Upload
arsy-mira-pertiwi
View
216
Download
0
Embed Size (px)
Citation preview
8/11/2019 Hypertention in Diabetic Kidney Disease
http://slidepdf.com/reader/full/hypertention-in-diabetic-kidney-disease 1/42
FOCUS ON ARB
Dr. I Gede Palgunadi, Sp.PD
1 September 2009
8/11/2019 Hypertention in Diabetic Kidney Disease
http://slidepdf.com/reader/full/hypertention-in-diabetic-kidney-disease 2/42
The World HealthOrganisation (WHO)Estimates
Prevalence of HypertensionThat >20% of The Worlds
!"rrent #d"lt Pop"lation HasHypertension
8/11/2019 Hypertention in Diabetic Kidney Disease
http://slidepdf.com/reader/full/hypertention-in-diabetic-kidney-disease 3/42
8/11/2019 Hypertention in Diabetic Kidney Disease
http://slidepdf.com/reader/full/hypertention-in-diabetic-kidney-disease 4/42
8/11/2019 Hypertention in Diabetic Kidney Disease
http://slidepdf.com/reader/full/hypertention-in-diabetic-kidney-disease 5/42
BLOOD PRESSURE CONTROL
GOALGOAL
Less than 140/90 mm Hg
orLess than 130/80 mm Hg
(diabetes)
orLess than 125/75 mm Hg
(rotein !ria "1g/da#)
1999 WHO/ISH Hypertension Guidelines. J Hypertens 1999;17:151-183! "osition St#te$ent. !i#%etes &#re '((';'5:S33-S)9
8/11/2019 Hypertention in Diabetic Kidney Disease
http://slidepdf.com/reader/full/hypertention-in-diabetic-kidney-disease 6/42
Total cases > 43 million adults
Prevalence of diabetes in Western
Pacific Region in 2003
International Diabetes Federation. Diabetes Atlas. 2nd Edition.www.eatlas.idf.org. Accessed 27 October 2!!".
Australia
".2#
!.$ million
%ew &ealand
7."#
!.2 million
'(ina
2.7#23.) million
Indonesia
*.$#
2.+ million
,ala-sia
$.4#*.3 million
a/an
".$#
".7 million
0(ili//ines
2.4#
*.! million
8/11/2019 Hypertention in Diabetic Kidney Disease
http://slidepdf.com/reader/full/hypertention-in-diabetic-kidney-disease 7/42
Ada/ted from 1O Diabetes 0rogramme Facts and Figures www.w(o.intdiabetesfactsworld5figuresen. Accessed * August 2!!".
Worldwide prevalence of
diabetes in 2000
%umber of /ersons6 +!!!
+!!!74!!!
7+!!!34$!!!
3+!!!!*4$$!!!
*+!!!!!4$$$!!!
> +!!!!!!
%o data a8ailable
8/11/2019 Hypertention in Diabetic Kidney Disease
http://slidepdf.com/reader/full/hypertention-in-diabetic-kidney-disease 8/42
Worldwide prevalence of
diabetes in 2030 (projected)
Total cases > 3!! million adults
%umber of /ersons6 +!!!
+!!!74!!!
7+!!!34$!!!
3+!!!!*4$$!!!
*+!!!!!4$$$!!!
> +!!!!!!
%o data a8ailable Ada/ted from 1O Diabetes 0rogramme Facts and Figures www.w(o.intdiabetesfactsworld5figuresen. Accessed * August 2!!".
8/11/2019 Hypertention in Diabetic Kidney Disease
http://slidepdf.com/reader/full/hypertention-in-diabetic-kidney-disease 9/42
8/11/2019 Hypertention in Diabetic Kidney Disease
http://slidepdf.com/reader/full/hypertention-in-diabetic-kidney-disease 10/42
8/11/2019 Hypertention in Diabetic Kidney Disease
http://slidepdf.com/reader/full/hypertention-in-diabetic-kidney-disease 11/42
8/11/2019 Hypertention in Diabetic Kidney Disease
http://slidepdf.com/reader/full/hypertention-in-diabetic-kidney-disease 12/42
hat is Diabetic Nephropathy?
Diabetic ne/(ro/at(- 9a term often used
interc(angeabl- wit( ‘diabetic kidney disease’
is a c(ronic /rogressi8e :idne- disease t(at de8elo/s
in ab!ut !ne t"ird of all /eo/le wit( diabetes
8/11/2019 Hypertention in Diabetic Kidney Disease
http://slidepdf.com/reader/full/hypertention-in-diabetic-kidney-disease 13/42
What is Diabetic Nephropathy?
