Download - Hiper fosfat
-
8/13/2019 Hiper fosfat
1/44
Hyperphosphatemia
and CKD progression
in predialysis patients
Dr. Y.W.J. Sijpkens, internist-nephrologist
Dept. of Nephrology
eiden !ni"ersity #edi$al Center,the Netherlands
-
8/13/2019 Hiper fosfat
2/44
2
Herman %oerhaa"e &'(()-'*+)
Professor in Medicine, Leiden University
-
8/13/2019 Hiper fosfat
3/44
3
Hyperphosphatemia1.
2. PREPARE PREdialysis PAtient REcord study
4. Hyer!os!ate"ia ro#ression factor
$. Hyer!os!ate"ia cardiovascular ris% factor
&. 'ti"al redialysis care !os!ate reduction
-
8/13/2019 Hiper fosfat
4/44
ormer definition predialysis
(reatinine clearance ) 2* "l+"in
eed of dialysis anticiated -it!in $12 "ont!s
P!ysician /ased education on dialysis "odalities
4
-
8/13/2019 Hiper fosfat
5/44
0
/01/0 2 predialysis patients
PREdialysis PAtients REcord study Retrosectiveco!ort study
Preare study #rou r. .. e%%er, LUM(5
& dialysis centers
046 incident redialysis atients 17772**15 follo- u until start of RR8, deat! or 1+1+2**0
data collection Hans Ma% 9nstitute
entry, e:it and renal function ara"eters
;onsored /y an unrestricted #rant fro" AM
-
8/13/2019 Hiper fosfat
6/44
P!os!ate levels availa/le
1.06 ""ol+l
2.31 ""ol+l
3.$3
-
8/13/2019 Hiper fosfat
7/446
/01/0 2 time to //3
Median follo-u ti"e= 336 days ran#e 3114425.
S4r"i"al and //3 free s4r"i"al
5 ( '6 ') 67 +5 +( 76 7)5.55
5.68
5.85
5.*8
'.55
start of RR8 1H2, P2, 8:5deat! on redialysis care
#onths on predialysis $are
-
8/13/2019 Hiper fosfat
8/44&
Proteinuria
Hyer#lyce"ia
Hyerurice"ia
Hyertension
'/esity
;"o%in#
>idney failure
-
8/13/2019 Hiper fosfat
9/447
hosphate 2 progression fa$tor9
-
8/13/2019 Hiper fosfat
10/441*
/01/0 2 progression fa$tors
actors, resent at t!e start of redialysis care,indeendently related /y linear re#ression to decline in renal
function, assessed as t!e sloe of MR clearances
"edian 6 ran#e 2445
youn#er a#e
!i#!er creatinine clearance
!i#!er systolic /lood ressure
"ore roteinuria
high phosphate
-
8/13/2019 Hiper fosfat
11/44
11
/01/0 2 phosphate le"els
!yer!os!ate"ia!yer!os!ate"ia lo-er
-
8/13/2019 Hiper fosfat
12/44
12
/01/0 2 &4nder4se of medi$ation/01/0 2 &4nder4se of medi$ation
9n t!e atients -it! a nor"al las"a !os!ate level 07B -ere rescri/ed a
!os!ate/indin# dru#, in t!e !yer!os!atae"ic atients $&B
n:87* entry e;it
&
-
8/13/2019 Hiper fosfat
13/44
13
hosphate - de$line in renal f4n$tione!rol. ial. 8ranslant. 2**6
or eac! "#+dl !i#!er !os!ate concentration, t!e "ean 70B (95
decline in renal function increased -it! *.104 *.*61*.2365 "l+"in+"ont!.
