Nefropatia diabetica 5 febb.

Transcript

Prevenzione e cura della malattia renale e
delle sue complicanze
nel paziente diabetico
con il contributo non condizionante di:
1
Cavenago di Brianza 25-26 febbraio
2011
La nefropatia nel paziente
diabetico
Screening, diagnosi e follow-up della nefropatia
nel paziente diabetico
2
1.
2.
3.
4.
5.
3
Cenni di epidemiologia del diabete
Epidemiologia della nefropatia diabetica
Diabete e malattia renale terminale
Diagnosi e storia naturale della nefropatia
diabetica
Misura della funzione renale e follow-up della
nefropatia nel diabete
Cavenago di Brianza 25-26 febbraio 2011
Diabetes

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
Diabetes is a disease of epidemic proportions, and
the number of people developing the disease is
growing every year.
The prevalence of type 2 diabetes and the burden of
disease caused by it have increased very rapidly worldwide
This has been fuelled by (i) ageing populations, (ii)
poor diet, and the (iii) concurrent epidemic of
obesity
Cardiovascular complications and renal disease are
two of the most costly and devastating health
problems linked with diabetes
Prevalence of diabetes world wide [article online]. Available from http/www.eatlas.idf.org, 2005.
4
Prevalenza del diabete
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Nel 2010, fra le persone di età compresa tra 20 e 79 anni, si
stimava una prevalenza del 6,4 % a livello mondiale
Nel 2030 si prevede che la prevalenza aumenterà fino al 7,7 %
Il diabete è causa di un eccesso di mortalità stimato in 3.96
milioni nell’età tra 20-79 anni corrispondente al 6,8 % di tutte
le morti globalmente ogni anno*.
80% delle persone con diabete vive in nazioni a medio o
basso reddito.
La maggior parte delle persone con diabete nelle nazioni a
medio basso reddito hanno un’età tra 45-64.
La mortalità per diabete tenderà verosimilmente ad
aumentare di più del 50% nei prossimi 10 anni senza
interventi urgenti.
* Diabetes Res Clin pract. 2010 :87 (1) 15-9
5
WHO data
Eccesso di
mortalità dovuta a
diabete
A = mortalità infantile e
adulta molto bassa
B= mortalità infantile e
adulta bassa
C= mortalità bassa infantile
e alta adulta
D= mortalità infantile ed
adulta alta
E = mortalità infantile alta
ed adulta molto alta
Roglic G, Unwin N, Bennet P et al (2005) The Burden of Mortality Attributable to Diabetes: Realistic estimates for the year 2000 Diabetes Care 28:9 2130-2135
6
Projected Percent Changes in diabetic
cases (2010-2030)
Afr (Africa), MENA (Middle East and North Africa), SEA (South East Asia), SACA (South and Central America), WP
(Western Pacific), NAC (North America and Carribean), EUR (Europe)
7
Estimated number of adult with
diabetes
Fonte : WHO
9
In Italia
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In Italia l’ISTAT stimava nell’annuario statistico 2009 una
prevalenza di diabete noto pari al 4,8% (5% donne, 4,6%
uomini ).
In base a questi dati le persone con diabete in Italia
dovrebbero essere circa 2,9 milioni.
La prevalenza è più bassa al Nord (4,2%) rispetto al
Centro (4,9%) e al Sud Italia (5,5%).
Indipendentemente dall’area geografica, la prevalenza
aumenta con l’età, passando dal 2,9% nella classe d’età 4554 anni al 18,9% nelle persone con età superiore a 75
anni
ISTAT 2009
10
Diabete in Italia
Prevalenza per sesso ed età
Dati Istat annuario 2009
11
Andamento prevalenza
Prevalenza Diabete per aree geografiche
Dati Istat annuario 2009
12
The prevalence of chronic kidney
disease in diabetes
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15
Diabetes is now the major cause of end stage
kidney failure in the world in both developed and
emerging nations
It is the primary diagnosis causing kidney disease
in 20-40% of people starting treatment for ESRD
worldwide
Diabetes and chronic kidney disease (CKD)
exhibit
synergistic
associations
with
cardiovascular disease and premature mortality
