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Taher Hegab, PharmD, PhD, BCPS

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Define Acute Kidney Injury (AKI) Distinguish prerenal from intrinsic and

postrenal causes of AKI

Be able to assess a patient for AKI List most important diagnostic test used in

evaluating patients with AKI

Develop treatment protocols for AKI

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AKI is defined as a decrease in glomerularfiltration rate occurring over hours to days.The decline in GFR is often accompanied bydecline in urine output

Also termed acute renal failure (old term),now only used for severe AKI

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The most recent AKI guidelines define AKI as:

Increase in Scr by 0.3 mg/dl ( 26.5 mmol/l)within 48 hours

Or

Increase in Scr to 1.5 times baseline, which isknown or presumed to have occurred within theprior 7 days

Or Urine volume 0.5 ml/kg/h for 6 hours.

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Stage Serum creatinine Urine output

1 1.51.9 times baselineOR0.3 mg/dl (26.5 mmol/l) increase

0.5 ml/kg/h for 612hours

2 2.02.9 times baseline 0.5 ml/kg/h for >12hours

3 3.0 times baselineOR

Increase in serum creatinine to 4.0mg/dl (353.6 mmol/l)ORInitiation of renal replacement therapyOR, In patients

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Not common in community Dehydration, some disease states and some medication

increase the risk Individuals with CKD is at higher risk NSAIDS, ACEI, ARB, contrast media are common

medication associated with AKI

Common in acute care disease states Very common in ICU setting AKI is associated with increased morbidity and

mortality Risk of death increases with increase in RIFLE

category or AKI stage

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KI

Pre-renal

(Decreased renal

perfusion/ normal renal

tissue)

Intrinsic

(Damage to the kidney/

ischemic or toxin)

Post-renal

(Obstruction or urine flow

bellow kidney) 9

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Intravascular volume Depletion: Dehydration from vomiting, diarrhea, decreased

intake, glucosuria, diabetes insipidus

Diuretics (excessive loss)

Hemorrhage Hypoalbuminemia

Skin losses

Burns

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Arterial hypotension: Sepsis, anaphylaxis

Decreased cardiac output: CHF, sepsis, pulmonary hypertension, aortic stenosis

Renal hypoperfusion ACE inhibitors, ARBs, renal artery stenosis, rental artery

emboli

BUN: Scr ratio > 20:1 indicates prerenal condition

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Prerenal azotemia: Azotemia associated with prerenal AKI

Azotemia: high levels of nitrogen waste in the bloodcauses confusion, alertness, low or no urine

output.

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Critical to identify patient at risk

Administration of wrong medication or notadministering enough volume may invoke AKI

Once AKI identified, must treat as soon aspossible to minimize or prevent permanentdamage

Correct the fluid states to restore renalperfusion

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Damage to the kidney itself

Damage can affect: Vasculature

Vasculitis, emboli, thrombocytopenia purpurea, accelerated HTN,

Glomeruli Lupus, post-streptococcal glomerulonephritis

Tubules (Acute tubular necrosis) (85% of cases) Ischemic (hypotension, vasoconstriction)

Exogenous toxins (contrast dye, heavy metals, aminoglycoside)

Endogenous toxins (Myoglobin, hemoglobin)

Interstitium (acute interstitial nephritis) Drugs (PCN, ciprofloxacin, sulfonamides)

Infections

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Renal Vasculature Damage:

Thromboemboli obstruct blood flow and cause anischemic event (just like an MI)

Emboli can develop/occur on arterial or venous sidekidney

Common event during vascular procedures(angioplasties and aortic manipulations as well asrenal vascular manipulations)

Can result as atrial fibrillation complication or muralthrombus complication (left ventricle)

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Tubular Damage Majority of cases (85%) caused by ATN;

50% ischemic (extended prerenal)

35% direct toxins

Tubules, have high oxygen demands, yetreceive low delivery compared to cortex,hence most affected by ischemia

