aminoglycoside-induced acute tubular necrosis phcl 442 lab discussion 2 raniah al-jaizani m.sc
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Aminoglycoside-Induced Acute Tubular Necrosis
Aminoglycoside-Induced Acute Tubular Necrosis
PHCL 442 Lab
Discussion 2
Raniah Al-Jaizani M.Sc
Classification of ARFClassification of ARF
Kidney
Glomerular & Tubular FunctionsGlomerular & Tubular Functions
Aminoglycoside-Induced ATNAminoglycoside-Induced ATN
Risk factors: Patient related:
Elderly Underlying renal disease Dehydration Hypotension/Shock syndrome Hepatorenal synderome
Aminoglycoside related:
AGs choice: geniamicin> toberamycin> amikacin Therapy > 3 days Multiple daily dosing Serum trough>2 mg/l
Aminoglycoside-Induced ATNAminoglycoside-Induced ATN
Risk factors (cont.):
Concomitant therapy:
Furosemide, Ampho B, Vancomycin, and Cyclosporine.
Aminoglycoside-Induced ATNAminoglycoside-Induced ATN
Mechanism
5% AGs actively reabsorbed by the proximal tubule cells
bind to brush-border cells (tubule lumen) pinocytosis & enter
interacellular space formation of myeloid bodies
releasing large conc. Of AGs & lysosomal enzymes in to tubule
lumen tubular destruction.
Rank order of nephrotoxicity:
Neomycin> gentamicin> toberamycin>amikacin>netilmicin> streptomycin
Aminoglycoside-Induced ATNAminoglycoside-Induced ATN
Extended interval dosing vs. Regular dosing
One large daily AGs dose Concentration-dependant killing activity High peak conc. improve efficacy & undetectable trough conc.
before next dose reduce toxicity Less costly
To prevent aminoglycoside-induced nephrotoxicity inclinical practice:To prevent aminoglycoside-induced nephrotoxicity inclinical practice:
Use aminoglycosides as an once daily dose rather than divided dose
especially in high-riskindividuals. Serial monitoring of renal function (serum creatinine) should be carried-
out for early detection of nephrotoxicity. Avoid combination of aminoglycosides with other potential nephrotoxins
(amphotericin, cisplatin, diuretics, contrastmaterial, etc.). During aminoglycoside therapy, ensure adequate hydration especially in
the elderly. Modify the dose according to GFR. Avoid aminoglycosides in a patient with liver disease.
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Amphotericin B-Induced NephrotoxicityAmphotericin B-Induced Nephrotoxicity
What is the mechanism of toxicity
and how to overcome it?
Assignments:
Word processing
Reference (s)
Answered by
Assignments:
Word processing
Reference (s)
Answered by
Diabetic nephropathyDiabetic nephropathy
Microvascular complication of diabetes resulting in
albuminuria and progressive decline in kidney function. The leading cause of ESRD
ESRD = End Stage Renal Disease
DM & Kidney DiseaseDM & Kidney Disease
ESRD in type I DM
DM = Diabetes Mellitus ESRD = End Stage Renal Disease 13
DM & Diabetic NephropathyDM & Diabetic Nephropathy
BP = Blood Pressure 14
Natural History of Diabetic NephropathyNatural History of Diabetic Nephropathy
Onset of DM
0 2-5 7 15 >20
Hyperfiltration(functional changes)Stage 1
Silent phase(structural changes)Stage 2
Incipient nephropathyStage 3
OvertnephropathyStage 4
Onset ofproteinuria
ESRDStage 5
Dialysis/Transplant
Time(yrs)
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Diabetic Nephropathy & AlbuminuriaDiabetic Nephropathy & Albuminuria
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Diabetic Nephropathy & AlbuminuriaDiabetic Nephropathy & Albuminuria
• Albuminuria is the earliest sign of kidney involvement in
patients with DM
• It correlates with the rate of progression of kidney disease
• Type I DM >5 years test for albuminuria annually
• Type II DM test for albuminuria annually starting from time
of diagnosis
• The presence of albuminuria indicates irreversible kidney
damage
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Management GoalsManagement Goals
• Delay the need for dialysis therapy as long as possible
• Manage 2ry complications
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Management StrategiesManagement Strategies
• Intensive glucose control
• Antihypertensive therapy
• Dietary protein restriction
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Intensive Glucose ControlIntensive Glucose Control
Glycemic control is indicated to reduce proteinuria & slow the
rate of decline in GFR
The ADA recommended goals:
Pre-prandial plasma glucose = 90 – 130 mg/dl
Peak post-prandial plasma glucose > 180 mg/dl
Hgb A1C > 7%
GFR = Glomerular Filtration Rate ADA = American Diabetes Association’s 20
Antihypertensive TherapyAntihypertensive Therapy
Untreated HTN is associated with reduction in GFR
The control of BP has been shown to slow the progression of
kidney disease and increase life expectancy in DM patients
HTN = HyperTeNsionBP = Blood Pressure 21
Antihypertensive TherapyAntihypertensive Therapy
To control BP ACEIs or ARBs are the preferred agents
They have been shown to reduce proteinuria & decrease rate of
decline in GFR
They are used an all diabetic patients & microalbuminuria even if
their BP is normal
BP goal in patients with DM & kidney disease is > 130/80 mm Hg
ACEIs= Angiotensin Converting Enzyme InhibitorsARBs = Angiotensin Receptor Blockers 22
Antihypertensive TherapyAntihypertensive Therapy
At initiation of therapy ACEIs & ARBs can increase SrCr by up to
30% which is acceptable
They are not used in patients with bilateral renal artery stenosis
Monitor for hyperkalemia
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Antihypertensive TherapyAntihypertensive Therapy
• Non-dihydropyridine calcium channel blocker (diltiazem &
verapamil) could be used in combination with ACEIs
• Diuretics can be used to control edema
• Other antihypertensive agents may be considered to control
BP
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Dietary Protein RestrictionDietary Protein Restriction
• High protein intake can increase intraglomerular pressure
thereby accelerating the progression of diabetic nephropathy
• Restrict protein intake to 0.6 – 0.8 g/kg/day
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Patient CasePatient Case
M.R. is a 32 y.o African American female (Wt 63 kg; Ht 5’8”) with a 15 years
history of type I Dm who present to the diabetes clinic with 1 week history of
nausea, vomiting and general malaise. She has been noncompliant with
regular appointments and her blood glucose>200mg/dl on prior evaluations,
with Hg A1C 8% 2 month ago.
Laboratory values:
Na 143 mEq/l; K 5.3 mEq/l; Cl 106 mEq/l; SrCr2.9 mg/dl; BUN 63 mg/dl;
and RBG 220 mg/dl; urinary albumin 700 mg/24 hr
PE:
Bp 155/102 mm Hg
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Patient CasePatient Case
1. What is the cause of M.R.’s advanced kidney disease?
2. How should M.R.’s kidney disease be managed?
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Patient CasePatient Case
K 5.3 mEq/l; Cl 106 mEq/l; SrCr2.9 mg/dl; BUN 63 mg/dl;
and RBG 220 mg/dl; Hg A1C 8%
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