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Dr. Eddy Susatyo, SpPD FinaSIMRSU dr. Sutrasno
Rembang
Gangguan sistem urologifokus gagal ginjal
STRUCTURE OF THE KIDNEYS
Chronic Kidney Disease ?
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
How About the Function of Renal ?
Fungsi ginjal
Regulasi volume cairan tubuh
Regulasi keseimbangan elektrolit
Regulasi keseimbangan asam basa
Regulasi tekanan darah (RAAS)
Ekskresi sampah metabolik
Regulasi erithropoesis
Metabolisme vit D
Sintesis prostaglandin
ADH
Angiotensin II
Ang II
Adrenal
Aldosteron
Kidney
Na+ excretion H2O excretion
Angiotensin I
Angiotensinogen
Renin
Brain
Lung
Hepar RAAS
The Most Common Causes of CKD
GlomerulonefritisPenyakit ginjal
herediterHipertensiUropathy obstruktifInfeksiNefropati diabetik
The Most Common Causes of CKD
Primary Diagnosis for Patients Who Start on Dialysis
Diabetes
50.1%
Hypertension
27%
Glomerulonephritis
13%
Other
10%
GlomerulonephritisOther
Hipertrofi sel renal
Ggn konstentrasi
urin
Penurunan GFR
CKD
Ggn fs ekskresi
Ggn fs non ekskresi
Pe ekskr ion H
Pe ekskr PO4
Pe ekskr kalium
Pe eksr sisa metab
Pe Reabs Na
Ggn Imun
prod eritropoetin
Pe abs Ca
Ggn Reproduksi
JENIS PEMERIKSAAN PENUNJANG
• Urinalisis• Evaluasi Fungsi Ginjal
• Evaluasi Serologis • Pemeriksaan Radiologis
• Biopsi Ginjal
Equations for Estimating GFR
Abbreviated MDRD Study Equation
GFR (mL/min/1.73 m2) = 186.3 X SCr -1.154 X Age-0.203
X 0.742 (if female) X 1.210 (if African American)
MDRD = Modification of Diet in Renal Disease; Ccr = creatinine clearance.Levey et al. Ann Intern Med. 2003;139:137-147.
Cockcroft-Gault Equation
Ccr = (mL/min)
(140 – Age) X Weight in kg
72 X SCr= 0.85 if female
CKD Progresses in Stages Defined by Kidney Function: GFR
20 Million People With CKD (1 in 9 adults) in the United States,Many More at Risk
70 (145-160by 2010)* 300,000<15 Kidney failure5
80 400,00015-29Severe decr in GFR4
15207,600,00030-59Mod dec. in GFR3
10605,300,00060-89Mild decr. in GFR2
11805,900,00090Kidney damage normal incr. GFR1
Patients/ NephrologistPrevalenceGFRDescription
CKD Stage
*Estimated maximal load of kidney failure patients/nephrologist.Adapted from NKF. Am J Kidney Dis. 2002;39(2 suppl 1):S1-S266.; Coresh et al. Am J Kidney Dis. 2003;41:1-12; and Wish. Nephrol News Issues. 1999;13:23, 27, 53.
Clinical Features – CKD 3-5
• Unintentional weight loss • Nausea, vomiting General ill
feeling • Fatigue; Headache; Frequent
hiccups • Generalized itching (pruritus) • Increased or decreased urine
output • Need to urinate at night,
polyuria • Easy bruising or bleeding
Clinical Features – CKD 3-5
• Blood in the vomit or in stools
• Decreased alertness; Muscle cramps
• Seizures; Agitation; Hypertension
• Peripheral sensory neuropathy
• Breath fetor; Loss of appetite;
• Uremic frost on the skin
• Uremic pericarditis, CHF
STAGES OF CKDSTAGES OF CKD
NORMAL INCREASED RISK DAMAGE LOW GFR
RENAL FAILURECKD
DEATHCOMPLICATIONS
Considerations for Patients with CKD?
• CVD
• Anemia
• Altered bone & mineral metabolism
Complications
• Higher level of proteinuria
• Higher BP
• Poor glycemic control
• Smoking
• Hyperlipidemia
• Drug use
• Diabetes
• Hypertension
• Older age
• Family history of CKD
• Racial or ethnic minority
• Other: low income, minimal education, kidney-mass reduction, known kidney disease
Progression Factors
Susceptibility Risk Factors
Levey et al. Ann Intern Med. 2003;139:137-147. USRDS. 1999 Annual Data Report. Available at: www.usrds.org.
What Are Progression Factors for CKD?
