ACUTE KIDNEY INJURY (AKI)

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ACUTE KIDNEY INJURY (AKI)

RSCM FKUI RSCM –FKUI

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Pendahuluan

• Sindrom yang ditandai oleh penurunan LFGSindrom yang ditandai oleh penurunan LFG secara mendadak dan cepat (hitungan jam‐ minggu) yang mengakibatkan terjadinya

minggu) yang mengakibatkan terjadinya retensi produk sisa nitrogen seperti ureum dan kreatinin

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Pendahuluan

• Peningkatan kreatinin serum 0 5 mg/dL dariPeningkatan kreatinin serum 0,5 mg/dL dari nilai sebelumnya, penurunan CCT hitung

sampai 50% atau penurunan fungsi ginjal yang sampai 50% atau penurunan fungsi ginjal yang mengakibatkan kebutuhan akan dialisis

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Definitions

Acute Renal Failure Acute Renal Failure

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Etiologi Prerenal

I. Hipovolemia

A. Perdarahan, luka bakar, dehidrasi

B. Gastrontestinal: muntah, diare, drainase bedah C. Renal: penggunaan diuretik,

diuresis osmotik (diabetes mellitus), hipoadrenal D. Sekuestrasi cairan di ruang ekstravaskuler:

pankreatitis, peritonitis, trauma, luka bakar, hipoalbuminemia berat II. Curah jantung rendah

A. Penyakit miokardium, katup, dan perikardium; y , p, p ; aritmia; tamponade

B. Lainnya: hipertensi pulmoner, emboli paru masif, ventilasi mekanik tekanan positifp

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Etiologi Prerenal

III. Perubahan rasio resistensi vaskular sistemik ginjal A. Vasodilatasi sistemik:

sepsis, obat antihipertensi, anestesia, anafilaksis B. Vasokonstriksi renal: hiperkalsemia,

norepinefrin, epinefrin, siklosporin, takrolimus, amfoterisin B C. Sirosis dengan asites (sindrom hepatorenal)

IV. Hipoperfusi renal dengan gangguan respon autoregulasi ginjal: Inhibitor siklooksigenase,

penghambat enzim pengkonversi angiotensin V. Sindrom hiperviskositas (jarang): p (j g)

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Etiologi renal

I Obstruksi renovaskular I. Obstruksi renovaskular II. Penyakit glomeruli

k i b l k

III. Nekrosis tubular akut IV. Nefritis interstitial

V. Obstruksi intratubular VI Penolakan allograf

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Etiologi post renal

I. Ureter I. Ureter

Batu, gumpalan darah, keganasan,

kompresi eksternal (fibrosis retroperitoneal) kompresi eksternal (fibrosis retroperitoneal) II. Leher kandung kemih

N i bl dd hi t fi t t b t

Neurogenic bladder, hipertrofi prostat, batu,

keganasan III U t

III. Uretra

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AKI: A Common, Serious Problem

% f ll h l d

• AKI is present in 5% of all hospitalized

patients, and up to 50% of patients in ICUs

li 0 80% i di l d

• Mortality rate 50 ‐ 80% in dialyzed ICU patients– 4 Million die each year of AKI

AKI i i di l i i f h

• AKI requiring dialysis is one of the most

important independent predictors of death in ICU patients

ICU patients

• 25% of ICU dialysis survivors progress to ESRD within 3 years

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RIFLE Criteria for Acute Renal Dysfunction High UO < 0.5 ml/kg/h x 6 hr Increased creatinin Risk UO Criteria GFR Criteria Category UO < 0.5 ml/kg/h x 12 hr Increased creatinine Injury Sensitivity x1.5 or GFR decrease > 25% x2 or GFR decrease > 50% High UO < 0.3 ml/kg/h x 24 hr Increase creatinine Failure PROGNOSIS PROGNOSIS Persistent ARF = complete loss of kidney

f ti 4 k Loss Specivity or Anuria x 12 hrs x3 or GFR decrease > 75%

End Stage Kidney Disease (> 3 months)

