The 2012 KDIGO guidelines on Acute Kidney Injury-

Transcription

1 The 2012 KDIGO guidelines on Acute Kidney Injury- Is there a need for an update and have the guidelines improved AKI prognosis? Norbert Lameire, MD,PhD Em prof of Medicine and Nephrology University Hospital Gent, Belgium Stuttgart, February 24, 2018

2 A selection of remaining uncertainties in AKI Is all AKI equal? Should management be individualized on a better phenotyping of AKI by etiology, severity of injury, and ability to recover? Can we predict/detect AKI early enough to modify outcome? Should biomarkers be incorporated in the diagnosis and result in earlier intervention and improvement of prognosis? What determines the long-term outcome of AKI? How can recovery be defined and can it be optimized? How do we optimize RRT and what parameters can be used for correct timing for initiation and stopping RRT? Does RRT modality affect long-term outcome?

3 AKI Syndromes Sepsis-associated AKI Nephrotoxic AKI Cardiorenal syndrome Hepato-renal syndrome Cardiac surgery-associated AKI Acute interstitial nephritis Glomerulonephritis/Vasculitis/ microangiopathy Obstructive AKI Abdominal compartment syndrome Rhabdomyolysis

4 Strength of recommendations and level of evidence of the 2012 KDIGO Clinical Practice Guidelines for AKI Total number of recommendations: 87

5 KDIGO definition and classification of AKI

6 A hypothetical example of real-time GFR and SCr values before and during an episode of AKI. Thomas et al, Kidney International (2015) 87, 62 73

7 Hospital mortality in different creatinine trajectories in hospital acquired AKI 18% 12% 5% 1,7% Hospital mortality THA-AKI: IRA hôpital assocée transitoire; 2HA-AKI transient hospital associated AKI ;IRA qui après résolution est suivie d une nouvelle rechute Warnock et al, Nephron 2015;131:

8 Potential SCr trajectories and AKI misclassification KD Liu et al, Kidney International Reports (2018) 3,

9 Classes of biomarkers in AKI Class of biomarker Biomarker Inflammatory Proinflammatory cytokines (IL 6, IL 18), Neutrophil gelatinase-associated lipocalin (NGAL) Cell injury Cell cycle markers Functional L-fatty acid binding protein (L-FABP), KIM- 1, sodium/hydrogen exchanger-3 (NHE-3) and Netrin-1; urinary tissue inhibitor of metalloproteinases-2 (TIMP-2) and insulinlike growth factor-binding protein 7 (IGFBP7) Cystatin C

10 AKI- a continuum? Structural Vaidya et al, Annu. Rev. Pharmacol. Toxicol. 2008, 48:

11 Early detection of AKI (left) and prediction of AKI recovery (right) with cell cycle biomarkers after post cardiac surgery AKI TMP2xIGFBP7 Non-AKI NGAL Meersch et al, PLoS ONE 9(3), 2014

12 Phenotyping AKI with biomarkers and SCr? Identification of clinically relevant structural kidney damage using biomarkers. Concurrent use of intrinsic kidney injury biomarkers and serum creatinine-based estimation of glomerular filtration rate (GFR) identifies at least 4 clinically relevant categories differentiating prerenal declines in GFR without structural injury and structural injury by biomarker positivity with or without changes in serum creatinine. Huen, Parikh Am J Physiol Renal Physiol 309: F406 F413, 2015.

13 Preventive strategy performed in high risk cardiac surgery AKI patients Application of the KDIGO care bundle reduced overall AKI at 72 h from 71% to 55.1% and the rates of moderate-tosevere AKI from 44.9% to 29.7%. (Pulse contour cardiac output) Meersch et al, Int Care Med 43(11): , 2017

14 Peak post-operative urine biomarkers are not independently associated with the outcome of AKI post cardiac surgery Peak post-operative plasma biomarkers are independently associated with CV events and mortality, Parikh et al, J Am Soc Nephrol 28(12): , 2017

15 Performance of SCr and Kidney Injury Biomarkers for Diagnosing Histologic Acute Tubular Injury Association of donor characteristics with 6-month recipient egfr. Adjusted 6m Recipinet egfr (95% CI) NS Moledina et al Am J Kidney Dis. 2017;70(6):

16 Principle of an electronic early alert system for AKI Haase M, et al, Electronic alerts for acute kidney injury a systematic review. Dtsch Arztebl Int 2017; 114: 1 8.

