Slides Nephrology Acute Kidney Injury

Acute Kidney Injury
Nephrology
With Amy Sussman, M.D.
Ce López, ce.lopez@iest.edu.mx
Powered by TCPDF (www.tcpdf.org)
© www.lecturio.com | This document is protected by copyright.
Learning Objectives
• Define acute kidney injury (AKI) and understand

terminology
• Understand the etiology/categories and diagnostic

approach to AKI
• Prerenal
• Intrinsic renal
• Postrenal
• General approach to the patient with AKI
• Treatment and prevention of AKI
Acute Kidney Injury (AKI)
Defined by:
• Abrupt loss of kidney function
• Retention of urea and other

nitrogenous waste products
• Dysregulation of extracellular
volume and electrolytes
Haymanj, PD
Terms You Should Know
Creatinine: Blood urea nitrogen (BUN):
• Breakdown product of creatine • Urea nitrogen formed from protein
phosphate in muscle catabolism by the liver
• Filtered by the kidney and used to • Filtered by the kidney and used as an
estimate kidney function/filtration additional measure of kidney function
• Inversely proportional to function: • High BUN generally reflects lower
the higher the creatinine, the lower the filtration
filtration
• Caveat: BUN can increase independent
of kidney function
< 500 mL urine output/24 h • Steroids, tetracycline antibiotics, or
Oliguria:
<0.5 ml/kg/h reabsorption of blood in GI tract
Anuria: < 100 mL urine output/24 h
Acute Kidney Injury (AKI) Is BAD!
In critically ill patients with AKI:
• Mortality between 40 60% in a

60-day-interval
• Hospital stay prolonged
Criteria for the Staging System by the Acute Kidney Injury Network
Absolute Change in Reduction in

creatinine serum creatinine urine output
Staging System for Acute Kidney Injury
48 hours
↑ Creatinine 3 4 times
from baseline or < 0.5 mL/kg/h for 24 h
Stage 3 > 4 mg/dL with acute or anuria for 12 h
Failure increase dL
Stage 2 ↑ Creatinine 2 3 times

Injury < 0.5 mL/kg/h for > 12 h
from baseline
Stage 1 ↑ Creatinine dL or
< 0.5 mL/kg/h for > 6 h
Risk 1.5 2 times from baseline
Serum creatinine criteria Urine output criteria

Staging System for Acute Kidney Injury
48 hours
↑ Creatinine 3 4 times
from baseline or < 0.5 mL/kg/h for 24 h
Stage 3 > 4 mg/dL with acute or anuria for 12 h
Failure increase dL
Stage 2 ↑ Creatinine 2 3 times

Injury The higher thefrom
stage the worse
baseline
the outcome!
< 0.5 mL/kg/h for > 12 h
Stage 1 ↑ Creatinine dL or
< 0.5 mL/kg/h for > 6 h
Risk 1.5 2 times from baseline
Serum creatinine criteria Urine output criteria

Problems of the Staging System
• Based on serum creatinine and urine output imperfect

biomarkers (biological markers for organ injury)
• ↑ Serum creatinine or ↓ urine output substantial

injury may have taken place
• Diminishes ability to begin treatments aimed at

preventing the loss of renal function
• Development of novel biomarkers (NGAL, KIM 1, NAG),

not ready
Conceptual Model for AKI
Susceptibility:
Blood volume Diabetes Complications
Age NSAID
Increased Kidney
Normal Damage ↓ GFR Death
risk failure
Insult and Staging

Creatinine level and urine output
injury are inadequate for defining when
the injury occurs
Categories of Acute Kidney Injury
Pre-renal Intrinsic renal Post-renal
• Volume depletion • Tubulointerstitial disease • Urinary obstruction

• Acute tubular
• Decreased effective necrosis
arterial blood volume
• Acute interstitial
nephritis
• Acute tubular
obstruction
• Vascular disease
• Glomerular disease
72-year-old Woman with Altered Mental Status Test case
You are asked to see a 72-year-old woman who is admitted to

the hospital from a skilled nursing facility. She has altered
mental status and her caregiver notes she has not been eating
or drinking for the past several days.
Physical exam: Orthostatic hypotension, tenting of her skin,
and dry mucous membranes
Labs: Serum creatinine 2.3 mg/dL (normal 0.5 1.0 mg/dL)
BUN high at 58 mg/dL (normal 5 20 mg/dL)
She is given 2 L of normal saline and her serum creatinine
decreases to 1.3 mg/dL the following morning.
What type of acute kidney injury does she have?

mental status and her caregiver notes she has not been eating Hypovolemia
Physical exam: Orthostatic hypotension, tenting of her skin, Signs of volume depletion
Labs: Serum creatinine 2.3 mg/dL (normal 0.5 1.0 mg/dL) Acute kidney injury
decreases to 1.3 mg/dL the following morning. Prerenal reversible injury

mental status and her caregiver notes she has not been eating Hypovolemia
Physical exam: Orthostatic hypotension, tenting of her skin, Signs of volume depletion
Labs: Serum creatinine 2.3 mg/dL (normal 0.5 1.0 mg/dL) Acute kidney injury
decreases to 1.3 mg/dL the following morning. Prerenal reversible injury

