KMA DIABETIC NEPHROPATHY - SLIDES OF THE YEAR.pptx

8/15/2019 KMA DIABETIC NEPHROPATHY - SLIDES OF THE YEAR.pptx

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Diabetic Kidney Disease

Professor S.O. McLigeyo

Consultant Physician andNephrologist


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Diabetes: the most common causeof ESRD

Primary diagnosis for patients who start dialysis

United States Renal Data S stem 200

No. of patients

95% C

!9"# !9"" !992 !99$ 2000 200# 200"0

!00

20000

#00

500

$00

&00

r 2'99."%2# (52#

2"!( 55 520(2#0

No. of dialysispatients

)tho*sands+

Dia,etes50.!%

-ypertension2&%

lomer*lonephritis

! %

/ther

!0%


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Change in the pattern of diabetickidney disease

Chroni glomer*lonephritis

Dia,eti nephropathy

"0

0

$0

2000

20

#0

200"

Per ent of all patients

1ear 200! 2002 200 200# 2005 200&200$


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8/145Carl ri 3ogensen


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Natural History of Type 2Diabetic Nephropathy

Rising serumcreatinine le els

!roteinuria

End"stagerenal disease

Clinical type 2 diabetes

#unctional changes$

Structural changes %

Rising blood pressure

Cardio ascular death

&icroalbuminuria

'nset of diabetes 2 ( )* 2* +* ,ears

4 idney si6e ↑( short7term 8R ↑, long7term 8R ↓ .

:3 thi ;ening ↑( mesangial e?7.


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16/1458ole et al Diabetolo ia !9

p ' 0.0# p @ 0.0000!

p ' 0.00

Diabetic ESRD patients are at particularly highrisk of cardio ascular complications

"

!"

2#

50

2

#"

Con entriAB-

s haemiheart disease

Cardiafail*re

Non7dia,eti SRDDia,eti SRDPre=alen e at initiation of dialysis )%+$0

#0

0

20

!0

0

50


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2"year mortality

)-*

*-.

*-/

*-0

*-1

*-(* 1 )2 )/ 2

Diabetics3n4/)5

Non"diabetics3n4)..5

&onths

Sur i alrate

2"year sur i al

*6

)*6

2*6

+*6

*6

(*6

Non"diabeticsDiabetics

C7 mortality Total

mortality

).6

26

))6

+)6

&ortality among HDpatients


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!roteinuria !redicts Stroke andCHD E ents in Type 2 Diabetes

U7Prot ' Urinary protein on entration.3iettinen - et al. Stroke- !99$ 2& 20 720 9.

)

*-.

*-/

*-0

*-1

*-(

** )* 2* +* * (* 1* 0*/* .*

S u r

i a

l c u r e s

f o r

C 7

m o r t a

l i t y

&onths

89

C' erall: p *-**)

8: ;"!rot )(* mg


19/1453atto ; et al Diabetes !99

Ell a*se C-D Stro;e /ther 3i roal,*min*ria)n' &+

!" )#9%+ ! )&2%+ 2 )!!%+ )!&%+

Normoal,*min*ria)n'!09+

!" )!&%+ & ) 9%+ 0 )0%+ !! )$!%+

Aithand Aithout

microalbuminuria


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Conclusions

@n subBects Aith type 2 diabetes andhypertension but Aith normoalbuminuriathe use of trandolapril plus erapamil and

trandolapril alone decreased the incidence ofmicroalbuminuria to a similar e tent- The

e ect of erapamil alone Aas similar to thatof placebo


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0

5

!0

!5

20

0 $ !2 !" 22 2#8ollow7*p )mo+

S*,Ge ts

)%+

Controlr,esartan !50 mgr,esartan 00 mg

@R&8 2 !rimary Endpoint Time to ' ert !roteinuria

Par=ing -7-( et al. N Engl F &ed 200! #5 "&07"&".


