ACUTE KIDNEY INJURY

CEDERA GINJAL AKUT (?)

Department of Internal Medicine

Faculty of Medicine - Mataram University

ACUTE RENAL FAILURE (ARF)

A common complication of critical illness, with high
mortality (50-80%)
No consensus definition of ARF and many different
definitions
- so, trials of prevention and therapy are not comparable

Mortality of ARF
Type of ARF

Mortality

ARF in the ICU associated with

respiratory failure and the
requirement of dialysis

> 90%

ARF in the ICU

72%

ARF in hospitalized patients,

not in the ICU

32%

ARF following i.v. contrast

34% (compared to 7% in controls)

Adjusted odds ratio of death: 5.5

ARF following cardiac surgery

64% (compared to 4.3% in controls)

Adjusted odds ratio of death: 7.9

Schrier RW, 2005; Manual of Nephrology

Comparisons of Acute Renal Failure by Site of Onset

Factor

Community

Hospital
ward

Intensive care
unit

Older

Older

Younger

Prerenal

30-50

30

20

Postrenal

20-40

10-20

Renal

15-30

30-50

70-80

Isolated (%)

80

70

10

Renal replacement
therapy need (%)

10

20

70

Mortality (%)

20

30

70

Age
Cause (%)

Schrier RW, 2007; Disease of The Kidney & Urinary Tract

DEFINITION
Conceptual :
is a sudden decrease in glomerular filtration (GFR) occurring
over a period of hours to days and resulting in the failure of
the kidney to excrete nitrogenous waste products and
maintain fluid and electrolyte homeostasis
Operational or clinical
an increase in creatinine of 50% above baseline per day
or an increase in creatinine of 0.5 mg per dl per day, if
initial serum creatinine 3 mg/dl
Manual of Nephrology, Schier 2006

RIPFLE diagnosis of ARF (ADQI = Acute Dialysis Quality Initiative)

Bellomo et al, Curr pin Crit Care 2002;6505-8
RIFLE Criteria for Acute Renal Dysfunction

Diagnosis
of ARF

Category

GFR Criteria

UO criteria

Risk

Increased creatinine x1.5

or GFR decrease > 25 %

UO < 0.5 ml/kg/h x 6 hr

Injury

Increased creatinine x2 or
GFR decrease > 50 %

UO < 0.5 ml/kg/h x 12 hr

Failure

Increased creatinine x3 or
GFR decrease > 75%

UO < 0.3 ml/kg/h x 24 hr

or Anuria x 12 hrs

Loss

Persistent ARF = complete loss kidney function

> 4 weeks

ESKD

END Stage Kidney Disease (> 3 months)

GFR = Glomerular Filtration Rate

UO = Urine Output

High
Sensitivity

High Specivity

ARF = Acute Renal Failure

ESKD = End Stage Kidney Disease

References:
Bellomo R, Kellum JA, Mehta R, Palevsky PM, Ronco C. Curr Opin Crit Care, 2002 Dec; 8(6):505-9.

CLASSIFICATION
Based on urine production
oligouric
non oligouric
Based on previous condition
acute renal failure
acute on chronic renal failure
Based on causes
prerenal
renal (intrinsic)
postrenal

Oligouric ARF
urine output less then 400 ml/day
60- 80 % of cases
worse prognosis
Nonoligouric ARF
urine out put 400 ml/days
20- 40 % of cases
better prognosis

Acute Renal Failure

previous normal kidney function

Acute on Chronic Renal Failure

initiated by Chronic Kidney Disease

Distinguishing between acute and acute on chronic renal failure

may be challenging
Favors chronic

Favors acute

History of kidney disease,

hypertension, abnormal urinalysis

Small kidney size

Urinalysis with broad casts (i.e.,

more than two or three white blood
cells in diameter)

Return of renal function to normal

with time

Low carbamylated hemoglobin

Hyperkalemia, acidemia.
Hyperphosphatemia,a anemiaa

More common in chronic renal failure

Schrier RW, 2007; Kidney & Urinary Tract

Prerenal

Renal

Postrenal

Causes of Prerenal ARF

ECF volume with

arterial underflilling

ECF volume

Renal
losses

Third space
losses

Gastrointestinal
losses
Cardiac output

Myocardial
infarction

Pericardial
tamponade,
Constrictive
pericarditis

Systemic arterial
vasodilation

Cirrhosis

Sepsis

Schrier RW, 2005; Manual of Nephrology

Causes of Renal ARF

Vascular
-

Interstitium

Tubular

renal a.

