A Comprehensive Approach to
Kidney Disease and Hypertension
Dr. Eddy Susatyo, SpPD
SubBag Ginjal dan Hipertensi
Ilmu Penyakit Dalam
RSI ARAFAH/ RSUD Rembang
Ginjal
Fungsi Ginjal
• Regulasi volume cairan
• Regulasi keseimbangan elektrolit
• Regulasi keseimbangan asam dan basa
• Regulasi tekanan darah (RAAS)
• Regulasi eritropoesis
• Ekskresi sampah metabolik
• Metabolisme vitamin D
• Sintesis prostaglandin
Apa penyebab Gagal Ginjal ?
Akut
Gagal Ginjal
Kronik
• Chronic
– CKD: Chronic Kidney Disease
• Acute
– ARF: Acute Renal Failure
– AKI: Acute Kidney Injury
• Acute Classification
– Pre-renal
– Renal
– Post-renal
The CKD problem
• Clinically silent in the early stages
• Cost of renal disease can be extreme to
health care service
• Effects of renal disease can be extreme on
patient
• Treatments now available to slow progression
• Need an “early warning” system for CKD
Diseases of the Kidney
•
•
•
•
•
Diabetes
Hypertension
Atherosclerosis
Glomerular diseases
Toxins
– Gentamicin
– NSAIDS
– Compound analgesics
• Inherited diseases
• Tubular disorders
All global renal diseases
affect glomerular
filtration rate (GFR)
• Glomerular Filtration Rate is the volume of fluid passing
through the glomerulus in a given period of time.
• Influenced by renal perfusion pressure, renal vascular
resistance, glomerular damage, post-glomerular
resistance.
• “Normal Range” approx 90 - 150 mL/min
– Approx 170 L per day
• A larger healthy person has a higher GFR
– Can be reported as 90 - 150 mL/min/1.73m2
• Values fall with increasing age
Other reasons for estimating the GFR
• Monitoring progression of CKD
• GFR estimates are used for drug dosing
decisions
– Dosing of renally excreted drugs
– Avoiding nephrotoxic drugs
• Risk factor for cardiovascular disease
mortality
• Renal involvement in systemic diseases, such
as diabetes mellitus or SLE
Estimate of GFR
•
•
•
•
Measured GFR
Serum creatinine
Creatinine clearance
Formulae based on serum creatinine
– Cockcroft and Gault
All based on measurements
– MDRD
of
serum
creatinine
• Other
– Eg Cystatin C
Equations for Estimating GFR
Abbreviated MDRD Study Equation
GFR (mL/min/1.73 m2) = 186.3  SCr -1.154  Age-0.203
 0.742 (if female)  1.210 (if African American)
Cockcroft-Gault Equation
Ccr =
(mL/min)
(140 – Age)  Weight in kg
72  SCr
MDRD = Modification of Diet in Renal Disease; Ccr = creatinine clearance.
Levey et al. Ann Intern Med. 2003;139:137-147.
 0.85 if female
Definition of CKD
• Kidney damage for 3 months
– Defined by structural or functional abnormalities of
the kidney,
with or without decreased glomerular filtration rate
(GFR)
• Reduced GFR for 3 months
• New staging for chronic kidney disease (CKD)
is primarily based on kidney function.
National Kidney Foundation (NKF). Am J Kidney Dis. 2002;39(2 suppl 1):S1-S266.
Prevalence of CKD
The Most
Common Causes of CKD
Other
10%
Diabetes
50.1%
Glomerulonephritis
13%
Hypertension
27%
Primary Diagnosis for Patients Who Start on Dialysis
STAGES OF CKD
NORMAL
INCREASED RISK
COMPLICATIONS
CKD
DEATH
DAMAGE
LOW GFR
RENAL FAILURE
Bagaimana dengan Anemia Renal ?
Anemia Rates Increase as Levels of CKD Severity
Progress