The signs of diabetic nephropathy are:The signs of diabetic nephropathy are:
• Rising urine albumin and protein excretionRising urine albumin and protein excretion
• Rising blood pressureRising blood pressure
• Declining kidney functionDeclining kidney function
This is associated with:This is associated with:
• A greatly increased risk of cardiovascular A greatly increased risk of cardiovascular
diseasedisease
• An increased risk of diabetic eye disease An increased risk of diabetic eye disease
(retinopathy)(retinopathy)
• An increased risk of diabetic nerve damage An increased risk of diabetic nerve damage
(neuropathy)(neuropathy)
8/11/2019 Hypertention in Diabetic Kidney Disease
http://slidepdf.com/reader/full/hypertention-in-diabetic-kidney-disease 14/42
Screening of microalbuminuria in patients with type
2 DM
$orma% &i'roa%b!min
!ria
%ini'a% *o+ert,
nehroath#
24 h !rinar#
a%b!min (mg/da#)-30 30300 "300
.A (µg/min) -20 20200 "200
.rine a%b!min
'reatinine ratio
-25 &a%es
-35 ema%es
1025 "25
!onnelly *!+ ,eun J&+ #nnin G. J Hypertens '((3;'1 suppl 10:S7-S1'
8/11/2019 Hypertention in Diabetic Kidney Disease
http://slidepdf.com/reader/full/hypertention-in-diabetic-kidney-disease 15/42
t!d# o!%ation re+a%en'e
.A1 6iabetes 29
Asian2 6iabetes and
h#ertension
40
nternationa%
(33 'o!ntries)3
6iabetes 39
L4
H#ertension and L:H 23
1. Jones & et #l. $ J idney !is '((';39:))5-59
'. Wu , et #l. !i#%etoloi# '((5;)8:17-'2
3. "#rin HH et #l. idney Int in press0). 4eldsen S et #l. J '((';'88:1)91-8
:AL$ O &OAL;.&$.A
8/11/2019 Hypertention in Diabetic Kidney Disease
http://slidepdf.com/reader/full/hypertention-in-diabetic-kidney-disease 16/42
StageStage Time after diagnosis ofTime after diagnosis of
diabetesdiabetes
FunctionFunction
Normal Normal !"# years!"# years • $ormal urine protein$ormal urine proteinexcretionexcretion
• $ormal blood$ormal blood
pressurepressure
• $ormal or high$ormal or high
kidney functionkidney function
Early kidney Early kidney
diseasedisease
#!"# years#!"# years • %icroalbuminuria%icroalbuminuria
• Slight increase inSlight increase in
blood pressureblood pressure
• $ormal kidney$ormal kidney
functionfunction
Proteinuria Proteinuria "!& years"!& years • 'igh levels of urine'igh levels of urineproteinprotein
• 'igh blood pressure'igh blood pressure
• Failing kidneyFailing kidney
functionfunction
End-stage disease End-stage disease "#! years"#! years • ery high urine ery high urineproteinprotein
Stages in the development of diabetic nephropathy
8/11/2019 Hypertention in Diabetic Kidney Disease
http://slidepdf.com/reader/full/hypertention-in-diabetic-kidney-disease 17/42
8/11/2019 Hypertention in Diabetic Kidney Disease
http://slidepdf.com/reader/full/hypertention-in-diabetic-kidney-disease 18/42
,ETA;O<I' AE,OD=%A,I'
lucose Flow /ressure
?asoacti8e
(ormones
9egAII endot(elin@
0' II
Ad8anced
gl-cation
'-to:ines
TF ?EF
↑E',
cross lin:ing↑
E',
E', A''B,B<ATIO%
↑
?ascular /ermeabilit-
0COTEI%BCIA
,etabolic dan (aemod-namic /at(ogenesis
of diabetic ne/(ro/at(-
8/11/2019 Hypertention in Diabetic Kidney Disease
http://slidepdf.com/reader/full/hypertention-in-diabetic-kidney-disease 19/42