- Goodpastures

- Acute Interstitial

ischemic

thrombosis

- S Lupus E

- nephritis (drug, etc)

toxin

renal v.

- RPGN

- SOP

pigmen

thrombosis
-

Glomerular

malignant
hypertension

Causes of Post renal ARF

Acute obstruction
intraureteral
extraureteral
bladder neck/urethral

PATHOGENESIS OF ARF
Vascular factors :
renal vasoconstriction
Tubular factors :
back leak of glomerular filtrate
decreased proximal tubular sodium reabsorption
increased tubuloglomerular feedback
tubular cast formation and obstruction
Inflammatory response :
endothelial injury
leukocyte adhesion/infiltration
inflammatory mediators

Pathogenesis of prerenal ARF

Hypovolemia

Baroreceptor activation

effective vascular
volume

neurohumoral respose
RAA axis

vasopressin

sympathetic nerve
system

Vasoconstriction
mesangial cell contraction
fluid & sodium absorption

GFR
From: Bakri S, 2005

The important mechanism of renal- vascular abnormality :

loss of renal autoregulation
renal vasoconstriction

Renal Ischemia

Vascular effects
Incerased cytosolic Ca2+
in afferent arterioles of
the glomerulus

Inflammatory mediators
(TNF-, IL-18)
Endothelial injury
Endothelial
ICAM-1 and P-selectin

Increased sensitivity
to vasoconstrictor
and renal nerve
stimulation; impaired
autoregulation

NO derived
from eNOS

ET

PGs

Neutrophil adhesion

Oxygen radicals

GFR
Vascular factors contributing to the pathogenesis of ischemic ARF.
ET, endothelin; PG, protaglandin.
Schrier RW, 2004; J Clin Invest. 114:5

Hypoxia / Ischemia

Caspase-3

Free cytosolic Ca2+

Calpastatin

Calpain

Caspase-1

Calpain

IL-18

Proximal tubular injury

Hipoxic/ischemic proximal tubular necrosis results in activation of cysteine
protease pathways involving calpains and both caspase-1 (an inflammatory
caspase) and caspase-3 (and executioner caspase involved in apoptosis
Schrier RW, 2004; J Clin Invest. 114:5

Renal Ischemia
Tubular effects
Intracellular calcium
NO from iNOS

Calpain, cPLA2,
actin breakdown

Caspases
Metalloproteinases
Deficient HSP

Cytoskeletal disruption

Altered gene response

cPLA2

Basolateral Na+/K+-ATPase

Proximal Na+ reabsorption

Detachment of viable
and nonviable tubular cells
Aberrant RGD
Integrin-mediated
adhesion

Adhesion to
THP, fibronectin

Necrosis/apoptosis
Cast formation

Distal NaCl delivery to

macula densa

Tubular obstruction
Tubuloglomerular feedback

GFR

Schrier RW, 2004; J Clin Invest. 114:5

Effects of ischemia on renal tubules in the pathogenesis of ischemic ARF

Mechanism of ARF in acute obstruction

Acute
Increased
peristalsis

Decreased
peristalsis

Chronic
Atonic
hydronephrosis

(Hours)

Prostaglandin
E2
Increased
hydrostatic pressure

(Days)

Thromboxane
Increased
A2
hydrostatic pressure

GFR

Increased renal
blood flow

GFR

Decreased renal
blood flow

Clinical Symposia, 2000

MANAGEMENT OF ARF
A. Conservative management
1. Exclude reversible/treatable causes of ARF
2. Obtain and maintain euvolemic state
3. Attempt to establish a urine output if patients oligouric
4. Provide adequate nutrition
5. Minimize use of invasive lines and procedures
6. Monitor drug usage, carefully, and modify dosage or
interval appropriately
7. Monitor and treat for clinical and biochemical
complications
B. Active management
. Renal Replacement Therapy

URETIC AND RENAL VASODILATORS IN AR

?!

