8/6/2019 Litio en Orina

1/2

Eu r J Clin Pharmacol (1990) 39:8%90EuropeanJournalof ( ~ [ ~ ( ~ ( ~

@ Springer-Verlag1990

T h e u s e o f a s i n g le n o n - t i m e d u r i n e c o l l e c t i o n in t h e c a l c u l a t io no f f r a c t i o n a l l i th i u m c l e a r a n c eM . O ' H a g a n a n d S . G r e e n eDep artm ent of Child Health, N inewells Hospital and M edical School, Dun dee, ScotlandReceived: M ay 19, 1989/Accepted in revised form: Febru ary 9, 1990

Summary . T h e f r a c t i o n a l c l e a r a n c e o f li t h i u m( C LL i /C L c R ) c a l c u l a t e d i n 1 5 n o r m a l h e a l t h y a d u l t s f r o m as i n g l e m o r n i n g u r i n e a l i q u o t c o l l e c t i o n , t o g e t h e r w i t h as in g le v e n o u s b l o o d s a m p l e ( F Q ) w a s c o m p a r e d w i t h t h ea v e r a g e C L Li /C L cR o b t a i n e d f r o m t h r e e t i m e d c o n s e c u -t i v e u r i n e c o l l e c t i o n s w i t h m i d - p o i n t b l o o d s a m p l i n g( F A B C ) . L i t h i u m h a d b e e n i n g e s t e d 1 5 - 1 8 h p r i o r t o t h ec o l l e c t i o n o f t h e s e s a m p l e s .

M e a n C L L i/ C L cR w a s s i m i l a r ( F Q , 0 .1 8 6 , F A B C ,0 . 17 7 ) , w i t h a h i g h l y s i g n i f i c a n t c o r r e l a t i o n i n e a c h i n d i-v i d u a l o f CLLi/CLcRm e a s u r e d b y e i t h e r m e t h o d ( r = 0 .9 7,P < 0 .0001) .P r o x i m a l t u b u l a r r e a b s o r p t i o n o f s o d i u m u s i n g li t h iu mc l e a r a n c e m a y b e c a l c u l a te d f r o m a s in g le u r i n e a n d b l o o ds a m p l e .Key words: L i t h i u m c l e a ra n c e ; p r o x i m a l t u b u l e , s o d i u m ,f r a c t i o n a l c l e a r a n c e

T h e r e n a l c l e a r a n c e o f l i t h i u m h a s b e e n e s t a b l i s h e d a s am e a s u r e o f t h e r e n a l h a n d l i n g o f so d i u m , w i t h f r a c ti o n a lc l e a r a n c e o f li t h i u m ( ie . i n r e l a t i o n t o c r e a t i n i n e c l e a r -a n c e , C L u / C L c R ) ta k e n a s a n e q u i v a l e n t m e a s u r e o f t h ef r a c ti o n a l p r o x i m a l t u b u l a r r e a b s o r p t i o n o f s o d i u m( F ra c P T R N a ) [ 1, 2 ]. T h e m e t h o d i s b a s e d o n t h e a s s u m p -t i o n t h a t l i t h i u m i s e x c l u s iv e l y a b s o r b e d i n th e p r o x i m a lt u b u l e a n d u n d e r p h y s i o lo g i c a l co n d i t i o n s th i s a s s u m p t i o nh a s b e e n v a l i d a t e d a s re g a r d s t h e c o n v u l u t e d p o r t i o n o ft h e p r o x i m a l t u b u l e [1 ].L i t h i u m c l e a r a n c e c a n b e m e a s u r e d i n t h e u s u al m a n -n e r b y m e a s u r i n g t h e a m o u n t o f l i th i u m e x c r e t e d b y t h ek i d n e y i n u n i t t i m e ( a f t e r i n g e s t i o n o f li t h i u m ) a n d d i v i d -i n g t h i s v a l u e b y t h e s e r u m l i t h i u m c o n c e n t r a t i o n . U s i n gt h is s t a n d a r d f o r m u l a o f U V / P f o r th e c a l c u l a t io n o f r e n a lc l e a r a n c e , t h e f o r m u l a o f f r a c t i o n a l c l e a r a n c e i s s i m p l i f ie dto [ULi] x [PcR]/[PLi] [ U cR] , w he r e [ U Li and [ U cR] eq ua lt h e u r i n e c o n c e n t r a t i o n o f l it h i u m a n d c r e a t i n in e r e s p e c -t i v e l y a n d [P Li] a n d [ Pc R ] e q u a l t h e p l a s m a / s e r u m c o n c e n -t r a t i o n o f l i t h i u m a n d c r e a t i n i n e r e s p e c t i v e l y : t h e u r i n ef l o w r a t e , V , i s e l i m i n a t e d f r o m t h e e q u a t i o n .

