PATOFISIOLOGI

GAGAL GINJAL KRONIK

Dr. Daru Jaka S, M.Sc., SpPD

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

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, vomitus, hiccup
Neurologic: insomnia, irritable,twitch, paresthesia,
restless leg
Libido , mens irregularity
Cardiopulmonary: cardiomegaly, oedema, pericarditis
Uremic encepahlopathy: asterixis, myoclonus, confusioncoma

PENYEBAB CKD
Non-Diabetes:
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
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/ELECTROLIT 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 UREMIA
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

Anemia

Myocardial work

CHF
Atherosclerosis

O2 demand

Na & water retention

HEMATOLOGIC
ANEMIA
COAGULOPATHY

ANEMIA
Characteristic: normochromic, normocytic
Cause:
Erythropoetin production,
Fe deficiency
Low grade hemolysis
Blood loss from platelet dysfunction
HD
GI bleeding

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.
2.
3.

Treating Reversible Causes of Renal Dysfunction

Slowing the Progression of Renal Disease
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, 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 0,50 mEq/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 13 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
Karakterisitik: anoreksia, gastric/duodenal ulcer
Penyebab: prod.amonia, siklus internal amonia-ureum
Terapi: H2-bloker, sukralfat, PPI

PHARMACEUTICAL CARE

TREATMENT OUTCOME
PREVENT PROGRESSION OF RENAL
DISEASE
PREVENT & MANAGE COMPLICATIONS

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

Estimate Renal Function

COCKROFT-GAULT

CrCl = (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 koagulasi
Karakteristik Pasien:
BP, BB, temp.,KU, kulit.
Terapi Obat: TDM, dosis, efek, adverse drug
reaction, nefrotoksisitas