Prerenal AKI due to volume depletion

• Acute tubular
• Decreased effective necrosis
nephritis
• Acute tubular
obstruction
Two Major Causes of Renal Hypoperfusion
True volume depletion Decreased effective arterial blood volume
• Loss of Na+ from the extracellular fluid • Refers to extracellular fluid volume in
volume the arterial circulation
• GI losses • Total ECF may be increased but arterial

blood volume perceived by
• Hemorrhagic shock baroreceptors in the carotid sinus and
glomerular afferent arterioles is low
• Renal losses  edematous states
• Heart failure
• Cutaneous losses
• Hepatic cirrhosis
• Sepsis
Glomerular Filtration Rate (GFR) under Autoregulatory Control
Afferent arteriole
Efferent
arteriole
Glomerular
capillary
network
Normal GFR maintained

© by Lecturio
↓ Renal perfusion Afferent arteriole (dilated)
Vasodilatory Efferent
prostaglandins arteriole
↑ Hydrostatic
pressure
Glomerular
capillary
network

© by Lecturio
Afferent arteriole (dilated) Angiotensin II
↓ Renal perfusion
Efferent
arteriole
(constricted)
↑ Hydrostatic
pressure
Glomerular
capillary
network

© by Lecturio
↓ Renal perfusion
↑ Filtration fraction
Activation of ↑ Oncotic pressure

angiotensin II and in post-glomerular
anti-diuretic hormone capillaries
↑ Salt and water absorption

in proximal tubule
↓ Urine Na+ and

concentrated urine
© by Lecturio
Perfusion Pressure in Presence of NSAIDs
NSAID
↓ GFR
© by Lecturio
Perfusion Pressure in Presence of NSAIDs
ACE inhibitor
/ARB
↓ GFR
© by Lecturio
Diagnostic Workup Patient History and Chart Review
• Vomiting, diarrhea, GI bleeding
• Heart failure, liver disease/cirrhosis, sepsis
Diagnostic Workup Physical Exam
• Orthostatic hypotension, skin tenting, dry

mucous membranes
• Elevated jugular venous pressure with

hypotension (heart failure), edema with
hypotension
Skin stays tented
© by Lecturio
Diagnostic Workup Physical Exam
• Orthostatic hypotension, skin tenting, dry

mucous membranes
• Elevated jugular venous pressure with Jugular

hypotension (heart failure), edema with vein
hypotension
© by Lecturio
Diagnostic Workup Laboratory Evaluation
• BUN: creatinine > 20:1 (normal 10:1)
• Urine osmolality > 500 mosm/kg
• Urine Na+ < 10 meq/L, urine Cl < 10 meq/L
• Urinalysis
• High specific gravity, no protein,
blood, or white blood cells
• Sediment review bland no casts,
no cells
© by Lecturio
Fractional Excretion of Na+ FENa
FENa measures the percent of filtered

Na+ excreted in the urine and is used to
differentiate between prerenal disease
and acute tubular necrosis.
Estimated by simultaneously obtaining urine

and plasma specimens of Na+ and creatinine:
x 100
x 100
𝑈𝑟𝑒𝑎
• FENa < 1% in prerenal disease and indicates that the

patient will be responsive to volume (i.e. IV fluids)
• Best to use when patients are oliguric
Pre-Renal Disease Treatment
Volume expansion with crystalloid (normal saline, lactated )

True volume depletion
to correct hypovolemia
Improve underlying condition:
Cardiac
Diuretics, vasodilators, and inotropes
hemodynamics
Liver failure Albumin, norepinephrine, midodrine
Sepsis Crystalloid antibiotics, vasopressor support

• Acute tubular
• Decreased effective
necrosis
nephritis
• Acute tubular
obstruction
Intrinsic Renal Disease
Tubulointerstitial Vascular Glomerular
F.l.t.r.: Libertas Academica, Figure 1A, https://www.flickr.com/photos/libertasacademica/7137093023, cropped and scaled, CC BY 2.0, flickr; ©
by Lecturio
Tubulointerstitial
• Acute tubular necrosis
• Acute interstitial nephritis
• Acute tubular obstruction
Libertas Academica, Figure 1A, https://www.flickr.com/photos/libertasacademica/7137093023, cropped and scaled, CC BY 2.0, flickr
56-year-old Man with Coronary Angiography Test case
You are asked to see a 56-year-old man who recently

underwent coronary angiography with stent placement to his
LAD for acute coronary syndrome. His serum creatinine was
noted to increase 2 days following the procedure.
Physical exam: unremarkable
Labs: serum creatinine 2.3 mg/dL (normal 0.5 1.0 mg/dL), was
0.9 mg/dL on the day of the angiography
BUN 28 mg/dL (normal 5 20 mg/dL)
He is given 2 L of normal saline but his creatinine is continuing
to rise.
What type of acute kidney injury does he have?
You are asked to see a 56-year-old man who recently Radio-contrast

underwent coronary angiography with stent placement to his administration from
LAD for acute coronary syndrome. His serum creatinine was angiography
Labs: serum creatinine 2.3 mg/dL (normal 0.5 1.0 mg/dL), was Tubular injury
He is given 2 L of normal saline but his creatinine is continuing Intrinsic renal disease
to rise.
You are asked to see a 56-year-old man who recently Radio-contrast

underwent coronary angiography with stent placement to his administration from
LAD for acute coronary syndrome. His serum creatinine was angiography
Labs: serum creatinine 2.3 mg/dL (normal 0.5 1.0 mg/dL), was Tubular injury
He is given 2 L of normal saline but his creatinine is continuing Intrinsic renal disease
to rise.

