Acute Kidney Injury. Dr S Mathavakkannan Consultant Nephrologist

Transcription

1 Acute Kidney Injury Dr S Mathavakkannan Consultant Nephrologist

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3 1. 2. Epidemiology 3. Physiology 4. Markers of Injury 5. Survival 6. Treatment 7. AKI Scope

4 1. ADQI 1. RIFLE Criteria 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; 2004 Risk (Class R) Injury (Class I) Failure (Class F)

5 Stra%fica%on Based on RIFLE RIFLE criteria for acute kidney injury are associated with hospital mortality in critically ill patients: a cohort analysis Hoste et al ; Critical Care 2006 (10) R73

6 Outcomes of all Patients based on RIFLE Class

7 Survival: Based on RIFLE Categorisation

8 1. ADQI 1. RIFLE Criteria 2. AKIN 1. Modified RIFLE Criteria 1. Serum rises by 26µmol/L from the baseline value within 48 hours 2. Serum rises 1.5 fold from the baseline value 3. urine output is < 0.5ml/kg/hr for >6 hours

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11 in AKI

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15 Incidence of AKI 1. US: 1. 1% % 2. UK: pmp pmp 3. AKI- RRT: pmp 3. Care: % of develop AKI % of admissions require RRT 3. AKI accounts 10% Hospital Days 4. AKI in Hospital: % mortality 2. Uncomplicted AKI: Mortality of 10% 3. AKI in organ failure: 50% 4. AKI requiring RRT in organ failure : 80%

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17 Study overview Proposed by the Renal Associa4on Prevalent and serious problem amongst hospitalised All hospital regardless of specialty, are at risk of AKI It is unknown to what degree strategies to reduce the risk of AKI are implemented

18 Primary aim To examine the process of care of who died in hospital with AKI, in order to remediable factors in the care received by these

19 Data returns

20 Key findings Only 50% of AKI care considered good Poor assessment of risk factors Unacceptable delay in of post- admission in AKI in 43% 22 died with a primary diagnosis of post- admission AKI which was predictable and avoidable Complica@ons missed (13%), avoidable (17%) or badly managed (22%)

21 NCEPOD Report 2009

22 Comprehensive Assessment in AKI 1. notes 2. AKI risk factors 1. age > 75 yrs 2. chronic kidney disease (CKD, egfr < 60 mls/min/ 1.73m 2 ) 3. Cardiac failure 4. Atherosclero@c peripheral vascular disease 5. Liver disease 6. Diabetes mellitus 7. Nephrotoxic medica@ons 3. poten@al causes for AKI including 3. reduced fluid intake 4. increased fluid losses 5. urinary tract symptoms 6. recent drug inges@on 7. sepsis 4. systemic clinical features 4. fever 5. rash 6. joint pains

23 Comprehensive Assessment in AKI general rash joint swelling assessment of volume status core temperature peripheral perfusion heart rate blood pressure jugular venous pressure signs of renovascular disease audible bruits impalpable peripheral pulses abdominal palpable bladder

24 biochemistry Urea and electrolytes haematology FBC urinalysis (± microscopy) microbiology urine culture (if is suspected) blood culture (if is suspected) renal immunology urinary biochemistry electrolytes osmolality ECG chest x- ray abdominal x- ray renal tract ultrasound (within 24hrs if suspected) kidney biopsy

25 Measurement of Crea%nine 1. Poor Biomarker 1. Jaffe (1886) 2. Inter- laboratory and interference 3. Interference 1. Protein, glucose, ascorbate, pyurvate, cephalosporins 2. Bilirubin 4. Assays 1. sarcosine oxidase 5. against IDMS

26 Proteinuria (3+ or >) Haematuria Lucocyturia Eosinophiluria Crystalluria EG TLS S, AcyC, IndinV, TriamT, Myoglobinuria Urine Microscopy

27 Urine Electrolyte 1. FE Na 2. FE Urea 3. Urinary Sodium 4. Free water clearence 5. Clearence 6. Blood 1. Pre- Renal Azotemia 2. ATN 3. Hepatorenal Syndrome

