October 2010 Acute Kidney Injury Michael Clarkson Department of Renal Medicine Cork University...

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October 2010 Acute Kidney Injury Michael Clarkson Department of Renal Medicine Cork University Hospital

Transcript of October 2010 Acute Kidney Injury Michael Clarkson Department of Renal Medicine Cork University...

Page 1: October 2010 Acute Kidney Injury Michael Clarkson Department of Renal Medicine Cork University Hospital.

October 2010

Acute Kidney Injury

Michael Clarkson

Department of Renal Medicine

Cork University Hospital

Page 2: October 2010 Acute Kidney Injury Michael Clarkson Department of Renal Medicine Cork University Hospital.

“Acute Renal Failure” Syndrome is not dichotomous Dynamic process

initiation, maintenance and recovery phases. Undue emphasis on whether or not renal

function has overtly failed. Minor decrements in glomerular filtration

associated with adverse clinical outcomes.

October 2010

Page 3: October 2010 Acute Kidney Injury Michael Clarkson Department of Renal Medicine Cork University Hospital.

October 2010

Terminology

Acute Renal Failure (ARF)

Acute Kidney Injury (AKI)

Acute Tubular Necrosis (ATN)

Page 4: October 2010 Acute Kidney Injury Michael Clarkson Department of Renal Medicine Cork University Hospital.

May 2007 AKI for the General Physician

Bellomo R, Ronco C, Mehta RL, Palevsky P; ADQI workgroup. Acute renal failure - definition, outcome measures, animal models, fluid therapy and information technology needs: the Second International Consensus Conference of the Acute Dialysis Quality Initiative (ADQI) Group. Crit Care 2004; 8:R204-12.

www.ADQI.net

Page 5: October 2010 Acute Kidney Injury Michael Clarkson Department of Renal Medicine Cork University Hospital.

R.I.F.L.E. R ISK

I NJURY

F AILURE

L OSS

E SKD

October 2010

Page 6: October 2010 Acute Kidney Injury Michael Clarkson Department of Renal Medicine Cork University Hospital.

Levels for definition R [Creat] x 1.5 <0.5 ml/kg/h x 6h

I [Creat] x 2.0 <0.5 ml/kg/hr x 12h

F [Creat] x 3.0 <0.3 ml/kg/hr x 24h [Creat] > 350 umol/l anuria x 12h

L complete loss of function > 4 weeks

E End Stage Kidney Disease > 13 weeks

October 2010

Page 7: October 2010 Acute Kidney Injury Michael Clarkson Department of Renal Medicine Cork University Hospital.

AKI Network Definition

AKI stage  Creatinine criteria  Urine output criteria

 I

↑ by >/= 25 µmol/L or ↑ to >/= 150% – 200%

Urine output < 0.5 ml/kg/hour for > 6 hours

II ↑ > 200% – 300% from baseline

Urine output < 0.5 ml/kg/hour for > 12 hours

III ↑> 300% or Creat>/= 350 µmol/L after a rise of at least 50µmol/Lor RRT

Urine output < 0.3 ml/kg/hour for > 24 hours or anuria for 12 hours

Page 8: October 2010 Acute Kidney Injury Michael Clarkson Department of Renal Medicine Cork University Hospital.

October 2010

RIFLE Criteria - Validity The outcome of acute renal failure in the intensive

care unit according to RIFLE: model application, sensitivity, and predictability. Abousaif et al. AJKD 2005.

RIFLE criteria for acute kidney injury are associated with hospital mortality in critically ill patients: a cohort analysis. Hoste et al. Crit Care 2005.

An assessment of the RIFLE criteria for acute renal failure in hospitalized patients. Uchino et al. Crit Care Med. 2006.

Page 9: October 2010 Acute Kidney Injury Michael Clarkson Department of Renal Medicine Cork University Hospital.

Consequences of AKI

Acute metabolic complications Acute cardiovascular complications Prolonged hospitalisation Resource consumption

Patient Death Common ESKD Uncommon

October 2010

Page 10: October 2010 Acute Kidney Injury Michael Clarkson Department of Renal Medicine Cork University Hospital.

