Manejo das Doenças cardiovasculares na DRD
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Manejo das Doenças Manejo das Doenças
cardiovasculares na DRD cardiovasculares na DRD
Maria Eugênia F Canziani UNIFESP
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DCV vs. DRCDCV vs. DRC OMS
DM – 217 milhões em 2005 366 milhões em 2030
“epidemia mundial de síndrome metabólica e DM”
Maior prevalência de DM
alta morbidade e mortalidade – aterosclerose
- Dça coronariana
- Ac. vascular cerebral
- Dça arterial periférica
Diabetes Care 2004, 27: 1047NEJM 1998, 339:229
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DCV vs. DRCDCV vs. DRC
Doenças Cardiovasculares
80% causas de óbito de pac. DM tipo 2
Estudos epidemiológicos
- DM vs. nDM 2 – 4 X risco DCV ( 12 X DM I)
Framingham Heart Study 2 – 10 X risco
- Dça coronariana, AVC, ICC, óbito DCV
Doença Renal Crônica
Diabetes Care 1979, 2: 120NEJM 1998, 339:229
AJKD 2005, 45:S1 USRDS 2005
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DCV vs. DRCDCV vs. DRC
7582 HA +DM projeto italiano
risco de HVE 23% para cada 21mL/min TFG
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USRDS – 1995 a 1999, n= 373.539 pac. início – diálise
38,4% HA+DM / 11,4% DM / 37,4% HA / 12,8% nada
0
1
2
3
4
5
6
ICC D Isq. IAM
DM + HÁ DM HÁ Nada
Odd
s ra
tio
DCV vs. DRCDCV vs. DRC
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DCV vs. DRCDCV vs. DRC
7788 pac ICC – 987 pares DRC vs. DRC + DM
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Diabetes
DCVDRC
Mortalidade
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DCV vs. DRCDCV vs. DRC
Hiperglicemia
Ativação PKC Oxidação glicose Formação AGEs Ativação via poliol
Metab. Ac.araquidônico
Atividade antiox.
Estresse oxidativo
Disfunção endotelial
Patogênese da hiperglicemia induzindo disfunção endotelial
Vasc Health and Risk Management 2007; 3(6):853
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disfunção endotelial placa aterosclerótica
New Engl J Med 1999 340(2):115
Evento Isquêmico
DCV vs. DRCDCV vs. DRC
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Colesterol (mg/dl) 202 120 – 357 51% > 200
HDL (mg/dl) 49 29 – 114 23% < 40
LDL (mg/dl) 111 15 – 251 65% > 100
TG (mg/dl) 146 38 – 1104 47% > 150
Perfil lipídico (n=96)
Precoce e qualitativa 87%
Tomiyama C, Canziani ME
Sobrepeso e obesidade (IMC>25) 53%
DCV vs. DRCDCV vs. DRC
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Síndrome MetabólicaObesidade centralPop. Geral DCV e mortalidadeassociação com dislipidemia tecido adiposo produz TNF,IL6 e IL1
Endocrin 2003, 144:2195
J. Clin. Investig, 112: 1785-1788, 2003.
DCV vs. DRCDCV vs. DRC
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ADIPONECTINA
DRC Inflamação + disfunção endotelial
DCV vs. DRCDCV vs. DRC
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Am J Kidney Dis, 2008Am J Kidney Dis, 2008
123 pacientes em conservador
correlação com a gordura visceral
medida pela CT
Fatores de risco DCV
(lípides, HOMA, PCR)
Calcificação coronariana e adipocinas ?
