AKI

ACUTE KIDNEY INJURY
Dr Ehab El Reweny
Lecturer of Critical Care Medicine

• There are more than 35 definitions of
AKI (formerly acute renal failure) in
literature.
Definition of AKI

Definition of AKI
• Rapid deterioration of kidney function:
 Increase in serum urea and creatinine.
 Electrolyte disorders (e.g. hyperkalaemia).
 Metabolic acidosis.
 Oliguria (< 400 mL/day urine).
Renal failure is defined as the cessation of kidney
function with or without changes in urine volume.

RIFLE criteria for diagnosis of AKI based on The
“Acute Dialysis Quality Initiative”
Increase in SCr Urine output
Risk of renal injury
Injury to the kidney
Failure of kidney function
0.3 mg/dl increase
2 X baseline
3 X baseline OR
> 0.5 mg/dl increase if
SCr >=4 mg/dl
< 0.5 ml/kg/hr for > 6 h
< 0.5 ml/kg/hr for >12h
Anuria for >12 h
Loss of kidney function
End-stage disease
Persistent renal failure
for > 4 weeks
Persistent renal failure
for > 3 months
Am J Kidney Dis. 2005 Dec;46(6):1038-48

RIFLE Criteria
Level
of
injury
Outcom
e
measure
s

From RIFLE to AKIN
Serum
Creatinine
Increase SCr
≥24.6mmol/L
2-3 folds
Stage 1
Stage 2
Stage 3

AKI
• Recently the Acute Kidney Injury Network
(AKIN) classification is based on RIFLE
system but with few modification:
1) It uses smaller increments in S.Crt.
2) It eliminates Loss & Failure.

The Acute Kidney Injury Network
Classification ( AKIN)

AKI
• 70% Non-oliguric , 30% Oliguric.
• Non-oliguric associated with better
prognosis and outcome.

EpidemiologyAKI occurs in :
 ≈ 7% of hospitalized patients.
 30 – 60 % of critically ill patients.
 5-6% of ICU patients with AKI require RRT.
 Often Multi-factorial.
Osterman M, Chang R: Acute Kidney Injury in the Intensive Care Unit according to RIFLE.
Critical Care Medicine 2007; 35:1837-1843.

Mortality according to RIFLE
Mortality increases proportionately with increasing severity of AKI
(using RIFLE).
AKI requiring RRT is an independent risk factor for in-hospital
mortality.
Mortality in pts with AKI requiring RRT 50-70%.
Coca S, Peixoto A, Garg A, et al.: The prognostic importance of a small acute decrement in kidney function in
hospitalized patients: a systematic review and meta-analysis. American Journal of Kidney Diseases 2007;
50:712-720.

Evaluation of Renal Failure
• Is the renal failure acute or chronic?
– laboratory values do not discriminate between acute vs.
chronic.
– oliguria supports a diagnosis of AKI.
• Clues to chronic disease
– Pre-existing illness – DM, HTN, age, vascular disease.
– Uremic symptoms – fatigue, nausea, anorexia, pruritis,
altered taste sensation, hiccups.
– Small, echogenic kidneys by ultrasound.

Differentiation of AKI
Prerenal
Ischaemic Toxic
ATN Interstitial Nephritis Glomerulonephritis
Renal Postrenal
AKI

Etiology of Community-Acquired and Hospital-Acquired ARF
Community-Acquirednnn Hospital-Acquired
Prerenal 70% Prerenal 20%
Intrinsic 20% Acute Tubular Necrosis 70%
Postrenal 10% Postrenal 10%

Prerenal AKI
Etiology:
• Inadequate renal blood perfusion:
– Reduction of blood volume.
– Reduction of blood pressure.
– Systemic vasodilation.

Prerenal ARF
• Possible causes:
– Dehydration (e.g. vomiting ,diarrhoea).
– Haemorrhage ,burn.
– Severe congestive heart failure
– Drugs (diuretics, non-steroidal anti-inflammatory
drugs, ACE-inhibitors in case of bilateral renal
artery stenosis).
– Selective renal ischemia.
• Fast correction of underlying cause results in renal recovery,
delay leads to acute tubular necrosis (ATN).