ESKD

function > 4 weeks

GFR=Glomerular Filtration Rate ARF; Acute Renal Failure

UO = Urine Output ESKD; End Stage Kidney Disease

References :

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Acute Kidney Injury Network (AKIN‐ 2005)

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Continuum of the renal injury

STAGE I

STAGE I STAGE IISTAGE II

STAGE I STAGE I STAGE II INJURY STAGE II INJURY STAGE V ESRD STAGE V ESRD STAGE III FAILURE STAGE III FAILURE STAGE IV LOSS STAGE IV LOSS RISK (R) RISK (R) INJURY (I) INJURY

(I) (E)(E)

FAILURE (F) FAILURE (F) (L)(L) Severity Outcome Severity Outcome

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Diagnosis AKI

• Anamnesis : harus terinci dan akuratAnamnesis : harus terinci dan akurat • Pemeriksaan fisik : rutin

b i ik d

• Laboratorium : pemeriksaan standar

• Kesulitan : membedakan akut dan kronik

• Tanda kronik : fatigue weight loss anorexiaTanda kronik : fatigue, weight loss, anorexia, nocturia, and pruritus

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Diagnosis of AKI is often delayed

• Elevation in serum creatinine is the current gold

t d d b t thi i bl ti

standard, but this is problematic

• Normal serum creatinine varies widely with age,

d di l l b li

gender, diet, muscle mass, muscle metabolism, medications, hydration status

k l d

• In AKI, serum creatinine can take several days to reach a new steady state

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Initial diagnostic tools in AKI

• History and Physical exam.

• Urinalysis

SG, PH, protein, blood, crystals, infection • Urine microscopyUrine microscopy

casts, cells (eosinophils) • Renal imaging

USG CT rografi non kontras USG, CT urografi non kontras • Markers of CKD

iPTH, size<9cm, anemia, high phosphate, low bicarb • Renal biopsy

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AKI: Urgent Need for Early Diagnosis

• Early forms of AKI are often reversible

y

• Early diagnosis may enable timely therapy

• The paucity of early biomarkers has

impaired our ability to institute timely

h

i h

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Bi

k

f

E l P di ti

Biomarkers for Early Prediction

of Acute Kidney Injury

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SEPSIS Current Clinical Scenario SEPSIS

CPB

WITH Early Biomarkers

CPB TRAUMA Normal Creatinine Elevated Creatinine CPB TRAUMA Early Detection CONTRAST Kidney Injury Acute Kidney Injury MORTALITY F il d CONTRAST ARDS Kidney Injury Acute Kidney Injury MORTALITY ARDS TOXINS Failed Intervention ARDS TOXINS Opportunity for Early Intervention Early Detection a b

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Potential Roles of Biomarkers in AKI

Early

Detection Prognosis Differential

Diagnosis Defined Timing &

Single Insult Severity of AKI Need for RRT • CPB • Contrast • Trauma • Chemotherapy • Location

(proximal vs distal tubule) • Etiology

(toxin ischemia sepsis)

Need for RRT Duration of AKI Response to • Chemotherapy _{(toxin, ischemia, sepsis)}

• ATN vs Pre‐renal • Acute vs Chronic

Treatment Length of stay Mortality

Undefined Timing & _Mortality Undefined Timing &

Multiple Insults • Sepsis

• ARDS C i i l Ill • Critical Illness

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Potential Biomarkers in AKI (Human Data) (Human Data) Early Detection Prognosis Detection Differential

Diagnosis IL – 18Mortality in ARDS (3) Duration of AKI (1) Cystatin C ICU (9) (+) ICU (10) (‐) IL – 18 CPB (1) ARDS (3) IL – 18

ATN vs other (13) Cystatin C

Need for RRT (16) KIM 1 ICU (10) ( ) NGAL CPB (4.5) Tubular Enzymes NGAL Duration of AKI (1) KIM – 1 ATN vs other (14) Na+ _{/ H}+ Exchanger PCI (6) D+HUS (8) ICU (11) KIM ‐ 1 Exchanger ATN vs other (15)

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NGAL

(N

t

h l G l ti

A

i t d Li

li )