DCV vs. DRCDCV vs. DRC
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DRC
Diabetes
DCV
DCV vs. DRCDCV vs. DRC
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P, 1,25(OH) vitD OsteodistrofiaAlteração do Metabolismo Mineral
Doença CardiovascularInflamação IL-6, TNFα,
CRP, oxLDL
Não tradicionais (relac. uremia)
Secreção Renina Hipertensão
Eritropoietina Anemia
DCV vs. DRCDCV vs. DRC
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DCV vs. DRCDCV vs. DRC
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Doença renal crônicaEstresse oxidativoAcúmulo de citocinasAcúmulo de AGEInfecções crônicasSobrecarga de volume e HASToxicidade urêmica
Sinais de ativaçãoTNF-α, IL-1OxidantesAGE/RAGELPS
Mediadores InflamatóriosCitocinas
Fatores de crescimento
Metaloproteinases
Pró-coagulantes
AteroscleroseOxidação do LDLMigração de leucócitosInflamaçãoProliferação de céls. Musc.Calcificação vascular ( fetuina)
Uremia Cél. Inflamatória Parede vascular
Transcrição
Genes inflamatórios
Inflamação
Stenvinkel P, Pecoits-Filho R, et al JASN 2003, 14:1927
DCV vs. DRCDCV vs. DRC
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DRC - Diabetes
DCV vs. DRCDCV vs. DRC
Doença de Baixo Remodelamento
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Cálcio
FósforoPTH
PTH
Calcificação
Depósito Tecidual
Cálcio
Fósforo
X
X
DCV vs. DRCDCV vs. DRC
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Tomografia Coronariana normal TC com calcificação
aorta
CD
CX
DA
DCV vs. DRCDCV vs. DRC
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Coronary calcification is associated with lower bone formation rate in CKD patients not yet in dialysis treatment.CristianneTomiyama1, Aluizio B. Carvalho1, Andrea Higa1, Vanda Jorgetti2, Sérgio A. Draibe1, Maria Eugênia F. Canziani1. 1Department of Internal Medicine/ Division of Nephrology, Federal University of São Paulo, São Paulo, Brazil; 2Department of Internal Medicine/ Division of Nephrology, University of São Paulo, São Paulo, Brazil
CT + biopsia óssea n= 50 51 ± 11anos, 68% masc, 30% DM, Clcr 39 ± 19 mL/min
BMI > 25 kg/m2 (%) 27 (54%)
Ionized calcium (mmol/L) 1.30 ± 0.06
Phosphorus (mg/dL) 3.8 ± 0.7
Alkaline phosphatase (U/L) 116 (37 – 634)
Intact parathyroid hormone (pg/mL) 83 (26 – 548)
25(OH) vitamin D (ng/mL) 30.8 ± 10.1
1.25 (OH)2 vitamin D (pg/mL) 39.9 ± 18.1
JBMR 2009- in press
Deficiência de Vitamina D – 10%Insuficiência de Vitamina D - 32%
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0%
20%
40%
60%
80%
100%
2 3 4
CKD Stages
% P
atie
nts
Low turnover Normal High turnover
Reference ranges
MALE FEMALE
Structure
BV/TV % 17.2 ± 5.7 24.0 6.1 21.8 7.2
Tb.Th μm 124.3 ± 26.8 127.9 29.7 126.0 28.8
Tb.Sp μm 658.3 ± 237.1 420.6 124.1 498.3 195.9
Tb.N n/mm 1.38 ± 0.38 1.89 0.42 1.76 0.52
Formation
OV/BV % 2.29 ± 2.5 2.9 2.7 1.55 1.9
Ob.S/BS % 1.8 ± 2.2 1.2 1.4 1.2 3.2
O.Th μm 7.8 ± 3.1 11.7 3.5 10.8 3.2
OS/BS % 15.5 ± 13.6 16.1 12.6 9.2 8.4
BFR/BS μm3/ μm2/day 0.017 ± 0.02 0.13 0.07 0.07 0.03
*MLT days 204.8 ± 240.5 21.3 2.3 23.7 2.7
Resorption
ES/BS % 7.8 ± 6.4 1.75 1.21 2.3 2.4
Oc.S/BS % 0.73 ± 0.79 0.03 0.11 0.03 0.06
Fibrosis
Fb.V/BV % 0.05 ± 0.10 0 0
Diabetes
Doença de baixoremodelamento
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Without calcification (n = 17)
With calcification (n = 33)
P
Age (years) 46 ± 12 54 ± 9 0.01Male gender (%) 47 79 0.02Diabetes (%) 18 51 0.03Creatinine clearance (ml/min/1,73m2) 38 ± 17 39 ± 19 0.81
Ionized calcium (mmol/L) 1.32 ± 0.04 1.29 ± 0.06 0.01
Phosphorus (mg/dL) 3.9 ± 0.6 3.7 ± 0.8 0.49
Intact parathyroid hormone (pg/mL) 92 (33 – 416) 108 (26 – 548) 0.12
Alkaline phosphatase (U/L) 95 (37 – 257) 122 (51 – 634) 0.52
1.25 (OH)2 vitamin D (pg/mL) 38.7 ± 14.3 41.2 ± 20.5 0.66
25(OH) vitamin D (ng/mL) 33.4 ± 9.9 29.4 ± 10.1 0.17
Bicarbonate (mEq/L) 24 ± 4 24 ± 3 0.62
BVTV (%) 18.8 ± 5.2 16.3 ± 5.8 0.16
OVBV (%) 2.4 ± 1.8 2.2 ± 2.8 0.20
Ob.S/BS (%) 2.00 ± 1.69 1.72 ± 2.43 0.21
ES/BS % 8.98 ± 6.82 6.81 ± 5.86 0.30
Oc.S/BS (%) 0.88 ± 0.70 0.65 ± 0.83 0.10
BFR (μ3/ μ2/day) 0.028 ± 0.021 0.012 ± 0.021 < 0.001
Regressão Logística ajustada para idade, sexo e DM BFR/BS (p = 0.009; OR= 0.15; 95% CI 0.036 - 0.619).
