Tutorial

Chronic Kidney Disease

Lana Novira Ys.

030.10.156

Epidemiologi
AS: 100 kasus CKD/juta penduduk/tahun;
meningkat 8% setiap tahun
Malaysia: 1800 kasus baru RF/ tahun
Negara berkembang lain: 40-60 kasus
CKD/juta penduduk/tahun

Definition of
Chronic Kidney Disease

AJKD 2002: 39(2)

Patogenesis

Patogenesis
Stadium dini kehilangan cadangan ginjal (renal reserve) :
GFR normal atau meningkat
Penurunan fungsi nefron progresif : ureum dan kreatinin
serum meningkat
GFR 60% : asimtomatik
GFR 30% : nokturia, lemah, mual, nafsu makan , BB
GFR < 30% : tanda uremia anemia, TD , gangguan
metabolisme fosfor & kalsium, gangguan keseimbangan
elektrolit, mudah terinfeksi saluran napas, cerna, dan kemih
GFR < 15% : komplikasi lebih serius; memerlukan terapi
pengganti ginjal (dialisis, transplantasi) RF

Stages of
Chronic Kidney Disease

AJKD 2002: 39(2)

Definition and Stages of

Chronic Kidney Disease

AJKD 2002: 39(2)

GFR
Kockcroft-Gault formula:
GFR (ml/mnt/1.73m2) = (140-umur) x kgBB

*)

72 x kreatinin plasma
*) pada perempuan dikalikan 0.85

Stages in Progression of CKD and

Therapeutic Strategies

AJKD 2002: 39(2)

Risk Factors for

Adverse Outcomes of CKD

AJKD 2002: 39(2)

Prevalence of Individuals at
Increased Risk for CKD

AJKD 2002: 39(2)

Potential Risk Factors for

Susceptibility to and
Initiation of CKD

AJKD 2002: 39(2)

Stages of CKD:
A Clinical Action Plan

AJKD 2002: 39(2)

Gambaran Klinis
Sesuai dengan penyakit yang mendasari
(DM, UTI, HT, dll)
Sindrom uremia: lemah, letargi, anoreksia,
mual-muntah, nokturia, volume overload,
neuropati perifer, pruritus)
Gejala komplikasi: HT, anemia, osteodistrofi
renal, payah jantung, asidosis metabolik,
gangguan keseimbangan elektrolit (sodium,
kalium, klorida)

Gambaran Laboratoris
Sesuai dengan penyakit yang mendasarinya
Penurunan fungsi ginjal: ureum-kreatinin ,
GFR
Kelainan biokimia darah: Hb , as. urat ,
hiper/hipokalemia, hiponatremia,
hiper/hipokloremia, hiperfosfatemia,
hipokalsemia, asidosis metabolik
Kelainan urinalisis: proteinuria, hematuria,
leukosuria

Gambaran Radiologis
Foto polos abdomen: batu radio-opak
USG ginjal: ukuran ginjal mengecil,
korteks menipis, hidronefrosis atau batu
ginjal

Penatalaksanaan
Terapi spesifik penyakit dasar (sebelum GFR turun. GFR
20-30% tidak berguna)
Pencegahan dan terapi terhadap kondisi komorbid
(gangguan keseimbangan cairan, HT tidak terkontrol,
UTI, obstr.sal.kemih)
Memperlambat perburukan fungsi ginjal
Pencegahan dan terapi penyakit kardiovaskular
(pengendalian DM, dislipidemia, HT, anemia, volume
overload)
Pencegahan dan terapi komplikasi
Terapi pengganti ginjal: dialisis, transplantasi

Menghambat Perburukan
Fungsi Ginjal

Menghambat Perburukan
Fungsi Ginjal
Pembatasan asupan protein (GFR60%):
0.6-0.8/kgBB/hari, kalori 30-35
kkal/kgBB/hari. Pantau status gizi, bila
malnutrisi tingkatkan asupan kalori dan
protein
Terapi farmakologis (mengurangi HT
intraglomerulus): ACE-I

Komplikasi
Derajat

Penjelasan

GFR

Komplikasi

Kerusakan ginjal 90
GFR normal

Kerusakan ginjal 60-89

Penurunan GFR
ringan

TD mulai

Penurunan GFR
sedang

30-59

Hiperfosfatemia
Hipokalsemia
Anemia
Hiperparatiroid
HT

Penurunan GFR
berat

15-29

Malnutrisi
Asidosis
metabolik
Cenderung
hiperkalemia
Dislipidemia

Gagal ginjal

<15

Gagal jantung
Uremia

Komplikasi

Diabetes
The Leading Cause of Kidney
Failure

Increased Mortality in Patients With Diabetes

and CKD: 2-Year Clinical Outcomes
100

No Events
ESRD, CKD Stage 5
Death

Patients (%)

80
60

61.6

67.6
84.0

40

6.1

2.9
20
0

15.7
+ DM,
- CKD

0.3

29.5

32.3

- DM,
+CKD

+ DM,
+ CKD

Medical Cohort
CKD identified as ICD-9-CM diagnosis code, includes CKD from diabetes, hypertension,
obstructive uropathy, and other diagnosis codes reported on USRDS ESRD registration forms.
DM = diabetes mellitus; ESRD = end-stage renal disease; ICD-9-CM = International Statistical
Classification of Diseases, 9th Revision, Clinical Modification.
Collins et al. Kidney Int. 2003;64(suppl 87):S24-S31.