AKI
• Pre-renal
• Decrease in RBF constriction of afferent arteriole
which serves to increase systemic blood pressure, but
does so at a cost of decreased RBF.
• At the same time, efferent arteriole constricts to attempt
to maintain GFR.
• As GFR decreases, amount of filtrate decreases. Urea is
reabsorbed in the distal tubule, leading to increased
tubular urea concentration and thus greater re-
absorption of urea into the blood.
– Creatinine cannot be reabsorbed, thus leading to a BUN/Cr
ratio of > 20 .

 Large Renal Vessel Disease
Thrombo-embolic disease
 Renal Microvasculature and Glomerular Disease
Inflammatory: glomerulonephritis, allograft rejection
Vasospastic: malignant hypertension, scleroderma crisis, pre-eclampsia, contrast
Hematologic: HUS-TTP, DIC
 Acute Tubular Necrosis (ATN)
Ischemic
Toxic
 Tubulo-interestitial Disease
Acute Interestitial Nephritis (AIN), Acute cellular allograft rejection, viral (HIV, BK virus),
infiltration (sarcoid)
 Intratubular Obstruction
myoglobin, hemoglobin, myeloma light chains, uric acid, tumor lysis, drugs ( acyclovir)
Intrinsic AKI

Acute Tubular Necrosis
– Most common cause of intrinsic cause of AKI.
– Often multifactorial.
– Ischemic ATN:
• Hypotension, sepsis, prolonged pre-renal state.
– Nephrotoxic ATN:
• Contrast, Antibiotics.

Risk Factors for ATN
• Volume depletion.
• Aminoglycosides.
• Radiocontrast.
• NSAIDs, Cox-2 inhibitors.
• Sepsis.
• Rhabdomyolysis.
• Preexisting renal disease.
• HTN.
• Diabetes mellitus.
• Age > 50 .
• Cirrhosis.

Aminoglycoside Nephrotoxicity
• Generally presents 1 week after exposure
• Non-oliguric
• Low trough levels do not guard against nephrotoxicity
• Incidence of ATN
– 10% after 1 week
– 40% after 2 weeks
• Risk factors for ATN
– Advanced age - Superimposed sepsis
– Liver disease - Hypotension

Radiocontrast-Induced AKI
• Induces renal vasoconstriction and direct cytotoxicity via
oxygen free radical formation.
• 12-24 hours post exposure.
• Peaks in 3-5 days.
• Risk factors:
– Renal insufficiency - Diabetes
– Advanced age - > 125 ml contrast
– Hypotension
• Usually non-oliguric ARF; irreversible ARF rare

• Avoid use of intravenous contrast in high risk
patients if possible.
• Use pre-procedure volume expansion using
NS 1 ml/kg/hr 12 hours pre/post.
• Mucomyst 600 BID pre/post (4 doses).
• Avoid concomitant use of nephrotoxic
medications if possible.
• Use low volume low- or iso-osmolar contrast.
Prevention of Contrast-Induced
Nephropathy

Interstitial AKI
• Acute interstitial nephritis:
– Allergic reaction to drugs (NSAID, antibiotics, diuretics).
• Bilateral bacterial pyelonephritis.
• Rare causes: Infiltration by leukaemia, lymphoma etc.

Common Causes of Drug Induced AIN
• NSAIDS
• Antibiotics
– Penicillins
• methacillin
• Ampicillin, amoxacillin, carbenacillin, oxacillin
• Cephalosporins
– Quinolones (ciprofloxacin)
– Anti-tuberculous medications (rifampin, INH, ethambutol)
– Sulfonamides .
• Miscellaneous
– Allopurinol, cimetidine, furosemide, thiazides .

Glomerulonephritis
• Rapid progressive glomerulonephritis with or
without antibodies against glomerular
basement membrane.
• Goodpasture syndrome (RPGN with anti-
GBM antibodies and lung disease).
• Post-streptococcal glomerulonephritis.
• Autoimmune vasculitis/inflammation of the
large or small renal blood vessels.

Postrenal AKI
Obstructive uropathy:
• Rare cause of AKI as one kidney is sufficient
to maintain adequate function.
• Causes:
– Benign prostatic hypertrophy.
– Carcinoma of the prostate.
– Urolithiasis.
– Retroperitoneal fibrosis,tumours.