Intrinsic renal disease acute tubular necrosis

• Acute tubular
necrosis
nephritis
• Acute tubular
obstruction
Tubulointerstitial
• Acute tubular necrosis
• Acute interstitial nephritis
• Acute tubular obstruction
Libertas Academica, Figure 1A, https://www.flickr.com/photos/libertasacademica/7137093023, cropped and scaled, CC BY 2.0, flickr
Acute Tubular Necrosis (Tubular Injury)
• Most common cause of acute intrinsic kidney injury
• Associated with a 4 6 fold increase in mortality
↓ Renal
perfusion
S3
TAL of
loop of
Henle
Necrosis Tubular
injury
© by Lecturio
Risk factors:
• Volume depletion
• Underlying chronic kidney disease
• Use of NSAIDs
• Diabetes mellitus
Pathophysiology multifactorial:
Changes in micro- Immunological

vascular blood flow factors
Endothelial and
epithelial cell injury
Intratubular
obstruction
© by Lecturio
Activation of Tubuloglomerular Feedback
Tubular flow ↓ Reabsorption of NaCl-

rate changes TAL of LOH
Alteration of Release of ↑ NaCl sensed by

GFR adenosine macula densa
Less ATP required

Oliguria
for reabsorption
Causes of Acute Tubular Necrosis
Decreased
Ischemia perfusion
• Acute drop in mean arterial

pressure
• Prolonged volume depletion
• Sepsis
© by Lecturio
Toxin
Radiocontrast media
• Iodinated contrast for CT scan
and angiography
Risk factors:
• Underlying chronic kidney
disease
• Diabetes mellitus
• Concurrent hypotension
MBq, PD
Toxin
Drugs
• Aminoglycosides
• Amphotericin B
• Cisplatin
Tend to be nonoliguric > 500mL
Urine output/24h
Heme pigments
• Rhabdomyolysis breakdown
of skeletal muscle (crush injury)
Toxin
Drugs
• Aminoglycosides
• Amphotericin B
• Cisplatin
Tend to be nonoliguric > 500mL
Urine output/24h
Heme pigments
• Rhabdomyolysis breakdown
of skeletal muscle (crush injury)
Eplasty. 2013; 13: ic35., Figure 3, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3589876/figure/F3/, CC BY 2.0, cropped

Acute Tubular Necrosis Diagnostic Workup History and Chart Review
• Prolonged period of hypotension

in the ICU
• Ischemia
• Exposure to radiocontrast
• CT scans
• Angiograms
• Sepsis
Acute Tubular Necrosis Diagnostic Workup History and Chart Review
• Drugs
• Aminoglycosides bacterial
infections
• Amphotericin for fungal

infections
• Crush injuries or found down for

prolonged time
• Rhabdomyolysis
Acute Tubular Necrosis Diagnostic Workup Laboratory Evaluation
• BUN: creatinine 10 15:1
• Urine Na+ and Cl > 20 meq/L
• FENa > 2%
• Urine analysis
• Isosthenuric specific gravity ~1.01

due to loss of concentrating ability
• Urine osmolality < 450 mOsm/kg
© by Lecturio
• May have low grade proteinuria
• ~ < 500 mg 1g per 24 h
• Due to impaired reabsorption of

protein at the proximal tubule
• Urine sediment
• Pigmented granular casts or free

floating tubular epithelial cells
© by Lecturio
• May have low grade proteinuria
• ~ < 500 mg 1g per 24 h
• Due to impaired reabsorption of

protein at the proximal tubule
• Urine sediment
• Pigmented granular casts or free

floating tubular epithelial cells
© by Wei Wong, M.D. & Amy Sussman, M.D., University of Arizona

Clinical Course of Acute Tubular Necrosis
Initiation phase Maintenance phase Recovery phase
0 7 14 21 days
• Creatinine plateaus • Excess solutes and water are excreted

in 7 10 days as tubule undergoes repair
• Marks the polyuric phase (days 10 14)

of ATN > 3 L of urine output per 24 h
• Recovery usually occurs between

days 14 21
Acute Tubular Necrosis Treatment/Prevention
Identify patients who are at risk Interventions that decrease risk
• Major surgery, shock • Optimizing volume status/maintain

