IIEMOGLOBIN, 1 ( 7 ) , 691-695 (1977)
SHORT COE(MUN1CATION
Hemoglobin Downloaded from informahealthcare.com by UB Kiel on 11/06/14 For personal use only.
HEMOGLOBIN F LEVELS 1 N PATlENTS WITH CHRONIC RtWAL FAII.IIRE
I n a r e c e n t s t u d y Kuratowska and L u t y d s k i ( 1 ) r e p o r t e d e l e v a t e d l e v e l s of Ilb F ( a v e r a g e v a l u e 2.4% w i t h a r a n g e o f 0-10%) in s e v e r a l p a t i e n t s w i t h c h r o n i c r e n a l f a i l u r e . These i n v e s t l g a t o r s s t u d i e d 36 c a s e s , many b e l n g in a t e r m i n a l p h a s e of r e n a l i n s u f f i c i e n c y . A d i r e c t c o r r e l a t i o n o f t h e Ilb F l e v e l w i t h t h e s e v e r l t y of anemia, and t h e conc e n t r a t i o n o f c r r n t i n i n e and urea in t h e serum a p p e a r e d e v i d e n t . In t h i s s h o r t communication w e r e p o r t d n t a o f s i m i l a r i n v e s t i g a t i o n s i n s l x t y t h r e e (63) p a t i e n t s w i t h c h r o n i c r e n a l f a i l u r e ; Ilh F h a s been q u a n t i t a t e d by t w o d i f f e r e n t p r o c e d u r e s . The 63 p a t i e n t s were 28 t o 47 y e a r s o l d . and i n c l u d e d 4 1 m a l e s and 22 f e m a l e s . The m a j o r i t y o f t h e p a t i e n t s had e e v r r e r e n a l i n s u f f i c i e n c y c a u s e d by c h r o n i c g l o m e r u l o n e p h r i t i s ; some had a m o d e r a t e t o w v e r e anemia ( T a b l e I ) . T w e n t y - t h r e e o f t h e 6 3 p a t i e n t s were u n d e r g o i n g p e r i o d i c hemodialysis. The c o n t r o l g r o u p c o n s i s t e d o f 110 h e a l t h y p e r s o n s who p a r t i c i p a t e d i n t e s t i n g programs o f tlir S i c k l e C e l l C e n t e r . Blood s a m p l e s were c o l l e c t e d in v a c u t a i n e r s w i t h EDTA as a n t i c o a g u l a n t t o b e u s e d f o r r o u t i n e hematology and hemoglobin a n a l y s e s . and w t t l i o u t a n a n t i c o a g u l a n t f o r b l o o d c l i e m l s t r y a n a l y s e s . Rocitlne h e m n t o l o g f c a n a l y s e s wrre made w i t h a Model S C o u l t e r C o u n t e r . Hemoglobin i n r e d c e l l h e m o l y s a t e was examined by s t a r c h g e l e l e c t r o p h o r e s i s a t pH 9 . 0 (Z), and by m i c r o c h r o m a t o g r a p h y t o d e t e r m i n e t h e l e v e l of Ilh A 2 ( 3 ) . Ilb F was q u a n t i t a t e d by a n a l k a l i d e n a t u r a t i o n method ( 4 1 , and by a r e c e n t l y d e v e l o p e d r a d i o i m n u n o a s s a y (5): t h e r e s u l t s a r e e x p r e s s e d as %FAD and Blood c h e m i s t r y a n a l y s e s were made by s t a n d a r d %FRIA, r e s p e c t i v e l y . automated procedures. T a b l e I s u n m a r i t e s t h e d a t a . The Ilh F l e v e l s (RR X F R ~ A )o f a 1 1 i n d i v i d u a l p a l i e n t o w i t h Ilb A and o f t h e n o r a a l c o n t r o l s a r e g i v e n i n Fig. 1. T h r e e p a t i e n t s had an abnormal hemoglobin: o n e URR homotygous t l i a l a s s e m i a and a t h i r d had a s i c k l e c e l l t r a i t f o r Ilb S. o n e had Hb S-6' ( T a b l e I ) . The a v e r a g e Hb PRIA l e v e l 6 i n t h e t w o g r o u p s o f p a t i e n t s . namely t h o s e u n d e r g o i n g h e a o d f a l y s i s and t h o s e who d i d n o t , were s l i g h t l y h i g h e r than t h a t of t h e c o n t r o l group; t h e d i f f e r e n c e . h o v e v e r , . i s not s i g n i f i c a n t (FpO.05) m a i n l y b e c a u s e of t h e v i d e r a n g e in v a l u e s i n t h e t h r e e g r o u p s . A few p a t i e n t s had a lib FRIA l e v e l above 1%(1.2: 1.4; 1.65; and 2.5%). b u t a c o r r e l a t i o n b e t v e e n t h e s e i n c r e a s e s and t h e e l e v a t e d l e v e l o f c r e a t i n i n e or t h e s e v e r i t y o f nriemia was not e v i d e n t .
