Update in the management of AKI Professor Harun-Ur-Rashid PhD, FCPS, FRCP Chief Consultant,Nephrology and Founder President Kidney Foundation, Bangladsh.

Update in the management of AKI

Professor Harun-Ur-Rashid PhD, FCPS, FRCP

Chief Consultant,Nephrology

and

Founder President

Kidney Foundation, Bangladsh

Introduction

• AKI is a global problem and occurs in the community and in the hospital

• It is a predictor of immediate and long term adverse outcomes.

• World wide incidence of AKI is poorly known

Incidence of AKI around the world

• USA - 24 cases /1000 discharge

• Kuwait - 4 per 100,000 cases / year

• Nigeria - 12 per year in children

• North India - 20 cases / 1000 discharge

• Bangladesh -24 cases /1000 discharge

in a tertiary care hospital

Definition of ARF

• AKI is defined by an abrupt decrease in kidney function that includes but not limited to ARF.

• It is a broad clinical syndrome with various aetiologies

KDIGO,2012

History of ARF

• Ischaemia Renalis -by William Heberden in 1802.

• Acute Bright’s disease-William oslears 1909.

• ARF- Homer W. Smith, 1951

• A 27 year male ,with severe diarrhoea for 2 days

• BP 90/60,develop oliguria

• Serum Cr 272 micromol,K-2.6,Na-123

• In next 2 days, S.Cr jumped to 450

What is the diagnosis ?

Rifle criteria for diagnosis and classification of AKI

Class Serum creatinine of GFR Urine output

Risk Increase in serum creatinine x 1.5 or GFR decrease >25%

Less than 0.5ml/kg/h for more than 6 hours

Injury Serum creatinine x 2 or GFR decreased >50%

Less than 0.5 ml/kg per hour for more than 12 hours

Failure Serum creatinine x 3, or serum creatinine >4mg/dl (>354 μmol/l) with an acute rise >0.5 mg/dl (>44 μmol/l) or GFR decreased >75%

Less than 0.3 ml/kg/h for 24 hours or anuria for 12 hours

Loss Persistent acute renal failure-complete loss of kidney function >4 weeks

End-stage kidney disease

ESRD>3 months

Criteria for diagnosis of AKI

• Increase in Scr. by ≥ 0.3 mg/dl (≥26.5 μmol/L) within 48 hours.

or

• Increase in Scr. to >1.5 times baseline which is known or presumed to have occurred within the prior 7 days

or

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

AKIN,2007

Staging of AKI

Stages Sr Cr Urine Output

1 1.5-1.9 times baseline or

≥0.3mg/dl (26.5 (μmol/L)

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

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

3. 3.0 times baseline Or

Increasing in Sr Cr to ≥ 4.0 mg/dl (≥353.6 μmol/L

Or Initiation of RRT

<0.3ml/kg/h for ≥ 24 hours

Anuria for ≥12 hours

AKIN criteria,2007

Diagnosis of AKI, CKD and AKD

Functional criteria Structural criteria

AKI Increase in SCr by 50% within 7 days, OR No criteria

Increase in SCr by 0.3 mg/dl (26.5µmol/l)

within 2 days, OR Oliguria

CKD GFR <60 ml/min per 1.73m2 >3 months Kidney damage for

>3 months

AKD AKI, OR Kidney damage for

GFR <60ml/min per 1.73m2 for <3 months, OR <3 months

Decrease in GFR by ≥35% or increase in

SCr by >50% for <3 months

NKD GFR ≥60ml/min per 1.73 m2 Stable SCr No damage

Classification of AKI

• Pre-renal

• Renal

• Post-renal

Classification of AKI

Pre-renal Cause:

• Hypovolemic state i.e Gastroenteritis

• Low cardiac out-put state ie CCF

• Systemic vasodilatation ie sepsis

• D.I.C

• Renal vasoconstriction ie cyclosporine

• Impaired renal auto reguletory response ie ACE. ARB, COX

• Plants and toxin

Classification of AKI

Renal Cause:

• AGN/RPGN

• Interstitial nephropathy

Post renal :

• Renal Stone disease

• Other obstructive disease

Risk assessment of AKI

Factors that cause AKI:

• Sepsis

• Critical illness

• Circulatory shock

• Burns

• Trauma

• Cardiac and Non-cardiac Surgery

• Nephrotoxic drug

• Radio contrast agent

• Poisonous plants and animal

Factors that determine susceptibility of AKI

• De hydration or Volume Depletion

• Advanced age

• Presence of CKD

• Chronic Disease i.e. heart, lung, liver

• DM

• Cancer

• Anaemia

Biomarkers for early diagnosis of AKI

Biomarkers Associated Injury

• Cystatin –C Proximal tubular Injury

• KIM-1 Ischaemic and Nephrotoxin

• NGAL Ischaemic and Nephrotoxin

• Cytokine- Toxic and

IL6,8,18 Delayed graft function

• a-GST Proximal and distal T injury

&

n-GST

Evaluation and general management of patients with AKI

• Patients should evaluate promptly to determine the cause.

• Monitor the patients with Scr & urine output .

• Manage according to cause & stage of AKI

• Evaluate patients at 3 months for resolution or worsening of preexisting CKD.

