Acute Kidney injury 2014

Transcription

1 Acute Kidney injury 2014 BWJ van Rensburg Division of Nephrology University of the Free State

2 After > 100 years unable to significantly influence the natural course of ATN Last 18 months: 2813 articles published

3 Aspects of AKI: Definitions / diagnosis Pathogenesis Prevention Optimizing support

4 Aspects of AKI: Definitions / diagnosis Pathogenesis Prevention Optimizing support

5 Acute Kidney injury Heterogenous syndrome defined by a rapid decline in GFR (hours days) Resulting in accumulation of waste products 2 Review found 35 definitions 1 1 Kellum JA, Levin N, Bauman C, Curr. Op. in Cr. care 2002; 8: Brenner & Rector s The Kidney 9 th ed Elsevier

6 Defining AKI - GFR We know: Small reduction in GFR translates into increased mortality risk (26,5μmol/L) ± Linear increase in mortality with decreasing GFR Problems in measuring GFR: S- creatinine needs to be in steady state to reflect GFR Urine volume does not reflect GFR

7 Definition of AKI Increase in s-creatinine of > 26,5 within 48h Increase in s-creatinine >1.5 x baseline (prior 7 days) Urine volume <0.5ml/kg/h for 6h KDIGO Clinical Practice Guideline for Acute Kidney Injury. Kidney inter., Suppl. 2012; 2: 1 138

8 Staging AKI Stage Serum creatinine Urine output x baseline <0.5ml/kg/h for 6-12h (or > 26,5 increase) x baseline < 0.5ml/kg/h for > 12h 3 3 x baseline < 0,3ml/kg/h for > 24h (or > 353,6μmol/L) KDIGO Clinical Practice Guideline for Acute Kidney Injury. Kidney inter., Suppl. 2012; 2: 1 138

9 Other terminology used in kidney disease CKD: GFR < 60ml/min/ 1.73m 2 for > 3months Kidney damage AKD: AKI GFR < 60ml/min/ 1.73m 2 for < 3months Kidney damage NKD: Stable GFR > 60ml/min/ 1.73m 2 No kidney damage KDIGO Clinical Practice Guideline for Acute Kidney Injury. Kidney inter., Suppl. 2012; 2: 1 138

10 Early detection of AKI Floege J, Johnson RJ, Feehally J: Comprehensive clinical Nephrology 4 th ed 2012 Elsevier Inc

11 How to use biomarkers efficiently in acute kidney injury none of the biomarkers has demonstrated a clear additional value beyond the traditional approach in clinical decision making in patients with AKI. Unscrutinized use of these biomarkers may distract from adequate clinical evaluation and carries the risk of worse instead of better patient outcome. Norbert H. Lameire, Raymond C. Vanholder and Wim A. Van Biesen Kidney International (2011) 79,

12 Aspects of AKI: Definitions / diagnosis Pathogenesis (pre-renal, renal + post renal) Prevention Optimizing support

13 Pathogenesis Ischeamic Toxic Sepsus Phases: Prerenal Initiation of injury Extension of injury Maintenance Repair

14 Response of a normal kidney to hypoperfusion (maintain GFR while increasing i/v volume) Glomerular Afferent vasodilatation (eicasonoids) Efferent vasoconstriction ( angiot. 2) Tubular Sodium absorption (aldosterone) Water absorption (ADH) NSAIDS ACE-I / ARB Urine: Low sodium High osmolality

15 Nephron 300 mosm/l po 2 = 80mmHg Cortex Increasing GFR increases tubular workload and may worsen tubular ischemia 1200 mosm/l po 2 = 15mmHg Medulla

16 Consequences of sublethal damage Endothelial cells Interventions: Swelling Anti ICAM-1, statins Leucocyte adhesion / activation Altered coagulation Protein C, Complement activation Soluble thrombomodulin Permeability* Tubular cells loss of polarity TGFeedback activation Apoptosis Cast obstruction Backleak* Adenosin receptor antagonists, Theophillin Caspase - I, IgF-1, EPO Uromodulin

17 Obstruction Several nephrons drain into a single collecting tubule Am J Kidney Dis. 2012;59(3):

18 Aspects of AKI: Definitions / diagnosis Pathogenesis Prevention Optimizing support

19 Susceptibility Prevention of AKI: risk assesment Dehydration Advanced age, race, gender CKD Exposure: Extra-renal disease, DM / CCF / liver Toxins: drugs, contrast hypotension, sepsis Major surgery, critical illness

20 Susceptibility Prevention of AKI: Pre-renal Dehydration Advanced age, race, gender CKD Exposure: Extra-renal disease, DM / CCF / liver Toxins: drugs, contrast hypotension, sepsis Major surgery, critical illness

21 Managing a hypotensive AKI patient ( Pre-renal first 6 hours) Restore intravascular volume Fluid controversy - Colloids (HES increase in AKI 1 ) Vasopressors - Chloride (acidosis) - Potassium (Ringers) - Even before fluid is fully replaced 2 - Norepinephrin / vasopressin - Systemic blood pressure improvement should override concerns of renal vasoconstriction 3 1) Intensive Care Med (2013) 39: ) N Engl J Med 2013;369: ) KDIGO:Acute Kidney Injury. Kidney inter., Suppl. 2012; 2: 1 138