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DCV vs. DRCDCV vs. DRC
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DCV vs. DRCDCV vs. DRC
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DCV vs. DRCDCV vs. DRC
Impact of vascular calcification in CKD patients not yet on dialysis
Watanabe R; Lemos MM; Draibe AS;Canziani ME
n = 117 pac, 2 anos de segmento
p= 0.051 p= 0.002
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AJKD, 2008
DCV vs. DRCDCV vs. DRC
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0 1 2 3 4 5 6 7 8 9 10 11 12 months
iCa P
Hb/Hct Kt/V Alk. Phos.
i-PTH
OPG, DPD,BAP Lipids Inflammation
Oxy. Stress 25 (OH)D MsCT
Bone biopsy
Physician
Nutrition
Sevelamer or Phoslo100 pacientes
64 pacientes
BO / Lab. dose quelante [Ca] dialisato Calcitriol
DCV vs. DRCDCV vs. DRC
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Basal 12-mesesNão-progressores 0.007 ± 0.008 0.11 ± 0.10
Progressores 0.01 ± 0.01 0.02 ± 0.02
Bone formation rate µm3/µm2/day
-0,05
0
0,05
0,1
0,15
0,2
0,25
Non-progressors Progressors
p = 0.003
Baixo remodelamento no início Não-progressores vs Progressores
Mudanças dos parâmentros histomorfométricos em 1 ano
DCV vs. DRCDCV vs. DRC
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Fatores de risco cumulativo para DCV na DRC
ICC
Ac. Vascular cerebral
HVED. Coronariana
D. Vascular periférica
IAM
Específico da uremiaanemia hiperpara P TFG
PCR
Tradicionais modificaveisHA Dislipidemia
Fumo
Tradicionais não modificaveisidade sexo Hist. familiar DM
Hiperglicemia
MANEJO
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DCV vs. DRCDCV vs. DRCMetasMetas
Parar fumar
PA < 130/80 mmHg
LDL < 100mg/dl
TG < 130mg/dl
HbA1c < 7%
Perder peso
Aspirina
Exercício
Dieta
AJKD 2007;49(2 Suppl2):S28
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DCV vs. DRCDCV vs. DRCInvestigaçãoInvestigação
AJKD 2007;49(2 Suppl2):S30
Teste esforço
Eco / Cintilografia - estresse farmacológico
CATE
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NEJM 2005;353:2643
Intensive diabetes treatment and cardiovascular disease in patients with type 1 diabetes.
Nathan DM, et all
42% risco 57% risco
DCV vs. DRCDCV vs. DRC
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Saída do plano
Morte (antes do Tx ou diálise)
Transplantado
Iniciou diálise
Nenhum dos anteriores
FG, 60-89Proteinúria (-)
(n=14.202)
14,9
10,2
0,01
0,06
74,8
2 FG= 60-89
Proteinúria (+)(n=1.741)
16,2
19,5
0,2
0,9
63,3
3FG= 30-59
(n=11.278)
10,3
24,3
0,2
1,1
64,2
4FG= 15-28
(n= 777)
6,6
45,7
2,3
17,6
27,8
Estágios da DRC
Arch Intern Med. 2004;164:659
n=27.997, 2 medidas Cl <90mL/min,seguimento 5 anos
DCV vs. DRCDCV vs. DRC