5 Key Steps in Evaluating Acute Renal
Failure
1) Obtain a thorough history and physical
examination.
2) Do everything you can to accurately
assess volume status.
3) Always order a renal ultrasound.
4) Look at the urine.
5) Review urine analysis.

AKI
– Identify an insult
• Volume depletion.
• Drug exposure.
• Contrast exposure.
• Infections .
• Endogenous toxins/insults – myoglobin, uric acid.

AKI
• Symptoms:
– Fever, rash, joint pains, myalgias
• Concern for SLE, vasculitis, acute interstitial
nephritis.
– Dyspnea – heart failure.
– Hemoptysis – Goodpasture’s.
– Preceding bloody diarrhea – HUS.
– Preceding pharyngitis – post-Strep GN, post-
infectious GN.

AKI
• Urine output.
– Abrupt anuria.
• Acute obstruction, severe acute GN, sudden
vascular catastrophe.
– Slowly diminishing.
• Ureteral stricture.
• Prostatic enlargement.
– Presence of hematuria
• Painless – suggests GN.
• Painful – suggest ureteral obstruction.

AKI
• Physical Exam.
– Skin:
• Petechiae – HSP.
• Malar rash – SLE.
– Eye:
• Papilledema – malignant HTN.
• Roth’s spots – endocarditis.
– CV:
• Rub – suggestive of uremic pericarditis, lupus.
• Gallop – suggesting CHF.

AKI
• Physical Exam.
– Assessing volume status.
• Is the patient intravascularly volume depleted?
– Neck veins – JVP
– Peripheral edema or lack of.
– Orthostatic vitals.
– Not always straightforward.
– Pt. may be edematous (low albumin) or have
significant right sided heart disease.

AKI
Lab work:
• Creatinine, BUN.
• CBC: anemia, thrombocytopenia.
• HCO3ˉ: anion gap, lactic acid, ketones.
• K.
• CPK/LDH/Uric acid/liver panel.
• Serologies:
– Complement.
– ESR, RF, ANA, ANCA, AntiGBM.
– Electrophoresis.
• Toxicology studies.

AKI
Radiology
• Ultrasound: evaluates renal size, able to detect masses,
obstruction, stones
• CT: detects masses, stones.
• MRI/MRA: can detect RAS
In the AKI setting, U/S provides most information

Creatinine
• Is a breakdown product of creatine phosphate released
from skeletal muscle at a steady rate & from protein diet.
• It is freely filtered by glomerulus.
• Is neither reabsorbed nor metabolized by kidneys .
• It is generally a more sensitive and specific test for renal
function than BUN.
• Normal range is 0.6-1.3 mg /dL.

Serum Creatinine
• Increased serum creatinine:
1 - Impaired renal function.
2 - Very high protein diet ( meat).
3- Anabolic steroid users.
4 - Athletes taking oral creatine.
5 - Vary large muscle mass: body builders, acromegaly.
6- Male sex.
7 – Rhabdomyolysis /crush injury.
8 – Drugs:
• Cimetidine.
• Trimethoprim.
• Amiloride.

Decreased Creatinine
1- Age ( 50- 90 years).
2- Female.
3- Malnutrition.
4- Muscle wasting.
5- Amputation ( LL > UL).

AKI
- Urea is substance resulting from protein metabolism .
- The real urea concentration is BUN x 2.14.
- Normal BUN range is 8-25 mg/dL .

Causes of Increased BUN
1– Increased protein catabolism:
• Increased dietary protein.
• Severe stress: MI, fever…….ect
• Rhabdomyolysis .
• Upper GI bleeding.
. Some drugs ( Tetracycline, Steriods…ect)
2 – Impaired renal function:
• Pre renal failure.
• Acute tubular necrosis.
• Post renal failure.

Causes of decreased BUN:
1-Volume expansion.1-Volume expansion.
2-Liver disease.2-Liver disease.
3-Severe malnutrition.3-Severe malnutrition.

