Acute Kidney Injury

Dr. Michel HelmyMarketing Manager – Acute TherapiesSouth East Europe, Middle East & Africa

CRRT Workshop

AKIAcute Kidney Injury

AKIAKIAcute Kidney InjuryAcute Kidney Injury

© 2012 – Michel Helmy 2

Anatomy of the KidneyApproximately 1,200 ml of blood or 25 % of Cardiac Output flows through the kidney in one minute

Renal arteryand vein

Fibrous capsule Cortex

Pyramid (medulla)

Ureter

Pelvis

Deep inside the cortex and the medulla regions are long hairpin-like structures called nephrons, these are the functional urine producing unit of the kidney


The NephronThe urine producing part of the kidney

Distal tubule

Collecting ductLoop of Henle

Peritubularcapillaries

Proximal tubule

Bowman’s capsule

Glomerulus Afferent arteriole(wider)

Efferent arteriole(narrow)

There are one million Nephrons in each kidney

The efferent arteriole, which is narrower than the afferent arteriole, creating a hydrostatic pressure in glomerulus


Renal Function

Secretion of three different hormones:

SECRETORY FUNCTIONEXCRETORY FUNCTION

Renin: regulate blood pressure

Vitamin D: regulate calcium uptake

Excretion product of the kidney: urine

EPO: regulate red blood cell production

Remove excess fluid

Remove waste products

Regulate acid/base balance

Regulate electrolyte levels

Urea & Creatinine


ARF… Definition .

• Definition:• A clinical syndrome characterized by rapid reduction in renal excretory function

underpinned by variety of causes.

Serum creatinine & urine output should continue to be viewed as the best existing markers for AKI

• Acute kidney injury causes are generally divided into

• Pre-renal

• Renal (intrinsic)

• Post-renal

relative incidence of each of these is dependent on age, gender and clinical setting.

• Glomerular Filtration Rate is reduced ….decreased urine excretion• Nitrogenous wastes accumulates in the body (uremia)• Metabolic & electrolytes disturbances


Definition: AKI = ARF?

ARF = Acute Renal FailureAKI = Acute Kidney Injury

Intended to describe the entire spectrum of disease from being relatively mild to severe.

Defined as renal function inadequate to clear the waste products of metabolism despite the absence of correction of hemodynamic or mechanical causes.

Clinical manifestations of renal failure include the following:•Uremic symptoms (drowsiness, nausea, hiccough, twitching)•Hyperkalemia•Hyponatremia•Metabolic acidosis

Defined as an abrupt change in serum creatinine and/or urine

output and classified accordingthe RIFLE criteria


Definition of AKI2.1.1:2.1.1:

Acute kidney injury (AKI) is defined as any of the following (Not Graded):

• Increase in SCr by ≥ 0.3 mg/dl (≥ 26.5 µmol/l) within 48 hours;

OROR

• Increase in SCr to ≥ 1.5 times baseline, which is known orpresumed to have occurred within prior 7 days

OROR

• Urine volume <0.5 ml/kg/h for 6 hours


Conclusion: AKI is not ARF

As you have seen, the terms acute kidney injury (AKI) and acute renal failure (ARF) are not synonymous. While the term renal failure is best reserved for patients who have lost renal function to the point that life can no longer be sustained without intervention, AKI is used to describe the milder as well as severe forms of acute renal dysfunction in patients.

Let us have a deeper look at the classification of AKI…


Diagnosis ARFIf the cause of ARF is not apparent, a large amount of blood tests and examination of a urine specimen is typically performed.

• Urea in blood

• Creatinine in blood

• Urine analysis

• Urine volume output

• Ultrasound of kidneys

Conventional Units < 1.5 mg 10 - 20 mg/dl

International Units 50 - 100 μmol /L 2.6 - 6.8 mmol /L

Normal adult blood values Creatinine BUN (Blood Urea Nitrogen)

Acute Renal Failure


Diagnosis AKIIf the cause of ARF is not apparent, a large amount of blood tests and

examination of a urine specimen is typically performed.

• Urea in blood

• Creatinine in blood

• Urine analysis

• Urine volume output

• Ultrasound of kidneys

Normal adult blood values Conventional Units International Units

Creatinine < 1.5 mg 50 - 100 μmol /L

BUN (Blood Urea Nitrogen) 10 -20 mg 2.6 - 6.8 mmol /L

Creatinine Clearance 90 – 130 16 -26 mg/kg/24 hrs

GFR 120 ml/min 180 L/day


AKI … in the ICUs .