-
8/13/2019 Hiper fosfat
14/44
14
%aseline phosphate - de$line in renal f4n$tion
8!e "ean value of las"a !os!ate in t!e first t!ree "ont!s of redialysis
care -as also indeendently associated -it! decline of function
Patients -it! nor"aliCation of !os!ate in 3 "ont!s s!o-ed an
i"rove"ent in t!e decline in function, -!ereas an increase in
!os!ate -as associated -it! a steeer decline in renal function
-
8/13/2019 Hiper fosfat
15/44
(lin D A" ;oc e!rol 2**$?1=&20&31
-
8/13/2019 Hiper fosfat
16/44
hosphate - interstitial $rystalliation9
(linical science 2**4?1*$ =047$1
-
8/13/2019 Hiper fosfat
17/44
Ure"ic rats !i#!!os!orus diet 3B sevela"er=
Reduction of foci of calcification and de#ree of tu/ulointerstitial fi/rosis
-
8/13/2019 Hiper fosfat
18/44
1&
hosphate - de$line in renal f4n$tion
(onfoundin# factors !yer!os!ate"ia arterial calcification !i#! ulse ressure, nondiin#FRR
vita"in deficiency infla""ation, roteinuria
!yerarat!yroidis" !i#! calciu" : !os!ate
rotein inta%e !i#! P(R
sodiu" inta%e !yertension, roteinuria
urine, fructose inta%e !yerurice"ia
calory inta%e o/esity
nicotine inta%e s"o%in#
-
8/13/2019 Hiper fosfat
19/44
17
Hyperphosphatemia and non-dipping hypertension
17* !yertensive su/ects -it! nor"al renal function? indeendent redictors
for non diin# !yertension $*B5 -ere P8H and !os!ate
A" D e!rol 2**6?26=01$
-
8/13/2019 Hiper fosfat
20/44
2*
hosphate and mortality
(rude "ortality ris% -as 1.20 *.&01.&45 er "#+dl increase in!os!ate, -!ic! increased to 1.$2 1.*22.075 after adust"ent for a#e,
se:, e
-
8/13/2019 Hiper fosfat
21/44
>esten/au", G. et al. D A" ;oc e!rol 2**0?1$=02*02&
-
8/13/2019 Hiper fosfat
22/44
228onelli, M. et al. (irculation 2**0?112=2$262$33
-
8/13/2019 Hiper fosfat
23/44
hosphate 2 "as$4lar $al$ifi$ation
Ca2+-binding proteins
(osteocalcin, osteopontin)
Na+ NPC
PO4-
Pi
Human aortic
smooth muscle cell (SMC)
BIOAPATITE
atri! "esicles
Cb#a-$ % core-binding #actor-$
(central transcription #actor #or osteogenic di##erentiation)
Cb#a-$
&C-genes
Al'aline pase
Collagen-ric
e!tracell*lar
atri!
-
8/13/2019 Hiper fosfat
24/44
24
/01/0 prospe$ti"e 2 st4dy design
"ulticenter rosectiveco!ort study et!erlands inclusion criteria
c!ronic %idney disease sta#e 9 ) 3* "l+"in5
redialysis care
inclusion until 0** atients,follo- u until start RR8, deat! or end of study
entry, follo-u si: "ont!s5 and e:it ara"eters
data collection Hans Ma% 9nstitute
endoints= decline in function, cardiovascular events,"ortality, Iuality of life
-
8/13/2019 Hiper fosfat
25/44
20
/01/0 - $on$l4sions
9ncident utc! redialysis atients 17772**15 !ad a "eanMR clearance of 13 "l+"in at entry and a "edian ti"e to
RR8 of 11 "ont!s -it! a lar#e ran#e.
Hyer!os!ate"ia -as found to act as
an indeendent (> ro#ression factor.
Hyer!os!ate"ia -as related -it!
an increased "ortality ris%
Prevention of !yer!os!ate"ia "i#!t i"rove renal and
cardiovascular outco"e.
-
8/13/2019 Hiper fosfat
26/44
2$
3oards E?etterF predialysis $are
-
8/13/2019 Hiper fosfat
27/44
26
!#C 2 $on$ept predialysis $lini$
Led /y nurse ractioner P5 (> 4, decline in function, candidate RR8
Gaseline visit 1 !our
Alternatin# visits P and ne!rolo#ist
(> action lan Predialysis #uidelines Masterlan, LUM(5
(o""unication /y Mirador, ia"ant, M'
Particiation in studies PREPARE, Masterlan5
-
8/13/2019 Hiper fosfat
28/44
2&
atient $entered, m4ltidis$iplinary $are
-
8/13/2019 Hiper fosfat
29/44
AD> 2**4?44=6*$
'lder a#e, ( and lac% of redialysis care indeendently redicted deat!
