Download Acute Kidney Injury (AKI)

ACUTE KIDNEY INJURY
Prof. Dr. Gülçin Kantarcı, MD
Internal Medicine and Nephrology
REFERENCE &SUGGESTED READING
 http://accessmedicine.com
Current Medical Diagnosis and Treatment, Maxine A. Papadakis, Stephen J.
McPhee, Eds. Michael W. Rabow, Associate Ed. Chapter 22. Kidney Disease
(ACUTE RENAL FAILURE: GENERAL)
Current Diagnosis & Treatment: Nephrology & Hypertension Edgar V. Lerma,
Jeffrey S. Berns, Allen R. Nissenson
Chapter 9-11-14 ACUTE RENAL FAILURE
 http://www.uptodate.com
(Overview of the management of acute kidney injury, Diagnostic approach to
the patient with acute kidney injury (acute renal failure) or chronic kidney
disease, Definition of acute kidney injury, Etiology and diagnosis of prerenal
disease and acute tubular necrosis in acute kidney injury, Crush-related acute
kidney injury )
CONTENTS
• Definitions of Acute Kidney Injury (AKI).
• Staging of AKI
• Diagnostic Work-Up for AKI
• Management of AKI
• Therapeutic approach to AKI
• Case presentations
Acute Kidney Injury (AKI)



Acute kidney injury (AKI) is the abrupt loss of kidney
function, resulting in the retention of urea and other
nitrogenous waste products and in the dysregulation of
extracellular volume and electrolytes.
The term AKI has largely replaced acute renal failure
(ARF), reflecting the recognition that smaller decrements
in kidney function that do not result in overt organ failure
are of substantial clinical relevance and are associated
with increased morbidity and mortality.
The term ARF is now reserved for severe AKI, usually
implying the need for renal replacement therapy.
AKI is defined as any of the following
• Increase in SCr by >0.3 mg/dl 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.
2012 KDIGO
Staging of AKI
2012 KDIGO
AKIN (Acute Kidney Injury Network)
Mehta et al. Critical Care 2007
Serum creatinine criteria
Increase in SCr >0.3 mg/dl or increase in SCr >1.5- to 2-fold Less than 0.5 ml/kg/hr for
from baseline
more than 6 hours
1
2
b Increase
in SCr > 2- to 3 fold from baseline
b
3
Urine output criteria
Increase in SCr > 3-fold from baseline or
SCr > 4.0mg/dl with an acute increase of at least 0.5 mg/dl
Less than 0.5 ml/kg/hr for
more than 12 hours
Less than 0.3 ml/kg/hr for
24 hours or
anuria for 12 hours
RIFLE kriterleri
(ADQI workgroup Crit Care 2004)
• The change in serum creatinine was specified as
occurring over not more than seven days. Subsequent to
publication of RIFLE, it was noted that the change in
serum creatinine concentrations do not correlate with the
percent decrease in GFR that is cited in the RIFLE
classification; a 1.5-fold increase in serum creatinine
corresponds to a 33 rather than 25 percent decrease in
GFR.
• However, given the absence of readily available methods
for measurement of GFR when serum creatinine is not in
steady state, as is the case during AKI, changes in GFR
are not included in the Acute Kidney Injury Network
(AKIN) and KDIGO 2012 classification system .
Risk factors that have been identified to
enhance the likelihood of AKI
• Elderly patients
• Diabetes mellitus
• Volume depletion
• Vascular surgery
• Chronic renal failure
• Multiple antibiotics, NSAIDs
• Multiple insult ( Kidney stones,
malignant diseases,etc)
Symptoms of Acute Kidney Injury
• anorexia, nausea, vomiting.
• Seizures and coma may occur if the condition is
untreated.
• Fluid, electrolyte, and acid-base disorders develop
quickly.
• Hypovolemia can cause states of low blood flow to the
kidneys, sometimes termed prerenal states, whereas
hypervolemia can result from intrinsic or postrenal
disease.
• Pericardial effusions can occur with uremia, and a
pericardial friction rub can be present
symptoms of prerenal AKI (60%)
symptoms related to hypovolemia, including thirst, decreased
urine output, dizziness, and orthostatic hypotension.
How can we distinguish Prerenal AKI?
• Ask about volume loss from vomiting, diarrhea, sweating,
polyuria, or hemorrhage.
• Patients with advanced cardiac failure leading to depressed
renal perfusion may present with orthopnea and
paroxysmal nocturnal dyspnea.
• Insensible fluid losses can result in severe hypovolemia in
patients with restricted fluid access and should be
suspected in elderly patients and in comatose or sedated
patients.