Epidemiology

October 2010

Page 11: October 2010 Acute Kidney Injury Michael Clarkson Department of Renal Medicine Cork University Hospital.

Madrid Acute Renal Failure StudyLiano F; Pascual J. Kidney Int 1996; 50: 811-8

Prospective, multi-centre, community-based 9 month period Creatinine >177mol/L 13 hospitals (4.2 million aged >14yrs)

209(195,223) cases pmp48% normal function at admission36% received RRT45% hospital mortality

October 2010

Page 12: October 2010 Acute Kidney Injury Michael Clarkson Department of Renal Medicine Cork University Hospital.

What kind of AKI? (Madrid Study)

0%10%20%30%40%50%60%70%80%90%

100%

ICU (n=253) Non-ICU (n=495)

Other

Atheroemboli

GN

AIN

Obstruction

Acute-on- Chronic

PreRenal

ATN

October 2010

Page 13: October 2010 Acute Kidney Injury Michael Clarkson Department of Renal Medicine Cork University Hospital.

Uchino S, Kellum JA, Bellomo R, et al. Acute Renal Failure in Critically Ill Patients: A Multinational Multicentre StudyJAMA 2005;294: 813-818.

BEST Kidney Investigators

54 Study Centres, 23 Countries, 15 months ~30 000 ICU admissions

5.5 to 6.0% AKI (<200ml/12h; [urea]>30mmol/l) 4.0 to 4.4% RRT (80% CRRT)

30% pre-existing renal dysfunction

October 2010

Page 14: October 2010 Acute Kidney Injury Michael Clarkson Department of Renal Medicine Cork University Hospital.

Uchino S, Kellum JA, Bellomo R, et al. Acute Renal Failure in Critically Ill Patients: A Multinational Multicentre StudyJAMA 2005;294: 813-818.

58.9

13 11.3 10.1 10

41.1

23.2

11.4

0

10

20

30

40

50

60

70

%

MedicalRespiratoryCardiovascularGastrointestinalSepsisSurgicalCardiovascularGI Tract

October 2010

Page 15: October 2010 Acute Kidney Injury Michael Clarkson Department of Renal Medicine Cork University Hospital.

Uchino S, Kellum JA, Bellomo R, et al. Acute Renal Failure in Critically Ill Patients: A Multinational Multicentre StudyJAMA 2005;294: 813-818.

ICU mortality 52% Subsequent hospital mortality 8%

Total mortality 58-62.5% SAPS-II predicted 45.6%

Independent of dialysis 83.7-88.8%

Septic shock, vasopressors, mechanical ventilation, HRS

October 2010

Page 16: October 2010 Acute Kidney Injury Michael Clarkson Department of Renal Medicine Cork University Hospital.

Nash K, Hafeez A, Hou S.Hospital-Acquired Renal Insufficiency.AJKD 2002;39(5): 930-6

4622 consecutive patients. Tertiary Referral Hospital.

AKI 7.2%

Risk Factors: CKD, Age, Race.

October 2010

Page 17: October 2010 Acute Kidney Injury Michael Clarkson Department of Renal Medicine Cork University Hospital.

Nash K, Hafeez A, Hou S.Hospital-Acquired Renal Insufficiency.AJKD 2002;39(5): 930-6

Causal Factors Renal Hypoperfusion

ECV, CHF, BP Medications / Contrast / Post-op / Sepsis / Non-renal Tx

Medications Aminoglycosides>NSAID>Pip-Tazo>Ampho>SMX-

TMP>Cya

Outcome Complete recovery 38%, Death 20%, HD 4%, CKD 38%

October 2010

Page 18: October 2010 Acute Kidney Injury Michael Clarkson Department of Renal Medicine Cork University Hospital.

Causes of Severe AKI Feest TG, Mistry CD, Grimes DS, Mallick NP.(from RA Study on Incidence of CRF)

36

14 1310 9

0

10

20

30

40

Obstruction Surgical Cardiovascular Sepsis ECF Depletion

% o

f ca

ses

October 2010

Page 19: October 2010 Acute Kidney Injury Michael Clarkson Department of Renal Medicine Cork University Hospital.

