ACUTE KIDNEY INJURY

(AKI)

01/11/2021
 Objectives

 Epidemiology
 Definition and Staging
 Etiology and Diagnostic
Approach
 Specific syndromes of AKI
 Treatment
 Biomarkers
 Acute kidney injury (AKI)

Definition
 a loss of renal function, measured by a decline in

glomerular filtration rate (GFR), (Hrs/days)

 variety of settings with varied clinical manifestations

 from a minimal but sustained elevation in serum

creatinine (SCr) to anuric renal failure

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 Epidemiology
 Global incidence is estimated 22% among hospitalized patients
(Meta-analysis, >3.5 million patients).
 57.3% ICU patients experience AKI in first week of
ICU admission (Cross-sectional study of 97 ICU from 33
countries).
 AKI in the developing world

Etiologies for AKI are region specific such as

 Envenomations from

 snakes, spiders, and bees;

 Infectious causes
 such as malaria
 Crush injuries and resultant rhabdomyolysis from
earthquakes

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 AKI and
CKD

 AKI associated with:

- 9 fold higher risk of CKD

- 3 fold higher risk of ESRD

Hsu RK, Hsu CY, Semin Nephrol

2016
AKI: definition
KDIGO criteria

 An increase in serum
creatinine of ≥0.3 mg/dL
(≥26.5 micromol/L) within
48 hours
 An increase in serum creation
of ≥1.5 times baseline, or
 Urine volume <0.5 mL/kg
per hour for more than 6
hours
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 KDIGO Staging for AKI Severity
Stage Serum creatinine Urine output
1 1.5-1.9 times baseline < 0.5 mL/kg/h
or for 6 h
≥0.3 mg/dL increase

2 2-2.9 times baseline < 0.5 mL/kg/h

for 12 h
3 3 times baseline < 0.3 mL/kg/h
or for 24 h
Increase in serum creatinine to ≥4 or
mg/dL Anuria for ≥12 h
or
Initiation of renal replacement
therapy

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Acute Kidney Injury Network (AKIN)
Criteria

Stage Cr Criteria UOP Criteria

1 Cr↑by 1.5-2x baseline or < 0.5 ml/kg/hr for 6hr
Cr↑by 0.3 mg/dl
2 Cr↑by 2-3x < 0.5 ml/kg/hr for
12hr
3 Cr↑by more than 3x or < 0.3 ml/kg/hr for
Cr↑by 0.5 if baseline 24hr
>4mg/dl Or anuria for 12h
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Definition and Staging

R=Risk, I=Injury, F=Failure, L=Loss, E=End

 Azotemia /uremia

Definitions
 Asymptomatic increase in serum urea and Cr

 Usually caused by inability of the kidney to excrete

urea, Cr and other nitrogen-containing compounds

in the blood
 Uremia: azotemia associated with symptoms of

kidney failure (e.g. anorexia, nausea, itch,

confusion)

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 Key Points
 UOP decrease often proceeds increase in
SCr
 Early intervention prevents severe AKI
and resultant CKD
AKI: causes

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Etiology and pathophysiology

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 AKI can be Prerenal, Intrinsic or Postrenal

Acute Kideny Injury

Prerenal
Postrenal
Uosm > 5000 mosm/kg
Uosm: variable
Una < 20meq/L
FEna < 1% Intrinsic Renal Diseases Una: low early, high late
FEna: variable
Microscopy - bland
Microscopy - bland

Acute Interstitial Nephritis Acute Glomerulonephritis

Ischemic / Toxic ATN
Uosm: variable, ~300 mosm.kg Uosm: variable (>400 in early GN)
Uosm ~ 300 mosm/kg
Una > 40 meq/L Una: variable (<20meq/l in early GN)
Una > 40meq/L FEna: variable, <1% in early GN
FEna > 2%
FEna > 2% Microscopy – hematuria, proteinuria
Microscopy – leukocytes,
Microscopy – dark pigment cast Erythrocyte casts (dysmorphic)
erythrocyts, leukocyte casts
 Prerenal AKI
Reduced Renal Perfusion
1. True volume depletion
 Hemorrhage
 Renal or extrarenal losses (GI, skin)

2. Decreased effective blood volume (EBV)

 Congestive heart failure
 Hepatorenal syndrome
 Third-space fluid accumulation
3. Increased renal vascular resistance
 Hypercalcemia
 NSAIDs
 Calcineurin inhibitors: cyclosporine, tacrolimus
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 ACE inhibitors or ARBs
 Prerenal AKI