(vasodilatory, hemorrhagic, hemodynamic stability
cardiogenic)
• Avoid nephrotoxins
• Comorbid conditions, e.g.:
chronic kidney disease, • Contrast-induced nephrotoxicity
peripheral vascular disease, • Volume expand with crystalloid pre- and
diabetes mellitus, malignancy, post-contrast
heart failure, malnourished
• Minimize contrast volume
There is no evidence that

diuretics are helpful during ATN.
35-year-old Woman with Increased Serum Creatinine Test case
You are asked to see a 35-year-old woman with increase in

serum creatinine from 0.7 mg/dL to 3.2 mg/dL. She is currently
in the ICU receiving nafcillin (a penicillin) by continuous infusion
for Staph aureus endocarditis.
Physical exam: Febrile, erythematous, maculopapular rash over
her thorax and extremities
Labs: Serum creatinine is 3.2 mg/dL (normal 0.5 1.0 mg/dL).
CBC has an increased number of eosinophils on the differential.
Urine analysis shows WBCs and white blood cell casts. Urine
culture was negative.

serum creatinine from 0.7 mg/dL to 3.2 mg/dL. She is currently Rise in serum creatinine
Labs: Serum creatinine is 3.2 mg/dL (normal 0.5 1.0 mg/dL). Allergic or hypersensitivity
CBC has an increased number of eosinophils on the differential. process
culture was negative. Allergic interstitial nephritis
Absence of bacteriuria

serum creatinine from 0.7 mg/dL to 3.2 mg/dL. She is currently Rise in serum creatinine
Labs: Serum creatinine is 3.2 mg/dL (normal 0.5 1.0 mg/dL). Allergic or hypersensitivity
CBC has an increased number of eosinophils on the differential. process
culture was negative. Allergic interstitial nephritis
Absence of bacteriuria
Acute/allergic interstitial nephritis

• Tubulointerstitial disease • Urinary obstruction

• Acute tubular
necrosis
nephritis
• Acute tubular
obstruction
Acute Interstitial Nephritis
Acute interstitial nephritis is an inflammatory

cell infiltration in the kidney interstitium
caused by an immune response.
Causes of Acute Interstitial Nephritis
Medication/drugs Autoimmune diseases Infection
• NSAIDs • syndrome • Legionella, leptospira
• Penicillins • Sarcoidosis • Cytomegalovirus
• Cephalosporins
• Sulfonamides
• Rifampin
• Ciprofloxacin
• Proton pump inhibitors
Acute Interstitial Nephritis Diagnostic Workup
History and chart review
• Drug exposure (variable latency)
Physical exam
• Fever, rash
© 2014 Kim et al.; licensee BioMed Central Ltd., https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4236634/figure/F1/, CC BY 4.0, no changes
Acute Interstitial Nephritis Diagnostic Workup Laboratory Evaluation
• Acute rise in serum creatinine that temporally

correlates with drug administration
• Peripheral eosinophilia on blood smear
• Eosinophiluria (urine eosinophils > 1%)
• Proteinuria typically < 1000 mg/day
• Urine sediment:
• White blood cells
• White blood cell casts Renal biopsy is needed for

definitive diagnosis!
Steven Fruitsmaak, Bacteriuria and pyuria, https://commons.wikimedia.org/wiki/File:Bacteriuria_pyuria.jpg, CC BY 4.0, cropped
Acute Interstitial Nephritis Treatment
Remove offending drug!
Short course of steroids may be indicated.
47-year-old Woman with Non- Test case
You are asked to see a 47-year-old woman who has a history

of Non- lymphoma. Her tumor is high grade but very
responsive to chemotherapy. She underwent her first cycle
2 days prior and now is admitted with hyperkalemia and
decreased urine output.
Physical exam: Unremarkable
Labs: Serum creatinine is 4.2 mg/dL (normal 0.5 1.0 mg/dL). K+
is 5.9 (normal 3.5 5.2 mEq/L), phosphorus 7 (normal 2.4 4.2
mg/dL), uric acid 15 mg/dL (normal 3.0 6.5 mg/dL)
Urine analysis shows uric acid crystals.
You are asked to see a 47-year-old woman who has a history Acute tubular obstruction
of Non- lymphoma. Her tumor is high grade but very from uric acid or tumor
responsive to chemotherapy. She underwent her first cycle lysis syndrome
decreased urine output. Oliguric

mg/dL), uric acid 15 mg/dL (normal 3.0 6.5 mg/dL) Acute tubular obstruction
You are asked to see a 47-year-old woman who has a history Acute tubular obstruction
of Non- lymphoma. Her tumor is high grade but very from uric acid or tumor
responsive to chemotherapy. She underwent her first cycle lysis syndrome
decreased urine output. Oliguric

mg/dL), uric acid 15 mg/dL (normal 3.0 6.5 mg/dL) Acute tubular obstruction
Acute tubular obstruction due to tumor lysis syndrome

