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983 A&B 15
Drug-induced Kidney Disease
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Drug-induced Kidney disease
1
Drug-induced Kidney disease
(1) In-community
AKI() 20% community acquired DIKD
ARF()()CHF(
) phenylephrinenorepinephrine ()
(2) In-hospital
AKI 60% drug induced ( AKI)
(3) DIN antibiotic (36%)NASIDsACEIs
Chemotherapeutic
agentsantiviral drugs antibiotic
(4) Antibiotic NASIDs DIN
Drug induced kidney disease
DIN GFR ScrBUN(2X)
1. Scr ( 20%)
(1) Scr(ex: )
(2) catabolism ()
2. Scr
Baseline Scr (mg/dL) Scr (mg/dL)
2 0.5
24.9 1
5 1.5
Scr2 mg/dL 30% Serum creatinine 0.5~1.5mg/dL
3. (Correlated temporally)(
)
DINDrug-induced nephrotoxicity DIKDdrug-induced kidney disease ARFAcute renal failure AKIAcute kidney injury DIN = DINKARF = AKI
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2
urine output ()(
)
(contrast media)NSAIDACEI
(malaise)(anorexia)(SOB )
:SOB=shortness of breath ()
Glomerular filtration
1.
(1) (metabolic acidosis)(bicarbonaturia)
(2) (glycosuria) DM
(3) PKMg ()
2.
(1) (polyurea)
(2)
(3)
()
1.
(1) N-acetyl- D-glucosaminase-glutamyltranspeptidaseglutathione S-
transferaseInterlukin-18 marker
2. kidney injury molecular-1 (KIM-1)
(1) KIM-1 12
12
3. 3 neutrophil gelatinase-associated lipocalin(NGAL)
RIFLE Criteria (2002) for acute renal dysfunction
: Acute Dialysis Quality Initiative Group (ADQI) AKI
GFR Criteria Urine output (UO) Criteria
Risk Creatinine 1.5x GFR25%
UO0.5ml/kg/h 6 hrs
Injury Creatinine 2x GFR50%
UO0.5ml/kg/h 12 hrs
Failure Creatinine 3x GFR75%
UO0.3ml/kg/h 12 hrs Anuria 12 hrs
Loss Persistent ARF = complete loss of kidney function4 weeks
ESKD End Stage Kidney Disease (3 month)
()
: 2005 Acute Kidney Injury Network (AKIN) RIFLE criteria AKIN criteria
AKIN criteria RIFLE criteria
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Drug-induced Kidney disease
3
: AKIN criteria
Diagnostic criteria: within 48 hrs
a. absolute increase in serum creatinine 0.3 mg/dl.
b. or a percentage increase in serum creatinine 50%
c. or a reduction in urine output ( 6 hours)
()
Drug induced renal structural-functional alterations
:
1. (Tubular epithelial cell damage)
(1) (Acute tubular necrosis)intrinsic ARF
(2) (Osmotic nephrosis)
2. (Hemodynamically-mediated kidney injury)functional ARF
3. (Obstructive nephropathy)postrenal ARF
(1) (Intratubular obstruction)
(2) (Nephrolithiasis)
(3) (Nephrocalcinosis)
: Nephrocalcinosis Ca2+ Ca2+
4. (Glomerular disease)intrinsic ARF
5. (Tubulointerstitial disease)
(1) (Acute allergic interstitial nephritis)intrinsic ARF
(2) (Chronic interstitial nephritis)
(3) (Papillary necrosis)
6. (intrinsic ARF)
: ( AKI AKI )
~ ? :
A. B.
C. D.
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4
(ARF)
Prerenal ARFFunctional ARF()
Intrinsic ARF
1. Wegener's granulomatosis()
2. (Acute tubular necrosis, ATN)
3. (Acute interstitial nephritis, AIN)
: Wegener's granulomatosis()
Ab(ANCAs (antineutrophil cytoplasmic antibody))
(97 )
Postrenal ARF(ureter obstruction)BPH anticolinergic
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Drug-induced Kidney disease
5
Agents implicated in drug-induced acute kidney injury
AKI ()
Drug Incidence % Level of evidence
Hemodynamic-mediated
Diuretic (furosemide>hydrochlorothiazide) 5-12 B
ACEI, ARB 6-38 B
cyclosporine 25-38 A
NSAID, COX 2 inhibitors 1-7 A
Acute tubular necrosis
aminoglycosides 5-25 A
Amphotericin B desoxycholate 20-65 A
Amphotericin B lipid-based 15-25 A
Radiocontrast media
CKD 0-10 A
11-20 A
CKD 15-55 A
CKD, 27-81 A
Cisplatin (dose dependent) 10-30 A
Ifosfamide 6 A
Acute interstitial nephritis
allopurinol NK C
-lactam antibiotics NK C
Ciprofloxacin NK C
Erythromycin NK C
H2 receptor antagonists NK C
Lithium NK B
Loop diuretics NK C
NSAIDs NK C
Phenytoin NK C
Proton pump inhibitors NK C
rifampin NK B
Thiazide diuretics NK C
Valproic acid NK C
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6
Nephrolithiasis
Acyclovir NK C
Allopurinol NK C
Foscarnet 1-5 A
Furosemide 14 B
Indinavir 12.4 A
Topiramate 1-3 A
sulfonamides 29 B
Zonisamide 1.9-4 B
Glomerulonephritis
Allopurinol NK B
Gold NK C
Hydralazine NK C
Lithium NK B
NSAIDs NK B
Penicillamine NK C
Phenytoin NK C
Propylthiouracil NK C
Rifampin NK C
1. General/Scr
2.