28 1. NGAL 2. KIM Cysta@n C 4. IL NAG 6. L- FABP Biomarkers of AKI

29 Urinary biomarkers for acute kidney injury (AKI) evaluated in at least 2 human studies (Belcher et al; AJKD; March 2011)

30 NGAL: in Pre- Renal vs AKI Scenario Singer et al; KI 16 March 2011

31 AKI- Strategies Major Surgery Sepsis: SIRS v CARS; EGDT; Volume and Pressor support; euglycemia; Low Tidal Vol CI- AKI Rhabdomyolysis

32 AKI: Strategies Contrast Induced AKI (CI- AKI) Parameter Number Number in Total n=12; 1854 of CI- AKI using bicarbonate n = 12; 1652; OR 0.46 ( ) Need for RRT n=9; 1215; OR 0.5 Survival n=11; 1640; OR 0.51 Bicarbonate use in CCF No difference in Survival; no excessive LVF episodes Compare with REMEDIAL (NS+NAC v NaHCO3+NAC v NAC+Vit C+NS Hoste et al AJKD 2009 Brer et al JASN

33 Contrast Induced AKI (CI- AKI)

34 Contrast Induced AKI (CI- AKI)

35 Flowchart of meta-analysis. Brar S S et al. CJASN 2009;4: by American Society of Nephrology

36 Forest plot of randomized trials meeting inclusion criteria. Brar S S et al. CJASN 2009;4: by American Society of Nephrology

37 AKI- Rhabdomyolysis Factors 1. Trauma 2. Burns 3. Compartment Syndrome 4. Drugs Coccaine 3. Ecstasy Management 1. Volume Assessment 2. Aggressive UO 100ml/hr 2. Urine ph>6.5

38 1. Fluid General Management 1. Crystalloid vs Colloid 2. Oliguric vs Non- Oliguric AKI 2. Pharmacological Therapy 1. Frusemide: 2. Dopamine 3. Fenoldopam 4. ANP

39 AKI- General Management: Fluid and Euglycemia Intensive Insulin Therapy and Pentastarch in Severe Sepsis N Engl J Med 2008;358:

40 AKI- General Management: Role of Frusemide Meta- analysis of frusemide to prevent or treat acute renal failure Ho and Sheridan BMJ ; 7565 pp445

41 Ho K M, Sheridan D J BMJ 2006;333:420 Effect of frusemide on in-hospital mortality and proportion of patients requiring renal replacement therapy or dialysis.

42 Number of dialysis sessions required after frusemide or control treatments. Ho K M, Sheridan D J BMJ 2006;333: by British Medical Journal Publishing Group

43 Proportion of patients remaining oliguric (urine output <500 ml/day) after frusemide or control treatments and those mentioning tinnitus or deafness. Ho K M, Sheridan D J BMJ 2006;333: by British Medical Journal Publishing Group

44 AKI- Pharmacological Fenoldopam Beneficial Impact of Fenoldopam in Cri%cally Ill Pa%ents With or at Risk for Acute Renal Failure: A Meta- Analysis of Randomized Clinical Trials Landoni et al; AJKD 2007 Parameter Results RCTs in Meta- analysis 16 Number of pa@ents 1290 Risk for AKI OR 0.43 Risk of Death 0.64 RRT Requirement OR 0.54 Hypotension Frequency in Fenoldopam group not higher ICU Stay Dopamine A 1 Receptor agonist 2. Short ac@ng 3. Decreases SVR 4. Increases both cor@cal and medullary blood flow

45 AKI- Pharmacological ANP CJASN 2009; Nigwekar et al; 19 Trials 1861 patients

46 AKI- General Management : Nutri@on 1. Calories: 25-35kcal/kg/day 2. Amino acids: 1.7g/kg/day 3. Die@cian Input within 24 hours 4. Supplement water soluble Vitamins if receiving RRT 5. Treat Hyperglycemia Cau@ously 6. Consider Selenium 7. Vit C supplementa@on not necessary 8. Vit K levels may be elevated 9. Enteral route vastly superior 10. Electrolyte disturbances to be treated as required