 Prerenal azotemia involves no parenchymal

damage to the kidney
 is rapidly reversible once intraglomerular
hemodynamics are restored
 Prerenal azotemia may coexist with other forms of
intrinsic AKI.
 Prolonged periods of prerenal azotemia may lead to
ischemic injury, often termed acute tubular
necrosis, or ATN 01/11/2021
 Compensatory renal physiologic changes

Mediators of this response include

angiotensin II, norepinephrine, and vasopressin
(ADH)
 GFR can be maintained despite reduced renal

blood flow by
 angiotensin II–mediated renal efferent

vasoconstriction, which maintains glomerular

capillary hydrostatic pressure closer to normal

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Compensatory renal physiologic changes

 Myogenic reflex within the afferent arteriole leads to

dilation in the setting of low perfusion

 Intrarenal biosynthesis of vasodilator prostaglandins

(prostacyclin, prostaglandin E), nitric oxide (NO) also
increase in response to low renal perfusion pressure

 tubuloglomerular feedback elicit dilation of the

juxtaposed afferent arteriole 01/11/2021
Compensatory renal physiologic changes

 Counterregulatory mechanisms to maintain GFR in

the face of systemic hypotension have limits

 Renal autoregulation usually fails once the systolic

blood pressure falls below 80 mmHg

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Prerenal AKI
Risk factors
 HTN

 Atherosclerosis

 Age

 Renovascular diseases

 Drugs (NSAIDs,)

 ACE inhibitors/ARBs

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Intrinsic AKI

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 Intrinsic AKI
1. Glomerular or microvascular disease

Rapid progressive Thrombotic microangiopathy (TMA)

glomerulonephritis (RPGN)
 Hemolytic-uremic syndrome (HUS)
 Granular immune complex
deposition (eg, postinfectious
 Thrombotic thrombocytopenic
purpura (TTP)
GN)
 Linear immune complex  Malignant hypertension
deposition (anti-GBM disease)
 Scleroderma renal crisis
 Pauci immune/ANCA-
associated vasculitis (eg,
Wegener
01/11/2021
granulomatosus)
 Intrinsic AKI
2. Acute tubular necrosis (ATN)
 Ischemic

 Hypotension
 Prolong prerenal state
 Sepsis syndrome
 Nephrotoxic
 Nephrotoxin: radiocontrast, antibiotics, anticancer drugs
 Intratubular pigments: heme proteins (rhabdomyolysis, hemolysis)
 Intratubular proteins: light chains (myeloma)
 Intratubular crystals: uric acid, oxalate, drugs (eg, acyclovir,
sulfonamide

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 Intrinsic AKI
3. Acute interstitial nephritis (AIN)

 Allergic interstitial nephritis: antibiotics, NSAIDs,

allopurinol, diuretics

 Infections: viral, bacterial, fungal

 Infiltration: lymphoma, leukemia, sarcoidosis

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 Intrinsic AKI
4. Vascular disease

 Renal artery: stenosis, thrombosis, atheroembolism,

vasculitis

 Renal vein: thrombosis, compression

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Drugs that contribute to acute kidney injury

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Post-renal AKI
Obstruction of Urine Flow
1. Intraurinary tract
 Intraluminal:
 stone, blood clot, sloughed papillae, crystal
 Intramural:
 tumor, infection, neurogenic drugs, stricture

2. Extraurinary tract
 Prostate: hypertrophy, cancer
 Retroperitoneal fibrosis, lymphoma

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POSTRENAL ACUTE KIDNEY INJURY

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 POSTRENAL ACUTE KIDNEY INJURY

 The pathophysiology
of postrenal AKI
involves
hemodynamic
alterations triggered
by an abrupt increase
in intratubular
pressures

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 Initial diagnostic work-up

 The distinction between AKI and chronic kidney disease

is important for proper diagnosis and treatment.
 Easy if recent baseline SCr concentration is available

 clues suggestive of CKD

radiologic studies
 (e.g., small, shrunken kidneys with cortical thinning on

renal ultrasound)
Labs
 normocytic anemia

 secondary hyperparathyroidism with hyperphosphatemia

and hypocalcemi 01/11/2021

 Initial diagnostic work-up

 No set of tests, however, can rule out AKI

superimposed on CKD since AKI is a frequent
complication in patients with CKD

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 Initial diagnostic work-up

Physical exam
 Blood pressure

 JVP

 Orthostatics

 Palpation of bladder for distention

 Exam for pulmonary and/or peripheral edema

 Signs of uremia (N/V, fatigue, mental status

changes, asterixis, pericardial rub)

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History and Physical Examination

 Careful history taking, and physical examination

often narrow the differential diagnosis for the cause
of AKI”
 think of prerenal in the following
 Vomiting, diarrhea, glycosuria causing polyuria
 Medications including diuretics, NSAIDs, ACE
inhibitors, and ARBs

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PRE RENAL
 urinalysis is unremarkable

 no protein
 no blood
 no abnormal casts
 no cells
 specific gravity is high

 urine [Na]is< normal…perfusion

kidney 10 mEq/l is not
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 RENAL
 nephrotic range proteinuria, hematuria, RBC/WBC casts..
glomerulonephritis

 low grade proteinuria, pyuria (eosinophiluria), WBC casts..