ATN can occur over hours to days

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Risk factors: CKD

Age > 65

Multi-organ system failure, sepsis

Drugs, infection, surgery, malignancy Bone marrow or solid organ transplantation

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Obstruction: Bladder outlet obstruction

Ureteral

Renal pelvis or tubules

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Outpatient: Change in urinary habits, sudden weight gain, or

flank pain

Inpatient: Usually recognized by clinician before the patient

Decrease in UOP

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Medical history Medical/medication history

Physical exam BP, weight, fluid status, urine output

Laboratory tests Chemistry, hematology, urine sediment, urinalysis,

serologic

Diagnostic Renal imaging

Renal biopsy (rarely)

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serum creatinine, BUN, K, and phosphorus. BUN: Scr ratio

> 20:1 may indicates prerenal condition

Ca and pH (metabolic acidosis)

in WBC if associated with sepsis

in eosinophil may indicate acute interstitialnephritis

Urine analysis: May contain cells, cast, andcrystals

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Urinalysis: Specific gravity: dilution or concentration of urine

(dehydration?)

Protein: indicate kidney damage (nephrotic syndrome orLupus)

Glucose: glucose diuresis Ketones: DKA? Not eating/drinking?

Blood / RBCs kidney stone? Glomerular disease?

Nitrite : UTI? Leukocyte esterase UTI? WBCs UTI? Pyelonephritis? Bacteria UTI?

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Urine sodium and fractional sodium excretion FeNa = (Urine Na x Plasma Cr)

(Plasma Na x Urine Cr)

Used in evaluation of AKI with oliguria

If FeNa < 1% and urine sodium < 20 mEq/L itis likely prerenal

IF > 2% and urine sodium > 40 mEq/Lsuggests acute tubular necrosis

Loop diuretics can increase FeNa

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Diagnostic procedures may be necessary to assistdiagnosis Abdominal radiography including kidneys, ureters and

bladder

Cat Scan (CT) Ultrasonography

Identifies small/shrunken kidneys (CKD)

Postrenal obstruction visible on ultrasound or CT

Cystoscopy/Biopsy may be necessary to identifymalignancy, prostate hypertrophy, uterinefibroids, some stones

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Calculated GFR using any method willoverestimate renal function especially whenrenal function is rapidly changing.

Monitor Scr changes from baseline, look atthe trend not the just the value

Monitor urine output changes

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Pre-renal Volume expansion

Normal saline, to enhance renal perfusion (or LR)(guideline recommended over colloids)

Follow chemistry (BUN, creatinine), urine output

Hold BP meds to ensure good renal perfusion (withinreason)

Isotonic crystalloids generally preferred overcolloids

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Intrinsic renal Stop potentially offending agent Supportive care Immunosuppressives ( lupus, TTP)

Monitor electrolytes, UOP Biopsy as last resort, if indicated

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Post-renal Remove obstruction

Foley placement!

Follow BUN, creatinine

Should improve slowly over several days

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Stop nephrotoxic drugs Stop ACE inhibitor / ARB

No NSAIDs Avoid aminoglycoside if possible

Adjust dose of renally eliminated drugs Can have catastrophic consequences

Antibiotics like ciprofloxacin, levofloxacin, most penicillinsand cephalosporins, vancomycin, aminoglycosides,ranitidine, enoxaparin, and many others

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Question:At what creatinine level should the patient bedialyzed?

Answer:Creatinine level does not matter

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cidosis: metabolic

Electrolytes: hyperkalemia, hypermagnesemia

Intoxication: if dialyzable (lithium, salicylate,methanol, ethylene glycol, theophylline)

Overload: pulmonary edema, CHF

Uremia: pericarditis, altered mental status

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Intermittent hemodialysis: Most common, available everywhere

Rapid removal of fluid and solute

Rapid correction of acid base disorders

Hypotension can be a concern

Continuous renal replacement therapy For hemodynamically unstable patients

Not available at all facilities, more expensive

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In critically ill patients, we suggest insulintherapy targeting plasma glucose 110149mg/dl (6.18.3 mmol/l). (2C)