PAZIENTI IN DIALISI
PER IRC DA NEFROPATIA DIABETICA
U.S.A.
Europa
Italia
0
10
20
30
40
%
16
50
Prevalent counts
& adjusted rates,
by primary
diagnosis
 USRDS 2009
Annual Data Report
December 31 point prevalent ESRD patients;
rates adjusted for age, gender, & race.
18
Incident counts
& adjusted rates,
by primary
diagnosis
 USRDS 2009
Annual Data Report
Incident ESRD patients; rates adjusted for age,
gender, & race.
19
Dal Registro Italiano Dialisi e Trapianto
NEFROPATIA PRIMITIVA
CASI INCIDENTI 2006
GN
10.5
PN/NI
7.3
CONG/ERED
6.8
VASCOLARE
23.6
DIABETE
17.5
SISTEMICHE
4.9
ALTRE
5.4
IGNOTA
15.7
NON INSERITA
8.3
0
5
10
15
20
25
30
Report Annuale RIDT 2008
Causa Primaria di ESRD (%)
20
Malattie renali primitive
dati registro lombardo (RLDT)
diabete
GN
vascolari
45,0
40,0
38,6
38,4
36,1
35,0
30,0
29,9
25,0
22,9
20,0
16,6
15,0
10,0
5,0
11,3
12,9
11,1
11,9
17,4
14,1
14,7
17,9
15,8
6,8
0,0
80-84
21
85-89
90-94
95-99
00-04
05-07
22
Definition of diabetic nephropathy
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Diabetic nephropathy has been classically defined by the
presence of proteinuria 0.5 g/24 h.
This stage has been referred to as overt nephropathy, clinical
nephropathy, proteinuria, or macroalbuminuria.
In the early 1980s, seminal studies from Europe revealed that
small amounts of albumin in the urine, not usually detected by
conventional methods, were predictive of the later
development of proteinuria in type 1 and type 2 diabetic
patients.
This stage of renal involvement was termed
microalbuminuria or incipient nephropathy
Diabetes Care 28:176–188, 2005
23
Diabetic nephropathy
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With improvement in the survival of patients with
diabetes, nephropathy has emerged as a major health
problem.
Known risk factors for the development of diabetic
nephropathy include (i)genetic predisposition, (ii)poor glycaemic
control, (iii) hypertension and (iiii) smoking.
The diagnosis of diabetic nephropathy is usually made clinically.
Other target organ involvement is often present.
90-95% of type 1 diabetics and about 70% of type 2 diabetics
with nephropathy will have retinopathy as well.
In the absence of retinopathy, non-diabetic renal disease may
need to be excluded
24
Nefropatie non diabetiche in diabetici
Variety of non-diabetic
renal diseases
Other clinical findings
Jianhui Zhou et al Nephrol Dial Transplant (2008) 23: 1940–1945
25
A differential diagnostic model of diabetic
nephropathy and non-diabetic renal diseases
Multivariate regression analysis results
Predictive value
Comparison of three diagnostic methods
26
Jianhui Zhou et al Nephrol Dial Transplant (2008) 23: 1940–1945
La nefropatia diabetica
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Sindrome clinica caratterizzata da: (i)albuminuria
persistente, (ii)ipertensione, (iii) costante declino della
funzione renale e (iiii) aumentata morbilità e (iiiii) mortalità
cardiovascolare
Il declino inarrestabile del GFR si presenta variabile da 1 a
24 ml/min/anno (media 12ml/min/anno) sia nei pazienti
con diabete di tipo 1 e 2.
Contemporaneamente la pressione sanguigna e la
proteinuria aumentano ( nel 40-50% dei casi si ha una
vera e propria sindrome nefrosica)
Vi è una stretta correlazione tra entità del danno
glomerulare e la funzione renale e la sua velocità di
riduzione
Natural history of type 1 diabetic
nephropathy
Functional and
structural
manifestations
of diabetic
nephropathy.
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28
Mechanisms in Diabetic
Nephropathy
Hyperglycemia
 Systemic hypertension
 Glomerular hyperfiltration
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Early, with onset of diabetes
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Late, with renal injury and nephron loss
 Reduced nephron number
 Genetic/racial
 Proteinuria
 AGEs
 Renal RAS
 Lipid abnormalities?