AIN

 low grade proteinuria, hematuria, hemegranular and

epithelial cell casts..
ATN

if urine is bland, it is very unlikely that there is intrinsic

renal damage 01/11/2021
POST RENAL

 urinalysis also unremarkable

 physical exam: distended bladder

 diagnosis usually made from imaging

 ultrasound  hydronephrosis
 diuresis after foley insertion

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 REDUCED GFR

urinalysis

normal abnormal* normal

PRE RENAL RENAL POST RENAL

cardiac stones
diabetes
dehydrated tumors
GN
vascular prostate
HTN drugs
serology
clinical Dx +/- biopsy** ultrasound
renal scan

* proteinuria, hematuria, RBC casts

** depends on GFR and urinalysis 01/11/2021
A good approach
 Make sure the patient is not dry or hypotensive
 try giving some fluid

 Put in a foley catheter … especially if male

 Stop toxic drugs // adjust doses of drugs

 diclofenac, ibuprofen, indomethacin,
 gentamicin, (vancomycin)

 Treat the underlying problem

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A good approach
Investigations
 blood: CBC, electrolytes, Cr, urea (think prerenal if

increase in urea is relatively greater than increase in

Cr), Ca2+ , PO·
 urine volume, C&S, R&M: sediment, casts, crystals

 urinary indices

 Foley catheterization (rule out bladder outlet

obstruction)
 fluid challenge (i.e. fluid bolus to rule out most pre-

renal causes) 01/11/2021

 Approach to AKI
Imaging
abdo U/S (assess kidney size, hydronephrosis, post-
renal obstruction)

indications for renal biopsy

 diagnosis is not certain

 prerenal azotemia or ATN is unlikely

 oliguria persists >4 wks

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 MANAGEMENT

Disease Specific Therapies

 if pre-renal  improve perfusion

 if post renal  relieve the obstruction

 if renal  treat the underlying GN or AIN and support the ATN

usually, prompt attention will quickly resolve renal dysfunction

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 MANAGEMENT
Non-Specific (Supportive) Therapies
 drug management

 fluid balance

 electrolyte homeostasis

 acid base balance

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FLUID BALANCE
 most patients with AKI lose ability to regulate volume status

 unable to dilute or concentrate urine

 excrete fixed amount of urine daily
 excrete fixed amount of sodium daily

 must regulate intake or overload will occur

 pulmonary edema

 similarly, if pt gets dehydrated after GFR starts to improve, kidney

function may not recover 01/11/2021
ELECTROLYTES
 problems can occur with:

 potassium
 sodium
 calcium
 phosphorus
 magnesium

 major clinical problem is hyperkalemia

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Complications
 Uremia

 Hypervolemia/ hypovolemia

 Hyponatremia

 Hyperkalemia

 Acidosis

 Hyperphosphatemia/hypocalcemia

 Bleeding

 Infectiosn/cardiac complications

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 Practice Question

A 74 year old man was hospitalized 3 days ago with cellulitis.

He has a history of HTN, HLD, PVD and has been non-
compliant with his medications. At presentation, his vitals were
T-37, BP-170/90, HR-90, RR-20 and Cr was 1.5. He was started
on Cefazolin and his home meds (Lisinopril, Metoprolol, HCTZ,
Amolodipine, Pravastatin and ASA) were restarted.
Today, his vitals are T-37, BP-110/55, HR-60, RR-16 and his
Cr is 2.7, FeNa-2.3%, UA shows trace protein and occasional
Granular casts. UOP has been stable.
What is the most likely cause of his AKI?
A. Acute Interstitial Nephritis
B. Benign Prostate Hypertrophy
C. Acute Tubular Necrosis
D. Prerenal Azotemia
 Take Home Points

 Identify AKI early on

 Monitor serum Cr for at risk patients
 Make sure I/Os are recorded correctly
 Diagnose as Prerenal, Intrinsic or Postrenal
 Detailed history
 Order routine labs including BMP, UA, Uosm, Ucr,
 Imaging studies as necessary
 Begin appropriate treatment
 Stop offending agent
 Fluids if appropriate
 Relieve obstruction
 Renal dosing of meds
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