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Telmisartan is not inferior to enalapril in pro iding long"termrenoprotection in persons

Aith type 2 diabetes and early nephroapthy

H The DET8@= 3Diabetics E posed to

Telmisartan and Enalapril5 study Aasdesigned to demonstrate that therenoprotecti e e ect of telmisartan anangiotensin @@>receptor blocker Aas

similar 3i-e- not inferior5 to that of once"daily enalapril


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@rbesartan+** mg


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!rimary Endpoint: @DNT Time toDoubling of Serum Creatinine ESRD

or Death

S u

b B e c t s r e a c h

i n g p r i m a r y

e n

d p o

i n t 3 6 5

* 1 )2 )/ 2 +* +1 2 / (#olloA"up 3mo5

1*

*

)*

2*

+*

*

(*

1*

0*r,esartan

Emlodipine

Control

RRR 2*6!4*-*2

RRR > 6!4NS

RRR 2+6!4*-**1

Aewis F et al. N Engl F &ed 200! #5 "5!7"$0.


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REN88


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En in=estigator initiated( m*lti enter( triple7,lind(randomi6ed( pla e,o7 ontrolled st*dy to

e=al*ate the renal prote ti=e effe ts oflosartan in patients with Iype 2 dia,etes

and nephropathy

)()+ !atientsI 2(* CentersI 2. Countries

REN88=

Red* tion of Endpoints in N DD3 with the 8 8 ntagonist =osartan

:renner :3 et al F Renin"8ngio"8ldo System 2000 !)#+ 2"7 5.


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2*** +2)I ) *


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Aisinopril #0 mgCandersartan !$ mg > Aisinopril 20 mg


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C8=& @@


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Conclusion

H8liskiren may ha e renoprotecti ee ects that are independent of itsblood"pressureMloAering e ect in

patients Aith hypertension type 2diabetes and nephropathy Ahoare recei ing the recommendedrenoprotecti e treatment

8li ki liG h i i


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8liskiren NeutraliGes the Rise in!R8 @nduced by an 8R9

[email protected]!( [email protected]! =s pla e,op *-***) s aliskiren< alsartan combination

1arows SE( et al- 200& )St*dy 2 2&+.

eometri mean hange from ,aseline in PRE at Kee; " )%+

L!00

0

!00

200

00

n'5!

!"n'59

!$04M

n'$!

J##44

n'5!

J&44MPla e,o

Elis;iren 00 mgBalsartan 20 mg Elis;iren?=alsartan 00? 20 mg

l k l h


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8liskiren NeutraliGes The Rise @n !R8@nduced 9y 8n 8CE @nhibitor

L"0

"0$0

#020

L20L#0L$0

!20!00

L$"

!!!Change in PRE from ,aseline )%+

n'&9

Elis;irenmonotherapy

n'n'&5

Ramiprilmonotherapy

Elis;iren?ramiprilom,ination

L##

0

ilo C et al- 200$ St*d 2 0& .

[email protected]! =s ,[email protected] =s alis;iren monotherapy and ramipril monotherapy

4

4

4


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@n t on o t e progress on o


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Adapted from Mitch W.E., N Engl J Med 2004;351 1!34"1!3#; $%ilope &.M.,

Type"2"DiabetesHypertension

EndothelialDysfunction

&icro8lbuminuria

8lbuminuria@mpaired

Renal#unction

8ngiotensin receptor blockers

TREND,

ESRD

=@#E"DiabetesDET8@=

@NN'78T@'N@R&8"2

&8R78=@DNT REN88=

8&8DE'7@78=D@

8CE inhibitors

Timeframe up to 2( years

TREND,

9ENED@CT &@CR' H'!E

@n t on o t e progress on odiabetic nephropathy by 8R9s or 8CE

inhibitors

DET8@= OO


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E ect of spironolactone ondiabetic nephropathy

E ecti eness of 8ldosterone 9lockade in !atients Pith Diabetic Nephropathy Ets*hisa Sato( Hypertension 2**+


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de -ee% '. 2010E%ropean $enal A ociation/E%ropean 'ial+ i and

ran plant A ociation ongre ; J%ne 2 , 2010; M%nich, erman+.

