TutorialChronic 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 (GFR≤60%): 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
KomplikasiDerajat Penjelasan GFR Komplikasi1 Kerusakan ginjal
GFR normal≥ 90 -
2 Kerusakan ginjal Penurunan GFR ringan
60-89 TD mulai ↑
3 Penurunan GFR sedang
30-59 HiperfosfatemiaHipokalsemiaAnemiaHiperparatiroidHT
4 Penurunan GFR berat
15-29 MalnutrisiAsidosis metabolikCenderung hiperkalemiaDislipidemia
5 Gagal ginjal <15 Gagal jantungUremia
Komplikasi
Diabetes
The Leading Cause of Kidney Failure
Increased Mortality in Patients With Diabetes and CKD: 2-Year Clinical Outcomes
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.
+ DM, - CKD
- DM,+CKD
+ DM,+ CKD
Medical Cohort
Patie
nts
(%)
0
20
40
60
80
100
84.067.6 61.6
No Events
29.515.7
32.3
DeathESRD, CKD Stage 5
0.3
2.9 6.1
© 2005 The Johns Hopkins University School of Medicine.
Proteinuria Predicts Stroke and CHD Events in Patients With Type 2
Diabetes
P<0.001
40
30
20
10
0Stroke CHD
Events80604020
0
0.5
0.6
0.7
0.8
0.9
1.0
Surv
ival
Cur
ves
for
CV
Mor
talit
y
Overall: P<0.001
Inci
denc
e (%
)
Follow-Up (mo)
CHD = coronary heart disease; Prot = urinary protein excretion; CV = cardiovascular.Miettinen et al. Stroke. 1996;27:2033-2039.
Prot 150-300 mg/LProt <150 mg/L Prot >300 mg/L
0 100
© 2005 The Johns Hopkins University School of Medicine.
Evidence for Effects of Good Glycemic Control on Complications, Including
Nephropathy
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.
Trial
Complication
DCCTA1C: (9
7%)N = 1441
Kumamoto
(9 7%)N = 110
UKPDS(8 7%)N = 5102
Retinopathy 76% 69% 17-21%
Nephropathy 54% 70% 24-33%
Neuropathy 60% – –
© 2005 The Johns Hopkins University School of Medicine.
Hypertension
The Second Leading cause of Kidney Failure
Recommendations for BP and RAS Management in CKD
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.
PatientGroup
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 GOALSRecommendations largely consistent across JNC 7, ADA, and K/DOQI
© 2005 The Johns Hopkins University School of Medicine.
ACEI/ARB & Reduced Risk of Rapid GFR Decline, Kidney Failure, or Death
-50
-40
-30
-20
-10
0
Com
posi
te R
isk
(%)*
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.]
Ramipril vs Amlodipine
P = 0.004
Ramipril vs Metoprolol
P = 0.04
Losartan vs Placebo P = 0.02
-38
-22-16
Irbesartan vs Placebo
P = 0.02
-20
Irbesartan vs Amlodipine
P = 0.006
-23
AASK (N=1094) RENAAL (N=1513) IDNT (N=1722)
© 2005 The Johns Hopkins University School of Medicine.
Relationship Between Achieved BP and GFR
-14-12-10-8-6-4-20
95 98 101 104 107 110 113 116 119
eGFR
(mL/
min
/1.7
3 m
2 ) per
y
MAP = Mean Arterial Pressure*
r = 0.69P<0.05
UntreatedHypertension
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
*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.
Anemia Prevalence by CKD Stage
Patie
nts
With
Ane
mia
* (%
)
0
10
20
30
40
50
60
70
1 2 3 4-5
NHANES IIINHANES 1999-2000
CKD Stage
© 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.
Patients With CHF and Anemia (n = 126, 91% CKD)
NYHA class = New York Heart Association classification; SOB = shortness of breath.Silverberg et al. Perit Dial Int. 2001;21(suppl 3):S236-S240.
Clinical Benefit of Anemia Correction: CHF and CKD
Parameter Before AfterHgb (g/dL) 10.3 13.1Serum creatinine (g/dL) 2.4 2.3∆GFR (mL/min/mo) -0.95 0.27NYHA class (0-4) 3.8 2.7Fatigue/SOB index (0-10) 8.9 2.7Hospitalizations 3.7 0.2Systolic BP (mm Hg) 132 131Diastolic BP (mm Hg) 75 76
© 2005 The Johns Hopkins University School of Medicine.
Secondary Hyperparathyroidism
An Early and Modifiable Complication of CKD
Calcitriol Decline and iPTH Elevation as CKD Progresses
N = 150.iPTH = intact PTH. Adapted from Martinez et al. Nephrol Dial Transplant. 1996;11(suppl 3):22-28.
eGFR (mL/min/1.73 m2)152535455565758595105
100
200
300
400
0
10
20
30
40
50
iPTH
(pg/
mL)
Cal
citr
iol
1,25
(OH
) 2D3 (
pg/m
L)
Stage 37.4 million
Stage 25.7 million
Stage 4300,000
CKD Stage 15.6 million
25
65
Low-NormalCalcitriol
High-Normal PTH
© 2005 The Johns Hopkins University School of Medicine.
Feedback Loops in SHPT
Ca = calcium; CVD = cardiovascular disease; P = phosphorus.Courtesy of Kevin Martin, MB, BCh.
PTH
Bone DiseaseFracturesBone pain
Marrow fibrosisErythropoietin resistance
Serum P1,25D
Calcitriol
Renal Failure
PTH
Systemic ToxicityCVD
HypertensionInflammationCalcification
Immunological
25D
Ca++
Decreased Vitamin D Receptors and Ca-Sensing Receptors
© 2005 The Johns Hopkins University School of Medicine.
-2.25-2.00-1.75-1.50-1.25-1.00-0.75-0.50-0.250.00
Spine Hip Arm
Bone
Min
eral
Den
sity
, Z-S
core
PTH <60 pg/mL PTH 60-120 pg/mL PTH >120 pg/mL
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.
Bone-Fracture Rate Increases as CKD Progresses: Fractures in Patients on
Dialysis
*Ratio of observed incidence of hip fracture in patients with kidney failure to expected incidenceof hip fracture in the general population.Adapted from Alem et al. Kidney Int. 2000;58:396-399.
0
5
10
100
<45 45-54 55-64 65-74 75-84 TotalAge (y)
Obs
erve
d/Ex
pect
ed
Inci
denc
e of
Hip
Fra
ctur
e* Male Relative Risk = 4.4Female Relative Risk = 4.4
Overall
15
20
80
100 8799
25 20
10 107.5 6.4
2.4 2.54.4 4.4
© 2005 The Johns Hopkins University School of Medicine.
Cardiovascular Outcomes Worsen With CKD Progression: 3-Y Follow-Up by eGFR
Levels
CHF = congestive heart failure.Anavekar et al. N Engl J Med. 2004;351:1285-1295.
0
10
20
30
40
50
60
CompositeEnd Point
Death FromCV Causes
Reinfarction CHF Stroke Resuscitation
Estim
ated
Eve
nt R
ate
(%)
75 60-74 45-59 <45P<0.001
eGFR (mL/min/1.73 m2)
© 2005 The Johns Hopkins University School of Medicine.
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