Increased in:
- Renal failure
– Gout
– Liver disease
– Lead poisoning
– Thiazide diuretics
– High dose aspirin
– Burns
– Crush injuries
– Severe hemolytic anemia
– Myeloproliferative disorders
– Plasma cell myeloma
– Tumor lysis: post chemotherapy
** Metabolite of purineMetabolite of purine
metabolism .metabolism .
**Filtered by the glomeruliFiltered by the glomeruli
and both reabsorbed andand both reabsorbed and
secreted by the renalsecreted by the renal
tubules.tubules.
Uric Acid

Unremarkable in pre and post renal causes.
Differentiates ATN vs. AIN. vs. AGN:
• Muddy brown casts in ATN.
• WBC casts in AIN.
• RBC casts in AGN.
Urine analysis

Urinalysis in Acute Kidney Injury
Prerenal
Postrenal
Glomerulopathy
Vasculitis
Pyelonephritis
Interstitial
nephritis
AIN
Athero-
embolic
ATN
Myoglobin
Uric acid Plasma cell
dyscrasia
Hematuria
RBC casts
proteinuria
WBC
WBC casts
Eosinophils
Pigmented
casts
Crystalluria Non-
albumin
proteinuria
Abnormal sedimentNormal/bland

Causes of false positive proteinuria
1- Urinary tract infection.
2- Sepsis.
3- Heart failure.
4- Severe exercise.
5- Heavy protein intake.
6- Menses.

• Urinary Neutrophil Gelatinase-Associated
Lipocalin (NGAL).
Ann Intern Med 2008;148:810-819
• Urinary Interleukin 18
Am J Kidney Dis 2004;43:405-414
• Urinary Kidney Injury Molecule 1 (KIM-1)
J Am Soc Nephrol 2007;18:904-912
New Biomarkers in AKI
Alternatives to Serum Creatinine

 Intravenous albumin significantly reduces the incidence of AKI and
mortality in patients with cirrhosis.
 Albumin decreases the incidence of AKI after large volume
paracentesis.
 Albumin and terlipressin decrease mortality in HRS.
Gluud L, Kjaer M, Christensen E: Terlipressin for hepatorenal syndrome. Cochrane Database Systematic Reviews
2006; CD005162.
Prevention of AKI in hepatic
dysfunction

Hepatorenal Syndrome
Major Criteria
• Chronic or acute liver disease with advanced hepatic
failure.
• Serum creatinine >1.5 mg/dL.
• Absence of shock, ongoing bacterial infection, fluid loss,
and current or recurrent treatment with nephrotoxic drugs.
Absence of gastrointestinal fluid losses (repeated vomiting
or intense diarrhea).
• No sustained improvement in renal function (decrease in
serum creatinine to 1.5 mg/dL or less after withdrawal of
diuretics and expansion of plasma volume with 1.5 L of
isotonic saline.

Hepatorenal syndrome
Minor Criteria
• Urine volume < 500 mL/day.
• Urine sodium < 10 mEq/L.
• Urine osmolality > plasma osmolality.
• Urine red blood cells < 50 per high-power
field.
• Serum sodium concentration < 130
mEq/L.

AKI – Prevention in Specific Cases
• Myoglobinuria
– Mechanism of toxicity:
• Tubular obstruction.
• Inhibition of glomerular flow by PGE inhibition.
– Treatments:
• Aggressive hydration to increase UOP.
• Alkalinization of urine.
• Mannitol/ Furosemide to increase UOP.
• Early Hemofiltration.

DD of AKIDD of AKI Prerenal Renal Postrenal
Urine sodium <20mEq/L >20mEq/L >20mEq/L
Urine Chloride <20mEq/L >20mEq/L >20mEq/L
FE Na <1% >2% >2%
Urine osmolarity >500 <350 <350
Urine/Serum Cr >40 <20 <20
Urine/Serum Urea >8 <3 <3
Serum BUN/Creat >20 ~10 ~10

Treatment is largely supportive in nature
Maintain renal perfusion.
Correct metabolic derangements.
Provide adequate nutrition.
? Role of diuretics.
Renal Replacement therapy remains the
cornerstone of management of minority of
patients with severe AKI
Management of AKI in ICU