A$GO<$$ <O ;LO= ( A; )A$GO<$$ <O ;LO= ( A; )
$e> tandard Antihiertensi erorman'e$e> tandard Antihiertensi erorman'e
A$GO<$$ <O ;LO= ( A; )A$GO<$$ <O ;LO= ( A; )
$e> tandard Antihiertensi erorman'e$e> tandard Antihiertensi erorman'e
8/11/2019 Hypertention in Diabetic Kidney Disease
http://slidepdf.com/reader/full/hypertention-in-diabetic-kidney-disease 20/42
RENOROTE!T"ON
• Ceduction of blood /ressure
• Ceduction of albuminuria
• %on blood /ressure de/endent action of
CAA bloc:ade
J Am oc !ep"rol #3$202%20&' 2002
8/11/2019 Hypertention in Diabetic Kidney Disease
http://slidepdf.com/reader/full/hypertention-in-diabetic-kidney-disease 21/42
Formation of
Angiotensin and
organs effected b-
t(eir actions
% Eng ,ed ?ol. 334
%O. 2+ *$$"
8/11/2019 Hypertention in Diabetic Kidney Disease
http://slidepdf.com/reader/full/hypertention-in-diabetic-kidney-disease 22/42
?erent " a?erent arterio%ar di%atation
A?erent " e?erent arterio%ar di%atation
↑ G%omer!%ar 'ai%%ar# ress!re(G)
↓ G%omer!%ar 'ai%%ar# ress!re(G)
Calcium Channel
Blockers
ACE inhibitors
6olins J"+ *#i4 . Se$in eprol 1991;11:538-)8
8/11/2019 Hypertention in Diabetic Kidney Disease
http://slidepdf.com/reader/full/hypertention-in-diabetic-kidney-disease 23/42
#T $#T $
#""R%
#T & #T &
A'E in(ibitor
Ang
Ang
'(-maseAng ↓ ;rad-:inin ↑
%O
0I2
• ?asoconstriction• Cenal sodium reabso/tion
• Aldosteron secretion
• -m/at(etic acti8ation
• 'ell growt( and /roliferation
• ?asodilatation
• Anti/roliferation
• A/o/tosis
8/11/2019 Hypertention in Diabetic Kidney Disease
http://slidepdf.com/reader/full/hypertention-in-diabetic-kidney-disease 24/42
=6$@ O<<O$ <=6$@ O<<O$ <
O A$GO<$$ <OO A$GO<$$ <O
;LO=;LO=
=6$@ O<<O$ <=6$@ O<<O$ <
O A$GO<$$ <OO A$GO<$$ <O
;LO=;LO=
8/11/2019 Hypertention in Diabetic Kidney Disease
http://slidepdf.com/reader/full/hypertention-in-diabetic-kidney-disease 25/42
8/11/2019 Hypertention in Diabetic Kidney Disease
http://slidepdf.com/reader/full/hypertention-in-diabetic-kidney-disease 26/42
A PRogram for Irbesartan Mortality and Morbidity Evaluation
Parving %' et al N Engl J Med 200#*3+,$-&0%-&-
8/11/2019 Hypertention in Diabetic Kidney Disease
http://slidepdf.com/reader/full/hypertention-in-diabetic-kidney-disease 27/42
A PRogram for Irbesartan Mortality and Morbidity Evaluation
8/11/2019 Hypertention in Diabetic Kidney Disease
http://slidepdf.com/reader/full/hypertention-in-diabetic-kidney-disease 28/42
Ob'ective :
• To e8aluate t(e AIICA irbesartan (as reno/rotecti8e
effects inde/endent of its im/act on s-stemic ;0 in
(-/ertensi8e t-/e 2 diabetic /atients wit(
/ersistent microalbuminuria
8/11/2019 Hypertention in Diabetic Kidney Disease
http://slidepdf.com/reader/full/hypertention-in-diabetic-kidney-disease 29/42
St(dy Design :
• ,ulticenter randomied doubleGblind /laceboG
controlled com/arison or irbesartan *+! mg and 3!!
mg 8ersus control 9/lacebo /lus ot(er
anti(-/ertensi8e agents eHcluding A'E in(ibitorsAIICAs and di(-dro/-ridine '';s@.
• +$! /atients wit( t-/e 2 diabetes microalbuminuria
92!G2!!µ
gmin@ normal renal function and(-/ertension were followed for an a8erage of 2 -ears.
