PATOFISIOLOGI & PENATALAKSANAAN GAGAL GINJAL KRONIK

Dra. WIDYATI, MClin Pharm, Apt

DEFINISI

Kidney damage for ≥ 3 months as defined by structural or functional abnormalities of the kidney, with or without decreased GFR, manifest by either: pathological abnormalities; or markers of kidney damage, including abnormalities in the composition of the blood or urine; or abnormalities in imaging tests.

GFR < 60 mL/min/1.73m2 for ≥ 3 months, with or without kidney damage.

(NKF-KDOQI)

CHRONIC KIDNEY DISEASE

PATOFISIOLOGI

CKD Manifest as a loss of renal reserve As CKD progress Pt may remain

asymptomatic As renal function worsen susceptible to

infection, poorly controlled hypertension

ESRD

Clinical state irreversible loss of endogenous renal function RRT permanent

Azotemia Uremic syndrome: anemia, malnutrition;

impaired carbohydrate metabolism,fats,and proteins; defective utilization of energy and metabolic bone disease

Symptoms & Signs Develop slowly and nonspecific Can be asymptomatic until stage 5 Manifestation: General: malaise, fatigue, weakness GI: anorexia, nausea, vomit, hiccup Neurologic: insomnia, irritable,twitch, paresthesia,

restless leg Libido , mens irregularity Cardiopulmonary: cardiomegaly, oedema, pericarditis Uremic encepahlopathy: asterixis, myoclonus, confusion-

coma

PENYEBAB CKD

Non-Diabet: Hipertensi, Renal Artery Stenosis Policystic kidney disease Glomerular disease Tubulointerstitial disease Obstructive Nephropathies Diabetes Mellitus

DIABETIK NEFROPATI Def: laju ekskresi albumin urin>300mg/24jam pd

Pt dg DM tanpa adanya penyakit ginjal lain (Selby,JAMA 1990)

Terjadi hampir 1/3 DM Tk albuminuria berhubungan dg tk gagal ginjal Faktor resiko perkembangan DN: Kontrol gula yg

buruk, HT, intake protein ,smoking, ,cholesterol Treatment: Insulin terapi, ACE inhibitor, restriksi

diet protein. Monitor: albuminuria, BP, komplikasi

COMPLICATIONS

HYPERKALEMIA ACID-BASE DISORDER CARDIOVASCULAR HEMATOLOGIC NEUROLOGIC DISORDERS OF MINERAL METABOLISM ENDOCRINE DISORDERS GI DISORDER HYPERURICEMIA

HYPERKALEMIA

K balance usually remain intact until GFR < 10ml/min

Endogenous causes: hemolysis, trauma, acidemic states, hyporeninemic hypoaldosteronism

Exogenous causes: diet, drugs that K secretion (spironolactone, ACE, NSAID)

Hyperkalemia arytmia, ECG change (QRS widen)

ACID-BASE DISORDER Inability of kidney to excrete acid generated

from protein metabolism Primarily due to loss of renal mass Ammonia production & urine buffer

production pH is maintained at 7,33-7,37 & bicarb

15meq/L Excess of H+ buffered by CaCO3 & CaPO4

Renal osteodystrophy

CARDIOVASCULAR

HYPERTENSION PERICARDITIS CONGESTIVE HEART FAILURE

HYPERTENSION

Causes: Salt & water retention due to inability to

excrete, adjust to variation in intake water, Na as renal failure worsen

Hyperreninemic states Exogenous erythropoetin Failure to control HT lead to progression of

renal damage

Pericarditis

Cause: retention of metabolic toxins Symptoms & signs: chest pain, fever,

pericardial effusion CO poor with distended Jugular Venous

Congestive Heart Failure

HT

Myocardial work ↑

O2 demand ↑

Atherosclerosis ↑

PTH

CHF

HEMATOLOGIC

ANEMIA COAGULOPATHY

ANEMIA

Characteristic: normochromic, normocytic Cause: erythropoetin production, Fe deficiency Low grade hemolysis Blood loss from platelet dysfunction HD

Coagulopathy

Platelet dysfunction Bleeding is prolong Platelet shows abnormal adhessiveness

and aggregation Sign: petechiae, purpura

NEUROLOGIC

Uremic encephalopathy Occur at CKD stage 5 or ESRD Cause: hiperPTH; Ca >12-15mg/dL Symptoms: difficulty in concentrating,

lethargy,confusion, coma Physical: nystagmus, weakness, asterixis,

hypereflexia Neuropathy: can be peripherally (restless legs, distal

pain, lost of tendon reflexes) and others (impotence, autonomic dysfunction)

DISORDERS OF MINERAL METABOLISM Renal Osteodystrophy: disorder of Ca, P and

bone. Form: osteomalacia, osteitis fibrosa cystica

GFR falls <25% impaired P excretion, renal conversion of vit D3, gut absorption of Ca

Hyperphosphatemia hypocalcemia PTH secretion bone turnover ↑

OTHERS

GI DISORDERS include: nasea, vomiting, anoreksia, gastric/duodenal ulcer

HYPERURICEMIA; impaired excretion of uric acid as renal function worsen

ENDOCRINE DISORDER

Renal insulin clearance insulin level↑ Glucose intolerance can occur when GFR<10-

