Acute Kidney Injury

Dr. Amit AgarwalMD, FIPNA,FISPN (AIIMS)

Consultant Pediatric Nephrologist

Acute Kidney Injury

Acute renal failure

Sudden loss of renal function, over hr-days, with

deranged fluid balance, acid base & electrolytes

Detect early AKI

Avoid nephrotoxic agents; prevent further injury

Fluid overload predicts mortality

Associated with prolonged hospital stay

KDIGO Clinical Practice Guidelines for Acute Kidney Injury: Kidney International 2012

Serum creatinine vs. Urine output

Serum creatinine: pitfalls

Varies: age, gender, muscle

Rises after 50% function lost

Tubular secretion

overestimates function

AKI: does not depict

function immediately

Methods of estimation

Easily dialyzed

Urine output is important

Duration & episodes

have prognostic value

Enables early diagnosis

Improves management

Useful chiefly in PICU

Canary in the coal mine

Factors affecting Creatinine

Emphasis on early recognition

Increase in Cr by ≥0.3 mg/dl within 48 hr

Increase in Cr to ≥1.5 times baseline, known or presumed to have occurred within prior 7 d

Urine volume <0.5 ml/kg/hr for 6 hr

Any of the following

Conceptual model for AKI

Clin J Am Soc Nephrol 2008; 3: 864–868

Severity of AKI determines outcome

AKI affects PICU mortalityNat Rev Nephrol 2010;6:393

RIFLE & stepwise increase in mortality KI 2008; 73, 538–546

24 studies (2004-07); 71000 patients

AKI level RR [95% CI] mortality

Risk 2.40 [1.9, 3.0]

Injury 4.15 [3.1, 5.5]

Failure 6.37 [5.1, 7.9] P <0.0001; vs. non-AKI

Distant effects of AKIDisrupted BBB

IL-6 mediated

Changes in

Organ function

Vascular inflammation

Cellular apoptosis

Transporter activity

Transcriptional changes

Oxidative stress

Etiology of AKI (%)

1972-79 N=142

1981-88 N=205

1991-2005 N=266

Diarrhea 35 17 10

HUS - 36 24

Infections 25 19 38

GN 30 13 8

Obstruction 3 3 6

Causes vary with age; determine mortality

Incident AKI 15%

AKI @ admission 5.5%

HUS

Septicemia

Rapidly progressive GN

Dehydration

2008N=514 screened

Indian J Pediatr 1980,17:405; Indian J Med Res 1990,92:404

Indian Pediatr 2012;49: 537-42

March 2008; 4:138-53

Developed nations: AKI chiefly in ICU; older kids; multiorgan failure & sepsis; high mortality

Developing world: AKI in the young; single diseases [gastroenteritis, malaria, sepsis, leptospirosis, HUS, enzyme deficiencies]

Evaluation

Blood counts

Urea, creatinine, electrolytes, calcium, phosphate

Blood pH, bicarbonate

Urinalysis; sodium, osmolality, fractional excretion Na

Chest X-ray; ECG

Abdominal ultrasonography

Determine etiology

HUS: Smear, platelets, reticulocytes, LDH; C3; shigatoxin

GN: ASO, C3, ANA, ANCA

Thrombosis: Doppler ultrasonography

Renal biopsy

Urinalysis provides critical information

Fluids in sepsis: Avoid early under treatment; late overload

Early goal directed therapy: prevents AKI

Saline & albumin as good

Hexastarch & AKI

Persistent overload:hypoxia, ARDS

Judicious fluid removal

EGDT (6 hr of dx)

MAP >65 mm Hg

CVP 8-12 mm

Venous saturation 80%

Urine output >0.5 ml/kg/h

Surviving Sepsis Campaign. Crit Care Med 2004;32:858Management of sepsis. N Engl J Med 2006;355:1699

Prevent nephrotoxicity

Aminoglycosides

Use suitable, less nephrotoxic alternatives

Administer as single dose daily regimen

Drug levels if multiple doses or single-daily dose for >48-hr

Use topical or local route, when feasible

Amphotericin

Use lipid formulations rather than conventional

Azoles and/or echinocandins, if equal efficacy assumed

Dose modification in renal failure

Prevent contrast nephropathy

High- ∼2000 mOsm/kg

Low- 600-800

Iso-osmolal 290; less toxic

Minimum contrast volume

Saline/bicarbonate based @ 1.0 ml/kg/h for 3–12 h before & 6–24 h after contrast exposure

Urine output (1.5 ml/kg/h)

Frusemide: Not associated with benefits for prevention

& treatment of AKI

Do not improve survival, recovery of renal function

Loop diuretics for AKI

Recommend not using diuretics to prevent AKI

Suggest not using diuretics to treat AKI, except for volume overload

Suggest not using diuretics to enhance recovery, or reduce duration or frequency of RRT