100
Anemia Prevalence (%)
80
60
10
Hgb Values
15
11-12 g/dL
10-11 g/dL
<10 g/dL
15
8
40
17
62
20
9
5
14
0
<2
8
43
20
2-2.9
3-3.9
Creatinine (mg/dL)
Chronic Kidney Disease (CKD) Progression
Hgb = hemoglobin.
Kausz et al. Dis Manage Health Outcomes. 2002;10:505-513.
≥4
Normal
Gagal Ginjal
Chronic kidney disease (CKD)
Anemia is an expected complication of CKD
Treatment
Increased cardiovascular morbidity
recombinant human erythropoietin
(r-HuEPO)
Left Ventricular Hypertrophy
(LVH)
Congestive Heart Failure (CHF)
Diambil : Jerome Rossert dkk, Nephrol Dial Transplant (2002) 17: 359–362
Why are CKD/ESRD Patients
Predisposed to CV Disease?
CKD/ESRD
ANEMIA
LIPIDS
INFLAMMATION plus CaP deposition
HTN
CAD and PVD
CV DISEASE AND DEATH
LVH/CHF
Why are CKD/ESRD Patients
Predisposed to CV Disease?
• 30-50% of ESRD patients have INFLAMMATION (increased
CRP, increased IL-6, decreased albumin)
– Increased CRP is a primary marker for inflammation predicting
cardiovascular disease in normal adults
– Increased CRP is the primary marker for increased cardiovascular
mortality on dialysis
• CKD/ESRD patients have metastatic calcification (coronary
arteries) because of secondary hyperparathyroidism and
elevated PO4 levels.
Bagaimana hubungan antara
hipertensi dengan CKD ?
Distribution of hypertensives (65-89 years)
MEN
WOMEN
ISOLATED
SYSTOLIC
ISOLATED
SYSTOLIC
63.6%
59.3%
30.3%
27.7%
8.7%
10.4%
COMBINED
COMBINED
ISOLATED
DIASTOLIC
ISOLATED
DIASTOLIC
Framingham study
Factors Affecting Blood Pressure
Blood
Pressure
=
Cardiac
Output
Amount of blood
ejected per minute
X
Total
Peripheral
Resistance
Blood flow through
blood vessels
Prevalence of HTN in CKD
80% of patients with
glomerulonephritis
and 30% of patients
with chronic interstitial
disease are
hypertensive.
Aggressive BP Control, Proteinuria and
CKD Progression – what is the optimal BP
for CKD?
0
<1 gm/D
-2
1-2.9
gm/D
>3 gm/D
-4
Mean fall
in GFR
-6
(ml/min/yr)
-8
<125/75
<140/90
*
*
-10
-12
GOAL BP<125/75 if >1 gm proteinuria
Klahr S et al, N Engl J
Med 330:877, 1994
Angiotensin II plays a central role in organ damage
Atherosclerosis*
Vasoconstriction
Vascular hypertrophy
Endothelial dysfunction
A II
LV hypertrophy
Fibrosis
Remodeling
Apoptosis
GFR
Proteinuria
Aldosterone release
Glomerular sclerosis
Stroke
Hypertension
Heart Failure
MI
Renal Failure
*Preclinical data.
LV = left ventricular; MI = myocardial infarction; GFR = glomerular filtration rate.
Death
Renin Angiotensin Aldosterone System
Non-ACE pathways




(eg, chymase)
Vasoconstriction
Cell growth
Na/H2O retention
Sympathetic activation
Angiotensinogen
Renin
AT1
Angiotensin I
Angiotensin II
ACE
Aldosterone
Cough,
angioedema
Benefits?
 Bradykinin
Inactive
fragments
AT2
 Vasodilation
 Antiproliferation
(kinins)
Increased
angiotensin II
Decreased
vasodilatory
prostaglandins
Low GFR
How About Renal Osteodystrophy
Bone Disease in CKD

Metabolic abnormalities



Hyperphosphatemia
Hypocalcemia
PTH elevation
Bone Disease in CKD

Renal Osteodystrophy

Osteomalacia / osteitis fibrosis cystica / osteosclerosis

Metastatic calcification

Vascular!
Bone Disease in CKD

Renal Osteodystrophy
Matur nuwun