PD
Derajat 1 2 3 4 5
Penjelasan Kerusakan ginjal dengan LFG normal atau Kerusakan ginjal dengan LFG ringan Kerusakan ginjal dengan LFG sedang Kerusakan ginjal dengan LFG berat Gagal ginjal
Diabetes melitus - Tipe 1 (7%) - Tipe 2 (37%) Hipertensi dan penyakit pembuluh darah besar Glomerulonefritis Nefritis interstitialis Kista dan penyakit bawaan lain Penyakit sistematik (misal, lupus dan vakulitis) Neoplasma Tidak diketahui Penyakit lain
44 %
27 % 10 % 4% 3% 2% 2% 4% 4%
Penyebab Gagal Ginjal yang Menjalani Hemodialisis di Indonesia Th. 2000 Penyebab Insiden
13%
10%
50%
Diabetes
Hypertension
Glomerulonephritis
Other
Cardiovascular complications
Microalbuminuria
Overt proteinuria
Glomerular hyperfiltation
Tubulointerstitial fibrosis
Endothelial dysfunction Risk factors Hypertension Lipid disorders Hyperinsulinemia Diabetes Smoking
Onset of diabetes
10
Years
20
30
50% Normoalbuminuria Diabetes duration Baseline AER Glycaemic control Genetic suspectibility Ethnic minorities 30% Sustained microalbuminuria Sustained Normoalbuminuria
30%
50%
Microalbuminuria 30%
Intermittent proteinuria
ECM ACCUMULATION
PROTEINURIA
Proteinuria
PAI-1
Aldosterone
Cytokine production
Pgt
ECM degradation
Inflammation
ECM accumulation
Inflammation
Angiotensin II
Glomerular capillary hypertension Cell and tissue growth
Glomerulosclerosis
RENOPROTECTION Reduction of blood pressure Reduction of albuminuria Non blood pressure dependent action of RAAS blockade
Microalbuminuria (MA) is defined as the presence of albumin in the urine above the normal range of less than 30 milligrams per
Local process
1. Increased intraglomerular capillary pressure 2. Increased shunting of albumin through glomerular membrane pores Systemic process 1. Activation of inflammatory mediators
Hyperinsulinemia
NIDDM
IDDM
Intermediate metabolites
Leaky endothelium
Modification of mesangium
Hyperfiltration
Involvement of glomerular membrane
Microalbuminuria
Hypertension + Microalbuminuria
NO
AGEs
Endothelial cell Factors that interact to produce and worsen atherosclerosis in people with renal disease Bakris, 2004
6
Normoalbuminuria
5 4 3 2 1 0
Female
Male
Microalbuminuria Normoalbuminuria
Microalbuminuria and ischemic heart disease (IHD) risk associated with blood pressure.
1 0.9 0.8
Survival probability None Light
Heavy
9 10 11 12 13 14 15 16 17
Survival among 3.234 patients with type II diabetes according to proteinuria level (WHO multinational study of vascular disease and diabetes)
J Hyp 2003; 21: 21.1
0.8
Proportion Surviving Normoalbuminuria
0.6
Microalbuminuria
0.4
0.2
Gross Proteinuria
10
12
Years of Follow-up
Valmadrid CT et al. Arch Intern Med 2000; 160:1093-1100
ADA Guidelines
Initial Agents of Choice
Level A evidence
In the treatment of albuminuria / Kidney Disease
Type 1 diabetes
Type 2 diabetes
ACE inhibitors
If one class is not tolerated, the other should be substituted Diabetes Care, Vol 25, suppl 1, January 2002
20 15 10 5 0 0
Subjects (%)
12 Follow-up (mo)
18
22
24
18 16 14 12 10 8 6 4 2 0
RRR=39% p=0.08
Subjects (%)
9.7
5.2
Control (n=201)
150 mg (n=195)
300 mg (n=194)
Irbesartan
Parving H-H et al., N Engl J Med 2001;345:870-878
Articles
-22% p<0.001
-32% p<0.001
20
p < 0.001
Placebo
15
10
Ramipril
0.25
0.20
Hazard
Placebo
0.15 0.10
ALL: RR: 0.81, CI: (0.74-0.88)
0.05
0.0
Years
Patients who started ACE inhibitor late do not reach the same Risk Reduction compared to those who started early!
Placebo
Ramipril
P=0.02 2.0 1.5 P=0.001 1.0 0.5 0 1 2 Time (years) 3 4.5
MICROHOPE STUDY
0.16
All-cause mortality
Kaplan-Meier rates
0.12
Placebo Ramipiril
0.08
0.04
Duration of follow-up (days) Kaplan-Meier survival curves for participants with diabetes
THE LANCET, Vol 355, January 22, 2000
Degradation Products
ACE Inhibitor
Angiotensin II Bradykinin
PPAR pathways
Angiotensin pathways
Insulin resistance
Dyslipidemia
Cell inflammation
Cell proliferation
Hypertension
Oxidative stress
Inhibition of atherosclerosis
Potention influence of ARBs on pathways that are likely primarily to mediate the antiatherosclerotic effects of peroxisome proliferator activated receptor gamma (PPAR) activation and angiotensin II receptor blockade
J Hypertension 2004, Vol 22 No. 12
Start low-dose sodium diet Add a low-dose ACEi or ARB Up-titrate ACEi or ARB to max tolerated dose Add a diuretic Add a low dose of another antiproteinuric agent (K<5.5 mEq/L K>5.5 mEq/L
Targets of the multidrug approach: Blood pressure <120/80 mmHg Proteinuria <0.3 g/24 h LDL <100 mg/dL LDL + VLDL <130 mg/dL HbA1c <7.5% (diabetics)
SUMMARY
MicroaIbuminuria in Diabetic Kidney Disease
An important indicator of risk of renal and cardiovascular disease A guide to the severity of renal and extrarenal manifestation of diabetes mellitus and hypertension Strong evidences shown that ACE inhibitor and ARBs