691 Copyright 01977 hy Marcel Dekkec. Inc. All Righlr Reserved Nrilher this work nor any part may he rrprodurrd or transmitted i n any form or hy any nteans, electronic or mrchanicrl. inclaclinl: photocopying, microfilming. and recordin#.or by any inlornulion storage and retrievalsystem. wilhoul permiwicm in wcitinR f r t m !he puhlishec.
SHORT COElENNICATION
692 TABLE I
Mean V a l u e s and Ranges of tlie Hb F L e v e l , t l i e Packed C e l l Volume, and t h e Serum C r e a t i n i n e L e v e l i n P a t i e n t s w i t h C h r o n i c Renal F a i l u r e
Number o f Cases
Clinical Condition*
Ilb Type
37
CRF (undlalyzed)
M
CRP (dialyzed)
M
Hemoglobin Downloaded from informahealthcare.com by UB Kiel on 11/06/14 For personal use only.
23
1
CRF
Hb F** (%FnrA) 0.39
llb F** (%FAD)
PCV
Creatlnlne mgfdl
111
6.2
0.29
0.6
(0.01-2.5) (0-3.4)
(0.18-0.42)
0.38 0.5 (0.02-1.65)(0-2.1)
(0.16-0.42)
(2.7-18.3)
14.3
0.27
(8.6-23.0)
AS
0.04
1.3
0.33
8.0
ss
3.2
2.7
0.16
4.4
13.6
14.2
0.24
5.6
(undlalyzed)
1
CHF (undialyred)
1
S-t)+-Tlaal CRF (undlalyzed)
110 Normal c o n t r o l s
0.27
AA
n.d.***
0.43 (0.34-0.5 3 ) (0-1.4)
(0.01-1.30) ~~
* ** *** ****
CRF XFRIA XFW
n.d.
--
~
~~
~~
~
_
~
****
_
= c h r o n i c renal f a l l u r e .
p e r c e n t Hb F d r t e r m l n e d by radioimmuno a s s a y ( 5 ) . p e r c e n t Hb F d e t e r m i n e d by a l k a l i d e n a t u r a t i o n ( 4 ) . not determlned.
Normal v a l u e s i n o u r l a b o r a t o r i e s .
The only d a t a f o r H b P i n p a t i e n t s w i t h c h r o n i c r e n a l f a l l u r e , r e p o r t e d by o t h e r s ( 1 ) . were o b t a i n e d by a n a l k a l i d e n a t u r a t i o n p r o c e d u r e . T h i s method 1s i n a c c u r a t e a t lw l e v e l s of Hb F (5) a n d , as i n d i c a t e d from t h e c o m p a r i s o n of FAD and FRIA v a l u e s f o u n d i n o u r p a t i e n t s ( F i g . 2 ) . t e n d s t o o v e r e s t i m a t e t h e Ilb F level. Our r e s u l t s o b t a i n e d w i t h t h e more a c c u r a t e radioimmuno a s s a y show t h a t t h e level OP Hb F is n o t s i g n i f i c a n t l y i n c r e a s e d i n t h e s e p a t i e n t s w i t h r e n a l f a i l u r e , and t h u s a r e a c t i v a t i o n of y c h a i n s t r u c t u r a l l o c i does n o t o c c u e in t h i s g r o u p w i t h t h i s chronic condition.
SlIORT COMMUNICATION
693 2 5
20
I 5
8
.
Hemoglobin Downloaded from informahealthcare.com by UB Kiel on 11/06/14 For personal use only.
I .o
09
4
a: 0 . 0 IL
0
a
0.1
0
.. Ir
0.6 0.5
0
0.4
0.3 0.2 0 .I CRF CRF UNDIALYZLD DIALYZED
(n-an
fn-23)
NORMAL CONTROLS
(n-flo)
FIGURE 1 The l e v e l nf f e t a l hemoglobin (XFRIA) in p a t i e n t s with chronic r e n a l f a i l u r e (CRF) and i n normal healthy c o n t r o l s .