• Acute tubular
necrosis
nephritis
• Acute tubular
obstruction
Acute Tubular Obstruction
Precipitation of a substance in tubules:
• Protein
• Urate
• Calcium phosphate
• Intratubular crystal
Occurs in setting of volume

depletion and acidic urine
© by Lecturio
Causes of Acute Tubular Obstruction
Cast nephropathy Tumor lysis syndrome
• Multiple myeloma (plasma cell • Occurs following chemotherapy

dyscrasia/malignancy)
• Large tumor burden
• Overproduction of immunoglobulin light
chains are produced and filtered into the • Intracellular release of uric acid,
urine phosphate, potassium
Causes of Acute Tubular Obstruction
Phosphorus-containing enemas Medications
• Bowel preparation for colonoscopy • Intravenous acyclovir
• Acute calcium phosphate deposition in • Methotrexate

tubules with associated interstitial
inflammation • Sulfonamide antibiotics
• Highest risk in patients with underlying

CKD
Acute Tubular Obstruction Diagnostic Workup History & Chart Review
• Known history of multiple myeloma
• Malignancy with recent chemotherapy

administration (tumor lysis syndrome)
•
oral sodium phosphorus laxative
• Medications review
• IV acyclovir, methotrexate, sulfonamides
Acute Tubular Obstruction Diagnostic Workup
Laboratory evaluation Laboratory evaluation
• Cast nephropathy
• Elevated free immunoglobulin light chains in serum
• immunolfixation
Laboratory evaluation
Tumor lysis syndrome Phosphate nephropathy
High phosphorus
High uric acid, phosphorus,
potassium levels in serum
Low calcium
Laboratory evaluation Laboratory evaluation
• Intratubular crystal precipitation from medications
• Urine sediment may demonstrate crystals from precipitated medication
Acute Tubular Obstruction Treatment
Cast nephropathy Tumor lysis syndrome
Chemotherapy agents Isotonic fluids (saline) and uric acid

(dexamethasone, proteasomal lowering agents (allopurinol or
inhibitor-based regimen) rasburicase)
Acute phosphate nephropathy

Medication-induced crystalline
(phosphorus containing
nephropathies
enemas/laxatives)
Supportive care Remove offending drug
63-year-old Man with Nausea, Fatigue and Lethargy Test case
You are asked to see a 63-year-old man who was admitted with
nausea, fatigue and lethargy. He is taking no new medications
other than clopidogrel which he started 5 weeks ago following
coronary angiography with stent placement to his left
circumflex.
Physical exam: Skin exam demonstrates livedo reticularis (lace-
like purplish discoloration)
CBC has an increased number of eosinophils on the differential.
Serum complement levels are low. Urine analysis is bland.
other than clopidogrel which he started 5 weeks ago following Renal atheroembolic disease
circumflex.
Physical exam: Skin exam demonstrates livedo reticularis (lace- Microvascular ischemia
Labs: Serum creatinine is 3.9 mg/dL (normal 0.5 1.0 mg/dL). Renal atheroembolic
CBC has an increased number of eosinophils on the differential. syndrome
Helps to distinguish
atherembolic disease from
What type of acute kidney injury does he have? ATN from radiocontrast
other than clopidogrel which he started 5 weeks ago following Renal atheroembolic disease
circumflex.
Physical exam: Skin exam demonstrates livedo reticularis (lace- Microvascular ischemia
Labs: Serum creatinine is 3.9 mg/dL (normal 0.5 1.0 mg/dL). Renal atheroembolic
CBC has an increased number of eosinophils on the differential. syndrome
Helps to distinguish
atherembolic disease from
What type of acute kidney injury does he have? ATN from radiocontrast
Renal atheroembolic disease

• Acute tubular
necrosis
nephritis
• Acute tubular
obstruction
Causes of Vascular Disease Renal Atheroembolic Disease
• Cholesterol emboli Plaque
• Patients with atherosclerotic disease following

manipulation of the aorta or large arteries
• Coronary angiography and percutaneous

coronary intervention
• Aortic manipulation
• Renal artery angioplasty/stent placement
• Cholesterol plaque breaks off after

manipulation
© by Lecturio
Plaque
• Embolizes distally  partial or total occlusion
of multiple small arteries or glomerular
arterioles
• Serum creatinine rise subacute occurs

between 2 8 weeks following
manipulation/procedure
• Contrast to radiocontrast exposure which

causes rise in creatinine within 72 h
• Associated with low complement in serum,

eosinophilia, and rash (livedo reticularis)
© by Lecturio
• Embolizes distally  partial or total occlusion

of multiple small arteries or glomerular
arterioles
• Serum creatinine rise subacute occurs

between 2 8 weeks following
manipulation/procedure
• Contrast to radiocontrast exposure which

causes rise in creatinine within 72 h
• Associated with low complement in serum,

eosinophilia, and rash (livedo reticularis)
© 2013 American Federation for Medical Research, Figure 2., https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4528787/figure/fig2-

2324709613479940/, CC BY 3.0, rotated
Causes of Vascular Disease Vasculitis
• Inflammation and necrosis

of small arteries and arterioles
• Polyarteritis nodosa
• Granulomatosis with polyangiitis
• Microscopic polyangiitis
©2012 Arora et al.; licensee BioMed Central Ltd., Figure 4, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3509389/figure/F4/, CC BY 2.0,
cropped

©2011 Ahmed et al; licensee BioMed Central Ltd., Figure 1, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3179762/figure/F1/, CC BY 2.0,
cropped