3. Mg (cisplatin/carboplatin-induced)
4. (Glomerulonephritis)
5. ()
Diuretics in edema
1. Furosemide vs torsemide( PO ) = 1:4
Furosemide vs bumetanide = 1:40
furosemide torsemide long duration ()
2. Ethacrynic acid sulfa drugs
3. Furosemide : ()()
: variable oral bioavailability(ex:
)rapid high bolus
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Drug-induced Kidney disease
7
4. diuretic resistance CIV (Continue IV)
intermittent bolus
CIV natriuresis high serum con
5. Furosemide loading 40-80mg CIV 10-20mg/hMax:480mg/day(!)
6. Clcr < 20mL/min HF, cirrhosis, nephrotic syn.
IV furosemide 30 oral metalazone 5mg (thiazide diuretics)
CKD ()
Drug Incidence % Level of evidence
Aristolochic acid NK B
Antipyretic analgesics 0.8-9% B
Carmustine NK C
Cidofovir NK C
Cisplatin NK C
Cyclosporine NK A
Gold salts 1-5% B
Ifosfamide 7-9% B
Indinavir NK C
Lithium 0.2-21% B
Lomustine NK C
Mitomycin NK C
D-Penicillamine 7% B
Propylthioruacil NK C
Streptozocin NK C
Tacrolimus NK A
~ ? A.
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8
:signs sym.
1.
BPnocturiaPeripheral edemaPulmanary edema
2.
(1) erthropoietin(Epotin )darbepoetin
(2) RBCDDAVP(desmopressin)conjugated estrogenerythropoietin
:Desmopressin vesopressin analogue Vesopressin
(3) SOB
3. phosphate binder (Sevelamer) Ca Vit. D analogs
: Sevelamar
Ca Vit D
4. ()
5. ()
6. Na polystyrene sulfonateIV CaInsulin + glucoseIV NaHCO3
1: Na polystyrene sulfonate Na K
2: K
K IV insulin + Glucose K
3: IV NaHCO3
7. ()
8. ()
9. ()
10. /()
11. ()Gold saltsD-penicilamineNSAID
12. ()
13. ()
14.
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Drug-induced Kidney disease
9
Tubular epithelial cell damage
2.
3. (Acute tubular necrosis, ATN)
(1) ATN Urinary indicesUrine Na40 mEq/LFENa2%urine / plasma Cr20
spGr1.01urine osm.300 mOsm/Kg
(2) ATN
Aminoglycosides Radiographic contrast media () Cisplatin
Carboplatin Amphotericin B
4. Osmotic nephrosis
(1) osmotic nephrosis
Mannitol(osmotic diuretics) Dextran
IV immunoglobulin Hyperosmolar sucrose
: !!!!
( 97 98 )
Aminoglycoside 10-25% 6-10( 5-7) 3-5
1. ScrClCr 2. (500ml/d)Mg K (
) : Oliguria (urine
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10
1. Drug-specific risk factors for acute kidney injury
Risk factor
ACEI NSAID Aminoglycosides Amphotericin B
Contrast media
CKD
D D D D D
D D D NK D
D D D D D
D D NK NK D
Dose / duration
P D D D P
2. (predisposing conditions)(Patient factor) (hypoalbuminemia)(diabetes, obstructive jaundice)G(-)K Mg
3. (AG factor) (1) AG ()(cationic amino group)
: amine group cation amine group !
Neomycin 6 GentamicinTobramycin 5 Amikacin 4 StreptomycinNetilmycin 3
(2) NMGM = tobramycin = amikacin = netilmycinSM (:) (3) AGs dosing(7-10 ) (4) Trough conc.2 mg/Lcp:
: AGs trough level < 2mg/L
(5) AG 4. Concomitant drug therapy(synergistic nephrotoxicity)
ExCyclosporineAmphotericin BVancomycindiureticsFurosemideCisplatin Iodinated radiocontrast mediaFoscarnetNSAID()
1. 2-4 Scr (Scr 0.5 mg/dL ) 2. 3. 4. ( AGs ) 5. ( Cockroft & Gault equation) (97 ) Cockroft & Gault equationmenCLcr = (140-age) ABW / Scr x 72
womenCLcr0.85
6. Modification of Diet in Renal Disease Study (MDRD) GFR GFR = 170 plasma Cr-0.999 age-0.176 0.762() 1.180() serum nitrogen conc.-0.17 serum albumin-0.318
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Drug-induced Kidney disease
11
1. FQ3rd 4th Cephalosporin
2. AGs
3. Once daily dosing(QD) ( TID)
(1) AGs concentration dependent activity ( Penicillin Time dependent)
(2) high peak concentrationAGs
uptake
(3) AGs Ctrough(Trough conc.2mg/L)
(4) Continuous rate gentamicin infusion AGs
uptake (!!)