• Human kidney has a compromised ability to
autoregulate in AKI.
• Maintaining haemodynamic stability and
avoiding volume depletion are a priority in
AKI.
Kelleher S, Robinette J, Conger J: Sympathetic nervous system in the loss of autoregulation
in acute renal failure. American Journal of Physiology 1984; 246: F379-386.
Maintaining renal perfusion

• The individual BP target depends on age, co-
morbidities (HTN) and the current acute
illness.
• A generally accepted target remains MAP ≥
65.
Bourgoin A, Leone M, Delmas A, et al.: Increasing mean arterial pressure in patients with septic shock:
Effects on oxygen variables and renal function. Critical Care Medicine 2005; 33:780-786
Maintaining renal perfusion

• No statistical difference between volume
resuscitation with saline or albumin in
survival rates or need for RRT.
Finfer S, Bellomo R, Boyce N, et al.: A comparison of albumin and saline for fluid resuscitation in the intensive
care unit. New England Journal of Medicine 2004; 350: 2247-2256.
Volume resuscitation – which fluid?

Fluid conservative therapy decreased ventilator
days and didn’t increase the need for RRT in
ARDS patients.
Association between positive fluid balance and
increased mortality in AKI patients.
Payen D, de Pont A, Sakr Y, et al.; A positive fluid balance is associated with worse outcome in
patients with acute renal failure. Critical Care 2008; 12: R74
Volume resuscitation – how much
fluid?

• There is no evidence that from a renal
protection standpoint, there is a vasopressor
agent of choice to improve kidney outcome.
Dennen P, Douglas I, Anderson R,: Acute Kidney Injury in the Intensive Care Unit: An update and primer
for the Intensivist. Critical Care Medicine 2010; 38:261-275.
Which inotrope/vasopressor?

Renal dose dopamine (<5 μg/kg of body weight/min)
increases RBF and, to a lesser extent, GFR. Dopamine is
unable to prevent or alter the course of ischaemic or
nephrotoxic AKI.
Furthermore, dopamine, even at low doses, can induce tachy-
arrhythmia’s, myocardial ischaemia, and extravasation out of
the vein can cause severe necrosis .Thus, the routine
administration of dopamine to patients for the prevention of
AKI or incipient AKI is no longer justified.
Lauschke A, Teichgraber U, Frei U, et al.: “Low-dose” dopamine worsens renal perfusion in patients
with acute renal failure. Kidney 2006; 69:1669-1674.
Renal vasodilators?

• 61 patients in 2 cardiothoracic ICU with post-op AKI assigned
to receive ANP (50ng/kg/min) or placebo.
• The need for RRT before day 21 after development of AKI was
significantly lower in ANP group (21% vs 47%)
• The need for RRT or death after day 21 was significantly lower
in ANP group (28% vs 57%)
Role of ANP analogues in AKI?
Crit Care Med. 2004 Jun;32(6):1310-5

Is there a role for Fenoldopam in prevention or
treatment of AKI in ICU setting?
 Dopamine-1 receptor agonist, lack of Dopamine-2, and alpha-
1 receptor effect, make it a potentially safer drug than
Dopamine.
 Reduces in hospital mortality and the need for RRT in AKI.
 Reverses renal hypoperfusion more effectively than renal dose
Dopamine
Crit Care Med. 2006 Mar;34(3):707-14

Is there a role for diuretics in the treatment of AKI in
ICU setting?
• Loop diuretics may convert an oliguric into a non-oliguric form
of AKI that may allow easier fluid and/or nutritional support of
the patient.
• Volume overload in AKI patients is common and diuretics may
provide symptomatic benefit in that situation. However, loop
diuretics are neither associated with improved survival, nor
with better recovery of renal function in AKI.
Crit Care Resusc. 2007 ;9(1):60-8

• The most recent trials seem to confirm a potential
positive preventive effect of N-acetylcysteine
(NAC), particularly in contrast-induced
nephropathy (CIN).
• NAC alone should never take the place of IV
hydration in patients at risk for CIN; fluids likely
have a more substantiated benefit.
NAC

• Erythropoietin (EPO) has tissue-protective
effects and prevents tissue damage during
ischaemia and inflammation, and currently
trials are performed with EPO in the
prevention of AKI post-cardiac surgery,
CIN and post-kidney transplantation.
EPO

AKI - Prevention
• Thyroxine:
– More rapid improvement of renal function in
animals.
• Theophyline:
Adenosine antagonist – prevents reduction in GFR.
• Growth Factors:
– After ischemic insult, infusion of IGF-I, Epidermal GF,
Hepatocyte GF improved GFR, diminished
morphologic injury, diminished mortality.