2005 The Johns Hopkins University School of Medicine.

Proteinuria Predicts Stroke and CHD

Events in Patients With Type 2
Diabetes
Prot <150 mg/L

Prot 150-300 mg/L

40

1.0

P<0.001

0.9

Incidence (%)

Survival Curves for

CV Mortality

Prot >300 mg/L

0.8
0.7
0.6
Overall: P<0.001

0.5

30
20
10
0

0
0

20

40

60

Follow-Up (mo)

80

100

Stroke

CHD
Events

CHD = coronary heart disease; Prot = urinary protein excretion; CV = cardiovascular.

Miettinen et al. Stroke. 1996;27:2033-2039.

2005 The Johns Hopkins University School of Medicine.

Evidence for Effects of Good Glycemic

Control on Complications, Including
Nephropathy
Trial

Complication
Retinopathy
Nephropathy
Neuropathy

DCCT
A1C: (9
7%)
N = 1441

Kumamot
o
(9 7%)
N = 110

UKPDS
(8 7%)
N = 5102

76%

69%

17-21%

70%

24-33%

54%
60%

DCCT = The Diabetes Control and Complications Trial.

DCCT Study Group. N Engl J Med. 1993;329:977-986; Ohkubo. Diabetes Res Clin Prac. 1995;28:103-117;
UKPDS Study Group. Lancet. 1998;352:837-853.
2005 The Johns Hopkins University School of Medicine.

Hypertension
The Second Leading cause of
Kidney Failure

Recommendations for BP and

RAS Management in CKD
Patient
Group

Goal BP
(mm Hg)

First Line

Adjunctive

+ Diabetes

<130/80

ACE-I or ARB Diuretics then CCB or BB

Diabetes
+ Proteinuria

<130/80

ACE-I or ARB Diuretics then CCB or BB

Diabetes
Proteinuria

<130/80

No specific preference:
Diuretics then ACE-I, ARB, CCB, or BB

EXPECT TO NEED TO USE 3+ AGENTS TO ACHIEVE GOALS

Recommendations largely consistent across JNC 7, ADA, and K/DOQI
BP = blood pressure; RAS = renin angiotensin system; CCB = calcium channel blocker;
BB = -blocker; JNC 7 = The Seventh Report of the Joint National Committee on Prevention,
Detection, Evaluation, and Treatment of High Blood Pressure.
ADA. Diabetes Care. 2005;28(suppl 1); Chobanian et al. JAMA. 2003;289:2560-2572; Kidney Disease Outcomes
Quality Initiatives (K/DOQI). Am J Kidney Dis. 2004;43(5 suppl 1):S1-S290.
2005 The Johns Hopkins University School of Medicine.

ACEI/ARB & Reduced Risk of Rapid GFR

Decline, Kidney Failure, or Death
AASK (N=1094)

RENAAL (N=1513)

-16
-22

-38

Ramipril vs
Metoprolol
P = 0.04

Losartan vs
Placebo
P = 0.02

IDNT (N=1722)

-20
Irbesartan

-23

vs Placebo Irbesartan
P = 0.02 vs Amlodipine
P = 0.006

Ramipril vs
Amlodipine
P = 0.004

Wright et al for the AASK Study Group. JAMA. 2002;288:2421-2431.

[AASK - African American Study of Kidney Disease and Hypertension]
Brenner et al for the RENAAL Study Investigators. N Engl J Med. 2001;345:861-869.
[RENAAL = Reduction of Endpoints in NIDDM with the Angiotensin II Antagonist Losartan]
Lewis et al for the Collaborative Study Group. N Engl J Med. 2001;345:851-860.
[IDNT = Irbesartan in Diabetic Nephropathy Trial.]
2005 The Johns Hopkins University School of Medicine.

Relationship Between Achieved BP

and GFR
MAP = Mean Arterial Pressure*

r = 0.69
P<0.05
Untreated
Hypertension
130/80

140/90

*MAP = [SBP + (2 DBP)]/3 mm Hg.

Summary of 9 studies used in figure.
Parving et al. 1989; Viberti et al. 1993; Klahr et al. 1993; Hebert et al. 1994; Lebovitz et al. 1994;
Moschio et al. 1996; Bakris et al. 1996; Bakris et al. 1997; GISEN Group. 1997.
Bakris et al. Am J Kidney Dis. 2000;36:646-661.
2005 The Johns Hopkins University School of Medicine.

