NEFROPATIA DIABETICA

Rene e gravidanza
Gestione multidisciplinare, recenti
acquisizioni e future strategie
Taormina, 15-16 aprile 2011
La gravidanza nella nefropatia
diabetica
Lucia Del Vecchio
Divisione di Nefrologia, Dialisi e Trapianto Renale
Ospedale A. Manzoni, Lecco
Global projections for the number of people with
diabetes (20-79 years), 2010-2030
Europe
World
2010
2030
Increase
55,2 mm
284,6 mm
66,2 mm
438,4 mm
20%
58,4%
IDF Atlas, 2009
Getting Heavier, Younger: Trajectories of
Obesity over the Life Course
Female
Joyce M. Lee et al Int J Obes (Lond). 2010 Apr;34(4):614-23.
Estimated number of prevalent cases of
type 1 diabetes in children, 0-14 years by
region, 2010
Nefropatia diabetica: qual è la storia naturale?
Qual è il rischio di pre-eclampsia nella nefropatia diabetica?
La gravidanza aumenta il rischio di progressione della nefropatia?
Quali sono i rischi a lungo termine per il nascituro?
Storia naturale della nefropatia diabetica
GFR
(ml/min)
Albuminuria
(g/die)
150
3
Nefropatia franca
2
100
Nefropatia incipiente
50
1
0.3 g/die
0
0
5
0
10
15
20
Tempo dalla diagnosi di diabete (anni)
25
NEFROPATIA DIABETICA: PREVALENZA
Diabetici tipo I
Il 35-45% sviluppa proteinuria nel corso della vita, generalmente
dopo 10-15 anni dall’esordio del diabete
Un 20-30% sviluppa solo microalbuminuria
Dopo 25 aa di diabete, il rischio di nefropatia diabetica diminuisce
Diabetici tipo II
Prevalenza: 8-10% dopo 5 anni dalla diagnosi
20-30% dopo 25 anni
Nefropatia diabetica: qual è la storia naturale?
Qual è il rischio di pre-eclampsia nella nefropatia diabetica?
La gravidanza aumenta il rischio di progressione della nefropatia?
Quali sono i rischi a lungo termine per il nascituro?
RESEARCH LETTERS
Pre-pregnancy microalbuminuria predicts pre-eclampsia in insulindependent diabetes mellitus.
Copenhagen Pre-eclampsia in Diabetic Pregnancy Study Group
Baseline data for women with IDDM according to pre-eclampsia
Ekbom P. Lancet 1999; 353(9150): 377
Pregnancy Outcome in Type 1 Diabetic
Women With Microalbuminuria
Prospective cohort study at the National University Hospital,
Copenhagen, from January 1996 to February 2000
240 Caucasian women with type 1 diabetes and pregnancy
(a living fetus before 17 weeks of gestation )
85%
Normoalbuminuria
11%
Microalbuminuria
5%
Macroalbuminuria
Ekbom P, et al. Diabetes Care 24: 1739–1744, 2001
Preterm delivery rates in relation to
urinary albumin excretion at baseline
Preeclampsia
Other causes
Ekbom P, et al. Diabetes Care 24: 1739–1744, 2001
Prospective study of 117 pregnant women with type 1 diabetes
Antihypertensive therapy, mainly methyldopa, was given to obtain
blood pressure < 135/85 mmHg
urinary albumin excretion <300 mg/24 h
Nielsen LR et al. Diabetes Care 32: 38–44, 2009
Clinical data in 117 women with type 1 diabetes
according to urinary albumin excretion
Normoalbuminuria Microalbuminuria Diabetic nephropathy
n
100
10
7
Duration of diabetes
(years)
16 (1–36)
14 (1–31)
20 (5–32)
UAE rate at inclusion
(mg/24 h)
7 (3–29)
91 (30–198)
690 (450–3,290)
SCr at inclusion
(mg/dl)
0.57 (0.37–0.84)
0.57 (0.46–0.78)
0,64 (0,47–1,07)