Controversy and still debated

Use of Diuretic and Renal vasodilators in ARF

1. success for converting an oligouric to an nonoligouric state
occurs when the duration of oliguric was brief
2. respond more readly to a continuous infusion rather than a
bolus of loop diuretic
3. a small controlled study suggest dopamine may be synergistic
with lop diuretic in conversion an oligouric to nonoligouric state
, but this issue still controversy
4. the complication rate of low-dose dopamine and continuous
infusion of loop diuretic appears to be low
Important : obstructive uropathy must be excluded
and prerenal factors corrected
Schrier, 2007

Other Pharmacologic Agents :

Inotropic support (norapenephrine)
Some studies suggest that in patients with septic shock,
norepinephrine induces a diuresis more effectively than
other vasoactive agents as dopamine
Atrial Natriuretic Peptide
No consistent evidence for a beneficial role of ANP in the
treatment of ARF
Insulin like growth factor 1
No beneficial effect

Nutritional support in ARF

The goal of nutritional support :
1. Restoration of metabolic homeostasis with
maintenance of fluid, electrolyte, and acid-base
balance
2. Preservation of lean body mass
3. Maximization of protein synthesis
4. Prevention of vitamin, mineral, and trace element
depletion

Recommendation of nutrition in ARF :

35 kcal/kg body weight/day
in sepsis, energy requirement can be increased by 25%
1,2 gm protein/kg body weight
ratio between glucose and fat 70/30
Careful attention to electrolyte (Potassium & Sodium )

RENAL REPLACEMENT THERAPY

The issues regarding renal replacement therapy in ARF
are currently the source of much debate and
investigations
when to start ?
what modality to use
how much is enough ?

When to start ?
earlier renal replacement therapy
prophylactic to keep BUN 90-100 mg/dl,
creatinine 9-10 mg/dl
Schier, 2007

Indications and criteria for initiating

renal replacement therapy in the intensive care unit
Bellomo R, Ronco C : Kidney int 1998;53 (66):S106-109
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.

Oliguria (urine output < 200 ml/12 hr)

Anuria/extreme oliguria (urine output < 50 ml/12 hr)
Hyperkalemia ([K+] > 6.5 mmol/liter)
Severe acidemia (pH < 7.1)
Azotemia (urea) > 30 mmol/liter)
Clinically significant organ (especially lung) edema
Uremic enchepalopathy
Uremic pericarditis
Uremic neuropathy/myopathy
Severe dysnatremia ([Na] > 160 or < 115 mmol/liter)
Hyperthermia/Hypothermia
Drug overdose with dialysable toxin

Indications
of dialysis

The presence of :
one of the above criteria is sufficient to initiate renal replacement therapy in a critically ill
patients
two of these criteria makes renal replacement urgent and mandatory.
combined derangements suggest initiation of renal replacement therapy even before the
above mentioned limits have been reached.

Dialysis modalities for acute renal failure

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

Adapted from 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.

The advantages and disadvantages of intermittent versus

continuous renal replacement therapies
ADVANTAGES

DISADVANTAGES

Intermittent
hemodialysis

Efficient and rapid removal of

volume and small molecules
Cost effective
Readily available

Central venous access required

Anticoagulation may be required
May not be tolerated by
hemodynamically unstable
patients

Continuous
hemofiltration

Excellent control of volume

enabling liberal use of
hyperalimentation, blood
products, etc.
Good removal of larger
molecules
Can be used in relatively
hypotensive patients

Central venous access required

Anticoagulation may be required
Labor intensive and expensive

Peritoneal dialysis

No need for anticoagulation

Cost-effective

Slow removal of uremic toxins

Risk of peritonitis
May be tolerated poorly in patients
with splanchnic hypo perfusion
Nephrology Secret, 2006

SUMMARY
ACUTE RENAL FAILURE (ARF)
A common critical condition with high mortality
No consensus in definition, lack of trial, and still lot
of debate
The classification depends on site of position and
etiology
Loss of autoregulation, vasoconstriction,
glomerulotubular damage, and inflammation is a main
pathogenesis
Some modality of treatments with a different result