Clues for Renal ARF (35%)
Glomerular diseases: Nephritic syndrome of hematuria, edema,
and HTN indicates a glomerular etiology of AKI. Query about
prior throat or skin infections.
Tubular diseases: ATN should be suspected in any patient
presenting after a period of hypotension secondary to cardiac
arrest, hemorrhage, sepsis, drug overdose, or surgery.
• A careful search for exposure to nephrotoxins (Vanco. /aminogli.
/NSAID/ Amphoterisin-B, Radiocontrast) should include a detailed
list of all current medications and any recent radiologic and
angiographic examinations
• Pigment-induced AKI should be suspected in patients with possible
rhabdomyolysis (muscular pain, recent coma, seizure, intoxication,
excessive exercise, limb ischemia) or hemolysis (recent blood
transfusion).
• Allergic interstitial nephritis should be suspected with fevers, rash,
arthralgias, and exposure to certain medications including NSAIDs
and antibiotics.
Diagnostic Work-Up for AKI
• History and physical examination
• Urinalysis: urine microscopy,urine chemistry
• Response to treatments (volume)
• Imaging (U/S)
• Serologies
• +/- Kidney biopsy
Diagnostic Work-Up for AKI
Management of AKI
• most cases of community-acquired AKI’s are secondary to
volume depletion, as many as 90% of cases are
estimated to have a potentially reversible cause.
• Hospital-acquired AKI often occurs in an ICU setting and
is commonly part of multiorgan failure.
RADIOCONTRAST NEPHRO.
Risk Factors
• Preexisting renal failure
• DN
• >2ml/kg Radio contrast
• volume depletion
• Age>60
• Hyperuricemia
• Hepatic failure
What can we do?
•Cr controls before the
exposure
•Non-Nephrotoc. Contrast
media
•Lower the contrast dose
•Hydration (Before 12
hour)%0.45 NaCL 100ml/hour
•Oral theophylline (200mg; 2x1)
•Onehour before-48 hours
•N-acetylcystein (600mg; 2x1)
•24 hour before-48 hours
Sodium bicarbonate solution for prevention of
contrast-induced nephropathy
• I.V. infusion: 154 mEq/L sodium bicarbonate in D5W
solution: 3 mL/kg/hour for 1 hour immediately before
contrast injection, then 1mL/kg/hour during contrast
exposure and for 6 hours after procedure
• To prepare solution, remove 154 mL from 1000 mL
bag of D5W; replace with 154 mL of 8.4% sodium
bicarbonate; resultant concentration is 154 mEq/L
CRUSH SYNDROME
 Severe systemic manifestation of trauma and ischaemia
involving soft tissues, principally skeletal muscle, due to
prolonged severe crushing.
 Crush injuries and prolonged compression of limbs are the
most important types of trauma encountered in earthquake
victims
 It leads to increased permeability of the cell membrane and
to the release of potassium, enzymes, and myoglobin from
within cells. Ischaemic renal dysfunction secondary to
hypotension and diminished renal perfusion results in acute
kidney injury.
CRUSH SYN. PREVENTION from AKI
• The general goals for preventive therapy in all cases of heme
pigment-induced AKI are the correction of volume depletion, if
present, and prevention of intratubular cast formation. In the case of
disaster crush victims preventive measures should be applied at the
disaster field, in the field hospitals, and after admission to regular
hospitals.
• The most important preventive measure at the disaster field is the
correction of volume depletion.
• The approach to prevention of AKI in the patient with rhabdomyolysis
due to crush syndrome varies based upon the location of the patient
and ability to closely monitor the victim.
Kantarci G, Vanholder R, Tuglular S, et al.
Am J Kidney Dis. 2002 Oct;40(4):682-9.
Acute renal failure due to crush syndrome during Marmara earthquake.
‘Acute on Chronic Renal Failure
Causes:
–Hypovolemi
–Nephrotox.
–Infection
–Obstruction
–Congestive heart failure
–Accelerated HT
Prevention
Biomarkers of AKI

Early diagnosis is essential for AKI because AKI is more readily
reversible in early stages

Diagnosis relies on functional parameters (Cr, UOP)

Even very small incremental increases (>0.3 mg/dL) in SCr
cause significant loss of function and increased morbidity and
mortality

Need a more sensitive biomarker to detect early injury
• Permit early targeted interventions to reverse or ameliorate AKI
• Cystatin C, urinary NGAL(Neutrophil gelatinase associated lipocalin),
IL-18, KIM-1(Kidney injury molecule)
Maintaining Renal Perfusion Pressure
• vasoconstrictors, vasopressor medications (eg,
norepinephrine) should be used only to treat
arterial hypotension (dopamine
,norepinephrine)
• target mean arterial pressure 60 to 65 mm Hg
(patients with long-standing hypertension and/or
renal vascular disease may require substantially
higher pressures to maintain renal perfusion)
• intra-abdominal hypertension is associated
with decreased renal perfusion and may result
in AKI.