A1C at inclusion
(%)
6.7 (4.9–10.8)
6.9 (5.8–10.5)
6.5 (5.7–7.8)
Nielsen LR et al. Diabetes Care 32: 38–44, 2009
Pregnancy outcomes in studies of type 1 diabetic women
from the same geographical area in Eastern Denmark
Microalbuminuria
Ekbom et al.,
2001
Nielsen et al.,
2006
Current study
11 (42)
4 (20)
0
250 (182–270)
259 (244–271)
264 (252–272)
Preterm delivery before
34 weeks (n)
6 (23)
0
0
Preterm delivery before
37 weeks (n)
16 (62)
8 (40)
2 (20)
3,124 ± 767
3,279 ± 663
3,471 ± 670
Perinatal mortality (n)
1 (4)
0
0
Major congenital
malformations (n)
1 (4)
0
0
Preeclampsia (n)
Gestational age at
delivery (days)
Birth weight (g)
Nielsen LR et al. Diabetes Care 32: 38–44, 2009
Pregnancy outcomes in studies of type 1 diabetic women
Macrolbuminuria
Dunne et al.,
1999
n
21
Ekbom et al.,
2001
Carr et al.,
2006
11
43
Current
study
7
UAE at inclusion
(mg/24 h)
—
1,120 (466–5,528)
3,170
690 (450–3,290)
Preeclampsia (n)
—
7 (64%)
15 (35%)
3 (43%)
243 (203–266)
—
238
258 (220–260)
12 (57.2%)
10 (91%)
16 (38.1%)†
5 (71%)
2,429 (985–4,140)
2,235 (1,038)
2,200
2,730 (601)
Duration of pregnancy
(days)
Preterm delivery
before 37 weeks (n)
Birth weight (g)
Nielsen LR et al. Diabetes Care 32: 38–44, 2009
61 consecutive singleton pregnancies in women with type 2 diabetes from
1996 to 2001
Pregnancy outcome was compared with that of pregnant women with type 1
diabetes during 1996–2000, the background population, and pregnant
women with type 2 diabetes during 1980–1992
Diabetes Care 28:323–328, 2005
Baseline data for pregnant women with diabetes
(1996–2001)
Type 2
Type 1
61
240
Age (years)
33.4 (31–38)
30.0 (27–33)
0.0001
BMI (kg/m2)
29.4 (27–35)
23.0 (21–26)
0.0001
2.0 (1–5)
14.0 (6–19)
0.0001
n
Duration of diabetes
(years)
P
Microalbuminuria
8 (13)
26 (11)
0.52
Macroalbuminuria
0 (0)
11 (5)
0.13
Proliferative retinopathy
0 (0)
25 (10)
0.01
6.8 (6.1–7.7)
7.0 (6.5–7.8)
0.41
HbA1c at admission (%)
Clausen TD et al. Diabetes Care 28:323–328, 2005
Complications in pregnancy in type 2 and
type 1 diabetes
14
12
10
P = NS
8
Pregnancy-induced
hypertension
6
Preeclampsia
4
2
12 30
0
4
0
type 1
type 2
Clausen TD et al. Diabetes Care 28:323–328, 2005
Perinatal outcome in pregnancy in type 2
and type 1 diabetes
Type 2
Type 1
P
Congenital malformations
4 (6.6)
7 (2.9)
0.24
Perinatal mortality
4 (6.7)
4 (1.7)
0.05
38.0 (37–39)
37.3 (36–38)
0.03
Birth <34 weeks
8 (14)
17 (7)
0.19
Birth <37 weeks’
18 (31)
87 (38)
0.29
Birth weight (g)
3,600 (3,095–3,990)
3,595 (3,064–3,925)
0.79
Gestational age (weeks)
Clausen TD et al. Diabetes Care 28:323–328, 2005
Ambulatory blood pressure as predictor of
preeclampsia in diabetic pregnancies and urinary
albumin excretion
Systolic blood pressure
N = 151
Diastolic blood pressure
Albumin excretion rate:
<30 mg/24 h
30-299 mg/24 h
>300 mg/24 h
Lauszus FL et al. Acta Obstet Gynecol Scand 2001; 80: 1096–1103
Nefropatia diabetica: qual è la storia naturale?
Qual è il rischio di pre-eclampsia nella nefropatia diabetica?
La gravidanza aumenta il rischio di progressione della nefropatia?
Quali sono i rischi a lungo termine per il nascituro?
