Acute Kidney Injury
Prof.Dr.Gülçin Kantarcı
Yeditepe University Nephrology
Department
Aims & objectives
• State the definition, pathophysiology,
clinical findings and prevention
methods of acute kidney injury
Reference
1.
Current Medical Diagnosis and Treatment, Maxine A.
Papadakis, Stephen J. McPhee, Eds. Michael W. Rabow, Associate Ed.
http://accessmedicine.com/resourceTOC.aspx?resourceID=1
Chapter 22. Kidney Disease (ACUTE RENAL FAILURE: GENERAL)
2.
Bates' Guide to Physical Examination & History Taking 11th
edition, Bickleys LS, Szilagyi PG; Lippincott Williams and Wilkins¸
3.
Kumar and Clark's Clinical Medicine, 8th edition; Kumar &
Clark, Elsevier
4.
Andreoli and Carpenter's Cecil Essentials of Medicine 8th
edition, Andreoli and Carpenter, Elsevier
PART 11: RENAL AND GENITOURINARY DISEASES 122: Acute Kidney
Injury , Bruce Molitoris Editor: Goldman, Lee
5.
CURRENT Diagnosis & Treatment: Nephrology & Hypertension
Edgar V. Lerma, Jeffrey S. Berns, Allen R. Nissenson (ACUTE RENAL
FAILURE Chapter 9-11-14)
PRESENTATION TOPICS
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•
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Essentials of Diagnosis
General Considerations
Clinical Findings
Classification & Etiology
ACUTE KIDNEY INJURY ( Acute renal
failure)
• also known as acute renal failure, is defined as a
sudden decrease in kidney function, resulting in
an inability to maintain acid-base, fluid and
electrolyte balance and to excrete nitrogenous
wastes
• It often results from major trauma, illness, or
surgery but is sometimes caused by a rapidly
progressive, intrinsic renal disease.
Kidney Disease: Improving Global Outcomes. Clinical practice guideline
on acute kidney injury. 2011. www.kdigo.org
• Serum creatinine rises ≥ 1.5 fold from the reference value, which is
known or presumed to have occurred within one week or
• urine output is < 0.5ml/kg/hr for >6 consecutive hours
• If a reference serum creatinine value is not available within 3
months (acceptable up to one year) and AKI is suspected
• repeat serum creatinine within 24 hours
• a reference serum creatinine value can be estimated from the nadir
serum creatinine value if patient recovers from AKI
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
Fluid overload in ARF
Diagnosis
• based on laboratory tests of renal function,
including serum creatinine.
• urinary sediment, and imaging are needed to
determine the cause.
CLINICAL CRITERIA

RIFLE criteria
(ADQI workgroup Crit Care 2004)

AKIN (Acute Kidney Injury Network)
(Mehta et al.Acute Kidney Injury Network Crit Care 2007)
RIFLE kriterleri
(ADQI workgroup Crit Care 2004)
AKIN (Acute Kidney Injury Network)
Mehta et al. Critical Care 2007
Serum creatinine criteria
1
2
3
Increase in serum creatinine of more than or equal to
0.3 mg/dl
(≥ 26.4 μmol/l)
or increase to more than or equal to 150% to 200%
(1.5- to 2-fold) from baseline
Increase in serum creatinine to more than 200% to
b 300%
b
(> 2- to 3 fold) from baseline
Increase in serum creatinine to more than 300% (> 3fold)
from baseline (or serum creatinine of more than or
equal to 4.0
mg/dl [≥ 354 μmol/l] with an acute increase of at least
0.5 mg/dl
Urine output criteria
Less than 0.5 ml/kg/hr
for more than 6
hours
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
Prerenal azotemia
• inadequate renal perfusion.
 causes ECF volume depletion
 cardiovascular disease.
Main cause of AKI
•
PRE-RENAL (%55-60)
Intravascular volume depletion
-Hemorrhage
-GI losses
-Renal losses
-Skin and mucous membrane losses
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•
•
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-Third space losses
Renal vasodilation
Systemic vasodilaton
Decreased cardiac output
Pharmocologic agent that acutely impair autoregulation & GFR
symptoms of prerenal AKI (ARF)
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.
Renal causes of AKI ( 35-40 %)
intrinsic renal disease or damage
• most common causes:
- prolonged renal ischemia
(post ischemic ATN)
-nephrotoxins.
• RPGN
Wegener / PAN/ Goodpasture
• Nephrotoc.
Vanco. /aminogli. /NSAID/ Amphoterisin-B, Radiocontrast
• Acute pyelonephritis
• Acute tubulointertisisel nephrithis (ATIN)
• Cholesterol crystal embolism
• Contrast nephropathy
Renal ARF
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.