Phillip M. Hall
30
Diabetes Spectrum Volume 19, Number 1, 2006
Patogenesi Nefropatia Diabetica
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L’iperfiltrazione glomerulare è comune nelle fasi iniziali della
malattia diabetica
Dilatazione glucosio-dipendente dell’arteriola
afferente, mediata da una serie di mediatori quali: (i) insulinlike growth factor 1(IGF-I),(ii) ossido nitrico, (iii)
prostaglandine. L’iperfiltrazione è predittiva dello sviluppo di
Nefropatia Diabetica specie nel tipo I°
Nei modelli sperimentali l’iperfiltrazione è il risultato della
dilatazione dell’arteriola afferente con concomitante
vasocostrizione dell’arteriola efferente, e aumento della
pressione idrostatica glomerulare
31
Schematic comparison
of a normal nephron,
a nephron in diabetic
nephropathy, and
a nephron in diabetic
nephropathy after
administration of
angiotensin-converting
enzyme (ACE)
inhibitor/angiotensin
receptor blocker(ARB)
Afferent vasodilation and efferent angiotensin II–mediated vasoconstriction in diabetes
causing glomerular hypertension, which is relieved by ACE inhibitor/ARB treatment.
Protein leakage into the filtrate and tubular loading with endocytosed protein cause an
inflammatory reaction promoting interstitial fibrosis.
This is reversed by ACE inhibitor/ARB treatment
32
Iperfiltrazione
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L’ iperfiltrazione si associa a glomerulomegalia e ad organomegalia
L’ingrandimento dei glomeruli è associato ad aumento del numero
dei capillari e della superficie di filtrazione
A livello glomerulare si osserva ipertrofia delle strutture, a livello
tubulo interstiziale anche proliferazione
Si correla alle alte concentrazioni di glucosio stimolando fattori di
crescita intrarenali quali IGF-I , epidermal growth factor, plateletderived growth factor, vascular endotelial growth factor
(VEGF), transforming growth factor ß (TGF-ß )
TGF-ß è sovraespresso nei glomeruli e nel tubulo-interstizio nei
modelli sperimentali e anche nel DM umano
Glucosio e AGEs stimolano la produzione di TGF-ß
33
Sviluppo della proteinuria
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L’ipertrofia e conseguente allargamento della GBM è associata con
accumulo di collagene tipo IV e con una netta riduzione dei
proteglicani a carica elettrica negativa.
Questa combinazione porta ad alterazione della struttura della GBM e
delle sue cariche elettrostatiche, contribuendo alla alterazione della
permeselettività e al passaggio di proteine (anioni)
La deplezione di cariche negative permette alle molecole polianioniche
di albumina di passare la barriera glomerulare. Negli stadi più
avanzati, la testura della GBM è alterata, creando falle e pori per il
passaggio di molecole a differente pm.
Recenti studi sulla funzione del podocita e delle slit-membranes hanno
avanzato il concetto che il podocita sia il primo attore nella genesi
della proteinuria presentando una ridotta espressione della
nefrina, proteina che controlla la permeabilità.
Gli ARBs intervengono nel ripristino della nefrina
35
Iperglicemia e Nefropatia Diabetica
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Lo scarso controllo glicemico e la durata della malattia sono i due fattori
principali per lo sviluppo della nefropatia diabetica
Vi sono varie evidenze che uno stretto controllo della glicemia possa
ritardare lo sviluppo della nefropatia
Lo studio UKPDS ha evidenziato che una riduzione dello 0,9% della
HbA1c nel Diabete tipo 2 riduce il rischio dello sviluppo delle
complicanze microvascolari compresa la nefropatia.
Il ripristino del controllo glicemico dopo trapianto di isole si associa con
alla regressione della glomerulosclerosi diabetica dopo 10 anni.