• Elevated creatinine may indicate CKD, but not all creatinine elevation is irreversible
• Key progression factors include– Elevated blood pressure (BP)– Proteinuria– Poorly controlled glucose in patients with
diabetes– Excess protein intake.– NSAIDs, contrast, aminoglycosides, other
Levey et al. Ann Intern Med. 2003;139:137-147.
15.729.5 32.3
84.067.6 61.6
0.3
2.96.1
0
20
40
60
80
100No EventsESRDDeath
2-year Follow-Up of Medicare Patients: Focus on Diabetes, CKD or Both
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.ESRD = end-stage renal disease; DM = diabetes mellitus; 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
LVH Increases With CKD Progression
eGFR (mL/min/1.73 meGFR (mL/min/1.73 m22))11
eGFR = estimated glomerular filtration rate.eGFR = estimated glomerular filtration rate.1. Levin et al. 1. Levin et al. Am J Kidney DisAm J Kidney Dis. 1999;34:125-134.. 1999;34:125-134.2. Foley et al. 2. Foley et al. J Nephrol.J Nephrol. 1998;11:239-245. 1998;11:239-245.
00
2020
4040
6060
8080
50-7550-75 25-5025-50 Dialysis Dialysis StartStart
LV
H a
t Baselin
e (%
)LV
H a
t Baselin
e (%
)
<25<25
Anemia Rates Increase as Levels of CKD Severity Progress
20
8
17
43
8
15
62
15
10
14
95
0
20
40
60
80
100
<2 2-2.9 3-3.9 ≥4
Creatinine (mg/dL)
An
em
ia P
revale
nce (%
)
Hgb = hemoglobin.Kausz et al. Dis Manage Health Outcomes. 2002;10:505-513.
Chronic Kidney Disease (CKD) Progression
Hgb Values
11-12 g/dL10-11 g/dL<10 g/dL
Specific Interventions for Complications of CKD
Adequate energy intake11-12 g/dL
LDL-C <100 mg/dL (70?) TG <150 mg/dLHDL-C >40 mg/dL
CKD stage 3 = 35-70 pg/mL 4 = 70-110 pg/mL
< 130/80 mm Hg
preprandial glucose 90-125 mg/dL A1C <7%
Target Goals
Dietary modification
Reach Hgb goal
Maintain lipids to target
PTH controlBP control
Glycemic control
Intervention
Dyslipidemia
AnemiaMalnutrition
Secondary HPTHypertension
Diabetes
Complication
A1C = glycosylated hemoglobin; HPT = hyperparathyroidism; PTH = parathyroid A1C = glycosylated hemoglobin; HPT = hyperparathyroidism; PTH = parathyroid hormone; LDL-C = low-density lipoprotein cholesterol; TG = triglycerides; HDL-C = high-hormone; LDL-C = low-density lipoprotein cholesterol; TG = triglycerides; HDL-C = high-density lipoprotein cholesterol; Hgb = hemoglobin. density lipoprotein cholesterol; Hgb = hemoglobin.
Summary: Clinical Actions for Progressive Stages of CKD
*Actions for each progressive stage of CKD also include all the actions for prior stages.NKF. Am J Kidney Dis. 2002;39(2 suppl 1):S1-S266.
Kidney replacement if uremia present<15 or dialysisKidney failure5
Prepare for kidney replacementEvaluate and treat complications
15-29Severe GFR4
Evaluate and treat complications*All actions for prior stages
30-59Moderate GFR3
Estimate progression*All actions for prior stages60-89Kidney damage
with mild GFR2
Diagnose and treat comorbid conditions Address progression factorsReduce/control CVD risk factors
90Kidney damage with normal or GFR
1
Evaluate for CKD Reduce/control CKD risk factors
90 with CKD risk factors
At increased riskRisk
Action*
GFR (mL/min/1.73
m2)Descripti
on
CKDStag
e
Cause of death in dialysis patients
cardiac disease
CVA
withrawal of RRT
malignancy
infection
others
unknown
Decisions in renal replacement
• Pre-dialysis care
• Active treatment- Peritoneal dialysis (PD)- Haemodialysis (HD)- Transplantation
• Conservative (non-dialytic) care. Symptom management.
Penatalaksanaan CKD
Ditujukan untuk mengurangi gejala klinik , mencegah komplikasi , mencegah progresifitas CKD, mempersiapkan initiasi dialisis
Uremia : diit protein 0,6 – 0,8 gr / kg bb / hariHiperkalemia : diit rendah kalium ; 60 – 80 meq/hariAsidosis metabolik : diit rendah protein / fosfat; HCO3
Stop rokokKontrol lipid ( preparat statin )HbA1C < 7 %
HipertensiAnemiaOsteodistrofi renalKomplikasi kardiovaskuler
How Do We Know if a Patient is Adequately Dialyzed?