Head Neck Pathol. 2016 Mar; 10(1): 32 39., © The Author(s) 2016, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4746140/figure/Fig1/, CC BY
4.0, cropped

Wiener Klinische Wochenschrift, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5318465/figure/Fig3/, CC BY 4.0, cropped

Causes of Vascular Disease Thrombotic Microangiopathies (TMA)
• Endothelial injury with formation of platelet thrombi occluding small vessels  ischemia
• Low platelets, microangiopathic hemolytic anemia (breakdown of red blood cells in

vessels)
• Thrombotic thrombocytopenic purpura (TTP)
• Shiga toxin-mediated hemolytic uremic syndrome (ST-HUS)
• Complement mediated TMA
• Drug-induced TMA
• Malignant hypertension
Vascular Disease Diagnostic Workup History and Chart Rview
• Aortic manipulation within past

2 8 weeks (cholesterol emboli)
• Mental status changes or diarrheal

prodrome (TMA TTP/HUS)
• Uncontrolled hypertension
(malignant hypertension)
Vascular Disease Diagnostic Workup Physical Exam
• Cholesterol emboli
• Rash (livedo reticularis)
• Blue toe syndrome
• Thrombotic microangiopathy
• Purpura and petechiae
• Blood pressure > 180/120 mm HG
© 2013 American Federation for Medical Research, Figure 2., https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4528787/figure/fig2-

2324709613479940/, CC BY 3.0, rotated
J Renal Inj Prev. 2013; 2(3): 107 108. © 2013 The Author(s); Published by Nickan Research Institute,
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4206019/figure/F01/, CC BY 4.0, cropped
Fukui S et al., https://openi.nlm.nih.gov/detailedresult?img=PMC4912258_medi-94-e1943-

g001&query=purpura%20leg&it=xg&lic=by&req=4&npos=7, CC BY 4.0, no changes
Vascular Disease Diagnostic Workup Laboratory Evaluation
• Low complements
• Peripheral eosinophilia
• Urine analysis is bland or may have

cholesterol crystals
Ed Uthman, Eosinophils in Peripheral Blood Smear, https://flic.kr/p/8epW6Y, CC BY 2.0, cropped, flickr

Vascular Disease Diagnostic Workup Laboratory Evaluation
• Thrombocytopenia (low platelets)
• Schistocytes (red blood cell

fragments on peripheral smear)
• Urine analysis may have red

blood cells
Isis325, ww325 schistocyte, https://flic.kr/p/dQJqT8, CC BY 2.0, cropped

Vascular Disease Treatment
Renal atheroembolic disease Thrombotic microangiopathies

(cholesterol emboli)
• TTP plasma exchange
• Supportive care
• Shiga-toxin HUS supportive care
• Complement mediated TMA

Vasculitis eculizumab
• Immune-mediated therapy • Drug-induced TMA remove

directed at underlying cause offending drug
62-year-old Woman with Nausea, Fatigue and Lethargy Test case
You are asked to see a 62-year-old woman who was admitted

with nausea, fatigue, lethargy, and hemoptysis.
Physical exam: Hypertensive 160/98 mm HG
Imaging: CXR shows bilateral interstitial infiltrates
Urine analysis shows, proteinuria, dysmorphic red blood cells
and red blood cell casts.

with nausea, fatigue, lethargy, and hemoptysis. Nephritic syndrome
Pulmonary renal syndrome
Imaging: CXR shows bilateral interstitial infiltrates (glomerular disease)
Urine analysis shows, proteinuria, dysmorphic red blood cells Nephritic process

with nausea, fatigue, lethargy, and hemoptysis. Nephritic syndrome
Pulmonary renal syndrome
Imaging: CXR shows bilateral interstitial infiltrates (glomerular disease)
Urine analysis shows, proteinuria, dysmorphic red blood cells Nephritic process
Nephritic syndrome, microscopic polyangiitis

• Acute tubular
necrosis
nephritis
• Acute tubular
obstruction
Rapidly Progressive Glomerulonephritis (RPGN)
Type I Type II
Anti-glomerular basement Immune complex diseases

membrane (anti-GBM)
disease • Lupus nephritis
Type III • IgA nephropathy
Pauci-immune/ • Post-infectious glomerulonephritis

ANCA-associated
vasculitis/glomerulonephritis • Membranoproliferative glomerulonephritis
Many disease involve the glomeruli but

only RPGNs present as acute kidney injury!
Glomerular Disease Diagnostic Workup Laboratory Evaluation
• Urine analysis
• Microscopic hematuria
• Proteinuria (less than nephrotic

range < 3.5 g/24 h)
© by Lecturio
• Urine sediment evaluation
• Dysmorphic red blood cells
• Red blood cell casts
• May have white blood cell casts
• Urine Na+ < 20 meq/L FENa
Renal biopsy is definitive.
© 2007 Javaid et al; licensee BioMed Central Ltd., Figure 4, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1885430/figure/F4/, CC BY 2.0, no
changes
© Dustri-Verlag Dr. K. Feistle, Figure 3, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4326856/figure/Figure3/, CC BY 2.5, no changes

© Rajasekaran et al. 2015, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4521341/figure/Fig1/, CC BY 4.0, no changes

