ACUTE KIDNEY INJURY

(AKI)

Dr. dr. Yenny Kandarini,Sp.PD-KGH,FINASIM

Division of Nephrology & Hypertension
Department of Internal Medicine
Udayana School of Medicine/Sanglah General Hospital
2018
Outline Presentation

 Definition of AKI
 Epidemiology of AKI
 Etiology of AKI
 Pathophysiology of AKI
 Evaluation of AKI
 Complications of AKI
 Treatments of AKI
 Conclusion
General Considerations

• Acute Kidney Injury (AKI)

• Life-threatening disease process
• AKI occurs in
• ≈ 7% of hospitalized patients.
• 36 – 67% of critically ill patients
(depending on the definition).
• 5-6% of ICU patients with AKI require RRT.

• Nash K, Hafeez A, Hou S: Hospital-acquired renal insufficiency. American Journal of Kidney

Diseases 2002; 39:930-936.
• Hoste E, Clermont G, Kersten A, et al.: RIFLE criteria for acute kidney injury are associated
with hospital mortality in critically ill patients: A cohort analysis. Critical Care 2006; 10:R73.
• Osterman M, Chang R: Acute Kidney Injury in the Intensive Care Unit according to RIFLE.
Critical Care Medicine 2007; 35:1837-1843.
Definition of AKI
• There are more than 35 definitions of AKI
(formerly acute renal failure) in literature!

Pendidikan Kedokteran
Definition of AKI

“An abrupt / rapid decrease in kidney function”

Broad clinical syndrome  encompassing

various etiologies

Decreased kidney function  retention of

metabolic waste product & dysregulation of
fluid, electrolyte, and acid-base homeostatis

Even mild & reversible AKI has important clinical

consequences  increased risk of death

National Kidney Foundation. KDIGO. Acute Kidney Injury

Guidelines. Kidney International Supplements (2012) 2, 19-36.
 Definition of AKI

Represented by Urine Production & Levels

Kidney Function
of Creatinine in Blood (Serum Creatinine)

Sharfuddin A, Weisbord S, Palevsky P, Molitoris B. Brenner and

Rectors: Acute Kidney Injury. 2015. Philadelphia. 1059-1085.
Definition of AKI

↓ Kidney Function

How severe it is?

Sharfuddin A, Weisbord S, Palevsky P, Molitoris B. Brenner and

Rectors: Acute Kidney Injury. 2015. Philadelphia. 1059-1085.
Epidemiology of AKI

AKI incidence Rarely documented

“Ice berg” phenomena  Hidden threat

Due to late recognition of the early sign

AKI Symptoms usually appears in advance injury

Oftenly co-existing with other co-morbidities

High mortality rate

Hoste EA, Schurgers M. Epidemiology of Acute Kidney Injury: How
Big is The Problem? Crit care med 2008;
36 (4 suppl): S146-S151
Epidemiology of AKI

Community-acquired AKI incidence

The incidence keeps on increasing every year

Increased of morbidity & mortality  burden

of medical cost

Cerda j, Lamiere N, Eggers P, et al. Epidemiology of Acute

Kidney Injury. Clin J Am Soc Nephrol 2008; 3: 881-886
Epidemiology of AKI
Hospital Based AKI incidence

A Non ICU B ICU

Lamiere N, Biesen V, Vanholder R. The Rise of Prevalence and the Fall of Mortality
of Patients with Acute Renal Failure: What The Analysis of Two Databases Does
and Does Not Tell Us. J Am Soc Nephrol 2006: 17: 923-925.
Major Disease Categories Causing
AKI
Disease Category Incidence
Prerenal azotemia caused by acute renal 55-60%
hypoperfusion
Intrinsic renal azotemia caused by acute diseases of 35-40%
renal parenchyma:
-Large renal vessels dis.
-Small renal vessels and glomerular dis.
-ATN (ischemic and toxic) *>90%*
-Tubulo-interestitial dis.
-Intratubular obstruccttion
Postrenal azotemia caused by acute obstruction of <5%
the urinary tract
Etiology of AKI

• Pre-Renal
Causes of AKI • Sudden and severe drop in blood
pressure(Shock) or interruption of blood
1 flow to the kidneys

• Renal
• Direct damage to the kidneys by
inflammation, toxins, drugs, infection, or
2 reduced blood supply

• Post-Renal
• Sudden obstruction of urine flow due to
enlarged prostate, kidney stones, bladder
3 tumor, or injury