(5)
a. AGs post-antibiotic effect (PAE)
b.
c.
d.
e.
f.
(6)
a. T1/2
b. post-antibiotic effect
c. MIC
d.
(7) Once daily regimen
a. Clcr60ml/min
b. Scr 0.5 mg/dL 48h 30%
c. (20% BSA )
d.
e. volume status ()
f. enterococcalendocarditismeningitis (AGs BBB)
: Enterococcal endocarditis G(+) gentamicin penicillin synergic effect() one-daily-dose
g.
4. Usual dose4-7mg/kg qd ( 4~5mg/kg qd)
:One daily dose (5mg/kg qd) 5mg/kg/d
5. Cmax/MIC10 ( ) 24h AUC/MIC70
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12
Radiographic contrast media()
7% AKI
1. ARF (34% vs 7%)(delirium) 2. (typical course) (enzymuria) 2 Scr (1-2 5 peak)4-10
3. 50%(oliguria) (500mL/d) 4. (granular cast)
1. (enzymuria) (1) GFR60mL/min/1.73m2 (decompensated kidney ) endothelinadenosine vasoconstrictor () (2)
2. (1) RBC crenation ()aggregation
( O2) NO (protective vasodilator) (2) (900~1780mOsm/kg)( 280~300mOsm/kg)
3.
1. Drug-specific risk factors for acute kidney injury
Risk factor
ACEI NSAID Aminoglycosides Amphotericin B
Contrast media
CKD
D D D D D
D D D NK D
D D D D D
D D NK NK D
Dose / duration
P D D D P
2. ( 2 ) 3. dehydration (-BUNScr201)
4. NSAIDCOX-2 inhibitorACEI hemodynamics 5. (multiple myeloma) 6. older hyperosmolar contrast agent (
)
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Drug-induced Kidney disease
13
: CIN Contrast induced nephropathy
(97 )
(ionic monomers)(>1400mOsm/kg)
(nonionic monomers)(500~850)(ionic
dimer) Ioxaglate 600
(nonionic dimer)iodixanol 290
() ()
(osmoticdieresis)
histamine
CIN v.s. = 1 v.s. 2
Cost-effective
()
(Scr2mg/dL)
()
Dialysis ( irreversible oliguric 500mL/d)
1. (low osmolality)
(1) Nonionic (iohexol, iopamidol)
(2) Ionic dimer (ioxaglate)
(3) Iso-osmolar dimeric nonionic (iodixanol)CKD
+Diabetes CIN
(4) Noniodinated contrast A2
2. (MRI)
3. ( A1)
4. medical history Scr
5. mL/sec / baseline Clcr
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14
ATN()
24 ()
1. CCBs 2. NSAIDCOX-2 ACEI
ARBDiuretics 3. 48h Metformin ARF
12h 12h Hydration0.45% NaCl 1mL/Kg/h (0.5mL/Kg/h in CHF)
N-acetylcysteine 600mg po bid x 1 doses N-acetylcysteine 600mg po bid x 3 dose 12h
Scr for 48-72h :(Risk Score6)
(97 )
Score
Hypotension SBP80
inotropic (dobuatamine) 5
IABP
() 24 5
CHF III & IV 5
Anemia()
HCT (Hematocrit )
39%for men
36%for women
3
3
100c.c. 1
Serum creatinine 1.5mg/dl 4
Estimate GFR 60ml/min/1.73m2
40-602
20-404
202
Risk Score6
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Drug-induced Kidney disease
15
Risk Score6 ()
Yes No
Yes No
1h IV 3ml/kg/h 1. D5W+NaHCO3 154mEq/l 2. NS
:NaHCO3 pH dependent
IV 1. 3ml/kg/h D5W+NaHCO3 154mEq/l 2. 6-12h NS 1mL/Kg/h
Vit C 3g
Vit C 2g bid 2 dose :Vit C
1. Acetylcysteine 600-1200mg bid 2 dose
2. 2h Vit C 3g Vit C 2g bid 2doses
Nonionic low osmolar
iso-osmolar contrast
Nonionic low osmolar
iso-osmolar contrast
1mL/kg/h
(6h for NaHCO312h for NS)
1mL/kg/h
(6h for NaHCO312h for NS)
NaHCO3
pH dependent
1
1h 3ml/Kg/h D5W
+NaHCO3 154mEq/L
,
6-12h NS 1mL/Kg/h
2 +
Acetylcysteine B1 600-
1200mg bid x 2doses
1 3(4)
2h Vit C 3g, 2g
bid x 2doses
1 1h 3ml/Kg/h
D5W +NaHCO3 154mEq/L B2
NS
2 Vit C 3g,
2g bid x 2doses
3 Nonionic low osmolar or
isoosmolar contrast
4 1mL/Kg/h
6h NaHCO3
12h NS
6
slide 31
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16
CisplatinCarboplatin
1980 70%(GFR 20-40%) 20-30% total dose(1mg/min in CHF)hydration ( pretreatment) :Cisplatin, Carboplatin
platinum
analog
1. cisplatin 2.
