FARMAKOTERAPI GAGAL GINJAL AKUT DAN

KRONIS
By Asih Puji Lestari, M.Sc., Apt
GAMBARAN KLINIS GGA
HB normal
Oliguric type
Non oliguric type (30-60%) prognosis lebih
baik causa AB / nephrotoxic agent
Umumnya reversible
Mortalitas tinggi: 40-60%
Frekuensi : 5-15% pasien rawat
PENYEBAB GGA
Pre-renal : Hypovolemic, hypotensi,
dehydrasi, syok
Renal (Intrinsic renal failure) ATN (acute
tubular nephrosis) or VMN (vascular
membrane nephrosis)
Post-renal : obstruksi, batu, prostat, trauma,
keganasan.
ANAMNESIS
Gastro Enteritis akut
Riwayat tindakan / operasi
Hipotensi shock
Hipertensi (accelerated / malignant)
Drugs
Renal disease
Acute on chronic
CLINICAL COURSE OF ARF
Onset Phase : oliguria, ureum creatinin
meningkat, gangguan elektrolit

Oliguric Phase : fluid overload, edema
ankle/pulmo, hyperkalemia cardiac,
arythmia, hyponatremia, acidosis, kussmaul
respiration.
ACUTE UREMIC SYNDROME
CVS : hipertensi, arythmia, CHF, pericarditis
Gastroinstestinal : anorexia, nausea,
vomithing, diarhea, bleeding, pancreatitis
CNS : cunfussion, twitching, asterixis,
soporosus coma
Hemopoetic system : bleeding, anemia
CLINICAL COURSE OF ARF (CONT)
Diuretic Phase : restorasi fungsi ginjal
1 hari s/d 2 minggu
Keseimbangan cairan, dehydrasi,
hypokalemia
Gejala-gejala hilang, nafsu makan pulih

MANAGEMENT OF ARF
Phase oliguri : cairan <500 cc/h, monitor
elektrolit : kalium, asupan kalori. Dialisis
Phase diuretik : keseimbangan cairan dan
elektrolit
Post diuretik : cairan / elektrolit
Prognosis : tergantung penyebab, usia,
comorbid, infeksi, multi organ
CRF = GGK = ESRD = CKD = PGK
Penurunan fungsi ginjal
Bertahap / progresif (tak disadari)
Sering tanpa gejala insidentil medical
check-up
GANGGUAN FUNGSI GINJAL
Klinis
Tanda, gejala, pemeriksaan fisik.
Laboratoris
Ureum , kreatitin , asam urat
Tes klirens kreatinin (TKK)


Rumus Cockrof-Gault
Kreatinin urin(mg/dL) x vol.urin(mL/24 jam
Kreatinin serum(mg/dL) x 1440
LFG = (140-umur) x BB (Kg)
72 x kreatinin serum (mg/dL
Wanita = 0,85 x pria
KRITERIA PGK
Kerusakan ginjal > 3 bln, struktural atau
fungsional dengan atau tanpa penurunan
LFG
Kelainan patologi atau
Tanda kerusakan ginjal dalam darah ataupun
urine atau pada pemeriksaan imaging

LFG < 60mL/m/1,73m2, > 3bln
GEJALA PGK
Nafsu makan hilang / kurang
Nausea vomiting
Gatal-gatal
Gangguan miksi, poli/oliguria, nokturia, dll
Gejala-gejala anemia
Insomnia
Gelisah
Gangguan mental / kesadaran coma
TANDA-TANDA PGK
Tidak ada tanda yang khas
Pucat, kurang gizi malnutrisi
Odema
Tanda-tanda garukan
Pigmentasi kulit
Proteinuria / hematuria
Bau uremia, sesak/asidosis
Ureum, kreatinin, asam urat meningkat
PENGOBATAN PGK
Penyakit / penyebab
Faktor resiko
Hipertensi
Hiperparatiroidim
Anemia
Dislipidemia

Hindari obat-obat nephrotoksik
Penyesuaian dosis obat-obatan
Persiapan terapi pengganti ginjal
PENGOBATAN PGK
Konservatif
Diet : rendah protein: 0,6-08 g/KgBB


Terapi Pengganti Ginjal (TPG)
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IMPLIKASI
FARMASI
KLINIK
PROBLEM
MEDIK
DRP
TREATMENT
OF ARF
TREATMENT
OF CKD
DRUG-
INDUCED
RENAL
FAILURE
PHARMACEUTICAL CARE IN RENAL
MEDICINE
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IMPLIKASI FARMASI KLINIK

