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