High doses: Ototoxicity

Renal vasodilators

Low dose Dopamine

Increases RBF & GFR

Does not prevent/alter course

Tachycardia, myocardial &

tissue ischemia

No role in preventing AKI

Fenoldopam

Reduced RRT (OR 0.4); mortality (OR 0.5)

Lower creatinine; less AKI [than dopamine]

Recommend not using dopamine to prevent or treat AKI (1A)

Suggest not using fenoldopam to prevent or treat AKI (2C)

Meta-analysis. Ann Intern Med 2005;142:510The myth. JAPI 2002; 50: 571–575

Meta-analysis. J Cardiothor Vasc Anesth 2008;22: 27

Blinded RCT. Crit Care Med 2005; 33: 2451

Fenoldopam vs. dopamine. Crit Care Med 2006;34:707

Suggest not using atrial natriuretic peptide

Maintaining nutrition: a challenge

Intake >20–30 kcal/kg/d

Avoid restricting proteins to prevent/delay RRT

Administering protein @

0.8–1.0 g/kg/d in patients not on dialysis

1.0–1.5 g/kg/d in patients with AKI on RRT

1.0-1.7 g/kg/d in those on CRRT, hypercatabolic

Nutrition preferably by enteral route

High catabolism & energy needs; dialysis losses

Begin renal replacement therapy early

Uremia

Late initiation urea >150: risk of dying

CJASN 2006;5:915

CVVH dosing requirementsEarly initiation: better outcomeLancet 2000; 356:26

Fluid overload

116 patients; 39% sepsis

<20% overload: 59% survival

>20% overload: 40% survival P<0.002

PRISM similarGoldstein, ppCRRT. KI 2005; 67: 653

Fluid overload >15%Independent risk factor for mortality

Fluid overload = fluid in (L) – fluid out (L) x 100weight @ admission (kg)

Manage complications & plan dialysis

Fluid overload

Pulmonary edema

Hypertension

Metabolic acidosis

Hyperkalemia

Hyponatremia

Severe anemia

Hyperphosphatemia

Initiate RRT emergently if life-threatening fluid,

electrolyte and acid-base imbalance exist

Consider broad clinical context, the presence of

conditions that can be modified with RRT & trends of

laboratory tests — when making the decision to start

RRT

Early initiation of dialysis

Intermittent vs. continuous therapies

RRT: Cost & expertise

Peritoneal dialysis: Continuous solute & fluid clearance

Less expertise, equipment

Surgically placed Tenckhoff, short-term catheters

Stiff catheters still used

Successful in most

Not efficient: severe fluid overload, lactic acidosis

Pulmonary compromise; abdominal surgery

Manual PD: labor intensive

If done correctly, PD achieves adequate solute & water clearances

Hemodialysis: Rapid ultrafiltration & solute removal

Technical expertise

HD machines, dialyzers

Access: internal jugular; femoral vein

Heparin, saline HD

Ultrafiltration (UF)

Dialysis disequilibrium

Phosphate depletion

Hypotension limits UF

Membrane biocompatibility

CRRT: continuous & predictable ultrafiltration & solute clearance

Trained personnel

Heparin, regional citrate

Prime extracorporeal circuit

High UF; enables dietary intakes

Hemodynamic instability, organ dysfunction, sepsis

Blood pump rate 3-5 ml/kg/min

UF rate: 35-50 ml/kg/h [2 l/h/1.73 m2]

http://www.pcrrt.com/index.html

Choice of RRT depends onclinical features & local expertise

Peritoneal dialysis: prefer if isolated ARF;

universally available

Hemodialysis: efficient; nursing expertise

Hemofiltration: increasingly used in PICU;

enables nutrition; risks of bleeding

Hemodynamically stable: Intermittent therapies are as good

Hemodynamically unstable: CRRT is mode of choice

Patients with AKI need follow up

Evaluate patients @ 3-mo after AKI

Manage CKD as per guidelines

Consider patients without CKD as being @ increased risk

Children should not die of AKI

Recognize patients @ risk; maintain volume, perfusion

Discontinue nephrotoxic agents; avoid radiocontrast

Dosage of most medications will change

Limited role of pharmacological interventions

Prompt renal replacement (not mode, nor dose)

determines outcome

Need prolonged follow up

Do what you do well and improve the care

of patients with AKI …. Tim Bunchman

0 By 25

• Thousands of people are still dying in vain of AKI, especially in less developed or emerging countries. AKI should no longer be a death sentence for these people. Nobody should die of preventable and treatable Acute Kidney Injury (AKI) by 2025!

G. Remuzzi, ISN President

Goals

• To address the current lack of data on the global burden of AKI, especially in low and middle-income countries. We hope to establish AKI as a contributor to the Global Burden of Disease

• To raise awareness of AKI across the global healthcare community including among healthcare professionals, patients and, more widely, among governments and public health institutions and the private sector

• To contribute to developing a sustainable infrastructure by implementing “need driven” approaches in selected areas for education and training and care delivery