20ml/min due to pheripheral insulin resistance. Testosterone libido, impotence Estrogen anovulatory Abnormalities in thyroxine, GH, aldosterone,

cortisol level

PHARMACOTHERAPY

1. Treating Reversible Causes of Renal Dysfunction

2. Slowing the Progression of Renal Disease

3. Treating Complications

Treating Reversible Causes Factors responsible for acute decrements in renal

function in CKD: volume depletion, CHF, nephrotoxic drugs, radiocontrast

Hypovolemia treatment: repletion, dose of diuretic,↑ Na intake

CKD + CHF treatment: Loop diuretic (maintaining fluid balance)

Use of Nephrotoxic drug: adjust dose, avoid Radiocontrast: use non-ionic contrast,hydration 12

hours before procedure

Slowing the Progression of RD

Systemic HT Generates ↑intraglomerular pressures and accelerate

glomerular sclerosis and RD Antihypertensive protect both renal & cardiovascular

Antihypertensive in non-proteinuric CKD unable to slow the progression

Agents: ACE,ARB, diuretic, Diltiazem, Verapamil, β-blocker

Dietary Protein intake Protein restriction to 0,6g/kg/day in pt not on dialysis Glycemic control Strict glycemic control

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 FeSO4

DISORDER OF MINERAL METABOLISM PTH↑, Ca Calcitriol, Ca CO3

Treating Complication

HIPERURICEMIA Krn kegagalan ginjal mengekskresi as urat. Terapi: Allopurinol atau dialisis.

ABNORMALITAS GI (lihat ARF)

Karakterisitik: anoreksia, gastrik/duodenal ulcer

Penyebab: prod. amonia , siklus internal amonia-urea

Terapi: Antasid, H2-bloker, sukralfat

PHARMACEUTICAL CARE

TREATMENT OUTCOME

PREVENT PROGRESSION OF RENAL DISEASE

PREVENT & MANAGE COMPLICATIONS

COMMON PROBLEM

PROBLEM MEDIK: Anemia, kelainan hematologi Hipertensi yang tidak terkontrol dg>3 AHT Uremia, acidosis Hiperuricemia, Hiperkalemia/Hipokalemia Gangguan GIT DRP: Over/low dose, cek apakah perlu penyesuaian Adrac Pemilihan obat yang kurang tepat

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, DOA, dan metode ekskresi.

Pilih obat dg nefrotoksisitas minimal Lakukan TDM Hindari penggunaan lama

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

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<IBWIBW : Pria 50+2.3/inch (TB>150 cm) Wanita: 45.5 + 2.3/inch (TB>150 cm) Pengukuran CrCl melalui urin tampung 24 jamCrCl= Uvol x [U Cr] [Cr*] x t* kadar pada midpoint pengumpulan urin

Populasi: Critically ill, trauma, post-op

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

MONITORING BIOKIMIA: Cr, BUN, elektrolit (Na, K, Ca, PO4),

keseimbangan asam-basa, albumin, BSL, Asam urat.

Hematologi: Hb, platelet, hematokrit, white cell count,

profil koagulasi Karakteristik Pasien: BP, BB, temp.,KU, kulit. Terapi Obat: TDM, dosis, efek, adverse drug

reaction, nefrotoksisitas

CASE1

Ny MS, 60 th, BB 55kg RP:DM, ESRD (routine on Dialysis) RO: Dexacap 3x25mg, Diltiazem 3x30mg,

Glurenorm1-0-0.Neurovit E 1x1tab,Allopurinol2x1tab

PC: Hyperglikemia, sesak napas, batuk kering,febris, hypertension ( 200/120mmHg)

Lab: Leukocyt 18000, Na 128 meq/dl,K 5,6 meq/dL, BSL 200mg/dl, Urat5,6mg/dl Cr PHD 7,5 mg/dl, BUN 89 mg/dl

Dx: CRF + febris,encephalopathy

Case 2 Ny H, 24th, BB 45kg TB 150cm PC: lemah, muntah, sesak napas RP: Hipertensi RO: Blopress 8mg Lab: Cr 14,7mg/dL, BUN 124 mg/dL, SGOT

(N), SGPT (N), Na 115meq/L, K 2,7 meq/L, BSL 90 mg/dL.

Dx: CRF, citto HD Apa rencana farmasis terhadap kasus ini?

CASE 3 Ny MS, 60 th, BB 55kg RP:DM, ESRD (routine on Dialysis) RO: Dexacap 3x25mg, Diltiazem 3x30mg,

Glurenorm1-0-0.Neurovit E 1x1tab,Allopurinol2x1tab

PC: Hyperglikemia, sesak napas, batuk kering,febris, hypertension ( 200/120mmHg)

Lab: Leukocyt 18000, Na 128 meq/dl,K 5,6 meq/dL, BSL 200mg/dl, Urat5,6mg/dl Cr PHD 7,5 mg/dl, BUN 89 mg/dl

Dx: CRF + febris,encephalopathy

DIABETIK NEFROPATI Terjadi hampir 1/3 DM Tk albuminuria berhubungan dg tk gagal

ginjal Faktor resiko perkembangan DN: Kontrol

gula yg buruk, HT, intake protein Treatment: Insulin terapi, ACE inhibitor,

restriksi diet protein. Monitor: albuminuria, BP, komplikasi