PATOFISIOLOGI GAGAL GINJAL KRONIKDr. Daru Jaka S, M.Sc., SpPD

DEFINISIKidney 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

CKDManifest as a loss of renal reserveAs CKD progress Pt may remain asymptomaticAs renal function worsen susceptible to infection, poorly controlled hypertension

ESRDClinical state irreversible loss of endogenous renal function RRT permanent AzotemiaUremic syndrome: anemia, malnutrition; impaired carbohydrate metabolism,fats,and proteins; defective utilization of energy and metabolic bone disease

Symptoms & SignsDevelop slowly and nonspecificCan be asymptomatic until stage 5Manifestation: General: malaise, fatigue, weaknessGI: anorexia, nausea, vomitus, hiccupNeurologic: insomnia, irritable,twitch, paresthesia, restless legLibido , mens irregularityCardiopulmonary: cardiomegaly, oedema, pericarditisUremic encepahlopathy: asterixis, myoclonus, confusion-coma

PENYEBAB CKDNon-Diabetes:Hipertensi, Renal Artery StenosisPolicystic kidney diseaseGlomerular diseaseTubulointerstitial diseaseObstructive NephropathiesDiabetes Mellitus

DIABETIK NEFROPATIDef: laju ekskresi albumin urin>300mg/24jam pd Pt dg DM tanpa adanya penyakit ginjal lain Terjadi hampir 1/3 DM Tk albuminuria berhubungan dg tk gagal ginjalFaktor resiko perkembangan DN: Kontrol gula yg buruk, HT, intake protein ,smoking, ,cholesterolTreatment: Insulin terapi, ACE inhibitor, restriksi diet protein.Monitor: albuminuria, BP, komplikasi

COMPLICATIONSHYPERKALEMIAACID-BASE DISORDERCARDIOVASCULARHEMATOLOGIC NEUROLOGICDISORDERS OF MINERAL/ELECTROLIT METABOLISMENDOCRINE DISORDERSGI DISORDERHYPERURICEMIA

HYPERKALEMIAK balance usually remain intact until GFR < 10ml/minEndogenous causes: hemolysis, trauma, acidemic states, hyporeninemic hypoaldosteronismExogenous causes: diet, drugs that K secretion (spironolactone, ACE, NSAID)Hyperkalemia arytmia, ECG change (QRS widen)

ACID-BASE DISORDERInability of kidney to excrete acid generated from protein metabolismPrimarily due to loss of renal massAmmonia production & urine buffer production pH is maintained at 7,33-7,37 & bicarb 15meq/LExcess of H+ buffered by CaCO3 & CaPO4 Renal osteodystrophy

CARDIOVASCULARHYPERTENSIONPERICARDITIS UREMIACONGESTIVE HEART FAILURE

HYPERTENSIONCauses:Salt & water retention due to inability to excrete, adjust to variation in intake water, Na as renal failure worsenHyperreninemic statesExogenous erythropoetinFailure to control HT lead to progression of renal damage

PericarditisCause: retention of metabolic toxinsSymptoms & signs: chest pain, fever, pericardial effusionCO poor with distended Jugular Venous

Congestive Heart FailureHTMyocardial work O2 demand Atherosclerosis AnemiaCHFNa & water retention

HEMATOLOGICANEMIACOAGULOPATHY

ANEMIACharacteristic: normochromic, normocyticCause: Erythropoetin production, Fe deficiencyLow grade hemolysisBlood loss from platelet dysfunctionHDGI bleeding

CoagulopathyPlatelet dysfunctionBleeding is prolongPlatelet shows abnormal adhessiveness and aggregationSign: petechiae, purpura

NEUROLOGICUremic encephalopathyOccur at CKD stage 5 or ESRDCause: hiperPTH; Ca >12-15mg/dLSymptoms: difficulty in concentrating, lethargy,confusion, comaPhysical: nystagmus, weakness, asterixis, hypereflexiaNeuropathy: can be peripherally (restless legs, distal pain, lost of tendon reflexes) and others (impotence, autonomic dysfunction)

DISORDERS OF MINERAL METABOLISMRenal Osteodystrophy: disorder of Ca, P and bone. Form: osteomalacia, osteitis fibrosa cysticaGFR falls

OTHERSGI DISORDERS include: nasea, vomiting, anoreksia, gastric/duodenal ulcerHYPERURICEMIA; impaired excretion of uric acid as renal function worsen

ENDOCRINE DISORDERRenal insulin clearance insulin levelGlucose intolerance can occur when GFR

PHARMACOTHERAPYTreating Reversible Causes of Renal DysfunctionSlowing the Progression of Renal DiseaseTreating Complications

Treating Reversible CausesFactors responsible for acute decrements in renal function in CKD: volume depletion, CHF, nephrotoxic drugs, radiocontrastHypovolemia treatment: repletion, dose of diuretic, Na intakeCKD + CHF treatment: Loop diuretic (maintaining fluid balance)Use of Nephrotoxic drug: adjust dose, avoidRadiocontrast: use non-ionic contrast,hydration 12 hours before procedure

Slowing the Progression of RDSystemic HTGenerates intraglomerular pressures and accelerate glomerular sclerosis and RD Antihypertensive protect both renal & cardiovascularAntihypertensive in non-proteinuric CKD unable to slow the progressionAgents: ACE,ARB, diuretic, Diltiazem, Verapamil, -blockerDietary Protein intakeProtein restriction to 0,6g/kg/day in pt not on dialysisGlycemic controlStrict glycemic control

Treating ComplicationHYPERKALEMIATreatment: iv Ca gluconate, insulin + glucose, Nabic, ion exchange resin, dialysisACIDOSISTreatment: Nabic 0,50 mEq/kg/d target Nabic level>22mEq/LHEMATOLOGIC 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 FeSO4DISORDER OF MINERAL METABOLISMPTH, Ca Calcitriol, Ca CO3

Treating ComplicationHIPERURICEMIAKrn kegagalan ginjal mengekskresi as urat.Terapi: Allopurinol atau dialisis.

ABNORMALITAS GI Karakterisitik: anoreksia, gastric/duodenal ulcerPenyebab: prod.amonia, siklus internal amonia-ureumTerapi: H2-bloker, sukralfat, PPI

PHARMACEUTICAL CARE

TREATMENT OUTCOMEPREVENT PROGRESSION OF RENAL DISEASEPREVENT & MANAGE COMPLICATIONS

Estimate Renal FunctionModified 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

Estimate Renal Function

COCKROFT-GAULTCrCl = (140-umur) x BB 72 x Serum creatinine(mol/L)

Goal: to assess the need of dossage adjustment

MONITORING BIOKIMIA:Cr, BUN, elektrolit (Na, K, Ca, PO4), keseimbangan asam-basa, albumin, asam urat.Hematologi:Hb, platelet, hematokrit, white cell count, profil koagulasiKarakteristik Pasien:BP, BB, temp.,KU, kulit.Terapi Obat: TDM, dosis, efek, adverse drug reaction, nefrotoksisitas