Taher Hegab, PharmD, PhD, BCPS

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

AKI is defined as a decrease in glomerular

filtration rate occurring over hours to days.
The decline in GFR is often accompanied by
decline in urine output

Also termed acute renal failure (old term),

now only used for severe AKI

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 is
known or presumed to have occurred within the
prior 7 days
Or
Urine volume 0.5 ml/kg/h for 6 hours.

Stage

Serum creatinine

Urine output

1.51.9 times baseline

OR
0.3 mg/dl (26.5 mmol/l) increase

0.5 ml/kg/h for 612

hours

2.02.9 times baseline

0.5 ml/kg/h for >12

hours

3.0 times baseline

OR
Increase in serum creatinine to 4.0
mg/dl (353.6 mmol/l)
OR
Initiation of renal replacement therapy
OR, In patients <18 years, decrease in
eGFR to <35 ml/min per 1.73 m2

<0.3 ml/kg/h for 24

hours
OR
Anuria for 12 hours

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

Pre-renal
(Decreased renal
perfusion/ normal renal
tissue)

AKI

Intrinsic
(Damage to the kidney/
ischemic or toxin)

Post-renal
(Obstruction or urine flow
bellow kidney)
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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 blood
causes confusion, alertness, low or no urine
output.

13

Critical to identify patient at risk

Administration of wrong medication or not

administering enough volume may invoke AKI

Once AKI identified, must treat as soon as

possible to minimize or prevent permanent
damage

Correct the fluid states to restore renal

perfusion
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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 an
ischemic event (just like an MI)
Emboli can develop/occur on arterial or venous side
kidney
Common event during vascular procedures
(angioplasties and aortic manipulations as well as
renal vascular manipulations)
Can result as atrial fibrillation complication or mural
thrombus 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, yet

receive low delivery compared to cortex,
hence most affected by ischemia
ATN can occur over hours to days
17

Risk factors:

CKD
Age > 65
Multi-organ system failure, sepsis
Drugs, infection, surgery, malignancy
Bone marrow or solid organ transplantation

18

Obstruction:
Bladder outlet obstruction
Ureteral
Renal pelvis or tubules

19

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 interstitial
nephritis
Urine analysis: May contain cells, cast, and
crystals

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Urinalysis:

Specific gravity: dilution or concentration of urine

(dehydration?)
Protein: indicate kidney damage (nephrotic syndrome or
Lupus)
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 it

is likely prerenal
IF > 2% and urine sodium > 40 mEq/L
suggests acute tubular necrosis

Loop diuretics can increase FeNa

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Diagnostic procedures may be necessary to assist

diagnosis
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 identify
malignancy, prostate hypertrophy, uterine
fibroids, some stones

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Calculated GFR using any method will

overestimate renal function especially when
renal function is rapidly changing.
Monitor Scr changes from baseline, look at
the 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 (within
reason)

Isotonic crystalloids generally preferred over

colloids

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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 penicillins
and cephalosporins, vancomycin, aminoglycosides,
ranitidine, enoxaparin, and many others

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Question:
At what creatinine level should the patient be
dialyzed?

Answer:
Creatinine level does not matter

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Acidosis: 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 insulin

therapy targeting plasma glucose 110149
mg/dl (6.18.3 mmol/l). (2C)
We suggest achieving a total energy intake of
2030 kcal/kg/d in patients with any stage of
AKI. (2C)

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We suggest administering 0.81.0 g/kg/d of

protein in noncatabolic AKI patients without
need for dialysis (2D), 1.01.5 g/kg/d in
patients with AKI on RRT (2D), and up to a
maximum of 1.7 g/kg/d in patients on
continuous renal replacement therapy (CRRT)
and in hypercatabolic patients. (2D)

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We recommend not using diuretics to prevent

AKI. (1B)
We suggest not using diuretics to treat AKI,
except in the management of volume
overload. (2C)
We recommend not using low-dose
dopamine to prevent or treat AKI. (1A)

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We suggest not using aminoglycosides for

the treatment of infections unless no suitable,
less nephrotoxic, therapeutic alternatives are
available. (2A)

We suggest that, in patients with normal

kidney function in steady state,
aminoglycosides are administered as a single
dose daily rather than multiple-dose daily
treatment regimens. (2B)
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We recommend monitoring aminoglycoside

drug levels when treatment with multiple
daily dosing is used for more than 24 hours.
(1A)

We suggest monitoring aminoglycoside drug

levels when treatment with single-daily
dosing is used for more than 48 hours. (2C)

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We suggest using topical or local applications

of aminoglycosides (e.g., respiratory aerosols,
instilled antibiotic beads), rather than i.v.
application, when feasible and suitable. (2B)

We suggest using lipid formulations of

amphotericin B rather than conventional
formulations of amphotericin B. (2A)

41

In the treatment of systemic mycoses or

parasitic infections, we recommend using
azole antifungal agents and/or the
echinocandins rather than conventional
amphotericin B, if equal therapeutic efficacy
can be assumed. (1A)
We suggest not using N-Acetyl Cysteine
(NAC) to prevent AKI in critically ill patients
with hypotension. (2D)
42

We recommend i.v. volume expansion with

either isotonic sodium chloride or sodium
bicarbonate 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 increased
risk of CI-AKI. (2D)

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We suggest not using diuretics to enhance

kidney function recovery, or to reduce the
duration or frequency of RRT. (2B)

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54yo M with AIDS (CD4 of 39) who presents

to the ED with altered mental status and
neurologic deficits. CT scan with contrast was
ordered to further investigate his condition.
His baseline creatinine is 1.4, but he returns
from the CT scan and now has creatinine of
2.5, 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 ED

with a cc of 4 days of nausea, vomiting and
diarrhea, with fever to 101OF. She has been
unable to keep any food down, and very little
in the way of liquids. Her son is in primary
school and had similar symptoms 1 week
ago. Creatinine is 2.0. Last one was 0.9
about 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 cancer

diagnosed in 2 years ago. It was metastatic to
his ribs at the time, so he was not a candidate
for prostatectomy. He has done well since
then on hormone therapy, but presents to
clinic today cc of abdominal pain and
decreased 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.

PNA Taher Hegab 2015

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