Sharfuddin A, Weisbord S, Palevsky P, Molitoris B. Brenner and

Rectors: Acute Kidney Injury. 2015. Philadelphia. 1059-1085.
Etiology of AKI

Sharfuddin A, Weisbord S, Palevsky P, Molitoris B. Brenner and Rectors: Acute Kidney Injury. 2015.
Philadelphia. 1059-1085.
Etiology of AKI

Sharfuddin A, Weisbord S, Palevsky P, Molitoris B. Brenner and Rectors: Acute Kidney Injury. 2015.
Philadelphia. 1059-1085.
Etiology of AKI

Jefferson JA, Thurman JM, Schrier RW. Comprehensive Clinical Nephrology : Acute Kidney Injury. 2010.
Philadelphia. 797-870
Pathophysiology of AKI

Variety of Animal and To describe and understand the

Cell culture models mechanism of injury happened in AKI

Prerenal Azotemia

Based
On Acute Tubular Necrosis
The (ATN)
Etiology
Post-renal Acute Kidney
Injury

Sharfuddin A, Weisbord S, Palevsky P, Molitoris B. Brenner and Rectors: Acute Kidney Injury. 2015.
Philadelphia. 1059-1085.
Pathophysiology of AKI

Prerenal Azotemia

Impaired Renal Fall in Glomerular Capillary

Perfusion Filtration (GFR) Pressure

Commonly secondary to Impaired Renal Filtration

function

Depletion of Normal or Urine Production ↓↓ &

extracellular Increase of Acummulation of waste
fluid extracellular fluid products (azotemia)

Ex: Diarrhea  Ex: Systemic Vasodilation

Dehydration (Sepsis), Cardiac (Pump) output
decrease
Jefferson JA, Thurman JM, Schrier RW. Comprehensive Clinical Nephrology : Acute Kidney Injury. 2010.
Philadelphia. 797-870
 AKI
RISK INJURY FAILURE
Dialysis Treatments
Prevention/ Prevention/
Supportive Maintenance

Creatinine
M/l
Urine
l/day

Zöllner,
Innere Medizin,
modified

Time / days

1. Damage 2. Oliguria / Anuria 3. Polyuria 4. Recovery

Damage to Complete Loss of Uncontrolled slow Recovery of
Renal Tissue Renal Function Urine Quantities Renal Function
(minutes to days)\ (up to 6 weeks) (1 - 2 weeks) (several months)
19
Pathophysiology of AKI
Pathophysiology of AKI

Acute Tubular Necrosis

(ATN)

Commonly occurs in Responsible for most cases

“high risk” settings of hospital acquired AKI

Ex: after vascular & cardiac surgery, severe burns,

pancreatitis, and chronic liver disease

The importance of Animal model illustrate Typical course of

combined injurious the fact that single uncomplicated ATN is
mechanism is insult alone is rarely recovery during 2-3
emphasized in ATN sufficient to induce ATN weeks

Jefferson JA, Thurman JM, Schrier RW. Comprehensive Clinical

Nephrology : Acute Kidney Injury. 2010. Philadelphia. 797-870
Pathophysiology of AKI

Tubular damage

Combination of
ischemic injury & direct
nephrotoxic

The most vulnerable part 

proximal tubule S3
segment & thick ascending
loop of Henle

Due to borderline blood

supply and high metabolic
demands in these area.
Jefferson JA, Thurman JM, Schrier RW. Comprehensive Clinical Nephrology : Acute
Kidney Injury. 2010. Philadelphia. 797-870
Pathophysiology of AKI
Post-renal Acute Kidney
Injury

Postrenal forms of AKI

Precipitation of insoluble crystals

Tubular (intrarenal) (phosphate, methrotrexate, acyclovir,
sulfonamides, indinavir, uric acid,
oxalic acid) or protein (hemoglobin,
Extrarenal myoglobin, paraprotein)

Obstruction of the extrarenal collecting Jefferson JA, Thurman JM, Schrier RW.
system at “any” level (renal pelvis, Comprehensive Clinical Nephrology :
ureters, bladder, urethra) Acute Kidney Injury. 2010. Philadelphia.
797-870
Evaluations of AKI

History Taking 1. Presence of risk factors ?

- Recent history of bleeding, water loss
Sacred 7 & (clinical setting associated with decrease of
Fundamental 4 intavascular volume)
- Diabetes, advanced age, hypertension, heart
disease
2. Previous episodes of renal disease ? (stone, cystic
disease)  URINE OUPUT for the last 6 hours?
3. History of nephrotoxic medication ? (anti TB,
NSAID, aminoglycoside, contrast agent)
4. Systemic disease ? (SLE, hyperuricemia)
5. Family history ?

