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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