We suggest achieving a total energy intake of2030 kcal/kg/d in patients with any stage ofAKI. (2C)

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We suggest administering 0.81.0 g/kg/d ofprotein in noncatabolic AKI patients withoutneed for dialysis (2D), 1.01.5 g/kg/d inpatients with AKI on RRT (2D), and up to a

maximum of 1.7 g/kg/d in patients oncontinuous renal replacement therapy (CRRT)and in hypercatabolic patients. (2D)

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We recommend not using diuretics to preventAKI. (1B)

We suggest not using diuretics to treat AKI,except in the management of volumeoverload. (2C)

We recommend not using low-dosedopamine to prevent or treat AKI. (1A)

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We suggest not using aminoglycosides forthe treatment of infections unless no suitable,less nephrotoxic, therapeutic alternatives areavailable. (2A)

We suggest that, in patients with normalkidney function in steady state,aminoglycosides are administered as a singledose daily rather than multiple-dose dailytreatment regimens. (2B)

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We recommend monitoring aminoglycosidedrug levels when treatment with multipledaily dosing is used for more than 24 hours.(1A)

We suggest monitoring aminoglycoside druglevels when treatment with single-dailydosing is used for more than 48 hours. (2C)

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We suggest using topical or local applicationsof aminoglycosides (e.g., respiratory aerosols,instilled antibiotic beads), rather than i.v.application, when feasible and suitable. (2B)

We suggest using lipid formulations ofamphotericin B rather than conventionalformulations of amphotericin B. (2A)

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In the treatment of systemic mycoses orparasitic infections, we recommend usingazole antifungal agents and/or theechinocandins rather than conventional

amphotericin B, if equal therapeutic efficacycan be assumed. (1A)

We suggest not using N-Acetyl Cysteine(NAC) to prevent AKI in critically ill patientswith hypotension. (2D)

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We recommend i.v. volume expansion witheither isotonic sodium chloride or sodiumbicarbonate solutions, rather than no i.v.volume expansion, in patients at increased

risk for CI-AKI. (1A)

We suggest using oral NAC, together with i.v.isotonic crystalloids, in patients at increasedrisk of CI-AKI. (2D)

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We suggest not using diuretics to enhancekidney function recovery, or to reduce theduration or frequency of RRT. (2B)

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54yo M with AIDS (CD4 of 39) who presentsto the ED with altered mental status andneurologic deficits. CT scan with contrast wasordered to further investigate his condition.

His baseline creatinine is 1.4, but he returnsfrom the CT scan and now has creatinine of2.5, with decreased urine output

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Is this AKI? What type is it most likely to be?

How would you manage this?

Answers: Yes, ATN from contrast, supportive care

Bonus:

How might you have prevented this?

A: Pre-hydration and N-acetylcystine prophylaxis

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42yo F with no significant PMH presents to EDwith a cc of 4 days of nausea, vomiting anddiarrhea, with fever to 101OF. She has beenunable to keep any food down, and very little

in the way of liquids. Her son is in primaryschool and had similar symptoms 1 weekago. Creatinine is 2.0. Last one was 0.9about a year ago.

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Is this AKI? What type is it most likely to be? What tests might you order? How would you manage this?

Answers: Yes

pre-renal from dehydration / volume depletion

Orthostatic vitals, BUN:Scr ratio, Give fluids (saline saline saline!), follow creatinine

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75yo M with history of prostate cancerdiagnosed in 2 years ago. It was metastatic tohis ribs at the time, so he was not a candidatefor prostatectomy. He has done well since

then on hormone therapy, but presents toclinic today cc of abdominal pain anddecreased urine output over the last 5 days,as well as irritability and back pain. His

creatinine is 8.5, up from a baseline of 1.4.

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Is this AKI? What type is it most likely to be? What tests might you order? How would you manage this?

Answers: Yes

Post-renal, from prostatic obstruction

Bladder scan or post-void residual; renal ultrasound

Foley placement, give fluids, follow UOP and creatinine

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Pharmacotherapy: Principles and Practice,2013.