Sharfuddin A, Weisbord S, Palevsky P, Molitoris B. Brenner and Rectors: Acute Kidney Injury. 2015.
Philadelphia. 1059-1085.
Evaluations of AKI

Physical 1. Suggestive of volume depletion

Examinations - Orthostatic hypotension (postural drop in
diastolic blood pressure 0f >10 mmHg) and
tachycardia (postural increase in heart rate of
> 10 beats /min)
- Reduced jugular venous pressure
- Diminished skin turgor,
- Dry mucous membranes
- The absence of axillary sweat
2. Signs of Chronic Kidney Disease
3. Signs of Cardiac Disease
4. Signs of Chronic liver disease

Sharfuddin A, Weisbord S, Palevsky P, Molitoris B. Brenner and Rectors: Acute Kidney Injury. 2015.
Philadelphia. 1059-1085.
Evaluations of AKI Lab Results

Urinalysis  gives abundant of

informations

Sediments in urine  clues in

differentiating causes of AKI

Urinalysis  may differentiate between

prerenal AKI & Acute Tubular Necrosis
(Renal) AKI

Sharfuddin A, Weisbord S, Palevsky P, Molitoris B. Brenner

and Rectors: Acute Kidney Injury. 2015. Philadelphia. 1059-
1085.
Evaluations of AKI Lab Results

The pattern and timing of change in BUN and

serum creatinine concentrations 
provide clues to the cause of AKI

Enhanced tubular rearbsoption of

Prerenal causes
filtered urea  BUN / SC ratio >20 :1

increase in BUN parallels with SC

Renal Causes ratio of approximately 10:1 maintained

The peak in serum creatinine level is

Contrast agents generally within 5 to 7 days post exposure

Nephrotoxic Aminoglycoside or cisplatin  often with

agents delayed onset of AKI (7 to 10 days)

Sharfuddin A, Weisbord S, Palevsky P, Molitoris B. Brenner and Rectors: Acute Kidney

Injury. 2015. Philadelphia. 1059-1085.
Evaluations of AKI

Novel Renal
Biomarkers

KIM-1
NGAL
Cystatin
C,
IL-8 Serum kreatinin
Volume urine
New Biomarkers in AKI
Alternatives to Serum Creatinine
• 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
Evaluations of AKI

Radiology Finding May identify  calcium-containing stones

that can cause obstructive disease

Assess cortical thickness, differences in

cortical and medullary density, the integrity
Abdominal of the collecting system, and kidney size
imaging highly
useful determine Computed Tomography (CT) may visualized
the cause of AKI obstruction caused by stones  avoid using
contrast agents

Reserved for patients  in whom prerenal

Renal Biopsy and postrenal AKI have been excluded and
the cause of intrinsic AKI is unclear

Sharfuddin A, Weisbord S, Palevsky P, Molitoris B. Brenner and Rectors: Acute Kidney

Injury. 2015. Philadelphia. 1059-1085.
Complications of AKI

Complications of Hyperkalemia is a common and potentially life-

Potasium threatening complication of AKI
Homeostasis
Serum K+ typically rises by 0.5 mEq/L/day in
oligoanuric patients

Mild hyperkalemia (<6.0 mEq/L) is usually

asymptomatic

Potasium level > 6.5mEq/L 

ECG abnormalities 
Peaked T waves, Prolongation of the PR
interval,flattening of P waves, Widening of the
QRS complex, and left axis deviation

Sharfuddin A, Weisbord S, Palevsky P, Molitoris B. Brenner and Rectors: Acute Kidney

Injury. 2015. Philadelphia. 1059-1085.
Complications of AKI

Complications of Predictably, AKI is commonly complicated by

Acid Base metabolic acidosis, typically with a widening of
Homeostasis the serum anion gap

Acidosis may be severe (daily fall in plasma

HCO3− of >2 mEq/L)

Complications of Mild hyperphosphatemia (5 to 10 mg/dL) is a

Mineral & Uric Acid common consequence of AKI
Homeostasis
Hyperphosphatemia may be severe (10 to 20
mg/dL high catabolism or with AKI
associated with rapid cell death
(rhabdomyolysis, severe burns, hemolysis, or
tumor lysis)
Sharfuddin A, Weisbord S, Palevsky P, Molitoris B. Brenner and Rectors: Acute Kidney
Injury. 2015. Philadelphia. 1059-1085.
Complications of AKI

Volume overload & Intravascular volume overload  consequence

cardiac of diminished salt & water excretion in AKI
complications
Moderate or severe hypertension  unusual in
ATN  suggest other diagnoses (renal
vasculature diseases)