Nello studio DCCT si è vista una importante riduzione della
progressione da normo a microalbuminuria e di altre complicanze
microvascolari.
36
Controllo del glucosio e complicanze
microvascolari
37
Aumento Gfr (Hyperfunction)
Danno funzionale dei podociti
Iperfiltrazione proteica
Aumento del traffico proteico
tubulare
Attivazione dei mediatori locali di
flogosi
Attivazione locale di fibroblasti e
fibrogenesi
Renal Scarring
38
Il rischio cumulativo di
sviluppare proteinuria
e di progredire verso
la insufficienza renale
cronica dalla
comparsa della
proteinuria è
praticamente
sovrapponibile per
il diabete tipo 1 e
tipo2
42
Terminology for the Kidney Disease of
Diabetes
New terminology to describe kidney disease attributable to diabetes is
introduced in the Diabetes and CKD guidelines.
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The purpose is to clarify communication among patients
caregivers, and policy makers. For this purpose and for consistency
with CKD classification, the term DKD is proposed for a
presumptive diagnosis of kidney disease caused by diabetes.
Although kidney biopsy is required to diagnose diabetic
glomerulopathy definitively, careful screening of diabetic patients
can, in most cases, identify persons most likely to have diabetic
glomerulopathy without the need for kidney biopsy
The term “diabetic nephropathy” should be replaced by DKD.
The term diabetic glomerulopathy should be reserved for biopsy-proven
kidney disease caused by diabetes.
43
Light microscopy of structural changes in
diabetic nephropathy
Normal glomerulus
44
Diffuse glomerular lesion:
widespread mesangial
expansion
Light microscopy of structural changes in
diabetic nephropathy
Nodular lesion: as well as mesangial
expansion, there is a typical KimmelstielWilson nodule at the top of the glomerulus
(arrow)
45
Nodular lesion: methenamine silver staining
showing the marked nodular expansion of
mesangial matrix.
Electron microscopy of structural changes
in diabetic nephropathy
Glomerular basement membranes
are diffusely thickened
46
The expanded mesangium encroaches
on the capillary spaces (arrows)
Nefropatia Diabetica (vasi)
Estesi depositi di materiale ialino nella parete dei
piccoli vasi. Ematossilina-eosina 250x
48
A. Vangelista
Nefropatia Diabetica
Immunofluorescenza. Positività lineare diffusa per IgG sulle pareti
capillari, la membrana capsulare e le membrane tubulari
A. Vangelista
49
Correlazioni clinico-patologiche
50
Mortalità e progressione della nefropatia diabetica
in relazione alla funzione renale
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53
Dati da
UKPDS
Prevention of the onset of diabetic
nephropathy
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Achieve normotension as low as tolerated with a therapy
regimen including an ACE-I or AT-1 receptor antagonist
Salt restriction(< 6 gr/die), recommended protein intake
(0.8 to 1.0 gr x Kg l-body weight)
Good control of hyperglycemia (target HBA1c < 7.0 %)
Cessation of smoking
Administration of statins
Weight loss (if obese), light regularly aerobic exercise
No use of minor analgesics
Avoidance of nephrotoxic medication (contrast
media, antibiotics, FANS)
54
Linee Guida
This publication of the Kidney Disease
Outcomes Quality Initiative™ (KDOQI™)
Clinical Practice Guidelines and Clinical
Practice
Recommendations
for
Diabetes and Chronic Kidney Disease
(CKD) represents the first guideline that
considers the unique aspects of the
evaluation, diagnosis, and management of the
complex patient with both diabetes mellitus
and CKD
The key points have been made that the
combination of CKD and diabetes
is a cardiovascular disease
multiplier, and that these patients are
at high risk of cardiovascular disease
55
Creatinina e misurazione del GFR