694 16
I 4 0
1.2
10
0 4
LL
0
Hemoglobin Downloaded from informahealthcare.com by UB Kiel on 11/06/14 For personal use only.
$ oe 06
0 4
02
I
02
0.4
06
00
10
I2
I4
16
FIGURE 2
A comparison of Lhe l e v e l s uf Hb F (XFAI, v e r s u s XFRIA) In p a t i e n t s w l t l i chronic renal f a i l u r e .
T h l s r e s e a r c h was i n part supported by United S t a t e s P u b l i c l l e a l t h S e r v l c e Research Grants IlLtl-05168 a i d IILB-15158. Departments of H e d l c l n e . C e l l Jnd Molecular E. C . Abraham T. Ozawa B i o l o g y . Comprehensive S i c k l e C e l l Center, Medical C o l l e g e of Georgld. and Veterans G. A . N l a z i Adminiatrat i o n l l o s p i t a l , Augusta. Ca., 30901, J . B . Iludson F . Gamer U.S.A. T.H.J. Huisman
SHORT COMMUNICATION
695 REFERENCES
1. Kurntowska. Z. and Lutybski. A . , E r y t l i r o p n i e s i s , Eds. Nnkao, K.. F i s h e r , J. W., and TnkIku, F., U n i v e r s i t y Pnrk Press, BnLtimore (London/Tokyo), 397. 1974. 2.
Efremov. G. D.. Huisman, T.1l.J.. Smith, L. I.., Wilson. J . B.. Kitchens. J . L., WrightRtOne, R. ti., and Adam%. I?. R . , J. Biol. Chem., 244: 6106, 1969.
Hemoglobin Downloaded from informahealthcare.com by UB Kiel on 11/06/14 For personal use only.
3.
Efremov, C. D.. Huiaiaan, T.H.J.. Bowman. K . , Wrightstone, R. N.. Schroeder, W. A., J. Lab. Clin. Hed., 3: 657, 1974.
4.
Betke, K.,
5.
Carver. F. A., Jones, C. S . , Baker, M. M.. A l t a y , C., Barton, B.. Gravely, H.. and Hui13la11, T.II.J., h e r . J. Hemat., 1: 459. 1977.
Received
Ftarti, 11. R..
June I ,
and S c h l i c h t . I., Nature,
1977; Accopfed Auguot 2, 1977
184:
and
877. 1959.
SHORT COE(MUN1CATION
Hemoglobin Downloaded from informahealthcare.com by UB Kiel on 11/06/14 For personal use only.
HEMOGLOBIN F LEVELS 1 N PATlENTS WITH CHRONIC RtWAL FAII.IIRE
I n a r e c e n t s t u d y Kuratowska and L u t y d s k i ( 1 ) r e p o r t e d e l e v a t e d l e v e l s of Ilb F ( a v e r a g e v a l u e 2.4% w i t h a r a n g e o f 0-10%) in s e v e r a l p a t i e n t s w i t h c h r o n i c r e n a l f a i l u r e . These i n v e s t l g a t o r s s t u d i e d 36 c a s e s , many b e l n g in a t e r m i n a l p h a s e of r e n a l i n s u f f i c i e n c y . A d i r e c t c o r r e l a t i o n o f t h e Ilb F l e v e l w i t h t h e s e v e r l t y of anemia, and t h e conc e n t r a t i o n o f c r r n t i n i n e and urea in t h e serum a p p e a r e d e v i d e n t . In t h i s s h o r t communication w e r e p o r t d n t a o f s i m i l a r i n v e s t i g a t i o n s i n s l x t y t h r e e (63) p a t i e n t s w i t h c h r o n i c r e n a l f a i l u r e ; Ilh F h a s been q u a n t i t a t e d by t w o d i f f e r e n t p r o c e d u r e s . The 63 p a t i e n t s were 28 t o 47 y e a r s o l d . and i n c l u d e d 4 1 m a l e s and 22 f e m a l e s . The m a j o r i t y o f t h e p a t i e n t s had e e v r r e r e n a l i n s u f f i c i e n c y c a u s e d by c h r o n i c g l o m e r u l o n e p h r i t i s ; some had a m o d e r a t e t o w v e r e anemia ( T a b l e I ) . T w e n t y - t h r e e o f t h e 6 3 p a t i e n t s were u n d e r g o i n g p e r i o d i c hemodialysis. The c o n t r o l g r o u p c o n s i s t e d o f 110 h e a l t h y p e r s o n s who p a r t i c i p a t e d i n t e s t i n g programs o