(Neutrophyl Gelatinase‐Associated Lipocalin)

• Protein yang terikat pada gelatinase dari selote ya g te at pada ge at ase da se neutrofil

• Normal : diekskresi dengan kadar sangat rendahg g dari jaringan tubuh

• Percobaan binatang : NGAL paling cepat dan secara bermakna meningkat akibat gangguan (injury) atau toksik pada ginjal

Di i di i AKI Æ 1 2 h i t d t k i b l

• Diagnosis dini AKI Æ 1‐2 hari terdeteksi sebelum kenaikan kreatinin

• Dapat diperiksa dari darah dan urine • Dapat diperiksa dari darah dan urine

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The Emerging Plasma

AKI Panel

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The Emerging Urineg g AKI Panel

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Treatment of AKI Treatment of AKI

• Treatment is largely supportive in nature!Treatment is largely supportive in nature! • Pharmacologic treatments under study:

Dopamine no benefit – Dopamine: no benefit

– Atrial Natriuretic Peptide (ANP) or ANP‐analogue (Anaritide): promising

( ) p g

– Human Insulin like growth factor 1: no benefit

• Renal Replacement therapy remains the p py

cornerstone of management of minority of patients with severe AKI

p

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Is there a role for Dopamine in prevention or t t t f AKI i ICU tti ?

treatment of AKI in ICU setting?

Clinical Outcomes:

• No effect on mortality

• No effect on the need for or incidence of Renal Replacement Therapy (RRT)

Therapy (RRT)

Renal Physiologic Outcomes:

• Diuretic effect and increased creatinine clearance on the first day which was not significant on the following days.

Adverse effect:

• on the immune, respiratory, and endocrine system.

Ann Intern Med. 2005;142:510‐524

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Role of ANP analogues in AKI?g

• 61 patients in 2 cardiothoracic ICU with post‐op AKI assigned i bi ANP (50 /k / i ) l b

to receive recombinent ANP (50ng/kg/min) or placebo

• The need for RRT before day 21 after development of AKI was • The need for RRT before day 21 after development of AKI was

significantly lower in ANP group (21% vs 47%)

• The need for RRT or death after day 21 was significantly lower in ANP group (28% vs 57%)

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Is there a role for diuretics in the treatment of AKI in ICU tti ?

ICU setting?

• PICARD Study:

Cohort study of 552 pts in 4 UC hospitals: Cohort study of 552 pts in 4 UC hospitals:

Odds Ratio In‐hospital Mortality 1.77 Non‐recovery of renal function 1.68

I d i t t d h t d ti f RRT ( h • Improved urine output and shorter duration of RRT (none has

clinical relevance in ICU pts)

• But diuretics continue to be used for volume control in AKI in ICU setting!

JAMA. 2002 Nov 27;288(20):2547‐53 Crit Care Resusc. 2007 Mar;9(1):60‐8

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Tatalaksana

• Terapi berdasarkan etiologi :Terapi berdasarkan etiologi : 1. Prerenal

2 l

2. Renal

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Terapi suportif

• Asupan nutrisi :Asupan nutrisi :

Kebutuhan kalori 30 Kal/kgBB ideal/hari

dit b h 15 20% (t d t k lik i/ t ) ditambah 15‐20% (terdapat komplikasi/stres)

Asupan protein : 1‐1,5 gram/kgBB ideal/hari pada GnGA berat

GnGA berat

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• Koreksi gangguan asam basaKoreksi gangguan asam basa • Koreksi gangguan elektrolit

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Terapi suportif – indikasi dialisis

Terapi suportif indikasi dialisis

– Oliguria – Anuria – Hiperkalemia (K >6,5 mEq/L) – Asidosis berat (pH <7,1) – Azotemia (ureum >200 mg/dL) – Edema paru – Ensefalopati uremikum – Perikarditis uremik – Neuropati/miopati uremik

– Disnatremia berat (Na >160 mEq/l atau <115 mEq/l)( q/ q/ ) – Hipertermia

– Kelebihan dosis obat yang dapat didialisis (keracunan)

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ACUTE KIDNEY INJURY (AKI)