66-year-old Man with Voiding Symptoms Test case
obstructive voiding symptoms (hesitancy, dribbling, double
voiding). His symptoms worsened after taking an over-the-
counter cold medicine.
Physical exam: Tender to palpation over his suprapubic
region
BUN is elevated to 49 mg/dL. Urine analysis is bland.
You are asked to see a 66-year-old man who was admitted with Benign prostatic hyperplasia/
obstructive voiding symptoms (hesitancy, dribbling, double hypertrophy (BPH)
counter cold medicine. Acute obstruction of urine
outflow in this setting
region
Labs: Serum creatinine is 2.0 mg/dL (normal 0.5 1.0 mg/dL). Urinary obstruction
You are asked to see a 66-year-old man who was admitted with Benign prostatic hyperplasia/
obstructive voiding symptoms (hesitancy, dribbling, double hypertrophy (BPH)
counter cold medicine. Acute obstruction of urine
outflow in this setting
region
Labs: Serum creatinine is 2.0 mg/dL (normal 0.5 1.0 mg/dL). Urinary obstruction

Post-renal, obstructive uropathy from benign
prostatic hyperplasia/hypertrophy (BPH)
Obstructive Uropathy
• Obstruction of the flow of urine anywhere from the

renal pelvis to the urethra
• Renal failure can be acute or subacute
Causes of Obstructive Uropathy
Calculi
• Stone at the ureteropelvic junction in a

solitary kidney or bilateral staghorn calculi
• Can be seen in younger and older adults
Anatomic abnormalities
(most commonly seen in children)
• Urethral valves
• Stricture
• Stenosis at the ureterovesical or

ureteropelvic junction
Dfaulder, My kidney stone https://www.flickr.com/photos/dfaulder/5507761503, CC BY 2.0, cropped, flickr
Causes of Obstructive Uropathy
Benign prostatic hyperplasia (BPH)
• Most common in men > 50 years
Urethral stricture
Malignancy
• Prostate, bladder, or extrarenal Prostate

pelvic neoplasms
• Compression of bilateral ureters
© by Lecturio
Obstructive Uropathy Diagnostic Workup History and Chart Review
• BPH: hesitancy, dribbling, double voiding
• Stones
• Flank pain
• Gross hematuria
• History of malignancy
Obstructive Uropathy Diagnostic Workup Physical Exam
• BPH: enlarged prostate on

digital rectal exam
• Stones: tenderness to
percussion at the costovertebral
angle
• Malignancy: palpation of an
abdominal/pelvic mass
Alan Hoofring, PD

digital rectal exam
angle
© by Lecturio

digital rectal exam
angle
© by Lecturio
Obstructive Uropathy Diagnostic Workup
Imaging
• Renal ultrasound
• Hydronephrosis
• CT of the abdomen/pelvis without
radiocontrast
• Best for calculi and pelvic masses
• BUN: Creatinine ratio > 20:1
• Urine sediment is bland or may contain
crystals in the case of calculi/stones
Morning2k, Ultrasonographic
Imaging
• Hydronephrosis
radiocontrast
©2013 Vallone et al; licensee BioMed Central Ltd., Figure 1, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3711724/figure/F1/, CC BY 2.0,
cropped
Imaging
• Hydronephrosis
radiocontrast
Obstructive Uropathy Treatment
BPH
• Urinary catheter insertion
• Removal of medications that can precipitate
obstruction (α agonists)
• Medical and surgical therapy for prostate
Stones
• Stone removal
• Ureteral stent placement
• Nephrostomy
© Waters et al.; licensee BioMed Central. 2014, Figure 1, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4323138/figure/Fig1/, CC BY 2.0, no

changes
Obstructive Uropathy Treatment
BPH
• Urinary catheter insertion
• Removal of medications that can precipitate
obstruction (α agonists)
• Medical and surgical therapy for prostate
Stones
• Stone removal
• Ureteral stent placement
• Nephrostomy
NIDDK, PD
Complications from Acute Kidney Injury
Uremia
• Nausea
• Vomiting
• Anorexia
• Dysgeusia
• Altered cognition
• Pericarditis
CDC, PD
Uremia
• Nausea
• Vomiting
• Anorexia
• Dysgeusia
• Pericarditis
CDC, PD
Uremia
• Nausea
• Vomiting
• Anorexia
• Dysgeusia
• Pericarditis
CDC, PD
Uremia
• Nausea
• Vomiting
• Anorexia
• Dysgeusia
• Pericarditis
Oleg Magni, CC0

Uremia
• Nausea
• Vomiting
• Anorexia
• Dysgeusia
• Pericarditis
Uremia
• Nausea
• Vomiting
• Anorexia
• Dysgeusia
• Pericarditis
© 2019, StatPearls Publishing LLC., https://www.ncbi.nlm.nih.gov/books/NBK536920/figure/article-26961.image.f1/, CC BY 4.0, no changes