(1) Carboplatin 90 AUCGFR (2) Oxaliplatin
1. 10-12 Scr peak21 2. Scr 3. (renal Mg wasting)() :premedicaiton
4. () (1) seizureneuromuscular irritabilitypersonality change (2) IV Mg 16mEq/d PO 20mEq tid
Calvert
formula
Total dose (mg) = target AUC (GFR + 25) 1. usual target AUCs()
(1) AUC = 6-8 (2) AUC = 4-6 (:AUC 4-5)
: Drug Information Handbook 18th Ed. 2009
1. (1) Cisplatin CYP2E1 reactive oxygen cell energy production : Cisplatin
Cisplatin (2) cellular protein SH groups mitochondrial DNA
2.
renal irradiation() AGsalcohol abuse()
1. 2. premedication : (1) MgSO4 ( Mg )
(2) Hydration () 3. vigorous saline
(1) 24h 1-4L (150-250mL/h)cisplatin (up to 24h) 4-8hurine output100mL/h 6h
(2) carboplatin ( AUC=8) 3L/m2 4. Cisplatin/NS ( cisplatin )
(1) cisplatin Cl ligand reactive aquated cmpd (Cl cisplatin aquation reaction reactive platinum)
(2) D5W :
Amphotericin B antifungal agent IV D5W Normal Saline NS Amphotericin B Cisplatin IV Normal Saline Cl Cisplatin D5W cisplatin Cl reactive Compound
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Drug-induced Kidney disease
17
5. Cisplatin 30 furosemide 20-40mgmannitol () 12.5-50g (10g/h 3h)
(1) urine output 100mL/h cisplatin ( saline 250mL/h) cisplatin
Amifostine
Amifostine (renoprotection, prodrug) 1. renoprotectionorganic thiophosphate (free thiol)
(1) normal cells cisplatin (2) (3) (neutropenia)
: ASCOThe American Society of Clinical Oncology
2. cisplatin 30 amifostine 910mg/m2/dIV 15 3. : 4. :
amifostine 24h (1) 5 (2) saline (3) (15-61% dose dependent)
: amifostine 5. Cisplatin/ifosfamide solid tumor amifostineGFR 6. pretreatment amifostine
Elderlyvolume depleted(CKD)
() (97 )
hypertonic saline (3% 250mL) tubular cisplatin uptake(HF )
Intraperitoneal() cisplatin + IV sodium
thiosulfate
sod thiosulfate cisplatin
: sod thiosulfate
N-acethylcysteine SH donor oxidative damage
disulfiram metabolite diethyldithiocarbamate CYP2E1 OH
radical ()
Melatonin
cisplatin-incorporated polymeric micelles
:
()
1. supportive care (dialysis) 2. ScrBUNMgKCa
3. Clcr30-60mL/min 50% dose
4. Clcr10-30mL/min
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18
Amphotericin B Desoxycholate
1. 300-400mg 2-3g 80%
2. (ARF) ARF mortality = 54% vs 16%
:Amphotericin B Antifungal drugs
3. GFR(azotemia)( KNaMg )
H+
4. GFR ScrBUN
5. BUN50mg/dL
1. ()
2.
(1) (amphotericin sterols
ionophore NaK ) cell lysis cytokine
(2) (amphotericin B )GFR
(3)
1. Drug-specific risk factors for acute kidney injury
Risk factor
ACEI NSAID Aminoglycosides Amphotericin B
Contrast media
CKD
D D D D D
D D D NK D
D D D D D
D D NK NK D
Dose / duration
P D D D P
2. (CKDchronic kidney disease)
3. mean daily dose35mg
4.
