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 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 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 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

Management of Hypotension and shock in AKI 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

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%) 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 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 4.3 Surgical 28.3 Metabolic/poisoning 0.0 4.3 Hepatic Gastrointestinal 4.3 Respiratory 10.9 Neurological 26.1 Cardiac 28.3 Sepsis/Septic Shock 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

Study period = January 2010- December 2010 Total No CAG = 111 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

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