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Acute Kidney Injury

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.

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Acute Kidney Injury

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  1. Acute Kidney Injury Michael Clarkson Department of Renal Medicine Cork University Hospital

  2. “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.

  3. Terminology Acute Renal Failure (ARF) Acute Kidney Injury (AKI) Acute Tubular Necrosis (ATN)

  4. 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 AKI for the General Physician

  5. R.I.F.L.E. • R ISK • I NJURY • F AILURE • L OSS • E SKD

  6. 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

  7. AKI Network Definition

  8. 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.

  9. Consequences of AKI • Acute metabolic complications • Acute cardiovascular complications • Prolonged hospitalisation • Resource consumption • Patient Death Common • ESKD Uncommon

  10. Epidemiology

  11. Madrid Acute Renal Failure StudyLiano F; Pascual J. Kidney Int 1996; 50: 811-8 • Prospective, multi-centre, community-based • 9 month period • Creatinine >177mol/L • 13 hospitals (4.2 million aged >14yrs) 209(195,223) cases pmp 48% normal function at admission 36% received RRT 45% hospital mortality

  12. What kind of AKI? (Madrid Study)

  13. 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

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

  15. 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

  16. 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.

  17. 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%

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

  19. Treatment

  20. How should AKI be treated..? • General therapy • Prevention • Specific therapy • RRT

  21. 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

  22. 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

  23. Rayner HC.A model undergraduate core curriculum in adult renal medicine.Med Teacher 1995; 17:409–2. • CVP / fluid status • Urinalysis • Ultrasound

  24. 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.)

  25. Prevention of AKI

  26. 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

  27. Which fluid? Crystaloid vs. Colloid

  28. 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.

  29. 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

  30. 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!

  31. 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 230mol/L on admission. • Defined hemodynamic targets: • MAP > 65mmHg, • CVP 10-12, • Urine output>0.5mls/kg/hr, • ScvO2>70%). • Significant decrease in mortality.

  32. Renal Replacement Therapy

  33. Please, Sir…..what’s the prescription….? 1. Remove the bad stuff 2. Leave the good stuff 3. Don’t be too rough 4. Don’t keep clotting 5. Don’t keep bleeding 6. Don’t be too expensive 7. Don’t be too complicated

  34. Some Physics (the fundamentals) Haemodialysis Solute removal by Diffusion Haemofiltration Solute removal by Convection

  35. Diffusion Haemodialysis Fast Sometimes not well tolerated Small molecules Clearance of drugs variable Requires dialysis expertise Convection Haemofiltration Slow Usually well tolerated Medium-sized molecules Clearance of most drugs Can be ‘run’ with less knowledge/expertise More expensive !!!!!!!!!!!!! What kind of RRT…….?

  36. 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.

  37. 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)

  38. 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)

  39. 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

  40. Renal Replacement Therapy • How much? • How often?

  41. Specific therapies for ATN • Diuretics • Dopamine / Fenoldopam • ANP / ANP analogues • Growth factors AKI for the General Physician

  42. 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.

  43. 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)

  44. Diuretics in AKI • Diuretics are not nephrotoxic • Doctors prescribing habits are nephrotoxic!

  45. 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 0.55-1.24 Power for >50% effect on AKI/RRT Kellum JA, Decker JM.Use of dopamine in acute renal failure: a meta-analysis.Crit Care Med 2001; 29: 1526-31.

  46. Renal-dose dopamine: from hypothesis to paradigm to dogma to myth and, finally, superstition? • Jones D, Bellomo R • J Intensive Care Med 2005;20: 247-8 AKI for the General Physician

  47. 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

  48. Is there hope……………?

  49. 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

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