17 Comparison of clinical outcomes between the usual care and alert groups-korean study Park et al, Am J Kidney Dis,71(1):

18 Current strategies for preventing AKI Hemodynamic management to prevent septic AKI Unknown exact mean arterial pressure and perfusion targets Restricted fluid strategies? Protocolized fluid and hemodynamic strategies? Hemodynamic management to prevent surgical AKI Perioperative hemodynamic optimization? Targets unknown Pharmacological and non-pharmacological strategies Avoidance of nephrotoxins Pickkers et al, Intensive Care Med (2017) 43:

19 Inidividualized goal-directed hemodynamic therapy of the macro-and microcirculation in sepsis Saugel et al, SHOCK, 43 : , 2015

20 Management of septic shock should be based on both global hemodynamic parameters and tools that reflect tissue perfusion SDF: side stream dark field Ait-Oufella et al, Curr Opin Crit Care 2015, 21:

21 Sublingual microperfusion in sepsis Trzeciak et al, Ann Emerg Med. 2007;49:88-98

22 Dogma s and traditional views on the long term prognosis of AKI survivors in the years The mortality risks are mainly determined by the clinical context In contrast with chronic kidney diseases is AKI in principle a reversible disease The majority of AKI patients will return to the same renal function as before the AKI episode An old adagium : «if the patients survive, so will their kidneys»

23 AKI stage and duration are independently associated wtih CV events or death in post cardiac surgery AKI Parikh et al, J Am Soc Nephrol 28: , 2017

24 Evolution of long term mortality in community acquired AKI Grampian population, Sawhney et al Am J Kidney Dis. 69(1):18-28, 2016

25 Cumulative incidence of mortality causes 1 year after hospital discharge post AKI- population-based study of residents in Ontario Total AKI: Total discharged : Total mortality: 28% Silver et al, J Am Soc Nephrol 29: ccc ccc, 2018

26 Post AKI cumulative mortality incidence and mortality causes in the year after hospital discharge population-based study of residents in Ontario Silver et al, J Am Soc Nephrol 29: ccc ccc, 2018

27 The interrelation between AKI-CKD-AKI

28 Only knowledge of basal renal function and pre AKI functional profile allow accurate determination of impact of AKI on the post AKI functional profile Liu et al, Curr Opin Nephrol Hypertens 18: , 2009

29 Difficulties to detect persistent kidney dysfunction after AKI in critically ill patients. Serum creatinine (log scale) in 221 hospitalizations with 3-12 mth FU Prowle et al, Clin J Am Soc Nephrol 9: , 2014

30 Definitions and epidemiology of early or late reversal and functional recovery of AKI in ICU Recovery: reversibility at hospital discharge AKI stage 2/3 ICU population Reversal: return to non AKI stage 5 profiles Kellum et al, Am J Respir Crit Care Med 195, , 2017

31 Different types of recovery after AKI-survival to death or RRT Kellum et al, Am J Respir Crit Care Med 195, , 2017

32 Development of CKD stage 3 or higher by 1 year after discharge according to AKI recovery pattern Heung et al, Am J Kidney Dis. 67(5): , 2016

33 Cumulative incidence of de novo CKD after recovered hospital acquired AKI among patients with normal baseline GFR Recovery : egfr value within at least 90% of baseline egfr occurring within 90 days of AKI De novo CKD: occurrence of 2 egfr values <59 ml/min 1.73m 2, separated in time by at least 90 but no more than 365 days. Bucaloiu et al, Kidney Int (2012) 81, ;

34 Three-year outcomes after AKI: results of a prospective parallel group cohort study 71±28 ml/min/1.73 m2 68 ±19 ml/min/1.73m² control AKI 68.4±21 ml/min/1.73 m2 60.7±21 ml/min/1.73 m2 At 3 years, the number of AKI patients with CKD progression was 30 (24.6%), compared with 10 (7.5%) of the non-exposed group, p< Horne KL, et al. BMJ Open 2017;7:e CKD progression: a decrease in egfr of 25% associated with a decline in egfr stage.