Treatment

October 2010

Page 20: October 2010 Acute Kidney Injury Michael Clarkson Department of Renal Medicine Cork University Hospital.

How should AKI be treated..?

General therapy

Prevention

Specific therapy

RRT

October 2010

Page 21: October 2010 Acute Kidney Injury Michael Clarkson Department of Renal Medicine Cork University Hospital.

How should AKI be treated..?

General Measures Discontinue offending agents Avoid nephrotoxins if possible Forensic attention to current / previous

Rx Meticulous attention to assessment of

ECV status

October 2010

Page 22: October 2010 Acute Kidney Injury Michael Clarkson Department of Renal Medicine Cork University Hospital.

P.E. Stevens, et al. Non-specialist management of acute renal failure. QJM 2001; 94: 533-40

East Kent (593 000) 12 month prospective study 486 cases p.m.p. [Creat]>300umol/l

Focus on initial assessment/management

October 2010

Page 23: October 2010 Acute Kidney Injury Michael Clarkson Department of Renal Medicine Cork University Hospital.

Rayner HC. A model undergraduate core curriculum in adult renal medicine. Med Teacher 1995; 17:409–2.

CVP / fluid status

Urinalysis

Ultrasound

36 month survival

0

10

20

30

40

50

%

3 assmt2 assmt1 assmt0 assmt

October 2010

Page 24: October 2010 Acute Kidney Injury Michael Clarkson Department of Renal Medicine Cork University Hospital.

AKI – Minimum Data Set Serial assessment / record of ECV status Renal profile, Ca2+, PO4-, ABG Urinalysis / urine output Nephrotoxic medication review Renal Ultrasound

Focused investigations (vasculitis, myeloma, uric acid, CPK etc.)

October 2010

Page 25: October 2010 Acute Kidney Injury Michael Clarkson Department of Renal Medicine Cork University Hospital.

Prevention of AKI

Page 26: October 2010 Acute Kidney Injury Michael Clarkson Department of Renal Medicine Cork University Hospital.

Prevention of AKI

Optimisation of ECV is single most important manoeuvre

Volume depletion is risk factor for AKI in multiple clinical situations

Endogenous Toxins Myoglobin Light chains Uric Acid

Exogenous Toxins Radiocontrast Aminoglycosides Cisplatin

October 2010

Page 27: October 2010 Acute Kidney Injury Michael Clarkson Department of Renal Medicine Cork University Hospital.

Which fluid?

Crystaloid vs. Colloid

Page 28: October 2010 Acute Kidney Injury Michael Clarkson Department of Renal Medicine Cork University Hospital.

Schierhout G et al. Fluid resuscitation with colloid or crystalloid solutions in critically ill patients: a systematic review of randomized trials. BMJ 1998;316:961-4.

37 RCTS 26 colloids vs. crystalloids (n = 1622). 10 colloid in hypertonic crystalloid vs. isotonic

crystalloid (n = 1422) 1 colloid in isotonic crystalloid with hypertonic

crystalloid (n = 38) Mortality RR 1.19 (0.98-1.45) No benefit from colloid Cost more.

October 2010

Page 29: October 2010 Acute Kidney Injury Michael Clarkson Department of Renal Medicine Cork University Hospital.

Finfer S et al. A comparison of albumin and saline for fluid resuscitation in the intensive care unit. N Engl J Med 2004;350:2247-56.

Saline versus Albumin Fluid Evaluation (SAFE) Study 16 ICUs in Australia and New Zealand. n=6997 4% Albumin vs. 0.9% NaCl

Outcomes: 28 Day Mortality RR 0.99 (0.91-1.09)

Days of RRT: Not significant

October 2010

Page 30: October 2010 Acute Kidney Injury Michael Clarkson Department of Renal Medicine Cork University Hospital.

Schortgen, F et al. Effects of hydroxyethylstarch and gelatin on renal function in severe sepsis: a multicentre randomised study. Lancet 2001;357:911-16.