47 AKI- General Principles: Place of Care Most AKI outside Renal Unit Factors + or non- renal organ failure Requirement for RRT Renal Specialist Input Key Interfaces Cri@cal care outreach Acute renal outreach Specialist renal/icu Interface Avoiding deficiencies in ini@al assessment and management Physiological Early Warning Scores (MEWS/PARA scoring) Educa@on Wrisen guidelines Senior Specialist Renal Input

48 AKI- General Principles: Place of Care 1. flow from care to renal services: a year- long survey in a cri@cal care network (Wright et al QJM Aug 2008) /527 pa@ents survived 2. Incidence of RRT in ICU 234 pmp/year 3. Dura@on of RRT in ICU: 4 DAYS /219 required renal support outside ICU 5. 74/129 were provided RRT in ICU as for single organ failure ICU days u@lised to provide this support 2. Kanagasundaram NS, Jones KE. Transfer of pa@ents with acute kidney injury to specialist renal services- - physiological early- warning systems, applied prior to transfer from outside hospitals, can iden@fy those at risk of deteriora@on. QJM 2008;101: SOFA Score to assess need for escala@on

49 Management in AKI Principles ü Volume ü Acid- base, electrolytes ü ü Adequate dosing if fails

50 RRT CRRT vs IHD Hybrid Therapies

51 Which When How much

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54 Dialysis therapies CVVHDF AN69 membrane ml/min blood flow Heparin or no IHD F50/60/80 Dialysers ml/min UF ml/h 3-4 hours

55 Story of beser haemodynamic stability in CRRT vs IHD Authors/Setting n Outcome ITU/1993/Davenport et al 32 combined AKI/hepatic failure Intermittent vs CAVH/ CAVHD 35 vs 25 treatments Increased ICP, decreased CO, decreased DO2 Van der Scheuren 1996 N=11 IHD increases systemic O2 consumption Heering 1997 N=33 Cytokine removal with CVVH, improvement in CV haemodynamics Misset 1996 N=27 CAVH vs HD; MAP changes similar in both groups John and Griesbach 2001 N=30 (20 cvvh 10 hd) CVVH vs HD in sepsis; drop in HR, slight increase BP, splanchnic perfusion parameters unchanged Kumar 2000 N=42 (25 EDD, 17 CVVH) 367 vs 117 treatment days, 7.5 vs 19.5 hours, Kielstein JT N= 39, (CVVH 19, EDD 20) Earlier correction of acidosis, less heparin

56 Evidence NephSAP September 2007

57 Uehlinger et al NDT 2005 Hypothesis: CVVHD beser in- hospital mortality length of hospital stay N 125 Definition of AKI CVVHDF 70 IHD 55 Matching Catecholamine use (75% overall) Ventilation (75%) Creatinine >350, UO <20ml/h Demographics Cause of AKI Severity of illness Identical in both arms Identical in both arms ICU Mortality 34% vs 38% In hospital mortality 47% vs 51% Duration of RRT Renal recovery Identical Recovery of renal func@on 97% (1 in each group HD dependant)

58 Blood pressure and of during ICU stay CVVHDF vs IHD

59 Hemodiafe (Vinsonneau et al, The Lancet 29 th July 2006) Eligibility: AKI >350; urea >36; UO <200ml/16h; need for RRT

60 Survival: 32.6% vs 31.5% IHD survival improved through trial period? CVVHDF dose inadequate

61 Flow chart of the SHARF 4 study. Lins R L et al. Nephrol. Dial. Transplant. 2009;24: The Author [2008]. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved. For Permissions, please journals.permissions@oxfordjournals.org