AKI - Prevention
•Mannitol
– May work by:
• Increasing flow through tubules, preventing
obstruction.
• Osmotic action, decreasing endothelial swelling.
• Decreased blood viscosity with increased renal
perfusion .
• Free radical scavenging.

• Initiation Phase (hours to days)
Continuous ischemic or toxic insult.
Evolving renal injury.
ATN is potentially preventable at this time.
• Maintenance Phase (typically 1-2 wks)
Maybe prolonged to 1-12 months.
Established renal injury.
• Recovery Phase
Gradual increase in UOP.
Gradual fall in SCr (may lag behind the onset of diuresis by
several days).
Natural Clinical Course of ATN

Acute
Treatment
• Water and sodium restriction.
• Protein restriction.
• Potassium and phosphate restriction.
• Adjust medication dosages.
• Avoidance of further insults:
– BP support.
– Nephrotoxins.

Hyperkalemia
• Highly Arrhythmogenic:
– Usually with progressive ECG changes
• Peaked T waves ---> Widened QRS.
– K> 5.5 meq/L needs evaluation/intervention
– Usually in setting of decrease GFR but:
• Medication also a common cause:
– ACEI.
– NSAIDS.
– Heparin.

Dialysis Indications
Oliguria (urine output <400 mL/24 h).
Anuria (urine output <100 mL/24 h).
Hyperkalaemia ([K] >6.5 mEq/L).
Severe acidaemia (pH <7.1).
Azotemia (urea >30 mg/dL).
Pulmonary oedema.
Uraemic encephalopathy.
Uraemic pericarditis.
Uraemic neuropathy/myopathy.
Severe dysnatraemia (Na <115 or >160 mEq/L).
Hyperthermia.
Drug overdose with dialyzable toxin.

Different Modalities
• IHD.
• PD.
• CRRT.

Intermittent haemodialysis
• Gold standard.
• Patient must be haemodynamically stable.
• Blood flow typically 200-400mL/min, filtration
rate of 300-2000mL/hr and urea clearance of
150/250mL/min.

Problems with IHD
• Removal of intravascular volume quicker
than it can be replaced from the
extravascular space can cause
cardiovascular collapse – particularly if
intravascularly deplete.
• Hypotension can cause ischaemic injury,
particulary in AKI or head injury.

Intermittent Hemodialysis
• Best therapy for severe
hyperkalemia.
• Limited anti-coagulation
time.
• Bedside vascular access
can be used.
• Hemodynamic instability.
• Rapid fluid and electrolyte
shifts
• Specialized personnel.
• Difficult in small infants.
Advantages Disadvantages

Common complications during IHD
1-Hypotension 20-60%.
2-Cardiac arryhythmias 5-60%.
3-Muscle cramps 5-20%.
4-Nausea &vomiting 5-15%.
5-Headacche 5-10 %.
6-Chest pains 2-5%.
7-Itching 5%.
8-Fever& chills <1%.

Less common complications
1-Disequilibrium syndrome.
2-Hypersensitivity reactions(dialysers reactions).
3-Intracranial bleeding.
4-Seizures.
5-Heamolysis.
6-Air embolism.
7- Dialysis related neutropenia.
8-Anticagulant complications (esp. bleeding risk).

Disequilibrium syndrome
Self-limiting syndrome typically after first
dialysis of very uraemic patients.
Characterised by nausea, vomiting, headache,
seizures and coma.
Syndrome is triggered by rapid reduction in
plasma osmolality causing cerebral oedema.
Treatment:
Supportive.
Hypertonic saline / mannitol.

SLED
• Inexpensive.
• Less hypotension.
• It can remove larger volumes of fluid or solute
than IHD.

Peritoneal dialysis
• Simple to set up & perform.
• Easy to use in infants.
• Hemodynamic stability.
• No anti-coagulation.
• Bedside peritoneal access.
• Unreliable ultrafiltration.
• Slow fluid & solute removal.
• Drainage failure & leakage.
• Catheter obstruction.
• Respiratory compromise.
• Hyperglycemia.
• Peritonitis.