8/11/2019 Hypertention in Diabetic Kidney Disease
http://slidepdf.com/reader/full/hypertention-in-diabetic-kidney-disease 30/42
rimary Endpoint :
• Time to first occurrence of clinical
/roteinuria 9diabetic ne/(ro/at(-@ defined
as albumin eHcretion rate 9AEC@ > 2!!µ
gminand an increase in AEC of at least 3!# from
baseline at 2 successi8e e8aluations
8/11/2019 Hypertention in Diabetic Kidney Disease
http://slidepdf.com/reader/full/hypertention-in-diabetic-kidney-disease 31/42
Secondary Endpoints :
• O8ernig(t AEC c(anges
• Estimated creatinine clearance c(anges
• Cegression to normoalbuminuria 96 2! µgmin@
at 2 -ears 9#@
8/11/2019 Hypertention in Diabetic Kidney Disease
http://slidepdf.com/reader/full/hypertention-in-diabetic-kidney-disease 32/42
RES)*TS :
• ignificant reduction in t(e /rogression toclinical /roteinuria
• ignificant increase in t(e number of /atients
regressing to normoalbuminuria 934# irbesartan3!! mg 2*# control /!.!!"@
• imilar le8els of ;0 reduction across all
treatment arms
• Irbesartan was safe and well tolerated
8/11/2019 Hypertention in Diabetic Kidney Disease
http://slidepdf.com/reader/full/hypertention-in-diabetic-kidney-disease 33/42
33
0
,
#0
#,
20
0 3 . #2 #- 22 2+/ollow%p (mo)
bjects
(1)
ontrol
rbesartan #,0 mg
rbesartan 300 mg
0rimar- End/oint Anal-sis in IC,A 2Time to First Occurrence of 'linical 0roteinuria
Parving %' et al N Engl J Med 200#*3+,$-&0%-&-
8/11/2019 Hypertention in Diabetic Kidney Disease
http://slidepdf.com/reader/full/hypertention-in-diabetic-kidney-disease 34/42
A PRogram for Irbesartan Mortality and Morbidity Evaluation
8/11/2019 Hypertention in Diabetic Kidney Disease
http://slidepdf.com/reader/full/hypertention-in-diabetic-kidney-disease 35/42
Ob'ective :
• To determine w(et(er t(e in(ibition of angiotensin II
acti8it- wit( t(e AIICA irbesartan alters t(e
/rogression of t-/e 2 diabetic ne/(ro/at(-
inde/endent of its im/act on s-stemic ;0
8/11/2019 Hypertention in Diabetic Kidney Disease
http://slidepdf.com/reader/full/hypertention-in-diabetic-kidney-disease 36/42
St(dy Design :
• ,ulticenter randomied doubleGblind /laceboG
controlled com/arison or irbesartan t(e '';
amlodi/ine and control 9/lacebo /lus ot(er
anti(-/ertensi8e agents eHcluding A'E in(ibitorsAIICAs and di(-dro/-ridine '';s@.
• *7*+ /atients wit( t-/e 2 diabetes /roteinuria ≥ $!!
mgd and (-/ertension were followed for an a8erageof 2 -ears.
8/11/2019 Hypertention in Diabetic Kidney Disease
http://slidepdf.com/reader/full/hypertention-in-diabetic-kidney-disease 37/42
rimary Endpoint :
• Time to t(e doubling of baseline serum
ceratinine 9e'r@ le8el or endGstage renal
disease 9ECD@ defined as t(e need fordial-sis or renal trans/lant or e'r > ".!
mgd<@ or allGcause mortalit-
8/11/2019 Hypertention in Diabetic Kidney Disease
http://slidepdf.com/reader/full/hypertention-in-diabetic-kidney-disease 38/42
Secondary Endpoints:
Time to com/osite end/oint of fatal or nonfatal '?e8ents
• '? deat(
• %onfatal ,I
• os/italiation for (eart failure
• 0ermanent neurologic deficit due to stro:e
• Abo8eGt(eGan:le am/utation
8/11/2019 Hypertention in Diabetic Kidney Disease
http://slidepdf.com/reader/full/hypertention-in-diabetic-kidney-disease 39/42
Res(lts :
• ignificant reduction in t(e /rogression of diabetic
ne/(ro/at(-
• ignificant reduction in t(e ris: of '? e8ents
across all treatment arms
• ignificant reduction in (os/italiation due to (eart
failure 8s amlodi/ine 9P 6!.!!*@
• imilar le8el of ;0 reduction across all treatmentarms
• Irbesartan was safe and well tolerated
8/11/2019 Hypertention in Diabetic Kidney Disease
http://slidepdf.com/reader/full/hypertention-in-diabetic-kidney-disease 40/42
bjects (1)
0 . #2 #- 2+ 30 3. +2 +- ,+
/ollow%p (mo)
.0
0
#0
20
30
+0
,0
.0
&0
rimary Endpoint #nalysis in "DNTTime to Doubling of erum 'reatinine ECD or Deat(
rbesartan
Amlodipine
ontrol
4ewis 5J et al N Engl J Med 200#*3+,$-,#%-.0
CCC 2!#
P !.!2P %
CCC 23#
P !.!!"
8/11/2019 Hypertention in Diabetic Kidney Disease
http://slidepdf.com/reader/full/hypertention-in-diabetic-kidney-disease 41/42
!ON!*)S"ON
T(e results of 0CI,E demonstrate t(at t(e
AIICA IC;EACTA% (as /rotecti8e effects for/atients wit( (-/ertension and t-/e 2
diabetes at earl- and late stages of renal
disease inde/endent of t(e effects on ;0.
8/11/2019 Hypertention in Diabetic Kidney Disease
http://slidepdf.com/reader/full/hypertention-in-diabetic-kidney-disease 42/42