Prof. DR. Dr. Endang Susalit, Sp.

PD-KGH
Pendidikan
: DOKTER, Fakultas Kedokteran Universitas Indonesia, Jakarta, 1972
SPESIALIS PENYAKIT DALAM, Bagian Ilmu Penyakit Dalam, Fakultas
Kedokteran Universitas Indonesia, Jakarta 1979
INTERNIST NEPHROLOGIST, Sub Spesialis Ginjal & Hipertensi - Konsultan,
Fakultas Kedokteran Universitas Indonesia, Jakarta, 1986
DOKTOR (S3), Program Pasca Sarjana Universitas Indonesia, Jakarta, 1996
GURU BESAR , di Fakultas Kedokteran Universitas Indonesia, Jakarta, 1998

Pekerjaan : Ketua Divisi Ginjal Hipertensi

Departemen Penyakit Dalam
FKUI/RS Dr. Cipto Mangunkusumo, Jakarta
2008-2011

Staf Divisi Ginjal Hipertensi

Departemen Penyakit Dalam
FKUI/ RS Dr. Cipto Mangunkusumo, Jakarta

Staf Pengajar di Bagian Ilmu Penyakit Dalam

FKUI/RSUPN Dr. Cipto Mangunkusumo, Jakarta
1979 – sekarang
 HIPERTENSI

PENYAKIT GINJAL KRONIK

Prevalence of Abnormalities at each level of GFR

Hypertension* Hemoglobin < 12.0 g/dL

Unable to walk 1/4 mile Serum albumin < 3.5 g/dL
Serum calcium < 8.5 mg/dL Serum phosphorus > 4.5 mg/dL
90
Proportion of population (%)

80
70
60
50
40
30
20
10
0
15-29 30-59 60-89 90+
Estimated GFR (ml/min/1.73 m2)

*>140/90 or antihypertensive medication p-trend < 0.001 for each abnormality

 CKD PATIENTS ARE COMPLEX

Patients with CKD

(eGFR < 60) have
a high incidence
of DM, HTN, CVD
and CHF
compared to
those without
moderate to
advanced CKD.

NHANES 2001–2008 participants age 20 & older.

USRDS Annual Data Report 2011 Fig 1.4, Vol 1

 ESRD is More Common than Death in
Blacks with Hypertensive Kidney Disease

AASK Trial, 1/3 of patients were < 50 y/o at enrollment

J Am Soc Nephrol 21: 1361-9, 2010
Reducing BP and progression of CKD –
MDRD trial

Close circles = usual BP130/80

Open circles = low BP125/75
Klahr et al NEJM 1994;330:877
 (CKD)

Hypertension
Progression of non-diabetic CKD
• Progression relates to
haemodynamic + metabolic factors
– Intra-glomerular hypertension
– glomerular hypertrophy
– albuminuria >1000 mg/day
(CKD)
 (Chronic Kidney Disease)

Hypertension
 Mechanism of RAAS
on the Stimulation of Sodium Retention

Opie L.H. et al, Drugs for the Heart 2001 ; 5 : 107 - 153
Glomerular Injury and Growth

Opie LH, Drugs for the heart, 2001 : 133

Ang II Increases Proximal Tubular Reabsorption

Hall J.E. et al, J Am Soc Nephrol 1999 ; 10 : S258 – S265

 Angiotensin II Induced Renal Fibrosis
Activation and recruitment of
inflammatory cells

Angiotensin Il Inflammatory Cells Chemotaxis

Chemokines
Renal Cells • MCP-1, RANTES
(mesangial, tubuloepithelial Adhesion molecules
interstitial fibroblasts) • VCAM-1
Cytokines, growth factors
Growth factors: TGFß, PDGF, CTGF
Cytokines: IL-6, TNFa
Chemokines: MCP-1, RANTES, OPN
Other: PA1, Metalloproteinases

 ECM production and  degradation

Proteinuria ECM accumulation Cell proliferation Inflammation

Renal Fibrosis

Mezzano, S.A. Hypertension 2001; 38(2) 635-638.

 Proposed Molecular Mechanism of
AT1-receptor-mediated Organ Damage in-vivo

KIM S, et al J Hypertens 1997 ; 15 (Suppl 6) : S3 – S7

 ÓTakeda Chemical Industries, 1999

Signal transduction pathways for the AT1 receptor

AII
Ca2+
AT1R

? G Protein
? PC PIP2
p2Iras PLC
PLC

JAK2 Raf-1
Raf -1 K DAG Ca2+
IP3
MEK
PKC IP3R l Fast contraction
MAPK l Hypertrophy/
Ca2+ hyperplasia
Endoplasmic l Protein kinase C
STAT91/113 p62TCF reticulum

C-fos
C-fos promoter c-fos
c- fos mRNA
Ros endorf f (19 98)
Role of Angiotensin II

Hypertension
Blockade of Angiotensin II
INDIKASI KHUSUS OBAT ANTIHIPERTENSI
Diuretik -blocker ACE ARB CCB
inhibitor

Gagal jantung • • • •
Pasca IM • •
Risiko
PJK
tinggi
• • • •
Diabetes • • • • •
Penyakit ginjal
kronik • •
Pencegahan
stroke • •
The JNC VII Report. JAMA 2003;289:2560-2572
The Predicted Effect of AIIRA vs ACE-I on GFR
in Chronic Progressive Renal Disease

Ichikawa I, Kidney Int 1996 ; 50 : 684 - 692

 Treatment of Hypertension: KDIGO
• Recommended that all CKD patients with no
proteinuria have a target BP ≤ 140/90

• Goal blood pressure for all CKD patients with

any degree of proteinuria: ≤ 130/80 (JNC8-
140/90)

• ARB or ACEI first line for any diabetic with

abnormal proteinuria, and for any CKD patient
with albumin excretion

• ACEI/ARB combination not recommended