6% hydroxyethylstarch or 3% fluid-modified gelatin. RCT, n=129

Acute renal failure RR 2·32 (CI 1·02–5·34).

6% hydroxyethylstarch is an independent risk factor for development of AKI

Do not use!

October 2010

Page 31: October 2010 Acute Kidney Injury Michael Clarkson Department of Renal Medicine Cork University Hospital.

Rivers E, et al. Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med 2001;345:1368-77

‘Goal-directed’ resuscitation in sepsis.

Mean creatinine 230mol/L on admission.

Defined hemodynamic targets: MAP > 65mmHg, CVP 10-12, Urine output>0.5mls/kg/hr, ScvO2>70%).

Significant decrease in mortality.

October 2010

Page 32: October 2010 Acute Kidney Injury Michael Clarkson Department of Renal Medicine Cork University Hospital.

Renal Replacement Therapy

October 2010

Page 33: October 2010 Acute Kidney Injury Michael Clarkson Department of Renal Medicine Cork University Hospital.

Please, Sir…..what’s the prescription….?

1. Remove the bad stuff

2. Leave the good stuff3. Don’t be too rough4. Don’t keep clotting5. Don’t keep bleeding6. Don’t be too

expensive7. Don’t be too

complicated

October 2010

Page 34: October 2010 Acute Kidney Injury Michael Clarkson Department of Renal Medicine Cork University Hospital.

Some Physics (the fundamentals)

Haemodialysis

Solute removal by

Diffusion

Haemofiltration

Solute removal by

Convection

October 2010

Page 35: October 2010 Acute Kidney Injury Michael Clarkson Department of Renal Medicine Cork University Hospital.

What kind of RRT…….?

Diffusion

Haemodialysis

FastSometimes not well toleratedSmall moleculesClearance of drugs variableRequires dialysis expertise

Convection

Haemofiltration

SlowUsually well toleratedMedium-sized moleculesClearance of most drugsCan be ‘run’ with less

knowledge/expertiseMore expensive !!!!!!!!!!!!!

October 2010

Page 36: October 2010 Acute Kidney Injury Michael Clarkson Department of Renal Medicine Cork University Hospital.

Intermittant HD vs. CRRT Swartz, et al.

Comparing continuous haemofiltration with hemodialysis in patients with severe acute renal failure.Am J Kidney Dis 1999; 34: 424-32

Mehta, et al. A randomized clinical trial of continuous versus intermittent dialysis for acute renal failure. Kidney Int 2001; 60:1154-63.

Uehlinger, et al. Comparison of continuous and intermittent renal replacement therapy for acute renal failure. Nephrol Dial Transplant 2005;20:1630-7.

October 2010

Page 37: October 2010 Acute Kidney Injury Michael Clarkson Department of Renal Medicine Cork University Hospital.

Tonelli, et al. Acute renal failure in the intensive care unit: a systematic review of the impact of dialytic modality on mortality and renal recovery. Am J Kidney Dis 2002;40:875-85

6 RCTs CRRT vs. HD N=624

• Mortality RR 0.96 (0.85-1.05)• Renal death RR 1.02 (0.85-1.08)• ESKD RR 1.02 (0.89-1.17)

October 2010

Page 38: October 2010 Acute Kidney Injury Michael Clarkson Department of Renal Medicine Cork University Hospital.

Kellum JA, et al. Continuous versus intermittent renal replacement therapy: a meta-analysis.Intensive Care Med 2002; 28: 29-37

Randomised & Observational Studies CRRT v HD Primary end-point RR cumulative mortality 13 studies (3 randomised) – 1400 patients Poor quality – only 6 corrected for severity

Overall RR 0.93 (0.79, 1.09) Adjusted for quality RR 0.72 (0.60, 0.87) Similar severity RR 0.48 (0.34, 0.69)

October 2010

Page 39: October 2010 Acute Kidney Injury Michael Clarkson Department of Renal Medicine Cork University Hospital.