Uremia Electrolyte abnormalities Chronic kidney disease
• Nausea • Hyperkalemia • Unresolved AKI or

repeated episodes of
• Vomiting • Aminoglycosides, AKI can lead to CKD
cisplatin can cause
• Anorexia hypokalemia due to
polyuria/increased
• Dysgeusia urinary flow
• Metabolic acidosis
• Extracellular volume
• Pericarditis excess
• Volume overload
(edema)
General Approach to a Patient with Acute Kidney Injury
Take a good history!
• Look for episodes of prolonged hypotension
• ICU septic shock
• Medication and nephrotoxin exposure
• Radiocontrast exposure
• NSAIDs, aminoglycosides, amphoteracin,

medications that can cause intratubular
crystal precipitation (Acyclovir)
• Medications that cause AIN (penicillins)
Do a good physical exam!
• Estimate volume status (neck veins, skin turgor)
• Look for rash (exanthematous drug rash or livedo

reticularis)
Imaging
• Ultrasound to rule out obstruction
Always look at the urine!
• Urine Na+ and FENa to distinguish between

prerenal disease and ATN
• Proteinuria and hematuria on urinanalysis points

to glomerular disease
• Crystals can be seen with intratubular crystal

obstruction and nephrolithiasis (stones)
Always look at the urine!
• Sediment review
• Muddy brown casts  ATN
• White blood cell casts  AIN
• Dysmorphic red blood cells, red blood

cell casts, white blood cell casts
 RPGN
• Renal biopsy in select cases
Treatment of Acute Kidney Injury General Principles
• Maintain renal arterial perfusion by

ensuring mean arterial pressure (MAP)
> 65/70 mm HG
• Avoid further nephrotoxic exposures

including
• NSAIDs, nephrotoxic medications
• Ensure renally cleared medications are
function or GFR
Treatment and Prevention of Acute Kidney Injury General Principles
Renal replacement therapy (dialysis)
• Indicated in patients who have

complications of acute kidney
injury
• Refractory acidemia
• Volume overload (extracellular

volume excess)
• Hyperkalemia
• Uremia
Anna Frodesiak, PD
This document is a property of: Ce López
Note: This document is copyright protected. It may not be copied, reproduced, used, or
distributed in any way without the written authorization of Lecturio GmbH.

Slides Nephrology Acute Kidney Injury

Uploaded by

Document Information

Original Title

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

Slides Nephrology Acute Kidney Injury

Uploaded by

Copyright:

Available Formats

Acute Kidney Injury

With Amy Sussman, M.D.

• Define acute kidney injury (AKI) and understand

• Understand the etiology/categories and diagnostic

• General approach to the patient with AKI

• Treatment and prevention of AKI

• Abrupt loss of kidney function

• Retention of urea and other

Anuria: < 100 mL urine output/24 h

In critically ill patients with AKI:

• Mortality between 40 60% in a

• Hospital stay prolonged

Absolute Change in Reduction in

Stage 2 ↑ Creatinine 2 3 times

Serum creatinine criteria Urine output criteria

Stage 2 ↑ Creatinine 2 3 times

Serum creatinine criteria Urine output criteria

• Based on serum creatinine and urine output imperfect

• ↑ Serum creatinine or ↓ urine output substantial

• Diminishes ability to begin treatments aimed at

• Development of novel biomarkers (NGAL, KIM 1, NAG),

Insult and Staging

Pre-renal Intrinsic renal Post-renal

• Volume depletion • Tubulointerstitial disease • Urinary obstruction

You are asked to see a 72-year-old woman who is admitted to

What type of acute kidney injury does she have?

You are asked to see a 72-year-old woman who is admitted to

What type of acute kidney injury does she have?

You are asked to see a 72-year-old woman who is admitted to

What type of acute kidney injury does she have?

Pre-renal Intrinsic renal Post-renal

• Volume depletion • Tubulointerstitial disease • Urinary obstruction

True volume depletion Decreased effective arterial blood volume

• GI losses • Total ECF may be increased but arterial

Normal GFR maintained

Normal GFR maintained

Normal GFR maintained

Activation of ↑ Oncotic pressure

↑ Salt and water absorption

↓ Urine Na+ and

• Vomiting, diarrhea, GI bleeding

• Heart failure, liver disease/cirrhosis, sepsis

• Orthostatic hypotension, skin tenting, dry

• Elevated jugular venous pressure with

Skin stays tented

• Orthostatic hypotension, skin tenting, dry

• Elevated jugular venous pressure with Jugular

• BUN: creatinine > 20:1 (normal 10:1)

• Urine osmolality > 500 mosm/kg

• Urine Na+ < 10 meq/L, urine Cl < 10 meq/L

FENa measures the percent of filtered

Estimated by simultaneously obtaining urine

• FENa < 1% in prerenal disease and indicates that the

• Best to use when patients are oliguric

Volume expansion with crystalloid (normal saline, lactated )

Improve underlying condition:

Liver failure Albumin, norepinephrine, midodrine

Sepsis Crystalloid antibiotics, vasopressor support

Pre-renal Intrinsic renal Post-renal

• Volume depletion • Tubulointerstitial disease • Urinary obstruction

Tubulointerstitial Vascular Glomerular

• Acute tubular necrosis

• Acute interstitial nephritis