Protracted periods of severe AKI or short

Uremic Syndrome intervals of catabolic, anuric AKI  often lead
to the development of uremic syndrome

Sharfuddin A, Weisbord S, Palevsky P, Molitoris B. Brenner and Rectors: Acute Kidney

Injury. 2015. Philadelphia. 1059-1085.
Complications of AKI
Complications of AKI

Complications Vigorous diuresis

during recovery
from AKI
Complicate recovery phase of AKI 
Precipitate intravascular volume depletion

Results in a delay in recovery of renal function

Delayed recovery of tubular Combined effects of an osmotic diuresis,

reabsorptive function relative excretion of retained salt and water
to glomerular filtration accumulated during AKI

Sharfuddin A, Weisbord S, Palevsky P, Molitoris B. Brenner and Rectors: Acute Kidney

Injury. 2015. Philadelphia. 1059-1085.
Treatments of AKI

Basic Principles

Diagnose AKI as early as possible  Assessing

etiology/causes of AKI  Assessing complications of AKI

Evaluate the stage of AKI  apply management based on

stage of AKI

Choosing the appropriate management  Conservative

(Supportive) or Renal Replacement Therapy (RRT)

Roesli R. Pengelolaan Konservatif (Supportif) “Memilih pengobatan yang tepat di saat yang
tepat”. Diagnosis & Pengelolaan Gangguan Ginjal Akut. Jakarta. 2011: 79-93.
Treatments of AKI

National Kidney Foundation. KDIGO. Acute Kidney Injury Guidelines. Kidney International
Supplements (2012) 2, 19-36.
 Treatments of AKI

Dialysis modalities for acute kidney injury

Intermittent therapies Continuous therapies

(up to 12 hours) (24 hours)
Hemodialysis Peritoneal dialysis
intermittent Ultrafiltration (SCUF)
daily Hemofiltration (CAVH, CVVH)
Hemodiafiltration Hemodialysis (CAVHD, CVVHD)
Slow Continuous Ultra-Filtration Hemodiafiltration (CAVHDF,
Extended Daily Dialysis CVVHDF)
Sustained Low Efficiency Dialysis

Mehta RL. Supportive therapies; intermittent hemodialysis, continuous renal replacement

therapies and peritoneal dialysis. In : Schrier RW, editor. Atlas of diseases of the kidney, Current
Medicine, Philadelphia: Blackwell Science; 1998: with permission.
 Treatments of AKI
Indication and Criteria for inisiate RRT in ICU setting
1 Oligouria (Urin Output <200/12 hours)
2 Severe Anuria/Oligouria (Urin Output <50cc/12 hours)
3 Hyperkalemia (K >6,5 mmol/L)
4 Severe Acidosis (Ph<7,1)
5 Azotemia (Urea >30 mmol/Liter)
6 Severe Clinical Manifestation (especially pulmonary edema)
7 Uremic Encephalopathy
8 Uremic Pericarditis
9 Uremic Neuropathy
10 Severe Dysnatremia(Na>160 or <115 mmol/L)
11 Hypertermia/Hypotermia
12 Drugs overdose that can be dialized
13 Bleeding diathesis
14 Refractory Hypertension
Bellomo R, Ronco C. Indications and Criteria For Initiating Renal Replacement Therapy in The Intensive Care Unit. Kidney
Int 2006; 70: 963-968.
 Metabolic Abnormality BUN >76 mg/fl Relative

BUN < 76 mg/dl Absolute

Hyperkalemia >6 mEQ/L Relative

Hyperkalemia > 6 MEq/L (With ECG Changes) Absolute

Dysnatremic Relative

Hypermagnesemia >8 mEQ/L Relative

Hypermagnesemia >8 mEQ/L (With Anuria or loss of Absolute

tendon reflexes)

Acidosis pH>7,15 Relative

pH<7,15 Absolute

Anuria/Oligouria RIFLE –R Relative

RIFLE – I Relative

RIFLE – F Relative

Volume overload Diuretic Sensitive Relative

Diuretic Resistant Absolute

Gibney N, Hoste E. Timing and Discontinuation of renal replacement therapy in AKI: Unanswered Key
Questions. Clin J Am Soe Nephrol 2008; 3: 876-880.
 Conclucions
ACUTE KIDNEY INJURY (AKI)
• A common critical condition with high mortality
• Early recognition  favors better prognosis
• The causes divided into prerenal, renal /intrinsic
and post renal
• Loss of autoregulation, vasoconstriction,
glomerulotubular damage, and inflammation is a
main pathogenesis
• Some modality of treatments with a different
result