5. CSA(cyclosporine)
6. 24h vs 4h GFR pretubular effect 24h
: 4h 4h 24h
7. BW 90Kg
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Drug-induced Kidney disease
19
1. 1.5-2g ( 6-10 )
2. CSA(cyclosporine)
3. (hydration)1L NS daily (sodium load 150mEq
)(H/T)(CHF)(edema)
4. mannitol infusion
5. D5W 250-500mL 0.1mg/mL () 0.25mg/mL ()
4-6h
(1) (chillsfeverhypotensionnausea) Premedication (
30-60 )
a. NSAID diphenhydramune
b. Acetaminophen+ diphenhydramune
c. Hydrocortisone50-100mg
d. (rigor) meperidine
6. liposomal amphotericin B (Ambisome)
lipid based AmB ( 8-28%)
(1) mammalian cell membrane amphotericin B
(2) AmB encapsulated liposome fungal ergosterol human ergosterol
translocate ()
(3) Lipid-based AmB is taken up by macrophages ()
macrophage AmB lipid AmB
(4) extracellular phospholipase lipid based AmB lipid
encasing AmB
(5) AmB HDL-C LDL-C ( HDL-C receptor )
(6) Lipid based AmB AmB toxic cytokineTNFinterleukin-1
1.
2. ScrBUN MgKCa
~ ? B.
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20
Hemodynamic mediated kidney injury
3.
(1)
(2) (angiotensin)
: (macula densa) renin
4.
()
NSAIDs PG (A II )
Mannitol tubuloglomerular feedback
ACEIARB Angiotensin II
neurohumoral renal hemodynamic control
CCBs
RBF
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Drug-induced Kidney disease
21
5.
(1) intraglomerular pressure
()
(2)
ACEIARBNSAID()CSATacrolimus()
6.
ACEIARB
1. 2-5 ( prodrug)
Scr 30% (0.1-0.3mg/dL)GFR urine output
(1) 1-2wkScr 0.5mg/dL ( hemodynamic mediated acute kidney injury) (2) 2-3wk Scr (3) : ACEI angiotensin II
ARB angiotensin II 2. Angiotensin GFR
(1) aldosterone (2)
3. ARB ACEI (ARF) (1) Angiotensin II receptors AT IAT II (2) ARB AT I AT I (CV effect)aldosterone - adrenergic stimulation
(3) ACEIARB ARF ARF
ACEI angiotensin II ARB (glomerular capillary hydrostatic pressure)
1. Drug-specific risk factors for acute kidney injury
Risk factor
ACEI NSAID Aminoglycosides Amphotericin B
Contrast media
CKD
D D D D D
D D D NK D
D D D D D
D D NK NK D
Dose / duration
P D D D P
2. angiotensin II (CHFGI fluid loss ) 3. (CSANSAIDs)
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22
1.
(1) captopril 6.25-12.5mg patient
(2)
2. 2-3
(1) CHF
(2) ACEI Bradykinin
3. NSAID ()( replete the
intravascular fluid volume, )
1. Scr ( ACEI Scr 20-30%2-3 ) Scr
urine output (ARF)
2. sodium polystyrene sulfate ()
3. (CHF) hydralazinenitrates
: hydralazine afterloadnitrates preload
4. CHF Scr 2-3mg/dL(97 )
NSAID
500,000 2.5million
1. NSAID ibuprofen
2. (low urine vol. & sodium)(edema) +/- BUN
ScrK
Pathogenesis
1. stressed angiotensinIInorepinephrine
endothelinvasopressin PG
2. renal PG (prostacyclinPGE2) vascular endothelial
glomerular mesangial cells
3. cyclooxygenase PG
AKI
Risk factor
1. high plasma renin
CHF (ejection fraction
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Drug-induced Kidney disease
23
1. acetaminophennonacetylated salicylatesaspirinnabumetontramadol selective COX-2 inhibitormeloxicamcelecoxibvaldecoxib GI
2. NSAID 3. sulindac
( potent NSAIDrenal PG renal sparing effect) (1) sulindac sulfide (active) reversibly oxidized back to sulindac
(prodrug renal PG ) (2) sulindac sulfide CYP450 dependent mixed function oxidases
sulindac sulfoxide (3) Sulindac (cirrhosis)(ascites) Sulindac renal sparing effect
Management
1. 2. 3. NSAID +/-( steroid-
prednisone 1mg/Kg/d for 4 wks)
Cyclosporine(CSA) and Tacrolimus
1. Calcineurin inhibitors : Calcineurin IL-2 cytotoxin T lymphocyte
2. Acute hemodynamic mediated kidney injury
CSA 80%
1. 4 presentations asym
(1) Scr (2) (ARF) (3) delay graft function () (4) hemolytic uremic sydrome.()
2.
Pathogenesis
1. thromboxane A2endothelin RAA 2. nitric oxideprostacyclin 3. >
Risk factor
1. 65 (AGs amphotericin BacyclovirketoconazolecotrimoxazoleNSAIDs)
2. CSA (CYP450)(ketoconazoleitraconazolefluconazole ClarithromycinEMTelithromycinRitonavirCCB) 3. CSA (rifampinisoniazidphenytoinphenobarbitalcarbamazepine)
1. PKPD 24h 2. trough conc. 100-250ng/mLAUC trough 4400-5500mcg/h/L 3. CSA(cyclosporine)tacrolimus
Management
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24
Obstructive Nephropathy
1.
