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8/13/2019 Hiper fosfat

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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


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2

Herman %oerhaa"e &'(()-'*+)

Professor in Medicine, Leiden University


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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


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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


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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


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P!os!ate levels availa/le

1.06 ""ol+l

2.31 ""ol+l

3.$3


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/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


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Proteinuria

Hyer#lyce"ia

Hyerurice"ia

Hyertension

'/esity

;"o%in#

>idney failure


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hosphate 2 progression fa$tor9


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/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


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/01/0 2 phosphate le"els

!yer!os!ate"ia!yer!os!ate"ia lo-er


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/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

&


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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!.


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%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


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(lin D A" ;oc e!rol 2**$?1=&20&31


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hosphate - interstitial $rystalliation9

(linical science 2**4?1*$ =047$1


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Ure"ic rats !i#!!os!orus diet 3B sevela"er=

Reduction of foci of calcification and de#ree of tu/ulointerstitial fi/rosis


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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#


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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$


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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


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>esten/au", G. et al. D A" ;oc e!rol 2**0?1$=02*02&


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228onelli, M. et al. (irculation 2**0?112=2$262$33


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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!


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/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


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/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.


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2$

3oards E?etterF predialysis $are


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!#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


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2&

atient $entered, m4ltidis$iplinary $are


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AD> 2**4?44=6*$

'lder a#e, ( and lac% of redialysis care indeendently redicted deat!


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3*

CKD a$tion plan


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#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


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!#C 2 o4t$ome parameters 655(


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hosphate ?alan$e

33


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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


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hosphate restri$tion 2 .dieeti$ht.nl


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hosphate ?inders - adheren$e

3$

AHERE(E


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CKD 2 $hroni$ inflammatory syndrome

36


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Hyperphosphatemia 2 pathogenesis9

9nfla""atie


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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


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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


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/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


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8 2**1?1$=2306

Predialysis care ) $ "., dia/etes, rior ( -ere indeendent redictors


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>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


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redialysis $are - target medi$ine 2 '.8mmol@l

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