K/DOQI Guidelines
Define Adequate Dialysis as:
• KT/V = 1.2 or greater
• URR = 65% or greater
URR% - Urea Reduction Ratio :
the percentage of urea removed during the treatment
KT/V :
Formula utilizing dialyzer urea clearance, treatment time and total body fluid
Example URRInitial (predialysis) urea level: 50 mg/dL
The postdialysis urea level: 15 mg/dL
The amount of urea removed: 50 mg/dL–15 mg/dL = 35mg/dL
URR% = Ur pre – Ur post x 100%
Ur Pre
35/50 = 70/100 = 70%
Recommended a minimum URR of 65 percent. The URR is usually measured only a month.
How AboutAcute kidney injury in Sepsis ?
Critical ill patient potentially AKI
AKI in ICU 5 –25% Mortality AKI 40-80%
RIFLE criteria for Acute Renal Dysfunction
Risk
Injury
Failure
Loss
ESRD
Abrupt (1-7 days) decrease (> 25%) in GFR orScr x 1.5Sustained (> 24 hrs)
ARF ~ earliest time point for provision of RRT
Irreversible ARF or persistent ARF > 4 wks
ESRD > 3 months
Non-Oliguria Oliguria
UO < .5/ml/kg/hx 24 hrAnuria x 12 hrs
UO < 0.5/ml/kg/hx 12 hr ??
Decreased UO relative to the fluid inputUO < 0.5/ml/kg/h x 6hr
Adjusted creat or GFR decrease> 50% orScr x 2
Adjusted creat or GFR decrease > 75%Scr x 3 or Scr > 4mg%When acute > 0.5mg%
Spec
ific
ity
Klasifikasi/staging AKI modifikasi RIFLE
Stadium kriteria kreatinin kriteria urin output
1.
Risk
serum kreatinin meningkat > 0,3 mg/dl atau meningkat lebih dari 150-200 % dari awal
< 0,5ml/kg per jam untuk >6jam
2.
Injury
serum kreatinin meningkat sampai > 200% sampai 300% dari data awal
< 0,5 ml/kg per jam untuk 12 jam
3.
Failure
serum kreatinin meningkat > 300%, (serum kreatinin > 4mg/dl dengan peningkatan akut 0,5mg/dl, indikasi untuk renal replacement therapy
<0,3 ml/kg per jam x 24 jam atau anuria x 12 jam
Mehta RL. Nephrology Self Assesment Program , Vol 6, No 5, Sept 2007
Loss Persistent renal failure for >4 weeks
ESRD Persistent renal failure for >3 months
Murray PT, Palevsky PM. Nephrology Self Assesment Program , Vol 6, No 5, Sept 2007
SepsisIschemic insult
Nephrotoxic insult
Complement activationEndotoxin releaseIschemia-reperfusion
Cellular activation(PMN, endothelial cells…)
Arachidonic acid metabolities
Proteases
Chemokines
Platelet activating factor
Serum creatinine
Oxygen free radicals
Nitric oxide
Heat shock proteins
Endothelins
Acute kidney injury Urinary KIM-1, NAG
Urine output GFR
Anti-inflamatorymediators
Pro-inflamatorymediators -
+
Pathogenic mechanism of sepsis related acute kidney injury
(1)Vasoconstriction
Renin-angiotensinendothelin
PGI2NO
(2)Obstruction
by casts
(3)Tubularbackleak
IschemiaNephrotoxins
Tubular damage(proximal tubules andascending thick limb)
(5)? Direct glomerular
effectGFR Oliguria
Tubularfluid flow
Intratubularpressure
Possible pathogenetic mechanisms in ATN.
(4)Interstitial
inflammation
Effects of ischemia on renal tubules in the pathogenesis of ischemic AKI
Schrier et al, J Clin Invest 2004, 114:5-14
Renal protection, there is damage before any symptom
MAP> 65 mmHg
CVP 8-12 mmHg (no ventilator)
12-15 mmHg (ventilator)
Urine > 0,5ml/BW/hour
SaO2 >70%
Koloid ,albumin ?
Renal Protection
Intensive insulin therapy sepsis by 45%
Blood glucose 80-110 mg/dl morbidity and mortality
Mechanism : bacterial phagocytosis and antiapoptotic effect of insulin
Tight control of blood glucose