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63 Preference of one modality over another Parameter CRRT IHD q IHD modality of choice for managing AKI in ICU (Mehta et al) Geography Europe/Australia/SE Asia US/Canada? Anticoagulation q Local preferences; >97% - of treatments for AKI in Australia + are CRRT Therapeutic q Haemodynamic agents stability governs - choice of therapy + Nutrition - + Volume q Con@nuous management removal of inflammatory? more error cytokines prone beser (?) easier Dialysate q Blood membrane contact Less is pro- inflammatory standardised across regions Haemodynamic stability + (perceived) - simpler Training Personnel intensive Relatively easier Ease of dialysis dose delivery? - + Convective clearence + BUT is it useful? _ Inflammatory cascade Dubious value None, may be less proinflammatory as bloodmembrane contact less Cost - +

64 AKI- RRT : Equipment 1. Dialyser: Synthe@c or Modified Cellulosaic 2. Bicarbonate buffer 3. Microbiological Integrity of Dialysate 4. An@coagula@on 1. Heparin vs Citrate 2. Prostacycline 3. Saline Flushes 4. Choice if HIT 1. Danaproid/Fondaparineux 2. Hirudin/Lepirudin 3. Argotroban 4. Nafamostat

65 Kt/V ~ 1.2 URR > 65% AKI- Dose of RRT Evidence: 1. Veteran Affairs/Na@onal Ins@tute of Health Acute Renal Failure Trial Network 2. Randomised Evalua@on of Normal Versus Augmented Level Renal Replacement Therapy (RENAL)

66 How much? Ronco et al Lancet July 2000 Efficacy of three different doses of CVVH

67 Intensity of Renal Support in Cri%cally Ill Pa%ents with Acute Kidney Injury

68 Intensity of Renal Support in Cri%cally Ill Pa%ents with Acute Kidney Injury Intense vs IHD/SLED CVVH at 35ml/kg/hour

69 Mortality at 60 days

70 RENAL Study Design

71 RENAL: Outcome Summary

72 AKI- When to Start RRT

73 Era Number Criteria 1960s/1970s/1980s 3 BUN mg/dl 1990s At least 2 of importance n=100; higher survival in early initiation n= 64, Cardiac ITU, 22 vs 43:: early/late PICARD n=243 Survival 80 & 65 (early) 75 & 59 (late) RR 1.85 (co-variate adj) RR 2.07 (propensity sco) BUT Urea cannot be a surrogate for dura@on of AKI AND spontaneous recovery or death without RRT <60 BUN group vs >60 8 hr oliguria / >84mg/dl <76mg/dl vs >76mg/dl

74 Early start a good idea How early is early AKI- When to Start RRT Perhaps Stage 3 of AKIN Balance Early start with Morbidity associated with RRT? Delays recovery from AKI Many pa@ents pull back from brink with suppor@ve therapy Urea of 28mmol/L a cut off? 21.5mmol/l? UO <100ml/ 8hr

75 PICARD Study ( Cho et al JASN 2006) Observa@onal study CRRT vs IHD Feb (1999- Aug 2001) (n=398, 206 CRRT, 198 IHD) AKI defini@on: q q q Increase in serum crea@nine by >44μmol/L from baseline, if baseline <132μmol/L Increase in serum crea@nine by >88μmol/L if baseline 132<B<440 Baseline CKD egfr<30ml/min Who got what? CRRT Respiratory organ failure Fluid overload IHD Older No PA monitoring Higher BUN and creatinine Non-white population Higher SBP

76 AKI- Timing of RRT Timing of renal replacement therapy and clinical outcomes in cri%cally ill pa%ents with severe acute kidney injury Beginning and Ending Therapy for the Kidney (BEST Kidney) Bagshaw et al; JoCC March 2009 Parameter Results Type 23 countries, 52 ICUs, 1238 Criteria Early vs Late Factors: Urea <24.2 vs >24.2 OR 0.92/1.25 (63.4 VS 61.4%) <309 vs >309 OR 0.46/0.51 (53.4 vs 71.3) ICU Stay: <2, 3-5, > vs 62.3 vs 59

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