Contra-indications to PD:
1- Recent abdominal surgery.
2- Ileus.
3- Severe respiratory disease.
4- Congenital communications between
abdomen / thorax.
5- Cellulitis of abdominal wall.
6- Pregnancy.

CRRT
• Less hypotension.
• Better control of uremia and clearance of solute from
the extravascular compartment.
• CRRT is able to remove larger fluid volumes, to have a
room for parenteral nutrition and multiple infusions in
critical care patients .
• CRRT may better preserve cerebral perfusion pressure.
• With CRRT there is more clearance of mediators of
the inflammatory cascade.
• More expensive.

The treatment of AKI with RRT has
the following goals
• To maintain fluid and electrolyte, acid-base,
and solute homeostasis.
• To prevent further insults to the kidney.
• To permit renal recovery.
• To allow other supportive measures (e.g.,
antibiotics, nutrition support)
Kidney Disease: Improving Global Outcomes (KDIGO), 2012

Diffusion or Convection
• Convective (hemofiltration)
• Diffusive (hemodialysis)
• Diffusion ＋ Convection
（ hemodiafiltration)

Ultrafiltration (..... convection)

Continuous veno-venous
haemodialysis (CVVHD)
• Continuous diffusive dialysis.
• Mostly small molecules
are removed.

heamofiltration (CVVH)
Convective dialysis.
Filtration rate is high.
Electrolyte replacement solution is
required.
Removes a lot of middle molecules, e.g.
cytokines.
Slow continuous ultra-filtration
(SCUF) is ‘slower’.

Continuous Hemofiltration
• Easy to use in ICU.
• Rapid electrolyte correction.
• Excellent solute clearances.
• Rapid acid/base correction .
• Controllable fluid balance.
• Tolerated by unstable pts.
• Systemic anticoagulation
(except citrate).
• Frequent filter clotting.

haematodiafiltration (CVVHDF)
• Diffusive and convective dialysis.
• Small and middle
molecules removed.
• Requires
replacement fluid.
• Most popular mode

Advantages of CRRT
Suitable for use in haemodynamically unstable patients.
Precise volume control, which is immediately adaptable to
changing circumstances.
Very effective control of uraemia, hypophosphataemia and
hyperkalaemia.
Rapid control of metabolic acidosis .
Safer for patients with brain injuries and cardiovascular
disorders .
May have an effect as an adjuvant therapy in sepsis.

Super High-Flux or High Cut-ff
Membranes
Achieve greater clearance of
inflammatory cytokines
- Superior elimination of IL-6
- Decrease need of Nor-adrenaline over
time

Disadvantages of CRRT
• Expensive.
• Anticoagulation – to prevent extracorporeal circuit
from clotting.
• Complications of line insertion and sepsis.
• Risk of line disconnection.
• Hypothermia.
• Severe depletion of electrolytes – particularly K+
and PO4.

Modality of renal replacement therapy
for patients with AKI
• We suggest using CRRT, rather than standard
intermittent RRT, for hemodynamically unstable patients
(2B).
In non-septic AKI, 20-25 ml/kg/h remains optimal.
• We suggest using CRRT, rather than intermittent RRT,
for AKI patients with acute brain injury or other causes
of increased intracranial pressure or generalized brain
edema. (2B).
In non-septic AKI, 20-25 ml/kg/h remains optimal.

AKI – RRT
Modality of CRRT for patients with SEPTIC AKI
• Septic AKI should be treated by continuous veno-venous
hemofiltration at 35 ml/kg/h.
New insights regarding rationale, therapeutic target and dose of hemofiltration and hybrid
therapies in septic acute kidney injury. Blood Purif. 2012;33:44-51

The optimal timing of RRT for AKI is not defined
Acute Kidney Injury

Maintaining fluid homeostasis
• Fluid overload in critical illness and AKI is associated
with adverse outcomes.
Sutherland SM, Zappitelli M, Alexander SR, et al. Fluid overload and mortality in
children receiving continuous renal replacement therapy:the prospective pediatric
continuous renal replacement therapy registry.Am J Kidney Dis 2010; 55: 316–325.