Are adverse pregnancy outcomes risk
factors for development of ESRD in
women with diabetes?
Medical Birth
Registry of
Norway
Norwegian
Renal
Registry
Norwegian
Cause of
Death
Registry
639 018 women with a first singleton delivery from 1967 to 1994
2204 women with diabetes before pregnancy
Pre-eclampsia in 13.2%, low birth weight offspring (<2.5 kg) in 11.0%
and preterm birth in 25.1%,
Sandvik MK et al. Nephrol Dial Transplant. 2010;25(11):3600-7
Adverse pregnancy outcomes in first pregnancy in women
with diabetes before first pregnancy and ESRD
Cumulative risk of ESRD
Diabetic nephropathy status: unknown
1 pregnancy
Preterm and
preeclampsia
1 pregnancy
Preterm or
Term preeclampsia
1 pregnancy
term birth
no preeclampsia
≥2 pregnancy
term and no
preeclampsia
≥2 pregnancy
term and
preeclampsia
Years after birth
Sandvik MK et al. Nephrol Dial Transplant. 2010;25(11):3600-7
Influence of pregnancy on progression of diabetic
nephropathy
5 patients with type 1 diabetes and overt nephropathy
After pregnancy renal function declined in all
cases (mean reduction rate of creatinine
clearance of 1.4 ml/min per month)
Mean proteinuria showed a transient 2.8fold increase during pregnancy; within 3-6
months after delivery it returned to the
same values as before pregnancy
Biesenbach G et al. Nephrol Dial Transplant 1992, 7: 105-109
Pregnancy and progression of diabetic nephropathy
93 patients with Type I diabetes and diabetic nephropathy
between 1970 and 1989 at Steno Diabetes Center
Non-pregnant
Pregnant
N = 67
sCr = 0.89 (0.26)
Albuminuria = 597 (460-776)
N = 26
sCr = 0.89 (0.26)
Albuminuria = 534 (437-652)
Rossing K, et al. Diabetologia 2002;45(1):36-41
Pregnancy and progression of diabetic nephropathy
Mean 1/sCr during follow up
Non-pregnant
Pregnant
Rossing K, et al. Diabetologia 2002;45(1):36-41
Risk of complications according to tratment
group and pregnancy status in the DCCT
Multicenter controlled clinical trial comparing intensive treatment with
conventional diabetes therapy in type 1 diabetes
180 women with 270 pregnancies and 500 women without pregnancy
Mean follow up: 6,5 years
Microalbuminuria
Albuminuria
P = NS
15
1,5
10
%
%
5
1
0,5
0
Pregnant
Intensive
P = NS
2
Not-pregnant
Conventional
0
Pregnant
Not-pregnant
Diabetes Care 23:1084–1091, 2000
The EURODIAB Prospective
Complications Study (PCS)
Random sample of 3250 patients with type 1 diabetes recruited from 31
centres in 16 European countries
1138 women with childbearing potential
425 childless women (1/4 with microalbuminuria) at baseline
102 (24%) gave birth
Nulliparous
267 normoalbuminuric
Parous
235 Nomoalbuminuric
Raised HbA1c was the only factor significantly
related to progression to microalbuminuria
32 (12%) progressed to
microalbuminuria
35 (15%) progressed to
microalbuminuria
Vérier-Mine O et al. Diab Med 2005; 22(11): 1503–9
Nefropatia diabetica: qual è la storia naturale?
Qual è il rischio di pre-eclampsia nella nefropatia diabetica?
La gravidanza aumenta il rischio di progressione della nefropatia?
Quali sono i rischi a lungo termine per il nascituro?
Diabetes 59:2631–2636, 2010
Conclusioni
Lo stadio della nefropatia predice il rischio
successivo di complicanze durante la
gravidanza
All’aumentare della proteinuria aumenta il rischio di preeclampsia
Il ruolo della gravidanza sulla successiva progressione della nefropatia
non è ancora completamente chiaro, anche se sembrerebbe avere un
ruolo modesto
Nelle donne con nefropatia diabetica la gravidanza
deve essere programmata:
stadiazione nefropatia e valutazione dei rischi
sospensione dei farmaci non sicuri in gravidanza
(ACE inibitori, sartani, statine)
Grazie per l’attenzione