-
8/13/2019 Hiper fosfat
30/44
3*
CKD a$tion plan
-
8/13/2019 Hiper fosfat
31/44
31
#4ltifa$torial, target dri"en
GloodressureGloodressure systolic RR ) 14* ""H#systolic RR ) 14* ""H# Al/u"inurieAl/u"inurie A(R ) 3* "#+""olA(R ) 3* "#+""ol
(!olesterol(!olesterol LL ) 2.$ ""ol+lLL ) 2.$ ""ol+l
;odiu" inta%e;odiu" inta%e a urine5 ) 1** ""ol+daya urine5 ) 1** ""ol+day
Uric acidUric acid uric acid ) *.3$ ""ol+luric acid ) *.3$ ""ol+l (!olecalciferol(!olecalciferol 20'H5 J 60 n"ol+l20'H5 J 60 n"ol+l
P!os!ateP!os!ate P ) 1.0 ""ol+lP ) 1.0 ""ol+l
(alciu"(alciu" (a ) 2.4 ""ol+l(a ) 2.4 ""ol+l
P8HP8H P8H 612 "ol+lP8H 612 "ol+l He"o#lo/inHe"o#lo/in H/ 6& ""ol+lH/ 6& ""ol+l
AcidosisAcidosis /icar/onate J 22 ""ol+l/icar/onate J 22 ""ol+l
E:erciseE:ercise J 0 days, J 3* "inutesJ 0 days, J 3* "inutes
;"o%in#;"o%in# * ci#arettes* ci#arettes
-
8/13/2019 Hiper fosfat
32/44
32
!#C 2 o4t$ome parameters 655(
-
8/13/2019 Hiper fosfat
33/44
hosphate ?alan$e
33
-
8/13/2019 Hiper fosfat
34/44
34
Hyperphosphatemia 2 treatment
P!os!ate restriction ) 1*** "#+day
P!os!ate /inders (alciu"car/onate+acetateK ) 10** "#+day5
;evela"er R+Rena#el5
Lant!anu"car/onate R+P!osrenol5
-
8/13/2019 Hiper fosfat
35/44
30
hosphate restri$tion 2 .dieeti$ht.nl
-
8/13/2019 Hiper fosfat
36/44
hosphate ?inders - adheren$e
3$
AHERE(E
-
8/13/2019 Hiper fosfat
37/44
CKD 2 $hroni$ inflammatory syndrome
36
-
8/13/2019 Hiper fosfat
38/44
Hyperphosphatemia 2 pathogenesis9
9nfla""atie
-
8/13/2019 Hiper fosfat
39/44
37
Hyperphosphatemia 2 treatment
'ti"iCin# /one !ealt! to reduce calcifications ita"in
(!olecalciferol
Alfacalcidol
Paricalcitol
Antiinfla""atory strate#ies E:cercise
RAA; /loc%ade
;tatins
;evela"erK
'ti"iCin# renal function Preservation residual renal function
Pree"tive translantation
-
8/13/2019 Hiper fosfat
40/44
4*
!#C 2 preempti"e transplantation
G
H
IG
IHJG
JH
KG
KH
LG
pro?a?ilityofpreempti"e3;
Year of transplantation
i"ing donation
fa"
lurd
;!ar increase in ree"tive livin# un5related donor translantation
-
8/13/2019 Hiper fosfat
41/44
41
/01/0 2 fa$tors related to late referral
(onsider ti"ely referral in atients -it! cystic disease, dia/etic ne!roat!y,
ro#ressive decline, ane"ia, !yer!os!ate"ia, lo- al/u"in
>/for less than ( months predialysis $areM =8
-
8/13/2019 Hiper fosfat
42/44
8 2**1?1$=2306
Predialysis care ) $ "., dia/etes, rior ( -ere indeendent redictors
-
8/13/2019 Hiper fosfat
43/44
43
>ptimal predialysis $are
(> sta#e 4 action lan
Prevention of decline in renal function P!os!ate reduction
Prevention of "eta/olic co"lications ;HP85
P!os!ate reduction Prevention of cardiovascular disease calcifications5
P!os!ate reduction
Ai" for ree"tive translantation
P!os!ate reduction Evidence/ased "ultidiscilinary redialysis clinic
-
8/13/2019 Hiper fosfat
44/44
redialysis $are - target medi$ine 2 '.8mmol@l