Estimasi fungsi ginjal: Cockroft-Gault, klirens
kreatinin
Tinjau perlu-tidaknya penyesuaian dosis.
Sesuaikan dosis khususnya pada Renally
excreted drug/metabolit
Ketahui metabolisme, aktivitas dan metode
ekskresi.
Pilih obat dg nefrotoksisitas minimal
Lakukan TDM
Hindari penggunaan lama
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IMPLIKASI FARMASI KLINIK
Monitor efektifitas, ADR, toksisitas lebih ketat
Gangguan GI:awasi peresepan antasid
Plasma protein binding:awas obat highly protein
bound (ikatan protein>90%)
Na & air retensi: cek Na-content
Awasi tekanan darah & efektivitas antihipertensi
Farmakodinamik: awasi obat yg CNS
sensitivity
Dialisis: sesuaikan dosis obat terdialisis

PRESENTASI KLINIK
Gagal ginjal Tunggal
Sebagai penyakit penyerta : Infeksi + CKD;
DM+CKD; Stroke+CKD; CKD + pembedahan
Sebagai akibat gangguan metabolik (Sepsis,
penurunan CO, hipovolemia): ARF
Drug-induced Renal failure

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PROBLEM MEDIK UMUM
SULITNYA PENATALAKSANAAN
KOMPLIKASI: Anemia, kelainan hematologi
Hipertensi yang tidak terkontrol dg>3 AHT
Uremia, acidosis
Hiperuricemia, Hiperkalemia/Hipokalemia
Gangguan GIT
Seringkali menjadi penyakit penyerta
CKD, ARF + Infeksi ( Pneumonia,
UTI/urinary tract infection)
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COMMON DRP
Pemilihan obat yang tidak tepat
Tidak ada penyesuaian dosis
ADR berpotensi besar untuk terjadi


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ACUTE RENAL FAILURE
Def: pe fs ginjal scr mendadak disertai
akumulasi produk nitrogen.
Anuria(<100 ml/24j) atau oligouria(100-400ml/24j)
Azotemia: pe nitrogen waste (BUN, Cr)
Uremia: syndrome akibat azotemia
(anorexia, nausea, vomiting, confusion)
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PENYEBAB ACUTE RENAL FAILURE
PRE-RENAL:CO, HIPOTENSI, OBSTRUKSI
VASKULER
INTRINSIK: ATN (acute tubular necrosis),
GLOMERULAR DAMAGE
POST-RENAL: OBSTRUKSI URETER, URETRA
&LEHER KANDUNG KENCING
DRUG INDUCED: AMFOTERISIN-B,
AMINOGLIKOSIDA, SULFONAMIDA
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Table 30-1 Causes of Acute
Renal Failure
Classification Common Clinical Disorders
Prerenal Azotemia Intravascular Volume Depletion
Hemorrhage (surgery, trauma)
Dehydration (gastrointestinal losses, aggressive
diuretic administration)
Severe burns
Hypovolemic shock
Sequestration (peritonitis, pancreatitis)
Decreased Effective Circulating Volume
Cirrhosis with ascites
Congestive heart failure
Hypotension, Shock Syndromes
Antihypertensive vasodilating medications
Septic shock
Cardiomyopathy
Increased Renal Vascular Occlusion or
Constriction
Bilateral renal artery stenosis
Unilateral renal stenosis in solitary kidney
Renal artery or vein thrombosis (embolism,
atherosclerosis)
Vasopressor medications (phenylephrine,
norepinephrine)
Functional Acute Renal Failure Afferent Arteriole Vasoconstrictors
Cyclosporine
Nonsteroidal anti-inflammatory drugs
Efferent Arteriole Vasodilators
Angiotensin-converting enzyme inhibitors
Angiotensin IIreceptor antagonists
Intrinsic Acute Renal Failure Glomerular Disorders
Glomerulonephritis
Systemic lupus erythematosus
Malignant hypertension
Vasculitic disorders (Wegener's granulomatosis)
Acute Tubular Necrosis
Prolonged prerenal states
Drug induced (contrast media, aminoglycosides,
amphotericin B)
Acute Interstitial Nephritis
Drug induced (quinolones, penicillins, sulfa drugs)
Postrenal Acute Renal Failure Ureter Obstruction (Bilateral or Unilateral in
Solitary Kidney)
Malignancy (prostate or cervical cancer)
Prostate hypertrophy Anticholinergic drugs (affect
bladder outlet muscles)
Renal calculi
PREVENTION:
Hidrasi dengan NS/0,5 NS
Ca-antagonis sebelum pemberian nefrotoksik