La creatininemia fornisce un dato approssimativo e poco attendibile sulla
funzione renale e la sua clearance è indaginosa e non scevra da errori sia nella
raccolta urinaria che nel campionamento del laboratorio, per l’uso nel followup pratico e negli screening di popolazione si usano equazioni semplificate che
partendo da un minimo data set predicono il GFR

CG (Cockcroft-Gault )e MDRD 4 var(Modification of Diet in Renal Disease)

C-G : 140-

età (anni) x peso corporeo (Kg) / 72 x creatinina serica (mg/dl) [♀= x 0.85 ]
MDRD: 186 (175) x (creatinina serica (mg/dl) -1.154)
femmina x 1,21 se African American
x (età (anni) -0.203) x 0,742 se
Nuova formula recentemente proposta per superare i problemi di linearità con il GFR
misurato

CKD-EPI: basata
sulla MDRD, introduce correzioni per il valore di creatinina
(> o < 0.7 nelle femmine) (< o > 0.9nei maschi) per il sesso e la etnia ( bianchi
o neri)
56
Relationship of Serum Creatinine Level to
Measured GFR in the Modification of Diet in Renal
Disease Study.
57
Comparison of performance of MDRD formula and
Chronic Kidney Disease Epidemiology Collaboration (CKDEPI) equations by estimated GFR in the external validation
dataset
Panel 1. Measured vs. estimated GFR. Panel 2. Difference between measured and estimated vs. estimated GFR. Shown are
smoothed regression line and 95% CI (computed using the lowess smoothing function in R), using quantile regression, excluding
lowest and highest 2.5% of estimated GFR values. To convert GFR from mL/min/1.73 m2 to mL/s/m2, multiply by 0.0167
Ann Intern Med. 2009 May 5; 150(9): 604–612.
58
Stadi della malattia renale cronica
NKF: K/DOQI2002
Stadio
Descrizione
GFR (ml/min)
1
Danno renale con GFR normale
>90
2
Danno renale lieve riduzione
GFR
60-89
3a
3b
45-59
Moderata riduzione GFR
30-44
4
Severa riduzione GFR
15-29
5
Insufficienza renale terminale
< 15/dialisi
Cavenago di Brianza 25-26
febbraio 2011
59
Screening and Diagnosis of DKD

Measurements of urinary albumin- creatinine ratio (ACR) in a spot urine
sample; (B)

Measurement of serum creatinine and estimation of GFR. (B)

An elevated ACR should be confirmed in the absence of urinary tract
infection with 2 additional first-void specimens collected over the next 3 to
6 month ( B)

Microalbuminuria is defined as an ACR between 30-300 mg/g creatinine

Macroalbuminuria is defined as an ACR > 300 mg/g creatinine

2 of 3 samples should fall within the microalbuminuric or macroalbuminuric
range to confirm classification

In most patients with diabetes, CKD should be attributable to diabetes if:
1)
Is present macroalbuminuria(B) or
2)
Microalbuminuria in the presence of diabetic retinopathy (B), or in type 1
diabetes of at least 10years’ duration. (A)
Guideline 1: Screening and Diagnosis of DKD American Journal of Kidney Diseases, Vol 49, No 2, Suppl 2 (February), 2007:
60
eGFR and staging DKD
•Evidence for the usefulness of estimated GFR (eGFR) alone as a
screening test for CKD in diabetes is less secure.
•Many patients with diabetes and CKD may have elevated or highnormal GFRs, particularly in the early years after diagnosis.
•Therefore, markers of kidney damage are required to detect early
stages of CKD
•eGFR alone can only detect CKD stage 3 or worse
•GFR would be measured in DKD
American Journal of Kidney Diseases, Vol 49, No 2, Suppl 2 (February), 2007: pp S13-S19
61
eGFR progression for presence of diabetes, vascular
disease, and both diabetes and vascular disease
Factors independently predicted CKD were:
baseline age (OR) 1.13 per 10 years, 95% CI, 1.03–1.24],
baseline eGFR (OR 0.69 per 10 units, 95% CI 0.65–
0.73), diabetes (OR 3.66, 95% CI 2.97–4.51)
vascular disease (OR 1.67, 95% CI 1.32–2.10)
Rebecca Hanratty, Michel Chonchol et al. Nephrol Dial Transplant (2010) 25: 801–807
62
Prevention of diabetic nephropathy