Renal Replacement Therapy Choice often dictated by…

Resources of the institution• CVVH not available

Technical expertise of the physician• Intensivist vs. nephrologist

Clinical status of the patient• Cerebral edema• Bleeding risk

October 2010

Page 40: October 2010 Acute Kidney Injury Michael Clarkson Department of Renal Medicine Cork University Hospital.

How much?

How often?

Renal Replacement Therapy

October 2010

Page 41: October 2010 Acute Kidney Injury Michael Clarkson Department of Renal Medicine Cork University Hospital.

May 2007 AKI for the General Physician

Specific therapies for ATN

Diuretics

Dopamine / Fenoldopam

ANP / ANP analogues

Growth factors

Page 42: October 2010 Acute Kidney Injury Michael Clarkson Department of Renal Medicine Cork University Hospital.

October 2010

Cantarovich F, et al. High-dose furosemide for established ARF: a prospective, randomized, double-blind, placebo-controlled, multicenter trial.Am J Kidney Dis. 2004; 44: 402-9.

338 AKI patients, stratified by severity 25mg/kg/day iv or 35mg/kg/day po v Placebo

Survival/renal recovery No difference 2litre diuresis achieved 57% v 33%

Mehta RL, et al; PICARD Study GroupDiuretics, mortality, and non-recovery of renal function in acute renal failure. JAMA 2002; 288: 2547-53.

Uchino S, et al; BEST Kidney Investigators Diuretics and mortality in acute renal failure. Crit Care Med 2004; 32: 1669-77.

Page 43: October 2010 Acute Kidney Injury Michael Clarkson Department of Renal Medicine Cork University Hospital.

Ho KM, Sheridan DJ. Meta-analysis of frusemide to prevent or treat acute renal failureBMJ 2006; 333:420.

9 RCTs

849 patients

In-hospital mortality, RRT, number of RRT treatments, persistent oliguria

No benefit

Deafness and tinnitus (RR 1.00,15.78)

October 2010

Page 44: October 2010 Acute Kidney Injury Michael Clarkson Department of Renal Medicine Cork University Hospital.

Diuretics in AKI Diuretics are not nephrotoxic

Doctors prescribing habits are nephrotoxic!

October 2010

Page 45: October 2010 Acute Kidney Injury Michael Clarkson Department of Renal Medicine Cork University Hospital.

Kellum JA, Decker JM.Use of dopamine in acute renal failure: a meta-analysis. Crit Care Med 2001; 29: 1526-31.

1966-2000 Prevention/Treatment

58 (n=2149) studies 24 (n=1019) outcome 17 (n= 854) RCT

Mortality 0.44-1.83

AKI 0.55-1.19

RRT 0.55-1.24Power for >50% effect on AKI/RRT

October 2010

Page 46: October 2010 Acute Kidney Injury Michael Clarkson Department of Renal Medicine Cork University Hospital.

May 2007 AKI for the General Physician

Renal-dose dopamine: from hypothesis to paradigm to dogma to myth and, finally, superstition?

Jones D, Bellomo RJ Intensive Care Med 2005;20: 247-8

Page 47: October 2010 Acute Kidney Injury Michael Clarkson Department of Renal Medicine Cork University Hospital.

Other Pharmacotherapies Recombinant Growth Factors

• Maybe good if you are small, white & furry with a long tail

• Not so good if you are anything else

Calcium Channel Blockers• No RCT suggest benefit• Risk hypotension

Theophyline• No RCT suggest clinically important benefit• Narrow therapeutic window

October 2010

Page 48: October 2010 Acute Kidney Injury Michael Clarkson Department of Renal Medicine Cork University Hospital.

October 2010

Is there hope……………?

Page 49: October 2010 Acute Kidney Injury Michael Clarkson Department of Renal Medicine Cork University Hospital.

October 2010

If I end up in your ICU with AKI………….

There is no pharmacologic treatment for established ATN

Excellence in generic supportive management

If you give me dopamine or thoughtlessly prescribed diuretics I’ll sue you

(I mean, haunt you………..)

Adequate dose CVVH

Intermittent HD only by an expert

My kidneys will get better if I do