• An estimated 5–20% of critically ill patients experience an episode of AKI during the course of their illness

• AKI requiring RRT has been reported in 4·9% of all admissions to intensive-care units(10)

• Data from the Intensive Care National Audit Research Centre suggests that AKI accounts for nearly 10% of all ICU bed days (11).

• AKI is common in hospitalized patients and also has a poor prognosis.

• Non-ICU AKI, in which the kidney is usually the only failed organ, carries a mortality rate of up to 10% (12,13).

• ICU AKI is often associated with sepsis and with non-renal organ system failure (14), with mortality rates of over 50%. These rates rise to 80% when RRT is required (15). Predictably, death rates increase with an increasing number of failing organ systems but over 65% of survivors recover renal function and discontinue RRT(1).

• AKI in ICUs is often only one facet of MOF, and frequently results from systemic inflammatory reaction or sepsis.


Incidence ARF Study

• Close to 30.000 patients were studied• Sept. 2000 to December 2001• 54 hospitals in 23 countries

Conclusion: The period prevalence of ARF requiring RRT ibetween 5% -Hospital m

JAMA

n ICU was 6 % and was associated with high

ortality rate.

2005; 294:813-818


Incidence of ARF Publication

This article states:Acute renal failure complicates the course of 7 - 23 % of patients in the Intensive Care Unit

Referring to publications 1 -4 in the reference list

Intensive Care in Nephrology (Taylor & Francis Group - 2005) Pages 99-111


Incidence of ARF in US. Publication

This publication states:The annual incidence of community-acquired ARF is approximately 100 case per 1 mdiagnosed in only 1% o sentation. On the other hand, hospital-acqu any as 4% of hospital adadPublished on

illion population, and it is f hospital admissions at pre

ired ARF occurs in as mmissions and 20% of critical care

missionswww.emedicine.com

Author: Richard Sinert, DO AProfessor of MCoauthor(s): Peter R. Peacock,

University of New York Health

ssociate Professor of Emergency Medicine, Clinical Assistant edicine, State University of New York College of Medicine;

Jr, MD Assistant Professor of Emergency Medicine, State

Sciences Center at Brooklyn,

http://www.emedicine.com/


Traditional classification of ARF

Pre-renal ARF Post-renal ARFIntrinsic-renal ARF

The causes of ARF are traditionally divided into three categories. Although this division is useful for classification, all three categories may occur simultaneously in a given patient. ARF is a complication that can occur following any medical condition. It can result from pre-renal causes, intrinsic renal causes or post-renal causes.

Acute Renal Failure


Pre-renal ARF

Kidney hypoperfusion (reduced blood supply) results in both renal ischemia (reduced supply of oxygenated blood) and low GFR

By far the most commonly type of ARF seen in ICU

Common causes:• intravascular volume depletion

dehydration, hemorrhage

• decreased cardiac outputcongestive heart failure, infarct

• systemic vasodilatation(dilation of blood vessels)anaphylactic shock, sepsis

Acute Renal Failure


Intrinsic ARF

Possible causes:

• miscellaneous renal diseases

• toxins

Necrosis (is Greek for dead) = death of cell and living tissueTubule is part of the Nephron, the urine forming part of the kidney

Acute Renal Failure

Intrinsic renal causes account for 35-40% of ARF cases. The causes of intrinsic renal failure are diseases or toxins causing damage of the small renal vessels and glomeruli, commonly resulting in acute tubular necrosis.


Post-renal ARF

Increased pressure on the Bowman’s capsule offers a resistance to normal filtration pressure, which causes an acute reduction in GFR

Cause:

acute obstruction of the flow of urine

Acute Renal Failure

Post-renal causes account only for about 5% of ARF cases. They are associated with acute obstruction of the flow of urine which can occurat any point in the urinary tract. The obstruction creates a back flow of urine in the kidney which results in an increased pressure on The Bowman’s capsule. The constant pressure offers a resistanceto the normal filtration pressure, which causes anacute reduction in GRF.


Causes of AKI

Volume-responsive AKI

Postoperative AKIHypotension

Sepsis-induced AKI

AKI is common in the critically ill, especially in patients with sepsis and other forms of systemic inflammation (e.g. major surgery, trauma, burns), but other causes must beconsidered. Let us look at the 4 most common causes first:

Now let’s go back to the concept of AKI!


• ADQI (Acute Dialysis Quality Initiative) is a process initiated by a group of physicians from different parts of the world, with the objective to seek consensus and evidence and establish guidelines towards AKI.