Data from secondary analyses of several studies reveal that ACE inhibitors and
angiotensin receptor blockers (ARBs), administered to patients without
diabetes, but with various cardiovascular conditions, can reduce the risk of
newonset type 2 diabetes by up to 25% .(a)

Examples are the DREAM study (Diabetes Reduction Assessment With Ramipril
and Rosiglitazone Medication) and the LIFE (Losartan Intervention For Endpoint
reduction in hypertension)study.

The first showed that ramipril therapy significantly increased regression to
normoglicemia(b).

The second showed that newonset diabetes occurred significantly less frequently
(P = 0.001) in the losartan- than in the atenolol-treated group (13.0 versus 17.4
per 1000 patient-years of follow-up) (c )
a) Scheen AJ. Renin-angiotensin system inhibition prevents type 2 diabetes mellitus. A meta-analysis of randomized clinical trials. Diabetes
Metab 2004; 30: 487–496
b) Bosch J,Yusuf S, GersteinHCet al. Effect of ramipril on the incidence of diabetes. N Engl J Med 2006; 355: 1551–1562
c) Dahlof B, Devereux RB, Kjeldsen SE et al. Cardiovascular morbidity and mortality in the Losartan Intervention For Endpoint reduction
inhypertension study (LIFE): a randomised trial against atenolol. Lancet 2002; 359: 995–1003
63
Nephropathy prevention

To reduce the risk or slow the progression of nephropathy
, optimize glucose control (level of evidence = A)

To reduce the risk or slow the progression of
nephropathy, optimize blood pressure control (level of
evidence = A)
A = Clear evidence from well-conducted, generalizable, randomized controlled trials that are adequately powered, including:
● Evidence from a well-conducted multicenter trial
● Evidence from a meta-analysis that incorporated quality ratings in the analysis
Diabetes care, vol 33, suppleme nt 1, January 2010
64
Prevention of microalbuminuria

ACE inhibitors have been shown to prevent or delay the development of
microalbuminuria in normoalbuminuric patients with type 2 diabetes.

The BENEDICT (Bergamo Nephrologic Diabetes Complication Trial) study
showed that treatment with trandolapril slowed the onset of persistent
microalbuminuria by 53%.

Interestingly, in the control arm of this study where the antihypertensive
verapamil was used alone, there was no reduction in the development of
microalbuminuria.

This clearly shows that, although blood pressure control is important in
diabetes, using an intervention in the renin–angiotensin–aldosterone system
(RAAS) is of important additive value in protective prevention of renal
disease .
Ruggenenti P, Fassi A, Ilieva AP et al. Preventing microalbuminuria in type 2 diabetes. N Engl J Med 2004; 351:
1941–1951
65
Early intervention