2.
3. Scr
4.
Intratubular obstruction ()
Acyclovirsulfadiazineindinavirfoscarnetmethotrexate
Extrarenal obstruction ()
TCAindinavir
Nephrolithiasis() Triamtereneindinavir
1.
2. (tumor lysis syn. in high-grade lymphomas (Burkitt subtype)
acute lymphoblastic leukemia ) :
(1) K catabolism
ARF(acute oliguric)
(anuric renal failure)
(2) tumor lysis syn.urine uric acid/Cr1
(3)
a. Pretreatment hydration (NS)2.5L/d pH 7chemo
2-3d allopurinol 300-600mg
b. Rasburicaserecombinant urate-oxidase uric acid
allantoin ( tumor lysis syn.)
chemo 4-24h IV 0.15-0.2mg/Kg/d for 5days
3. (Rhabdomyolysis)Myoglobin
a. HMG CoA reductase inhibitor (statin ) gemfibrozilniacinCYP3A4 inhibitors
(CSAEMitraconazole statin )
b. CNS (alcohol, )(pressure necrosis)
c. CNS stimulants (amphetamines, cocaine, ecstasy, phencyclidine)
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Drug-induced Kidney disease
25
4. Urine pH = 4.5)
(1) acyclovir
(2) sulfadiazine acetylsulfadiazine
!
(3) (AKI, acute kidney injury) (congenital nephrotic syndrome)
Vit C oxalate
a. Thiazide Ca
b. Allopurinol 200mg/d purineuric acid Ca oxalate
c. K citrateK-Mg citrate (10meq, 1.08g 2-4 /d)
Ca oxalate
(4) MTX (methotrexate) 300mg/m2
a. MTX 12h 24-48h hydration urine output 1.5-2L/m2
b. urine pH7 sodium bicarbonate
: methotrexate (oligo-anuric kidney injury)
c. Leucovorin rescueMTX infusion24h leucovorin 10-15mg/m2 q6h for 8-10 doses
rescue therapy MTX 48h MTX level leucovorin
MTX 5 x 10-8M
5. pH = 6 Indinavir (protease inhibitor)(8%)
(nephrolithiasis -) 2-3L fluid/d
() 75% Indinavir ( indinavir )
6. Foscarnet (Antiviral pyrophosphate analog CMV retinitis CMV )
Ca+2 Ca foscarnet (glomerulonephritis)
7. LMW dextran dextran (volume expansion, rheological effect)
filtered dextran kidney injury
8. Triamterene calculi
(@@)
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26
(1) (volume expansion)(100-200mL/h 24h)
(2)
(3)
a. (methotrexate, sulfonamide)
b. (indinavir, other protease inhibitors)
c. (PH>7.15) ARF
d.
a. NaHCO3 50mEq/L
b. acetazolamide 500mg 2-4 /d ()
: Acetazolamide : carbonic anhydrase inhibitor Diuretic Cl HCO3-
FDA
c. pot. Citrate(K citrate) 10meq, 1.08g 2-4 /d
d.
Glomerular Disease
1.
(1) NASID (2) penicillamine (3) Gold
(4) Heroin abuse
a. focal segmetnal glomerulosclerosis (FSGS)++
b. Heroin
c. IV virus
(5) Pamidronate ()
malignancy-associated hypercalcemia FSGS
2. NSAID Nephrotoxicity
Hemodynamic mediated kidney injury
Glomerular disease Acute allergic interstitial nephritis
Papillary necrosis ()
intraglomerular pressure
Immune(lymphokines )
Delayed hypersensitivity idiosyncratic
phenacetin acetaminophen
+/- GFR ()
humoral immune reactions cell-mediated injury
Prednisolone 0.5-1mg/Kg /d for 3-4wks
Prednisolone 1mg/Kg/d for 4wks
acetaminophen reduced glutathione
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Drug-induced Kidney disease
27
Tubulointerstitial disease
1.
2. delayed hypersensitivity(type IV)
3.
(1)
a.
b. (humoral immune reactions)
hapten host protein
c. (cell-mediated injury) mononuclear
inflammation
(2)
a.
b. (originates) papillae ()
4.