PHARMACOLOGIC TREATMENT:
Fluid therapy
Diuretics to change oliguria to non-oliguric state
Low dose dopamin (1-3ug/kg/menit) infusion bila
respon diuretik
Ca- channel blocker
Dialysis
Treatment of infections aggresively
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Segera koreksi penyebab reversibel nya:
Koreksi ketidakseimbangan cairan dan elektrolit
juga sangat penting.
Dukungan perfusi ginjal dengan baik Volume
pengisian atau terapi yang meningkatkan
pengiriman oksigen ginjal
Pengobatan infeksi agresif
Pengobatan komplikasi
Dialisis
Kembalinya volume intravaskular dan tekanan
arteri rata-rata baseline sangat penting terutama
untuk pasien yang menderita GGA prerenal
Type of fluid: NS or 0.45% saline.
Rate: 50-100ml/h, lower rate for impaired
cardiac function
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To convert a patient's condition from oliguric to
nonoliguric renal failure
Choice: Loop diuretics, often administered as a
continuous infusion adverse effects such
as myalgias and ototoxicity
correction of hypovolemia is essential and
cardiac output must be maximized before loop
is administered
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to selectively vasodilate renal arterioles,
increase renal blood flow, and improve the
GFR
Doses of 1-5 mcg/kg/min.
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Ca Gluconate iv 10 ml of 10% sol
Insulin 10 U iv + Glucose 25g
Inhaled beta-agonist
Nabic iv
Cation exchange resin
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pH < 7,2, bicab < 15mEq/l
Nabic iv or oral
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Choice: Captopril or ARB or amlodipine or
diuretics

Perhatikan kenaikan kreatinin

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CHRONIC KIDNEY DISEASE (CKD)
Def:penurunan fs ginjal scr perlahan ditandai
BUN, CrCl, gejala uremia.

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TREATMENT OUTCOME
MEMPERLAMBAT PENYAKIT GINJAL
SCR PROGESIF
MENCEGAH & MENGELOLA
KOMPLIKASI

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COMPLICATIONS
HYPERKALEMIA
ACID-BASE DISORDER
CARDIOVASCULAR
HEMATOLOGIC
NEUROLOGIC
ENDOCRINE DISORDERS
GI DISORDER
HYPERURICEMIA
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ESTIMATE RENAL FUNCTION
Goal: to assess the need of dossage adjustment
COCKROFT-GAULT
CrCl = 1.23(pria)or 1.04 (wanita) x(140-umur)x BB
Serum creatinine(mol/L)
BB: gunakan IBW kecuali BB<IBW
IBW : Pria 50+2.3/inch (TB>150 cm)
Wanita: 45.5 + 2.3/inch (TB>150 cm)
Pengukuran CrCl melalui urin tampung 24 jam
CrCl= Uvol x [U Cr]
[Cr*] x t
* kadar pada midpoint pengumpulan urin
Populasi: Critically ill, trauma, post-op


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ESTIMATE RENAL FUNCTION
Modified Diet in Renal Disease (MDRD)
GFR (mL/min/1.73 m 2) = 186 x [Cr]
1.154 x (Age) 0.203 x (0.742 if female) x
(1.210 if African American)
SCr: serum creatinine in mg/dL; age in years
SLOWING THE PROGRESSION OF RENAL DISEASE
sistemik HT
Menghasilkan tekanan intraglomerular dan
mempercepat sclerosis glomerulus dan Penyakit Ginjal
antihipertensi melindungi ginjal & kardiovaskular
Antihipertensi pada Penyakit Ginjal Kronis non-
proteinuric dapat memperlambat perkembangan
Agen: ACE, ARB, diuretik, Diltiazem, Verapamil, -
blocker
Asupan Protein Diet
pembatasan protein 0,6 g / kg / hari dalam tidak pada
dialisis
Kontrol glikemik
kontrol glikemik yang ketat
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SLOWING THE PROGRESSION OF RD
DIABETICS:
Deteksi dini mikroalbuminuria ACE I
BP control
Koreksi abnormalitas lipid
NON_DIABETICS:
BP control
Proteinuria: ACE I, Ca-antagonist
TREATMENT OF COMPLICATIONS

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TREATING COMPLICATION
HYPERKALEMIA
Treatment: iv Ca gluconate, insulin +glucose, Nabic, ion
exchange resin, dialysis
ACIDOSIS
Treatment: Nabic 0,51mEq/kg/d target Nabic level>22mEq/L
HEMATOLOGIC
Anemia: erythropoetin started 50U/kg 1-2 x/week s.c.(iron
stores must be adequate), iron supplementaion if ferritin <
100g/ml with 1-3 x 325mg FeSO
4
DISORDER OF MINERAL METABOLISM
PTH, Ca Calcitriol, Ca CO
3