Treatment and prevention of AKI

• Management of Specific cause

• Management of Hypotension and shock

• Treatment of infection

• Glycaemic control and nutrition support

• Use of diuretic

• Vasodilator therapy

• Growth factor intervention

• Role of Erythropoietin

• RRT

Management of Hypotenison and shock in AKI

Careful titration of fluid:

• ORS for children and infant

• IV isotonic Saline for adults

• 4% albumin Vs saline for ICU

• Hydroxyethyl Starch Vs Albumin for ICU

Bouchard J,MehtaRL,2010;Finfer et al, N Engl J Med,2004

Vasoachive medication:

• Non epinephrine, dopamine or vasopressin only after dehydration is corrected to maintain BP

-Useful in septic shock, burns, liver failure

-Not suitable for Cardiogenic shock

Marik,Intensive Care Med,2002;KellumJA,Decker J,2001

Management of Hypotension and shock in AKI

Glycaemic control and nutritional support in AKI

Tight glycaemic control :

• Pl. glucose -80-110 mg/dl• Total calorie intake -20-30 kcal/kg• Protein intake -0.8-1.0 g/ kg/day-

noncatabolic state -1.0-1.5 g/kg/day- Catabolic state

Van den Berghe et al,N Engl J Med,2001

Role of Diuretics in AKI

• No evidence to reduce incidence or severity of AKI

• Indicate only if patients are volume over loaded

• Diuretic only Convert oliguric to non oliguric

• It promote earlier diuresis but no effect on survival

Ho and Power;Anaesthesia,2010;Cantarovich et al,Am J Kid Dis,2004

Role of Vasodilator therapy in AKI

• Low dose dopamine – no benifit

• Fenoldopen – not useful

• Atrial natruretic peptide - not useful

Friedrich et al, Ann. Intern med,2005

Growth factor intervention in AKI

• Recombinant human IGF-1- Not useful

Hirscberg et al,Kid Int,1999

Role of EPO in the prevention of AKI

• Use of Erythropoetin in the Prevention of

AKI in ICU –Not Useful

Endre et al,Kid Int,2010

Role of RRT in AKI

• Indicated only if Acute and severe renal failure, volume over load, hyperkalema, acidosis & symptoms of uraemia

• Intermittent HD and CRRT- found equally effective

• SLED – combines both IHD and CRRT

Rabindranath et al,Syst. Review,2007;

Bagshaw et al,Crit Care Med,2008.

Role of PD Vs HD in AKI

• Optimum Treatment of AKI remain uncertain

• Studies looking at various therapeutic approach give different results

• Optimum dose of PD is uncertain

• Considered reasonable Treatment in Developing Countries

Karen Yeates,PDI,2012

Comparing PD and EBP for RRT

Variable Phu et al., 2002 (2) Reference Gabriel et al., 2009 (4)

George et al.,

2011 (12)

Country Vietnam Brazil India

Setting ICU Mostly ICU (77%) ICU

Patietns

Study group (n) 70 120 50

Mean age (years) 35.5 63.4 46.9

Sepsis (%) 31.4 44.5 38

PD technique

Exchanges Manual Cycler Manual

EBP technique

Type CVVH Daily intermittent HD CVVHDF

Mortality on PD [n/N(%)] 17/36 (47) 35/60 (58) 18/25 (72)

Mortality on EBP [n/N(%)] 5/34 (15) 32/60 (53) 21/25 (84)

AKI in ICU in a Tartiary Care Hospital

AKI in a ICU in a tartiary care hospital in Dhaka

• Study period = Jan 2010- Dec 2010

• Total No patients studied = 121

• No of AKI detected (RIFLE criteria) = 46(38%)

Mean age: 50±12 yrs.(Range 18-80 yrs;

M 72,F 49)

Alam B et al ,2011

Causes of AKI in ICU patients

Trauma

Surgical

Metabolic/poisoning

Hepatic

Gastrointestinal

Respiratory Neurological

Cardiac Sepsis/Septic Shock

4.3

28.3

0.0

4.3 4.3

10.9 26.1

28.3 45.7

Par cent

Severity of AKI as RIFLE criteria

no. %

• Risk - 23 19.0

• Injury -15 12.4

• Failure - 8 6.6

AKI following Coronary Angiography

AKI following Contrast during elective CAG and percutanious intervention

• Study period = January 2010- December 2010

Total No CAG = 111

Mean age =51.9± 9.6 yrs

• Non-ionic radio contrast agent used

• AKI detected in 13 (11.7%)

Alam M,et al,2011

Risk factors for contrast induced AKI:

• Diabetes mellitus• Pre-existing renal insufficiency • HTN• ACE/ARB/NSAIDs

• LVEF-40%• Dose of Contrast:

What are the precaution needed before doing CAG:

• Evaluate the risk : Baseline Sr Cr ≥115μmol in men and ≥88.4μmol in female

• Risk out weigh potential benefits – use contrast

• Use low –osmolar or iso-osmolor contrast and volume as low as possible

• Volume status be optimized before administration of contrast

Summary and Conclusion

• AKI is a global problem and is common, harmful and a treatable condition

• Etiological factors are rapidly changing all over the world

• Early diagnosis and appropriate management can improve the overall prognosis of AKI