Acute allergic interstitial nephritis PenicillinNSAIDs
Chronic interstitial nephritis CSALiAritolochic acid
Papillary necrosis Combined phenacetinaspirincaffeine analgesic
acute allergic interstitial nephritis
(acute allergic interstitial nephritis)( AKI 3)
( Penicillins NSAIDs)
(1) Antimicrobials Acyclovir, AGs, amphotericin B, aztreonam, cephalosporins, ciprofloxacin, EM, EMB, indinavir, PNs(methicillin), rifampin, sulfonamides, tetracyclins, trimethoprim, sulfamethoxazole, vancomycin
(2) Diuretics Acetazolamide, amiloride, chlorthalidone, furosemide, triamterene, thiazides
(3) Neuropsychiatrics Carbamazepine, Li, phenobarbital, phenytoin, valproic acid
(4) NSAIDs Aspirin, indomethacin, naproxen, ibuprofen, diflunisal, piroxicam, ketoprofen, phenylbutazone, diclofenac, zomepirac
(5) Miscellaneous Acetaminophen, allopurinol, INF-, azathioprine, captopril, cimetidine, clofibrate, CSA, glyburide, gold, methyldopa, omeprazole, PAS, phenylpropanolamine, propylthiouracil, , ranitidine, sulfinpyrazone, warfarin sodium
( 97)
-
28
1. Penicillins
(1) Methicillin prototype ()
(2) 14 (6-10) fever (80%)
maculopapular rash (25%)eosinophilia (80%)pyuria +hematuria
(90%), low-level proteinuria (90%)oliguria (20%) in severe cases of AIN
leukocytosisIgE
: EosinophiluriaAIN marker eosinophil
(3)
(4) Corticosteroids ARF ( guideline )
(5) Prednisone 1mg/Kg for 7 days
(6) Dialysis in oliguria
: Penicillins corticosteroids
2. NSAIDs
(1) Clinical presentationfenoprofen allergic interstitial nephritisprototype 50%
(2) T cell
(3)
(4)
(5) Gallium-67 renal imaging
a. minimal change disease
b. positive scan
(6) allergic hypersensitivity response idiosyncratic hypersensitivity
(7) Prevention idiosyncratic S/S
(8) Management
a. Prednisone 1mg/Kg/d for 4 wks
b. NSAID (fenoprofen) idiosyncratic hypersensitivity type-2
reaction steroid
~ ? C.
-
Drug-induced Kidney disease
29
Chronic interstitial nephritis
Li 1.
(1) (Nephrotic diabetes insipidus) () 87% (2) (acute tubular necrosis) (3) chronic tubulointestitial (4) nephritis ( ) (5) incomplete distal renal tubular acidosis
: 2. U/A : RBC, WBC, granular cast( urine ) 3. Pathogenesis ADH () 4. Risk factor
(1) Li conc.() (2)
(3) Scr2.5mg/dlBUN (4) neuroleptic agents
(5) Li + furosemide Li Li conc weakness, tremor, excessive thirst, confusion
5. Prevention
, ( )
6. Management Li amiloride()
~ ? D.
-
30
Renal Replacement Therapy (RRT ) ~ AEIOU
Indication for Renal Replacement Therapy
Clinical Setting
A Acidbase abnormalities
() Metabolic acidosis resulting from the accumulation of organic and inorganic acid
E Electrolyte imbalance
() Hyperkalemia, hypermagnesemia
I Intoxications
() Salicylates, lithium, methanol, ethylene glycol, theophylline, phenobarbital
O fluid overload () Postoperative fluid gain
U Uremia () High catabolism of acute renal failure
Continuous renal replacement therapy (CRRT)
1. ARF , uremic toxin, K CRRTCRRT 2. , hypercatabolism CRRT
(1) CAVH / CVVH (Continuous arteriovenous or venovenous hemofiltration) sepsis
cytokine HDvasopressor (2) CAVHD / CVVHD (Continuous arteriovenous or venovenous hemodialysis) (3) CAVHDF / CVVHDF (Contnuous arteriovenous or venovenous hemodiafiltration) Li, MTX, procainamide, valproic acid
3. H- hemofiltration R(replacement) HD hemodialysis Di(dialysate) HDF hemodiafiltration R Di
4. CRRT mode (1) CAVH / CVVH convection / ultrafiltration ( plasma water into
the ultrafiltrate ) (2) CAVHDF / CVVHDF CAVH / CVVH convection / ultrafiltration plasma water
5. (HDF)(sieving coefficient SC) blood flow rate, Ultrafiltration rate, dialysate flow rateCRRT
-
Drug-induced Kidney disease
31
Cyclosporine (CSA) Tacrolimus 1.
(1) acute hemodynamically mediated kidney injury GFR ()
:(p20) (2) >6-12 chronic interstitial nephritis (3) 6-12 - dose limiting adverse effect
2.
endothelin-1 nitric acid transforming growth factor-
3. Risk factor 50y/ocyclosporine / tacrolimus ARF 3-12m postOP ARF
4. (1) (2) twice weekly -
5. prednisolone, azathioprine
Aristolochic scid 1.
(1) Aristolochia fangchi (Guang fang ji ) aristolochic acid () (2) Chinese herb nephropathy ()3-5%
2.
(1) Scr
(2) atopical urothelial cell
(3) 6-24 ESRD (end-stage reanal disease) (4) nephroureterectomy 40-46% urothelial transitional cell
carcinoma() 3.
aristolactam Iaristolactam II DNA adducts () , DNA
4. (1) (2) dexfenfluramine +/- phentermine
5.