Immediate therapy
• The management of life-threatening fluid and electrolyte
abnormalities due to acute kidney injury (AKI) should be
started immediately. Common complications of AKI
include the following:
●Fluid overload
●Hyperkalemia (serum potassium >5.5 mEq/L) or a rapidly
increasing serum potassium
●Signs of uremia, such as pericarditis, or an otherwise
unexplained decline in mental status
●Severe metabolic acidosis (pH <7.1)
• Patients with any of these complications despite
appropriate medical therapy generally require urgent
dialysis
Pharmacologic Strategies for AKI
Prevention
• Loop Diuretics (?)
• Mannitol (an osmotic diuretic ) (?)
• Dopamine (increases GFR by direct vasodilation through
dopaminergic receptors, by increasing the cardiac output
by β-adrenergic stimulation or by increasing perfusion
pressure by α-stimulation )
• Fenoldopam (dopamine-1 receptor agonist )
• Natriuretic Peptides (ANP, BNP)
o preglomerular vasodilation
o postglomerular vasoconstriction
o natriuresis and diuresis
o increase the GFR
Therapoetic approach to AKI
• Prerenal 
Management of hypovolemia and
hypoperfusion.
• Renal 
Theraphy of causes, plasmaferesis,
immunsup.
• Post renal 
obstruction
INDICATIONS FOR INITIATION OF
DIALYSIS IN AKI
• Refractory fluid overload
• Hyperkalemia (plasma potassium concentration >6.5
mEq/L) or rapidly rising potassium levels
• Signs of uremia, such as pericarditis, neuropathy, or an
otherwise unexplained decline in mental status
• Metabolic acidosis (pH less than 7.1)
• Certain alcohol and drug intoxications
Mortality/Morbidity
• AKI is not a benign disease. In a recent study, a
31% mortality rate was noted in patients with AKI
not requiring dialysis, ICU mortality 50-69 %
• Mortality rates are generally lower for nonoliguric
AKI (>400 mL/d) than for oliguric (<400 mL/d) AKI,
reflecting the fact that nonoliguric AKI is usually
caused by drug-induced nephrotoxicity and
interstitial nephritis
CASE 1
• A 68 year old man is admitted to Yeditepe U. MF hospital.
He has been complaining of decreased urine output over
the last two days. He has Type 2 Diabetes for 12 years.
• Had coronary angiography 5 days ago-uneventfully
• No symptoms of BPH
• Pre-angiographic S.Cr- 2 mg/dl
• History of 20 years hypertension + NIDDM
• No extra fluids before or after procedure
PHYSICAL EXAMINATION
• BP: 160/100mmHg; P:98/min/R W: 79 kg
• The number of breaths per minute: 24/min
• Raised JVP
• Pretibial Edema (+)
• Orthopneic
• Dyspneic with crackles over the lung bases
LABORATORY
• S. Cr: 4.5 mg/dl ; BUN:50 mg/dl, Na 134
mEq/L
• What other features would you like to
see?
• Serum Potassium
• Serum Sodium
• Urine sodium
• Ultrasound
• Chest –X ray
• Glycemic evaluation
AKI due to contrast nephropathy
Prevention for CIN
• Main risk factors for CIN are estimated GFR < 50 mL/min/1.73m2,
•
•
•
•
•
•
•
diabetes, hypovolemia
Other risk factors include age over 75, HF, cirrhosis, hypertension,
proteinuria, concomitant use of NSAIDs, intra-arterial injection of
contrast, and high doses of contrast
Serum creatinine levels peak at 3 days postexposure and usually
return to baseline within 10 days.
It is not clear how to best prevent CIN
The lowest dose of contrast possible should be used.
Low osmolar contrast agents may be better.
Hydration with IV 0.9 normal saline may be preventive; the optimal
duration of hydration is not clear.
Although N-acetylcysteine and IV sodium bicarbonate are sometimes
used, the data demonstrating efficacy are inconsistent.
CASE 2
A 77-year-old male is admitted to the hospital with chief
complaint of generalized weakness and potassium level
of 6.5 mEq/L.
The patient has had poor PO intake of fluids and food for
the last 2 days.
The patient has severe osteoarthritis and takes high-dose
nonsteroidal antiinflammatory drugs (NSAIDs).