35 Cumulative incidences of subsequent renal progression (solid line) for those with (red) and without (blue) an AKI admission in 2003, grouped by 1 year post-episode egfr and accounting for the competing risk of death (dashed line) Grampian study population Sawhney et al Kidney Int (2):

36 Long-term survival and renal outcome in a prospective single center study Schiffl et al, Clin Kidney J (2012) 5:

37 Absolute or conventional parameters for initiating RRT in AKI Parameter Hyperkalemia Metabolic acidosis ph 7.15 Definition Serum K > 6.5 mmol/l or raidly rising or refractory to standard supportive medical therapy Uremia Urea > 36 mmol/l (equals BUN ~ 100 mg/dl; blood urea = 216 mg/dl) Anuria/Oliguria Fluid overload Urine output < 0.3 ml/kg.hr for 24 hrs or anuria for 12 hrs Pulmonary edema not responding to diuretics and defined by the presence of all of the following factors: > 10% fluid accumulation ( cumulative fluid balance/ baseline weight > 10%) urine output < 0.5 ml/kg/hr for 12 hours and severily impaired oxygenation (Pa O2/Fi O2 < 200 as indicated by respiratory Sequential Organ Failure Assessment (SOFA) score 3

38 Differences in design and outcomes between the ELAIN and AKIKI trials Bagshaw, Wald, Nature Reviews in Nephrol 2016

39 Advantages and shortcomings of earlier RRT initiation in AKI Advantages More effective reversal of volume expansion, particularly in diureticresistant patients Better control of electrolyte and acid base status Pro active clearance of toxic low and middle molecular weight solutes Avoidance of AKI-related emergencies, (eg cardiac dysrhythmias related to hyperkalemia Shortcomings Exposure to complications associated with supplemental vascular access (both at time of insertion and therafter- infections, thrombosis, emboli, ) Exposure to complications associated with RRT (e.g. intradialytic hypotension, dysrhythmias, clearance of antibioticshypokalemia, hypoglycemia..) Higher cost, especially if patient was destined to recover kidney function Adapted from Wald, Bagshaw, Semin Nephrol 36:78-84, 2016

40 Recovery from AKI at 90 days (A) and 1 yr (B)- impact of RRT modality Liang et al, Clin J Am Soc Nephrol 11: 30 38, 2016

41 Referral to nephrologist after AKI Mortalité pendant le FU d un an: 22%. L incidence cumulative d adressage au nephrologue avant décès, commençement de dialyse, ou amélioration de la function rénale était 8,5% Siew et al,j Am Soc Nephrol 23: , 2012

42 Survival during FU by specialty of severe AKI adult patients in Ontario Harel et al, Kidney Intl (2013) 83,

43 Disparity between opinions of nephrologists and actual practices in the FU of post AKI patients (Ontario) 27% 87% Karsanji et al, Clin J Am Soc Nephrol Nov 7;12(11):

44 Role of nephrologists in FU of post AKI patient Nephrological aspects Cardiovascular aspects Patient s advocate FU of Serum Creatinine FU of hypertension Avoiding of potentionally nephrotoxic drugs and interventions FU of proteinuria Monitoring cholesterol Education of patients and families Metabolic control Treatment of renal anemia Prevention of new AKI episodes Preparation of chronic RRT Control of circulating volume Adaptation of drug dosing Reinstitution of previously administered drugs (aspirin, statins, ACE, ARBS Education of nonnephrological specialists Education of general practitioners Silver, Siew Adv Chronic Kidney Dis. 2017;24(4): )

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46 Performance of SCr and Kidney Injury Biomarkers for Diagnosing Histologic Acute Tubular Injury Association of donor characteristics with 6-month recipient egfr. NS Moledina et al Am J Kidney Dis. 2017;70(6):

47 Pt 1 Estimating Kinetic GFR when the SCr Is Changing Acutely Pt 2 Chen S J Am Soc Nephrol 24: , 2013

48 Incidence and stages of AKI in hospitalized patients according to the RIFLE,AKIN, KDIGO, and Creat Kinetics definition Zeng et al, Clin J Am Soc Nephrol 9: 12 20, 2014.