hypertention in diabetic kidney disease

8/11/2019 Hypertention in Diabetic Kidney Disease

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FOCUS ON ARB

Dr. I Gede Palgunadi, Sp.PD

1 September 2009



The World HealthOrganisation (WHO)Estimates

Prevalence of HypertensionThat >20% of The Worlds

!"rrent #d"lt Pop"lation HasHypertension



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



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



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



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!!".



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



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)



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'



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



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



,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(-



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



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



Formation of

Angiotensin and

organs effected b-

t(eir actions

% Eng ,ed ?ol. 334

%O. 2+ *$$"



?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



#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



=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=



A PRogram for Irbesartan Mortality and Morbidity Evaluation

Parving %' et al N Engl J Med 200#*3+,$-&0%-&-



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



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.



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



Secondary Endpoints :

• O8ernig(t AEC c(anges

• Estimated creatinine clearance c(anges

• Cegression to normoalbuminuria 96 2! µgmin@

at 2 -ears 9#@



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



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%-&-



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



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.



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-



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



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



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 !.!!"



!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.

hypertention in diabetic kidney disease

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