Past medical history (PMH)
Obesity, obstructive sleep apnea (OSA), hypertension
(HTN), osteoarthritis (OA).
Medications
ibuprofen, acetaminophen, lisinopril
Physical examination
• Dry mucosal membranes (MM).
Chest: Clear Chest sounds.( Bronchovesicular )
CVS: Aritmia +
Abdomen: Soft, NT, ND, +BS.
Extremities: no edema.
Laboratory
• Hb: 14.7g/dl Htc:46%
• Na: 149mEq/L K: 6.5 mEq/L
• Serum BUN: 48mg/dl ;Kr: 2.8mg/dL
1. What is the most likely diagnosis?
2. How to confirm the diagnosis?
3. What other tests would you order?
FENa, percent
=
UNa x SCr
———————
SNa x UCr
x
100
• What is the most likely diagnosis?
Prerenal ARF due to volume depletion
• How to confirm the diagnosis?
*Urine analysis
*Urinary sodium and creatinine to calculate the fractional
excretion of sodium (FENA)
• What other tests would you order?
Renal ultrasound to rule out urinary obstruction
and nephrolithiasis
• Urinary Na: 12 mEq/L ; Cr: 27mg/dL
Kidney US
What treatment would you start for this
patient?
• Insulin 10 units IV with D50, 1amp. IV x 1.
• Kayexalate 45 gm po x 1.(880 mg polistiren sulfonat
•
•
•
•
kalsiyum 2x1, 3x1)
Foley catheter.
Strict I/O.
Isotonic NaCl at 150 cc/hr x 2 L, then 125 cc/hr, adjust the
rate of IVF according to I/O, avoid fluid overload.
Hold ACEi and NSAIDs
What did we learn from this case?
• The fractional excretion of sodium (FENa) is useful in
diagnosing pre-renal ARF.
• FENa is less than 1 % in many patients with prerenal
ARF. Intravenous hydration is the mainstay of treatment.
Case 3
• A 82-year-old male who is a nursing home resident due to
advanced Parkinson's disease is admitted to the hospital
with chief complaint of generalized weakness.
• The patient has had poor PO intake of fluids and food for
the last 3-4 days.
• PMH:
HTN, Parkinson's disease, hypothyroidism
Medications:
Carbidopa-Levodopa (Sinemet), levothyroxine (Synthroid),
HCTZ
Physical examination:
Dry MM
Chest:Clear Chest sounds.( Bronchovesicular )
CVS: Clear S1+S2+
Abdomen: Soft, NT, ND, +BS
Extremities: no edema, rigidity and spasticity +
• BUN 48 mg/dL
• Cr 2.1 mg/dL
• Serum Na 138 mEq/L
• Serum K 5.6
• Urine Na 165 mEq/L
• Urine Cr 87 mg/dL
• What is the most likely diagnosis?
Prerenal ARF due to volume depletion
• How to confirm the diagnosis?
*Urine analysis
*Urinary sodium and creatinine to calculate the fractional
excretion of sodium (FENA)
• What other tests would you order?
Renal ultrasound to rule out urinary obstruction
and nephrolithiasis
• Does FENa higher than 1% rules out prerenal ARF?
No. Patients who receive diuretics may have prerenal ARF
with FENa greater than 1% due to diuretic-induced sodium
excretion.
Final diagnosis:
Pre-renal acute renal failure due to dehydration. FENa is
higher than 1% due to diuretics.
• In patients who are receiving diuretics and
suppose to have prerenal AKI
• what else do we need for to the proper
diagnosis ?
Limitations of FENa
■The FENa criterion of less than 1 percent to diagnose
prerenal disease applies only to patients with a marked
reduction in glomerular filtration rate.
■Single measurements of serum creatinine may not
provide an accurate estimate of the GFR.
■FENa can be less than 1 percent in ATN superimposed
upon a chronic prerenal disease, such as cirrhosis or heart
failure
■The FENa may be above 1 percent when prerenal
disease occurs in patients with chronic kidney disease or
any cause of sodium wasting, such as diuretic therapy
while the diuretic is still acting.
What did we learn from this case?
• The fractional excretion of sodium (FENa) is useful in
diagnosing prerenal ARF. FENa is less than 1 % in most
patients with pre-renal ARF.
Patients who receive diuretics may have prerenal acute renal
failure but the fractional excretion of sodium may be increased
by diuretic-induced sodium excretion. Therefore, these patients
may have FENa greater than 1% in the presence of prerenal
ARF.
In patients who are receiving diuretics, a fractional excretion of
urea (FEUrea) can be useful since urea transport is not
affected by diuretics. FEUrea of less than 35% is suggestive of
a pre-renal state.