-
32
Renal thrombosis
1. Thrombotic microangiopathy ( Hemolytic uremic syn thrombotic thrombocytopenic purpura , CNS , )
2. mitomycin C (
-
Drug-induced Kidney disease
33
Renal vasculitis
(Thrombotic microangiopathy) hemolytic uremic syndrome thrombotic thrombocytopenic purpuraCNS
mitomycin C (
-
34
(1)9. CpCtrough Tobramycin Theophylline Li carbamazepine
(2)10.Aminoglycosides once daily dosing T1/2 Postantibiotic effect MIC
(A)11. gentamicin
gentamicin
(A)5 mg/kg, qd (B)1 mg/kg, tid (C)5 mg/kg, q8h (D)2 mg/kg, q12h
(D)12.gentamicin
(A)25 g/mL (B)25 mg/mL (C)30 g/mL (D)
(D) 13. gentamicintrough
(A) (B) (C) (D)
(1)14. ARF ionic contrast medium NS
NaHCO3 N-acetylcystine
(2)15. CT propranolol diclofenac
acetaminophen amlodipine
(B)16.radiocontrast media
acute tubular necrosis
(A)0.45% 0.9% NaCl (B)ACE inhibitors (C)Calcium channel blocker (D)Dopamine
(B)17.radiocontrast mediaacute
tubular necrosis
(A)
(B) 0.45%0.9% NaCl
(C) dopamine
(D) captopril
(3)18. Contrast mediumAcetylcysteine CCB
Diuretics Labetalol
(B)19.
(A)NSAIDs (B)Calcium channel blocker (C)ACE inhibitors (D)Metformin
(C)20.
(A)Celecoxib (B)Nifedipine (C)N-Acetylcysteine (D)Enalapril
(D)21 cisplatin
(A)mannitol (B) (C)amifostine (D)
(A)22. cisplatin
(A) 2-3 (B) (C) 4 furosemide
100-200 mL (D) 4 mannitol 100-200 mL
(B)23.
( A ) Azacytidine ( B ) Cisplatin ( C ) Dacarbazine ( D ) Vincristine
-
Drug-induced Kidney disease
35
(B)24. amphotericin B desoxycholate
(A)diluent (B)
250 mL (C) (D)
(C)25. postrenal acute renal failure ? triamterene aspirin indinavir
methotrexate
(A) (B) (C) (D)
(D)26.10%AIDSindinavir
( A ) indinavir ( B ) ( C ) ( D )
(C)27.postrenal acute renal failure
(A)Penicillin (B)Aminoglycoside (C)Methotrexate (D)Amphotericin B
(C)28.postrenal obstruction
(A)Ampicillin (B)Celecoxib (C)Methotrexate (D)Tobramycin
(B)29. methotrexate
(A) 48 leucovorin rescue (B)Leucovorin methotrexate
(C) 24 100-200 mL (D)
methotrexate
(3)30.Acute myelogenous loukemia 28mg/dLScr 26mg/ dL Tumor lysis
syndrone ? probenecid colchicine allopurinol indomethacin
(2)31.? naproxen labetalol cyclosporine amphotericin B
(B)32.
(A)Aminoglycosides (B)Erythromycin(C)
NSAIDs (D)
(1)33. Carboplatin Doxorubicin 5FU
Paclitaxel
Calvert formula (Drug Information Handbook 18th Ed. 2009)
total dose (mg) = target AUC x (GFR + 25)
usual target AUCs
previously untreated patients: 6-8
previously treated patients: 4-6
(A)34. ATNacute tubular necrosis
furosemide 80 mg 1 1 mL/kg/hr
(A) furosemide 400 mg (B) 6-8 furosemide 100 mg (C)
furosemide 200 mgchlorothiazide 500 mg (D) 12
chlorothiazide 500 mg
-
36
(C)35. ATNacute tubular
necrosis1. NSAID 2. aminoglycoside 3. acyclovir 4. amphotericin B 5. hydralazine
(A)1, 2, 3 (B)1, 4, 5 (C)2, 4 (D)3, 5
(B)36.
( A ) Enalapril ( B ) Metoprolol ( C ) Naproxen ( D ) Trichlormethiazide
(B)37. 22 mg/dL 2.1 mg/dLurine
alkalinization
(A)Sodium bicarbonate IVpotassium bicarbonate IV
(B) potassium citrate 1 g 3 6
(C)Acetazolamide
(D) pH 8.5
(B)38. (A)-Aminocaproic acid
(B)Aristolochic acid (C)-Hydroxybutyric acid (D)Pipemidic acid
(A)39.aristolochic acid (A)interstitial
nephritis (B)hemodynamic (C)postrenal obstruction
(D)acute tubular nephritis
(B)40. (A) (B)
(C) (D)
(D)41.
(A) (B) (C) (D)
(A)42. captopril losartan
(A) (B) (C) (D)
-
983 A&B 15 ~ ~
983 A&B
O