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The IRMA-2 (Irbesartan in Reduction of Microalbuminuria -2)
study was the first to demonstrate that ARBs can prevent
the further development of albuminuria in hypertensive type 2
diabetic patients with microalbuminuria, and delay progression
to overt nephropathy .
Overt diabetic nephropathy was reached in 14.9% of placebotreated participants, and in 9.7% and 5.2% of those receiving
low- dose(150 mg) and high-dose (300 mg)
irbesartan, respectively
The renoprotective effect was sustained after the cessation of
treatment
66
IRMA II Change in
Urinary Albumin Excretion*
% change in urinary
albumin excretion
20
Placebo
10
0
-10
150 mg of irbesartan
-20
-30
300 mg of irbesartan
-40
-50
0
3
6
12
18
Months of Follow-up
*P<0.001 for difference between both irbesartan groups and placebo
Parving HH, et al. N Engl J Med. 2001;345(12):870-878.
67
22
24
IRMA II Incidence of Progression
to Diabetic Nephropathy
Incidence of Diabetic
Nephropathy (%)
20
P<0.001 for difference between
300 mg irbesartan group and placebo
15
Placebo
150 mg of
irbesartan
10
Placebo (n)
Irbesartan
150 mg (n)
Irbesartan
300 mg
5
0
300 mg of
irbesartan
18
22
24
154
139
129
36
167
161
148
142
45
180
172
159
150
49
0
3
6
201
201
164
195
195
194
194
Parving
68HH, et al. N Engl J Med. 2001;345(12):870-878.
12
Months of Follow-up
Reduction of the risk of diabetic
nephropathy progression
Data shown (relative risk
reductions versus placebo) for
the primary composite
endpoint of doubling of serum
creatinine, onset of ESRD or
death from any cause [IDNT (b)
and RENAAL (a) trials]; or for
the primary outcome of time to
the onset of diabetic
nephropathy [IRMA-2 trial(c )]
a) Brenner BM, Cooper ME, de Zeeuw D et al. Effects of losartan on renal and cardiovascular
outcomes in patients with type 2 diabetes and nephropathy. N Engl J Med 2001; 345: 861–869
b) Lewis EJ, Hunsicker LG,ClarkeWRet al.Renoprotective effect of the angiotensin-receptor
antagonist irbesartan in patients with nephropathy due to type 2 diabetes. N Engl J Med 2001;
345: 851–860
c) Parving HH, Lehnert H, Brochner-Mortensen J et al. The effect of irbesartan on the development
of diabetic nephropathy in patients with type 2 diabetes. N Engl J Med 2001; 345: 870–878
69
Conventional versus intensive
treatment
Proliferative
Retinopathy
Conventional
treatment group
HbA1C = 9%
Intensive treatment
group HbA1C= 7 %
Diabetic
Nephropathy
Cardiovascular
disease
50%
25%
14%
21%
9%
9%
After 30 years of diabetes type 1 cumulative incidence.
DCCT/EDIC research Group. Modern-day clinical course of type 1 diabetes mellitus after 30 years’ duration.
Arch Intern Med 2009;169:1307-1316
78
Relative Effects of
Glucose-Control Strategy
on All Prespecified
Primary and Secondary
Outcomes
The ADVANCE Collaborative Group* N Engl J Med 2008;358:2560-72.
A strategy of intensive glucose control, involving gliclazide (modified release) and other drugs as required, that lowered the glycated hemoglobin value to
6.5% yielded a 10% relative reduction in the combined outcome of major macrovascular and microvascular events, primarily as a consequence of a 21%
relative reduction in nephropathy.
79
Factors affecting survival in
diabetes type 1- Finnish
cohort
Diabetes 58(7):16518, 2009 Jul
Cox-adjusted survival of individuals with type 1 diabetes
from the FinnDiane study, stratified for the presence and
severity of albuminuria (A), estimated GFR (B), and the
presence and severity of retinopathy (C) at baseline
81
Blood pressure level and rate of GFR decline in
controlled trials of DKD
Systolic blood pressure
(SBP) and mean rate of
calculated or directly
measured GFR decline in
the studies of DKD.
Results not adjusted for
other factors associated
with rate of decline in GFR.
The dotted line represents a
flattening of possible benefit
of blood pressure lowering
at blood pressure levels less
than 140 mmHg.
-Parving HH et al. Br Med J, 1989 –Estacio R et al. Diabetes Care, 2000
-Viberti GC et al. JAMA, 1993 -Lewis EJ et al. N Engl J Med, 2001
-Lewis EJ et al. N Engl J Med, 1993 -Bakris, GL et al. Arch Intern Med, 2003
-Lebovitz H et al. Kidney Int, 1994 -Bakris GL et al. Kidney Int, 1996
-Bakris GL Hypertension, 1997
Bakris GL, et al. Am J Kidney Dis. 2000;36(3):646-661.
84
Evidence-Based Interventions to Prevent
Development of Diabetes or Prevent Diabetic
Nephropathy
85
86
88

Nefropatia diabetica 5 febb.

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