 659. Miles, B. E., Pton, A., nd de Wrdener, H. E. (1954). Mximum urine concentrtion. British Medicljournl, 2, 91. Osvth, P., Kovcs, K., Lerchner, J., nd God6, B. (197). Development of topic llergy to synthetic lysine vsopressin in child suffering from Hnd-Schiiller-Christin disese. Allergie und Asthm, 16, 97. Polcek, E., Vocel, J., Neugebuerov, L., Sebkov, M., nd Vechet6v, E. (1965). The osmotic concentrting bility in helthy infnts nd children. Archives of Disese in Childhood, 4, 291. Roth, J., Glick, S. M., Klein, L. A., nd Petersen, M. J. (1966). Specific ntibody to vsopressin in mn. journl of Clinicl Endocrinology, 26, 671. Vvr, I., Mchov, A., Holecek, V., Cort, J. H., Zorl, M., nd Sorm, F. (1968). Effect of synthetic nlogue of vsopressin in nimls nd in ptients with dibetes insipidus. Lncet, 1, 948. West, C. D., Treger, J., nd Kpln, S. A. (1955). A comprison of the reltive effectiveness of hydropeni nd of pitressin in producing concentrted urine. Journl of Clinicl Investigtion, 34, 887. Winberg, J. (1959). Determintion of renl concentrtion cpcity in infnts nd children without renl disese. Act Peditric Scndinvic, 48, 318. Correspondence to Dr. A. S. Aronson, Brnkliniken, Lsrettet, S Lund, Sweden. Arch Dis Child: first published s /dc on 1 August Downloded from on 26 Februry 219 by guest. Protected by copyright.