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KOMPLIKASI CKD
1. Na & H2O IMBALANCE
CrCl<25 ml/minpenyesuaian ginjal thd perub Na
dan H2O intake berkurang.
Strategi: ESRD fluid & Na restriction, Loop
diuretics.
2. ACID-BASE IMBALANCE
Lihat ARF, dosis Nabic 0,5-3mmol/kg/day
3. POTASSIUM IMBALANCE
Hiperkalemia , K>6.5 mmol/L
Tanda: perub ECG, weakness, confuse, paralisis
(ya/tdk)
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KOMPLIKASI CKD (CONTINUE)
Terapi:
o Ca(Cl)2 10%5-10 ml iv 1-3 ,u/ aritmia
o Nabic 50 mmol iv 3-5 , ulangi 10-15
o Glukosa + insulin reguler
o Cation exchange resin 4x15-30g po
o Dialisis
Hipokalemia
Krn intake kurang, GI loss, terapi diuretik
dan renal tubular acidosis
Terapi:KCl iv dg speed 10mmol/jam, tablet K
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KOMPLIKASI CKD (CONTINUE)
4. ABNORMALITAS Ca dan Phosphat
Karakteristik: Hipokalsemia, hiperphosphatemia,
sekresi PTH, renal osteodistrofi.
Penyebab: CrCl 5-15ml/minekskresi PO4,
absorbsi Ca krn prod vit D3
Terapi: restriksi diet PO4, antasida, Vitamin D3,
CaCO3
Terapi hipokalsemia bila PO4 < 55-60 mg/L
5. ABNORMALITAS Platelett dan Bleeding
Uremia GI bleed, purpura
Terapi: transfusi platelett, PRC, dialisis
6. Anemia
Terapi: penggantian Fe dan As folat, erythropoetin 3
x 50-100 unit/kg/mg iv/sc

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KOMPLIKASI CKD (CONTINUE)
7. ABNORMALITAS KARBOHIDRAT
Diabetes krn CRF
Terapi: Insulin, Tolbutamide.
8. HIPERURICEMIA
Krn kegagalan ginjal mengekskresi as urat.
Terapi: Allopurinol atau dialisis.
9. HIPERTENSI
Karakteristik: BPseiring memburuknya fs ginjal
Penyebab: abnormalitas renin-angiotensin, ekspansi
volume ekstrasel.
10. ABNORMALITAS GI (lihat ARF)
Karakterisitik: anoreksia, gastrik/duodenal ulcer
Penyebab: prod. amonia , siklus internal amonia-urea
Terapi: Antasid, H2-bloker, sukralfat


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CRF
12. GANGGUAN DERMATOLOGI
Terapi: antihistamin, topical emollient.
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MONITORING
BIOKIMIA:
Cr, BUN, elektrolit (Na, K, Ca, PO4), keseimbangan
asam-basa, albumin, Asam urat, ABG.

HEMATOLOGI:
Hb,Fe,Folat, Hct, Thrombo.

KARAKTERISTIK PASIEN:
BP, BB, temp.,KU, kulit.

TERAPI OBAT: TDM, dosis, efek,ADR,
nefrotoksisitas
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HEMODIALISIS
Suatu prosedur di mana darah pasien
diheparinisasi kemudian dipompakan melalui
dialyser. Proses yang terjadi dalam dialyser
adalah difusi pasif melalui membran
semipermeabel kedalam larutan dialysis.
Komplikasi hemodialysis
Access problem: infeksi, pembekuan, iskemia.
Procedure problem: hipotensi, emboli, kram otot,
pruritis, bleeding.
Pengaruhi clearance obat : BM, hidrofilik, ikatan
protein , Vd
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DRUG-INDUCED RENAL FAILURE
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Table 30-5 Risk Factors for Developing Aminoglycoside Nephrotoxicity
Patient Factors
Elderly
Underlying renal disease
Dehydration
Hypotension and shock syndromes
Hepatorenal syndrome
Aminoglycoside Factors
Aminoglycoside choice: gentamicin > tobramycin > amikacin
Therapy >3 days
Multiple daily dosing
Serum trough >2 mg/L
Recent aminoglycoside therapy
Concomitant Drug Therapy
Amphotericin B
Cisplatinum
Cyclosporine
Foscarnet
Furosemide
Radiocontrast media
Vancomycin
TERIMAKASIH . . .