Postischemic acute tubular
necrosis (ATN)
• Postischemic acute tubular necrosis (ATN) can
result from prolonged hypotension due most
commonly to:
•Major surgery (particularly cardiac surgery,
abdominal aortic aneurysm surgery, and surgery
to correct obstructive jaundice)
•Sepsis
•Marked hypovolemia
•Severe pancreatitis
Pathophysiology of Postischemic
acute tubular necrosis (ATN)
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Endothelial injury from vascular perturbations
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Ischemia/hypoxemia (including re-perfusion injury)
Tubular cell necrosis/apoptosis
• Shed into lumen, tubular obstruction
• Decreased tubular flow
• Tubulo-glomerular back-leak leads to decreased GFR
Formation of inflammatory mediators
•
Oxidative stress, cytokine release
Abolishment of renal autoregulation
•
Intrarenal vasocontriction > vasodilatation
Pathophysiology 2
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
AKI involves both vascular and tubular
effects
AKI that secondary to sepsis;sympathetic
system and renin-angiotensin-aldosterone
system are stimulated and cause renal
vasoconstriction
Diagnostic Work-Up for AKI
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History and physical examination
Urinalysis, urine microscopy
Urine chemistry
Response to treatments (volume)
Imaging (U/S)
Serologies
+/- Kidney biopsy
Nephrotoxicity
Acute tubuler injury
•Aminoglycosides
•Acyclovir
•Indinavir
•Cysplatin
•Cyclosporin
•cephalosporines
•Amphotericin
Hemodynamic disregulation
•ACEI
•ATII RB
•Cyclosporin
•NSAID
•Radiocontrast Nephrotoxicity
Acute int. nephritis
All drugs
RADIOCONTRAST NEPHRO.
Risk Factors
• Preexisting renal failure
• DM
• >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 or
sodyum bicarbonate
•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 trauma of the muscles
• MYOGLOBIN
Glomerular filtrate
• Dehidratation
• Tubular obstruction is depens upon the death cell and gelous
Myoglobin
Crush Syndrome
• Hypovolaemic shock (due to sequestration of water in the injured
muscle cells)
• Dark urine (Due to high concentration of myoglobin in the
gloemerular filtrate which comes from the swollen muscles)
• Hyperkalemia (release of cellular potassium by the injured muscle
cells)
This can also lead to:
• Metabolic acidosis (release of cellular phosphate and sulphate by
the injured muscle cells)
• Acute Kidney Injury
• Disseminated intravascular coagulation (DIC)
CRUSH SYN. PREVENTION from AKI
• The general goals for preventive therapy in all cases of heme pigmentinduced 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.
Fluid Replacement
• Normotension %0.45 NaCl
• Hypotension  Cause ?
• Bleeding ?
E.S
• Dehidratation?
%0.9 NaCl
• Compartment Syn?
Mannitol
To prevent ARF:
• i.v. fluid 1L/hr ( During first hours 1-1.5 lt )
• Fluid
%0.45 NaCl
Postrenal azotemia
• obstructive nephropathy is due to various
types of obstruction in the voiding and
collecting parts of the urinary system
POST-RENAL (<%5)
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Early diagnosis is important
Urinary obstr.
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Bilateral obstruction of the ureter, pelvis
BPH, Prostate Ca
Cervix, ovarian Ca
uretral masses, Stones
Ureteral obstrustion (stone, mass)
DM papillary nec.
AKI
In 748 AKI patients
ATN —% 45
Prerenal —% 21
Acute on Chronic — %13
Urinary tract — %10
GN or vasculitis— %4
AIN — %2
Atheroembolism — %1
Liano, F, Pascual, J, and the Madrid Acute Renal Failure Study Group.
Epidemiology of acute renal failure: A prospective, multicenter, community-based study.
Kidney Int 1996.
‘Acute on Chronic Renal Failure
Causes:
–Hypovolemi
–Nephrotox.
–Infection
–Obstruction
–KKY
–Accelerated HT
ARF IN ICU
27%
ARF
MOF+ARF
73%
ARF ın ICU is the part of MOF
Kidney Int 1998;53: S16-S24
AKI in ICU
• AKI requiring dialysis reduced
survival %50,
• Hospital mortality %69
• After 6-12 months %70 still
survived
MORTALTY IS CORRELATED WITH NUMBER OF ORGANS
100
100
91
80
80
60
40
53
30
20
İzole aby
2 OSY
3 OSY
4 OSY
5 OSY
0
MODS+ABY
Kidney Int 1998;53: S16-S24
Diagnosis of AKI
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Diagnosis relies on functional parameters (Cr, UOP)
AKI is more readily reversible in early stages
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)
• Even very small incremental increases (>0.3 mg/dL) in SCr
cause significant loss of function and increased morbidity and
mortality
• Early diagnosis is essential
Diagnostic Work-Up for AKI
THERAPHY
• Prerenal
Management of hypovolemia and
hypoperfusion.
• Renal
Theraphy of causes, plasmaferesis,
immunsup.
• Post renal
obstruction
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.
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
SUGGESTED READING
Goldman's Cecile
Medicine 24th edition
Elsevier
Goldman L,
Schafer AI
The Cleveland Clinic
Intensive Review of
Internal Medicine 5th
edition
Lippincott
Williams and
Wilkins
Stoller JK,
Michota FA,
Mandell BF
CURRENT Diagnosis & Treatment: Nephrology &
Hypertension Edgar V. Lerma, Jeffrey S. Berns, Allen R.
Nissenson (ACUTE RENAL FAILURE Chapter 9-11-14)