Anemia
A Modifiable and Funded Risk
Factor

Anemia Prevalence by CKD

Stage
Patients With Anemia* (%)

NHANES III
NHANES 1999-2000

CKD Stage
*NHANES participants aged 20 y with anemia as defined by WHO criteria: hemoglobin (Hgb)
<12 g/dL for women, and Hgb <13 g/dL for men.
USRDS 2004 Annual Data Report. The data reported here have been supplied by the USRDS. The interpretation and
reporting of these data are the responsibility of the author(s) and in no way should be seen as an official policy or
interpretation of the U.S. government. Available at: www.usrds.org. Accessed 3/28/05.
2005 The Johns Hopkins University School of Medicine.

Anemia Treatment Eligibility

Serum Creatinine (2.0 mg/dl or above)
or
Creatinine Clearance (45 ml/min or
below) and
Hemoglobin (11g/dl or below) or
Hematocrit (33% or below) or
Symptoms of anemia

Consequences of Anemia in CKD

Reduced oxygen delivery to tissues
Decrease in Hgb compensated by increased cardiac
output
Progressive cardiac damage and progressive renal
damage1
Increased mortality risk2
Reduced quality of life (QOL)3
Fatigue
Diminished exercise capacity
Reduced cognitive function
Left ventricular hypertrophy (LVH)4
1. Silverberg et al. Blood Purif. 2003;21:124-130. 2. Collins et al. Semin Nephrol. 2000;20:345-349; 3. The US
Recombinant Human Erythropoietin Study Group. Am J Kidney Dis. 1991;18:50-59; 4. Levin. Semin Dial.
2003;16:101-105.
2005 The Johns Hopkins University School of Medicine.

Clinical Benefit of Anemia Correction:

CHF and CKD
Patients With CHF and Anemia (n = 126, 91% CKD)

Parameter

Before

After

10.3

13.1

2.4

2.3

-0.95

0.27

NYHA class (0-4)

3.8

2.7

Fatigue/SOB index (0-10)

8.9

2.7

Hospitalizations

3.7

0.2

Systolic BP (mm Hg)

132

131

Diastolic BP (mm Hg)

75

76

Hgb (g/dL)
Serum creatinine (g/dL)
GFR (mL/min/mo)

NYHA class = New York Heart Association classification;

2005 The Johns Hopkins University School of Medicine.
SOB = shortness of breath.
Silverberg et al. Perit Dial Int. 2001;21(suppl 3):S236-S240.

Secondary
Hyperparathyroidism
An Early and Modifiable
Complication of CKD

Calcitriol Decline and iPTH Elevation

as CKD Progresses
CKD Stage 1
5.6 million

Stage 2
5.7 million

Stage 3
7.4 million

Stage 4
300,000

40
30
25
20

300
Low-Normal
Calcitriol

200

10
0

400
iPTH (pg/mL)

Calcitriol
1,25(OH)2D3 (pg/mL)

50

100
High-Normal 65
PTH
105

95

85

75

65

55

45

35

25

15

eGFR (mL/min/1.73 m2)

N = 150.
iPTH = intact PTH.
Adapted from Martinez et al. Nephrol Dial Transplant. 1996;11(suppl
3):22-28.
2005 The
Johns Hopkins University School of Medicine.

Feedback Loops in SHPT

Decreased Vitamin D Receptors
and Ca-Sensing Receptors

PTH

PTH

Ca++
Bone Disease
Fractures
Serum P
Bone pain
Marrow fibrosis
Erythropoietin resistance

1,25D
Calcitriol

Systemic Toxicity
CVD
Hypertension
Inflammation
Calcification
Immunological

25D
Renal Failure
Ca = calcium; CVD = cardiovascular disease; P = phosphorus.
Courtesy of Kevin Martin, MB, BCh.

2005 The Johns Hopkins University School of Medicine.

Bone Loss Correlates With Severity of

SHPT in CKD Stages 3 and 4

*
*
*

*P<0.05 compared with patients with PTH in the normal range.

Z-Score = comparison to the mean value for women at a similar risk, including age,
weight, and ethnicity.
Rix et al. Kidney Int. 1999;56:1084-1093.

2005 The Johns Hopkins University School of Medicine.

Observed/Expected
Incidence of Hip Fracture*

Bone-Fracture Rate Increases as CKD

Progresses: Fractures in Patients on
Dialysis
100

87

Overall
Male Relative Risk = 4.4
Female Relative Risk = 4.4

99

80

25 20

20
15

10 10

10

7.5

6.4

2.4 2.5

4.4 4.4

0
<45

45-54

55-64
65-74
Age (y)

75-84

Total

*Ratio of observed incidence of hip fracture in patients with kidney failure to expected incidence
of hip fracture in the general population.
Adapted from Alem et al. Kidney Int. 2000;58:396-399.

2005 The Johns Hopkins University School of Medicine.

Cardiovascular Outcomes Worsen With

CKD Progression: 3-Y Follow-Up by eGFR
Levels
eGFR (mL/min/1.73 m )
Estimated Event Rate (%)

P<0.001

CHF = congestive heart failure.

Anavekar et al. N Engl J Med. 2004;351:1285-1295.

75
60-74
45-59
<45

2005 The Johns Hopkins University School of Medicine.

Thank you