A Comprehensive Approach to

Kidney Disease and Hypertension

PAWANG HAZWAN
Unit Ginjal dan Hipertensi
Ilmu Penyakit Dalam
 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
All global renal diseases
Toxins
Gentamicin
affect glomerular
NSAIDS filtration rate (GFR)
Compound analgesics
Inherited diseases
Tubular disorders
 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.

 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
 Sign n Symptoms
Uraemia symptoms;
Bad breath (urinous,ammonia)
Oedema (eyes, face, arms,hands, feet)
Hypertension
Extended neck veins
Fatigue (anaemia,toxic substances)
Neurological disturbances
(lethargy, confusion,sleep disorders)

J Winterbottom 2005
 Sign n Symptoms

Nausea & vomiting

Headaches
Pruritus (phosphate, calcium, aluminium)
Breathlessness
Bone & joint problems (calcium/phosphate
imbalances,VitD deficiency,demineralization)
Bone pain

J Winterbottom 2005
 Investigation
Hb
Urea n electrolyte
Creatinine
Alk phosphatase
PTH
Urine
imaging

J Winterbottom 2005
Bagaimana dengan Anemia Renal ?
 Anemia Rates Increase as Levels of CKD Severity
Progress
100

Hgb Values
Anemia Prevalence (%)

10
80
15 11-12 g/dL
60 15
10-11 g/dL
<10 g/dL
8
40 17
62
9 8 43
20 5
20
14
0
<2 2-2.9 3-3.9 4
Creatinine (mg/dL)
Chronic Kidney Disease (CKD) Progression

Hgb = hemoglobin.
Kausz et al. Dis Manage Health Outcomes. 2002;10:505-513.
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: 359362
 Why are CKD/ESRD Patients
Predisposed to CV Disease?

CKD/ESRD

ANEMIA INFLAMMATION plus CaP deposition LVH/CHF

LIPIDS HTN
CAD and PVD

CV DISEASE AND DEATH

 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
ISOLATED
SYSTOLIC
SYSTOLIC

59.3% 63.6%

30.3% 27.7%
10.4% 8.7%

COMBINED
COMBINED

ISOLATED ISOLATED
DIASTOLIC DIASTOLIC

Framingham study
 Factors Affecting Blood Pressure

Blood Cardiac Total

Pressure = Output X Peripheral
Resistance
Amount of blood
ejected per minute 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 1-2.9 >3 gm/D
-2 gm/D

-4
Mean fall
<125/75
in GFR -6
(ml/min/yr) * <140/90
-8 *

-10
Klahr S et al, N Engl J
-12
Med 330:877, 1994
GOAL BP<125/75 if >1 gm proteinuria
Angiotensin II plays a central role in organ damage

Atherosclerosis* Stroke
Vasoconstriction
Vascular hypertrophy
Endothelial dysfunction Hypertension

A II LV hypertrophy
Fibrosis
Remodeling Heart Failure Death
Apoptosis MI

GFR
Proteinuria Renal Failure
Aldosterone release
Glomerular sclerosis

*Preclinical data.
LV = left ventricular; MI = myocardial infarction; GFR = glomerular filtration rate.
 Renin Angiotensin Aldosterone System

Non-ACE pathways Vasoconstriction

(eg, chymase) Cell growth
Na/H2O retention
Sympathetic activation
Angiotensinogen

Renin Angiotensin I AT1

Angiotensin II
ACE
Aldosterone AT2

Cough, Vasodilation
Inactive Antiproliferation
angioedema Bradykinin fragments (kinins)
Benefits?
Decreased Increased
vasodilatory angiotensin II
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