f tlir S i c k l e C e l l C e n t e r . Blood s a m p l e s were c o l l e c t e d in v a c u t a i n e r s w i t h EDTA as a n t i c o a g u l a n t t o b e u s e d f o r r o u t i n e hematology and hemoglobin a n a l y s e s . and w t t l i o u t a n a n t i c o a g u l a n t f o r b l o o d c l i e m l s t r y a n a l y s e s . Rocitlne h e m n t o l o g f c a n a l y s e s wrre made w i t h a Model S C o u l t e r C o u n t e r . Hemoglobin i n r e d c e l l h e m o l y s a t e was examined by s t a r c h g e l e l e c t r o p h o r e s i s a t pH 9 . 0 (Z), and by m i c r o c h r o m a t o g r a p h y t o d e t e r m i n e t h e l e v e l of Ilh A 2 ( 3 ) . Ilb F was q u a n t i t a t e d by a n a l k a l i d e n a t u r a t i o n method ( 4 1 , and by a r e c e n t l y d e v e l o p e d r a d i o i m n u n o a s s a y (5): t h e r e s u l t s a r e e x p r e s s e d as %FAD and Blood c h e m i s t r y a n a l y s e s were made by s t a n d a r d %FRIA, r e s p e c t i v e l y . automated procedures. T a b l e I s u n m a r i t e s t h e d a t a . The Ilh F l e v e l s (RR X F R ~ A )o f a 1 1 i n d i v i d u a l p a l i e n t o w i t h Ilb A and o f t h e n o r a a l c o n t r o l s a r e g i v e n i n Fig. 1. T h r e e p a t i e n t s had an abnormal hemoglobin: o n e URR homotygous t l i a l a s s e m i a and a t h i r d had a s i c k l e c e l l t r a i t f o r Ilb S. o n e had Hb S-6' ( T a b l e I ) . The a v e r a g e Hb PRIA l e v e l 6 i n t h e t w o g r o u p s o f p a t i e n t s . namely t h o s e u n d e r g o i n g h e a o d f a l y s i s and t h o s e who d i d n o t , were s l i g h t l y h i g h e r than t h a t of t h e c o n t r o l group; t h e d i f f e r e n c e . h o v e v e r , . i s not s i g n i f i c a n t (FpO.05) m a i n l y b e c a u s e of t h e v i d e r a n g e in v a l u e s i n t h e t h r e e g r o u p s . A few p a t i e n t s had a lib FRIA l e v e l above 1%(1.2: 1.4; 1.65; and 2.5%). b u t a c o r r e l a t i o n b e t v e e n t h e s e i n c r e a s e s and t h e e l e v a t e d l e v e l o f c r e a t i n i n e or t h e s e v e r i t y o f nriemia was not e v i d e n t .
691 Copyright 01977 hy Marcel Dekkec. Inc. All Righlr Reserved Nrilher this work nor any part may he rrprodurrd or transmitted i n any form or hy any nteans, electronic or mrchanicrl. inclaclinl: photocopying, microfilming. and recordin#.or by any inlornulion storage and retrievalsystem. wilhoul permiwicm in wcitinR f r t m !he puhlishec.
SHORT COElENNICATION
692 TABLE I
Mean V a l u e s and Ranges of tlie Hb F L e v e l , t l i e Packed C e l l Volume, and t h e Serum C r e a t i n i n e L e v e l i n P a t i e n t s w i t h C h r o n i c Renal F a i l u r e
Number o f Cases
Clinical Condition*
Ilb Type
37
CRF (undlalyzed)
M
CRP (dialyzed)
M
Hemoglobin Downloaded from informahealthcare.com by UB Kiel on 11/06/14 For personal use only.
23
1
CRF
Hb F** (%FnrA) 0.39
llb F** (%FAD)
PCV
Creatlnlne mgfdl
111
6.2
0.29
0.6
(0.01-2.5) (0-3.4)
(0.18-0.42)
0.38 0.5 (0.02-1.65)(0-2.1)
(0.16-0.42)
(2.7-18.3)
14.3
0.27
(8.6-23.0)
AS
0.04
1.3
0.33
8.0
ss
3.2
2.7
0.16
4.4
13.6
14.2
0.24
5.6
(undlalyzed)
1
CHF (undialyred)
1
S-t)+-Tlaal CRF (undlalyzed)
110 Normal c o n t r o l s
0.27
AA
n.d.***
0.43 (0.34-0.5 3 ) (0-1.4)
(0.01-1.30) ~~
* ** *** ****
CRF XFRIA XFW
n.d.