D e s p i t e t h i s s i m p l i f i c a t i o n , c l i n i c a l s t u d i e s c a l c u l a t i n gF r ac P T R N a f r o m t h e r e n a l c l e a r a n c e o f l i t h iu m h a v e u s e d

t h e c o l l e c t i o n o f th e t i m e d u r i n e s p e c i m e n w i t h m i d p o i n tb l o o d s a m p l i n g . V i n c e n t e t al r e c e n t l y r e p o r t e d a s i m p li -f i ed m e t h o d f o r e v a l u a ti n g p r o x i m a l t u b u l a r f lu i d r ea b -s o r p t i o n [3 ] b u t t h e y s t il l r e q u i r e d a s h o r t a c c u r a t e l y t i m e du r i n e c o l l e c t i o n .

A c c e p t a b i l i t y o f c li n i ca l s t u d i e s t o c h i l d r e n a n d a d u l t sr e q u i r e s t h a t u r i n e a n d b l o o d s a m p l i n g i s k e p t t o a m i n i -m u m . D a y t i m e u r i n e c o l l e c t io n s a r e n o t o r i o u s l y in a c c u -r a t e p a r t i c u l a r l y i n c h i l d r e n . H o m e b a s e d i n v e s t i g a t i o n sr e q u i r e v e r y s i m p l e p r o t o c o l s . W e t h e r e f o r e d e v i s e d as t u d y p r o t o c o l t o c o m p a r e t h e C L u / C L c R c a l c u l a te d f r o ma s in g l e m o r n i n g u r i n e a l i q u o t c o l l e c t i o n w i t h CLLi/CLcRd e r i v e d f r o m s t a n d a r d t i m e d u r i n e c o l le c t io n s .

S u b j e c t s a n d m e t h o dFifteen healthy adult volunteers ingested lithium carb onate at a doseof 10 mg- kg- ~ not exceeding 750 mg in total) at 18.00 h w ith theirevening meal. The y were then allowed to ingest only water until mid-

Table 1. Th e fractional clearance values (% ) for the aliquot urinespecimen (Fo), each of the timed urine specimens (Fa, Fm Fc) respec-tively, and the me an fractional clearance of the 3 timed u rine speci-men s (FABc) n each individua lPatie nt F o FA FB Fc FABcNumber

1 17.4 17.4 18.9 19.5 18.62 23.8 23.8 20.2 20.4 21.43 10.0 10.0 10.3 10.0 10.14 23.4 23.4 22.8 22.0 22.75 14.1 14.1 12.2 10.3 12.26 28.6 28.6 29.4 28.9 28.97 20.0 20.0 18.6 15.3 17.98 17.9 17.9 15.4 15.1 16.19 12.4 12.4 10.9 10.7 13.310 14.4 14.4 14.9 14.6 14.611 20.8 20.8 18.3 14.2 17.712 24.6 24.4 21.2 21.9 22.513 16.3 16.3 17.0 13.5 15.614 20.4 20.4 22.0 19.4 20.615 15.7 15.7 14.3 14.9 14.9M ean 18.6 17.7(SD) (5.1) (5.0)

8/6/2019 Litio en Orina

2/2

900 . 3

0 . 2 6

0 . 2 2 -F Q

0 . 1 8 -

0 . 1 4 -

0 . 1 "I I I I I I

0 . 1 0 . 1 4 0 , 1 8 0 . 2 2 0 . 2 6 0 , 3F A B CFig.1. Th e relationship b etween fractional clearanc e of lithium(CLLi/CLcR) calculated from a single mornin g urinary aliquot (FQ )and the average taken f rom three consecu tive t imed ur ine samples(FABC) in fifteen no rm al adults (r = 0.97, P < 0.001)

day the next day. The re we re no other restrictions and they conti-nued with their norma l working day.Four t imed separate urine collections from 23.00-07.30 (O),07.30-08.30 (A), 08.30-10.00 (B), and 10.00-12.00 h (C ) we re ob-tained fro m each individual. The 08.30 h urine w as also used as asingle aliquot urine (Q). Venous blo od samples we re taken at 08.30and 11.00 h. Urine and se rum creatinine and l i thium levels we reme asure d togethe r with the volu me of each urine collection. Lithiumwas measured by f lame photom etry and creatin ine by a m odif iedJaf fe technique [4].Lithium and creatinine clearances were calculated for each sep-arate t ime d urine collection (using UV/P) and again designated O ,A, B , C w ith aIl values corrected to 1.73 m2 SA. Fractional clearancefor the urine aliquot [Q] was calculated without th e m easure of V, i . e.[ E L i ] X [ P c R ] / [ U c R ] X [ P L i ]-

Resu l t s

T h e s e r u m c r e a t i n in e o f e a c h i n d i v id u a l w a s w i t h in t h en o r m a l r a n g e a n d r a n g e d f r o m 6 0 - 1 1 8 g m o l . 1 - 1 . T h es e r u m l i t h i u m l e v e l t a k e n a t 0 8 .3 0 h i n e a c h i n d i v i d u a l w a sn e a r l y i d e n t i c a l t o t h e s a m p l e t a k e n a t 1 1 . 00 h . ( M e a n( S D ) 0 8 .3 0 h = 0 . 2 4 ( 0 .4 7 ), 1 1 .0 0 h = 0 . 2 2 ( 0 .4 5 ) m m o l -1 -1 ). A s b l o o d a n d u r i n e l i t h iu m c o n c e n t r a t i o n s w o u l d d e -c l in e d u r i n g t h e 1 2 h f o l lo w i n g i n g e s t i o n t h e o v e r n i g h ts a m p l e s w e r e n o t i n c l u d e d i n t h e c a l c u l a t i o n o f f r a c t i o n a lc l e a r a n c e .