!=8NET @: Summary of renal ad erse e ents 365

8d erse e ent

Rosu astatin)* mg


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CJD and 9icarbonate Supplementation

&ahaBan et al 2*)*


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'riginal 8rticle 9ardo olone &ethyl )an oral antio


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Study ' er ieA

H 8dults Aith type 2 diabetesand CJD Aere assigned torecei e bardo olonemethyl at a dose of 2( mg0( mg or )(* mg oncedaily or placebo-

H Drug treatment Aasassociated Aith impro edestimated L#R a ndingthat persisted throughoutthe (2"Aeek treatment


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E ects of 9ardo olone &ethyl on the Estimated Llomerular #iltration Rate 3L#R5-

!ergola !E et al- N Engl F &ed 2*))I+1(:+20"++1


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Conclusions

H 9ardo olone methyl Aasassociated Aithimpro ement in theestimated L#R in patientsAith ad anced CJD andtype 2 diabetes at 2Aeeks-

H The impro ement persistedat (2 Aeeks suggestingthat bardo olone methylmay ha e promise for the


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'riginal 8rticle Llucose Control and 7ascular Complications in

7eterans Aith Type 2 Diabetes

Killiam D* ;worth( 3.D.( Carlos E,raira( 3.D.( Ihomas 3orit6( 3.S.( Domeni Reda( Ph.D.(Ni holas man*ele( 3.D.( Peter D. Rea=en( 3.D.( 8ran;lin F. ie=e( 3.D.( Ph.D.( Fennifer

3ar;s( 3.D.( Stephen N. Da=is( 3.D.( Rodney -ayward( 3.D.( St*art R. Karren( F.D.(Pharm.D.( Ste=en oldman( 3.D.( 3adeline 3 Carren( Ph.D.( 3.P.-.( 3ary llen Bite;(Killiam . -enderson( Ph.D.( rant D. -*ang( 3.P.-.( Ph.D.( for the BEDI n=estigators

N ngl F 3edBol*me $0)2+ !297! 9

Fan*ary "( 2009


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Conclusion

H@ntensi e glucose control in patientsAith poorly controlled type 2diabetes had no signi cant e ect onthe rates of maBor cardio asculare ents death or micro ascularcomplications Aith the e ception ofprogression of albuminuria 3! 4

*-*)5


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'riginal 8rticle @ntensi e 9lood Llucose Control and 7ascular

'utcomes in !atients Aith Type 2 Diabetes

Ihe EDBENC Colla,orati=e ro*p

N ngl F 3edBol*me 5")2#+ 25$0725&2

F*ne !2( 200"

!rimary end"point


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EDBENC olla,orati=e gro*p. N F3( p*,lished on line F*ne $th

42P'0.0!

442P'0.0!#

3a ro=as *lar 55& )!0.0%+ 590 )!0.$%+ $% )7$ to !$+

3i ro=as *lar 52$ )9.#%+ $05 )!0.9%+ !#% ) to 2 +

Com,ined ma ro>mi o !009 )!".!%+ !!!$ )20.0%+ !0% )2 to !"+

ntensi=e Standard)n'5(5&!+ )n'5(5$9+

Relati=e ris;red* tion )95% C +

8a=o*rsntensi=e

8a=o*rsStandard

-a6ard ratio

0.5 !.0 2.0

4

44

!rimary end pointCombined maBor macro or micro ascular e ent

& B i l


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EDBENC olla,orati=e gro*p. N F3( p*,lished on line F*ne $th

&aBor micro ascular e ents

4

44

42P'0.0!#

442P'0.00$


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Conclusion

H8 strategy of intensi e glucosecontrol in ol ing gliclaGide3modi ed release5 and other drugsas re uired that loAered theglycated hemoglobin alue to 1-(6yielded a )*6 relati e reduction inthe combined outcome of maBor

macro ascular and micro asculare ents primarily as a conse uenceof a 2)6 relati e reduction innephropathy


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DCCT


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KMA DIABETIC NEPHROPATHY - SLIDES OF THE YEAR.pptx

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