--
~
~~
~~
~
_
~
****
_
= c h r o n i c renal f a l l u r e .
p e r c e n t Hb F d r t e r m l n e d by radioimmuno a s s a y ( 5 ) . p e r c e n t Hb F d e t e r m i n e d by a l k a l i d e n a t u r a t i o n ( 4 ) . not determlned.
Normal v a l u e s i n o u r l a b o r a t o r i e s .
The only d a t a f o r H b P i n p a t i e n t s w i t h c h r o n i c r e n a l f a l l u r e , r e p o r t e d by o t h e r s ( 1 ) . were o b t a i n e d by a n a l k a l i d e n a t u r a t i o n p r o c e d u r e . T h i s method 1s i n a c c u r a t e a t lw l e v e l s of Hb F (5) a n d , as i n d i c a t e d from t h e c o m p a r i s o n of FAD and FRIA v a l u e s f o u n d i n o u r p a t i e n t s ( F i g . 2 ) . t e n d s t o o v e r e s t i m a t e t h e Ilb F level. Our r e s u l t s o b t a i n e d w i t h t h e more a c c u r a t e radioimmuno a s s a y show t h a t t h e level OP Hb F is n o t s i g n i f i c a n t l y i n c r e a s e d i n t h e s e p a t i e n t s w i t h r e n a l f a i l u r e , and t h u s a r e a c t i v a t i o n of y c h a i n s t r u c t u r a l l o c i does n o t o c c u e in t h i s g r o u p w i t h t h i s chronic condition.
SlIORT COMMUNICATION
693 2 5
20
I 5
8
.
Hemoglobin Downloaded from informahealthcare.com by UB Kiel on 11/06/14 For personal use only.
I .o
09
4
a: 0 . 0 IL
0
a
0.1
0
.. Ir
0.6 0.5
0
0.4
0.3 0.2 0 .I CRF CRF UNDIALYZLD DIALYZED
(n-an
fn-23)
NORMAL CONTROLS
(n-flo)
FIGURE 1 The l e v e l nf f e t a l hemoglobin (XFRIA) in p a t i e n t s with chronic r e n a l f a i l u r e (CRF) and i n normal healthy c o n t r o l s .
694 16
I 4 0
1.2
10
0 4
LL
0
Hemoglobin Downloaded from informahealthcare.com by UB Kiel on 11/06/14 For personal use only.
$ oe 06
0 4
02
I
02
0.4
06
00
10
I2
I4
16
FIGURE 2
A comparison of Lhe l e v e l s uf Hb F (XFAI, v e r s u s XFRIA) In p a t i e n t s w l t l i chronic renal f a i l u r e .
T h l s r e s e a r c h was i n part supported by United S t a t e s P u b l i c l l e a l t h S e r v l c e Research Grants IlLtl-05168 a i d IILB-15158. Departments of H e d l c l n e . C e l l Jnd Molecular E. C . Abraham T. Ozawa B i o l o g y . Comprehensive S i c k l e C e l l Center, Medical C o l l e g e of Georgld. and Veterans G. A . N l a z i Adminiatrat i o n l l o s p i t a l , Augusta. Ca., 30901, J . B . Iludson F . Gamer U.S.A. T.H.J. Huisman
SHORT COMMUNICATION
695 REFERENCES
1. Kurntowska. Z. and Lutybski. A . , E r y t l i r o p n i e s i s , Eds. Nnkao, K.. F i s h e r , J. W., and TnkIku, F., U n i v e r s i t y Pnrk Press, BnLtimore (London/Tokyo), 397. 1974. 2.
Efremov. G. D.. Huisman, T.1l.J.. Smith, L. I.., Wilson. J . B.. Kitchens. J . L., WrightRtOne, R. ti., and Adam%. I?. R . , J. Biol. Chem., 244: 6106, 1969.
Hemoglobin Downloaded from informahealthcare.com by UB Kiel on 11/06/14 For personal use only.
3.
Efremov, C. D.. Huiaiaan, T.H.J.. Bowman. K . , Wrightstone, R. N.. Schroeder, W. A., J. Lab. Clin. Hed., 3: 657, 1974.
4.
Betke, K.,
5.
Carver. F. A., Jones, C. S . , Baker, M. M.. A l t a y , C., Barton, B.. Gravely, H.. and Hui13la11, T.II.J., h e r . J. Hemat., 1: 459. 1977.
Received
Ftarti, 11. R..
June I ,
and S c h l i c h t . I., Nature,
1977; Accopfed Auguot 2, 1977
184:
and
877. 1959.