M. O 'H ag an and S. Gree n: Fractional l i thium clearanceT h e f r a c t io n a l c l e a r a n c e f o r e a c h t i m e d u r i n e s p e -

c i m e n t o g e t h e r w i t h t h e a l i q u o t i s g i v e n i n t h e t a b l e . N os i gn i fi c an t d if f e r e n c e w a s n o t e d b e t w e e n t h e m e a n ( S D )o f t h e a l i q u o t C L L ~ /C L cR ( F Q ) ( 0 .1 8 6 ( 0 .5 1 ) ) a n d t h e m e a n( S D ) o f th e a v e r a g e C L L i/ C Lc ~ c a lc u l a t e d f r o m t h e t h r e em o r n i n g u r i n e c o l l e c t i o n s ( F A B C ) ( 0 . 1 7 7 ( 0 . 5 0 ) ) . A h i g hc o r r e l a t i o n w a s s e e n b e t w e e n C L L i/ CL c R c a l c u l a te d f r o mt h e a l i q u o t ( F Q ) a n d t h e m e a n o f t h e t i m e d u r i n e s p e c i-m e n s ( F A B C ) i n e a c h i n d iv i d u a l . ( F ig . 1 )

Di scu s s i on

T h e h i g h c o r r e l a t i o n c o e f f i c i e n t a n d s i m i l a r v a l u e s o fC L L i/ C L cR c a l c u l a t e d f r o m t h e a l i q u o t u r i n e a n d t h e t i m e du r i ne c o l le c t i on i m p l i e s t h a t a n a c c u r a t e m e a s u r e o f th ef r a c t io n a l c l e a r a n c e o f li t h iu m c a n b e o b t a i n e d u s i n g o n l ya s i n g l e m o r n i n g u r i n e a l i q u o t . T h e f a c t t h a t t o c a l c u l a t et h e f r a c t io n a l c l e a r a n c e d o e s n o t i n v o l v e t he n e e d t o k n o wt h e v o l u m e o f u r in e c o l l e c t e d ( s e e f o r m u l a ) m a k e s t h e i n -v e s t ig a t i v e p r o c e d u r e e a s i e r to p e r f o r m a s o n l y o n e n o n -t i m e d u r i n e a l i q u o t i s r e q u i r e d . S i m i l a r l y o n l y o n e b l o o ds a m p l e is r e q u i r e d g i v e n t h e c o n s t a n t c o n c e n t r a t i o n o f li -t h i u m o v e r t h e t i m e p e r i o d.

T h i s s i m p l if i e d p r o t o c o l w o u l d t h e r e f o r e a l lo w f o r t h em e a s u r e m e n t o f p ro x i m a l t u b u l a r h a n d li n g o f s o d iu m i nl a r g e g r o u p s o f s u b j e c t s u n d e r a v a r i e t y o f c o n d i t i o n s i n-c l u di n g h o m e b a s e d s t u d ie s . A n e x a m p l e o f s u ch a s t u d yw o u l d b e t h e i n v e s t i g a t i o n o f r e n a l h a n d l i n g o f s o d i u m i nc h i ld r e n a n d t e e n a g e r s w i t h i n s u l i n - d e p e n d e n t d i a b e te s ,o r t h e a s s e s s m e n t o f r e n a l s a l t h a n d l i n g i n e s s e n t i a l h y p e r -t e n s i o n .Acknowledgements.We thank M rs Vera Murray for help in p repar-ing this manuscript.

Re f e r en c e s1. Tho ms on K (1984) Lithium clearance: a new m ethod for deter-mining proximal and distal tubular reabsorption of sodium andwater. Nep hron 37:217-2332. Brochner-Mortensen J, Stockel M, Sorensen PJ, Neilsen AH ,Ditzel J (1984) Proximal glomerulotubular balance in patientswith type i (insulin-dependen t) diabetes me llitus. Diabetologia27:189-1923 . Vincent HH , Boer WH , Went ing G J , Schaeletamp M AD H,W eirm ar W (1987) Simplified meth od for evaluating prox imal tu-

bular fluid reabsorption. Lan cet I114564. Larsen K (1972) Creatinine assay by a reaction-kinetic approach.Cl in C hem Acta 41 :209-217

Dr . M . O 'Ha g anDep ar tm en t o f Ch i ld H ea l t hNinewells Hospital and M edical SchoolDu n d ee DD1 9 S YScotland UK