• Observational studies:
– Single-center observational studies that were restricted to AKI after trauma
(HD) and coronary artery bypass surgery (CVVHDF, CVVH)
early starters - BUN 15 mM, late starters - BUN 33 mM
Conclusion: Suggested a benefit (survival ) to RRT initiation at early start
(at lower BUN concentrations)
Timing of initiation of RRT on outcome
Gettings LG, Intensive Care Med 1999; 25: 805–813., Demirkilic U, J Card Surg 2004; 19: 17–20.
Elahi MM, Eur J Cardiothorac Surg 2004; 26: 1027–1031.
early vs. late initiation

• Observational studies:
– A prospective multicenter observational cohort study
243 patients, adjusted for age, hepatic failure, sepsis,
thrombocytopenia, and SCr
Conclusion: initiation of RRT at higher BUN [blood urea > 27.1
mmol/l] was associated with an increased risk of death.
Liu KD, et al. Timing of initiation of dialysis in critically ill patients with acute kidney injury.
Clin J Am Soc Nephrol 2006; 1:915–919.

Late initiation of renal replacement therapy is associated with worse
outcomes in acute kidney injury after major abdominal surgery.
Shiao CC, et al. Crit Care 2009; 13: R171.
Underscore the importance of predicting prognoses of major abdominal surgical patients
with AKI by using RIFLE classification
indications for RRT

Timing of renal replacement therapy initiation in acute
renal failure: a meta-analysis
• Meta-analysis of randomized trials, early RRT
was associated with a nonsignificant 36%
mortality risk reduction (RR, 0.64; 95%
confidence interval, 0.40 to 1.05; P = 0.08)
• In cohort studies, early RRT was associated
with a statistically significant 28% mortality
risk reduction (RR, 0.72; 95% confidence
interval, 0.64 to 0.82; P < 0.001).
Seabra VF, Balk EM, Liangos O, Sosa MA, Cendoroglo M, Jaber BL. Am J Kidney Dis. 2008;52:272–284

• Initiate RRT emergently when
• Life-threatening changes in fluid.
• Electrolyte.
• Acid-base balance.
• Uremic complications: pericarditis, pleuritis,
encephalopathy, coagulopathy
The optimal timing of dialysis for AKI
= Indications for RRT

Only one RCT has evaluated the effect of timing of
initiation of RRT on outcome
AKI

• Bouman et al. Effects of early high-volume continuous venovenous
hemofiltration on survival and recovery of renal function in intensive
care patients with acute renal failure: a prospective, randomized trial
– Randomized 106 critically ill patients with AKI to early vs. late initiation of RRT
– The early initiation group started RRT within 12 hours oliguria (30 ml/h for 6 hours,
not responding to diuretics or hemodynamic optimization) or CrCl < 20 ml/min
The late-initiation group started RRT when classic indications were met
– Conclusion: did not find differences in ICU or hospital mortality, or in renal recovery among
survivors
Bouman CS, Oudemans-Van Straaten HM, Tijssen JG, Zandstra DF, Kesecioglu J. Crit Care Med 2002; 30: 2205–2211.
Department of Intensive Care, Academic Medical Center, Amsterdam, The Netherlands

• Analysis of a multicenter observational cohort showed that
mean daily fluid balance in AKI patients was significantly
more positive among nonsurvivors than survivors.
• Payen D, de Pont AC, Sakr Y, et al. A positive fluid balance is associated with a worse outcome in patients with acute renal
failure. Crit Care 2008;12: R74.
• Survivors had lower fluid accumulation at dialysis
initiation compared to nonsurvivors (8.8% vs. 14.2% of
baseline body weight; P=0.01 adjusted for dialysis
modality and severity score).
• PICARD: Liu KD, et al. Timing of initiation of dialysis in critically ill patients with acute kidney injury. Clin J Am Soc
Nephrol 2006; 1:915–919.
Maintaining fluid homeostasis

"Genius is one per cent inspiration and ninety-nine per cent
perspiration. Accordingly, a 'genius' is often merely a talented
person who has done all of his or her homework."
--Thomas Edison

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