• They have proposed the RIFLE classification as a definition of AKI. RIFLE defines three grades of severity of ARF on the basis of either an acute increase in serum creatinine, decrease in GFR or decreased urine output.

•• ClassificationClassification

•• RRiskisk

•• IInjurynjury

•• FFailureailure

Outcome:Outcome:

•• LLossoss

•• EEndnd--stage renal diseasestage renal disease

AKI … Stages (RIFLE Criteria) .


Classification of AKI according to RIFLE criteriaRIFLE criteria

RIFLE defines three grades of severity of AKI on the basis of either:

• acute increase in serum creatinine

• decrease in GFR

• decreased urine output.

Second International Consensus Conference of the Acute Dialysis Quality Initiative (ADQI) Group. Crit Care. 2004

Gambro Acute Therapies supports the RIFLE definition of AKI

22

Staging of AKI2.1.2:2.1.2:AKI is staged for severity according to the following criteria (below). (Not Graded)

Stage Serum Creatinine Urine Output

1 1.5-1.9 times baseline OR≥0.3 mg/dl (≥ 26.5 µmol/l) increase

<0.5 ml/kg/h for 6-12 hours

2 2.0-2.9 times baseline <0.5 ml/kg/h for ≥12 hours

3 3.0 times baseline OR increase in serum creatinine to ≥4.0 mg/dl (≥ 353.6 µmol/l) OR initiation of renal replacement therapy OR, in patients <18 years, decrease in eGFR to <35 ml/min per 1.73 m2

<0.3 ml/kg/h for ≥ 24 hours OR Anuria for ≥12 hours


RIFLE criteria: Urine Output• Approximately 50-60% of AKI cases are non-oliguric• Patients may continue to make urine despite an inadequate glomerular

filtration• Although prognosis is often better if urine output is maintained, use of

diuretics to promote urine output does not seem to improve outcome (and some studies even suggests harm)

Anuria: <100 ml/24 hour

Oliguria: 100-400 ml/24 hour

Nonoliguria: >400 ml/24 hour

Definition

Now when do we talk of ‘Oliguria’? And when is a patient ‘non-oliguric’?


Initial treatment of AKIFocused on fluid management

1. Hypovolemia potentiates and exacerbates all forms of ARF

2. Reversal of hypovolemia by rapid fluid infusion can be sufficient to treat many forms of ARF

3. Rapid fluid infusion can result in life-threatening fluid overload

4. Urinary Catheter for measurement of Urine Output

5. Section 3 of the KDIGO Guideline addresses approaches to preventprogression of AKI. An important recommendation supported by 1B evidence is not to use diuretics to prevent AKInot to use diuretics to prevent AKI. This continues to be a first line therapy used by many physicians upon suspicion of AKI.

Challenging fluid management problems

2- Renal Replacement Therapy in AKI


Classification of RRT

RRT Dialysis Modalities

Intermittent Continuous

IHD SLEDD / EDD PD CRRT

PD is an intra-corporeal (inside the body) treatment all other modalities

are extra-corporeal (outside the body) treatments


Continuous renal replacement therapy (CRRT) has become the preferred treatment

of acute kidney injury

CRRT has been proven to be suitable in patients with hemodynamic instability in the intensive care setting and studies have confirmed its benefits with respect to solute and fluid removal.

History of AKI Management .

CRRT5%

peritonealdialysis

5%

intermittenthemodialysis

90%

CRRT27%

intermittenthemodialysis

73%

late 90’s

IHD10 to 20%

CRRT80 to 90%

3rd MillenniumARF in the ICUARF in the ICU mid 80’s


Outcomes of AKIOutcomes (or endpoints) regarding AKI can either be defined as a

measurement (i.e. serum creatinine) or an event (i.e. death or need for dialysis).

Some of these endpoints are:

Survival / Mortality

Recovery of Renal Function

Economic Analysis

Morbidity


Can be defined as lack of need for Renal Replacement Therapy. Therefore it is importantto know when a kidney has recovered completelyor partial.Let us see how this works!


Renal Recovery: How to define?Complete recovery:Return to near baseline GFR

Partial recovery:Failure to return to baselinebut without the need for chronicrenal replacement

Complete Renal Recovery is defined when:Serum Creatinine (SCrt) is not more than 50% increased from baseline

example: if baseline SCrt is 1 mg/dL (88 mmol/L) complete recovery is said to occur if the new steady state SCrt is <1.5 mg/dL (133 mmol/L)

Partial Renal Recovery is defined when:The above condition for complete recovery is not met but the patient does

not require chronic dialysis (i.e. renal ‘loss’ has not occurred)


Acute Kidney Injury

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