22 Strategies in management of sepsis Protocol / Goal driven MAP >65mmHg CVP Urine output >0,5ml/min/h CvO Sat > 70% Glucose control Insulin therapy (glucose 6,1-8,3mmol/L) KDIGO Clinical Practice Guideline for Acute Kidney Injury. Kidney inter., Suppl. 2012; 2: 1 138

23 Diuretics Of no proven benefit in preventing or improving outcomes in AKI Helpful in managing fluid overload in early AKI Should be stopped once RRT is started KDIGO Clinical Practice Guideline for Acute Kidney Injury. Kidney inter., Suppl. 2012; 2: 1 138

24 Diuretics Constant infusion: Lower [peak], 30% more natriuresis If bolus did not work, infusion probably won t either 2012 UpToDate

25 Susceptibility Prevention of AKI: risk assessment Dehydration Advanced age, race, gender CKD Exposure: Extra-renal disease, DM / CCF / liver Toxins: drugs, contrast hypotension, sepsis Major surgery, critical illness

26 Intra-abdominal pressure is important Definitions: (based on bladder pressure) normal < 7mmHg intra-abdominal hypertension > 12mmHg Abdominal compartment syndrome > 20mmHg Association of IAH with AKI (dose dependant effect) Medical and surgical causes Early decompression (medically and surgically) De Waele JJ, De Laet I, Kirkpatrick AW et al. Am J Kidney Dis. 57(1):

27 AKI affects other vital organs Anesthesiology, V 116 No 5, May 2012, p 1139

28 Liver failure (hepatorenal syndrome) Typically: Usually cirrhotic liver, precipitated by a large fluid shift Renal vasoconstriction with splanchnic vasodilatation Indistinguishable from pre-renal failure Management: Fluid challenge albumin Vasoconstrictors Dialysis similar indications, but prognosis depends on liver disease Annals of Hepatology Vol 2; no 3; 2012 p

29 Cardiac failure (cardiorenal syndrome -2) Management of refractory edema with combination diuretic therapy (systolic dysfunction with hypotension): Prerenal failure and hyponatremia Hyperkalemia Management: Reduce / stop ACE-I, beta Blockers I/V inotropes?vasopressin antagonists?ultrafiltration Clin J Am Soc Nephrol 8: , October, 2013

30 Susceptibility Prevention of AKI: risk assessment Dehydration Advanced age, race, gender CKD Exposure: Extra-renal disease, DM / CCF / liver Toxins: drugs, contrast hypotension, sepsis Major surgery, critical illness

31 Avoiding toxins -Contrast Recommendations: Consider alternative imaging methods Use the lowest possible dose of contrast Use iso or low osmolar contrast media Iv volume expansion with isotonic crystalloids Oral NAC No prophylactic dialysis KDIGO Clinical Practice Guideline for Acute Kidney Injury. Kidney inter., Suppl. 2012; 2: 1 138

32 Endogenous toxins: Heme: (hemolysis + rhabdomyolysis) K + Phosphate Calcium Fluid: maintain urine volume ml/h?bicarbonate containing solutions (U-pH > 6,5) Uric acid: (tumour lysis) K + Phosphate Calcium uric acid Fluid Allopurinol Rasburicase

33 Susceptibility Exposure: Prevention of AKI: risk assessment Dehydration Advanced age, race, gender Chronic kidney disease (CKD) Extra-renal disease, DM / CCF / liver Toxins: drugs, contrast hypotension, sepsis Major surgery, critical illness

34 Surgery No perioperative intervention of proven benefit 1 (Dopamine, Fluids, Diuretics, EPO, ANP, Ca channel blockers, ACE-I) Mostly found in: Abdominal aortic aneurism repair Obstructive jaundice patients Cardiac surgery: AKI in up to 40%, dialysis required in 1% 2 Human model to study AKI 1) The Cochrane Library 2013, Issue 9 2) Ann Thorac Surg 2011;92:

35 Remote Ischemic preconditioning Protection conferred to tissue by previous sub lethal ischemia Remote localized ischemia may protect distant tissue Study patients 1 : RCT of 120 adult patients for elective cardiac surgery Intervention: remote ischemic preconditioning: (automated thigh tourniquet) three 5-min intervals of lower extremity ischemia separated by 5-min intervals of reperfusion Outcome: AKI 1) Kidney International (2011) 80,

36 Remote Ischemic preconditioning Cardiac surgery 1 Contrast (angiography) 2 1) Kidney International (2011) 80, ) J Am Soc Nephrol 25: , 2014

37 Aspects of AKI: Definitions / diagnosis Pathogenesis Prevention Optimizing support

38 Non dialytic management Hyperkalemia shifting may impair efficacy of dialysis Fluid Overloaded patients have a poorer prognosis Metabolic acidosis Targets unsure (?ph 7,1 and s-bicarbonate < 6 mmol/l) No RCT available 1 1 The Cochrane Library 2012, Issue 6

39 Non dialytic management Nutrition: (Modify RRT to cater for the needs of the patient) total energy intake kcal/kg/d Protein undialysed 0,8-1 g/kg/d On RRT 1-1,5 g/kg/d Max (CRRT or hyper catabolic) 1,7 g/kg/d

40 RRT in AKI clinical questions: 1 Starting dialysis (when?) May be harmful, nephrologists v/s the rest 2 Modality (how?) clinical characteristics + local facilities 3 Dialysis dose (how much?) 4 Stopping dialysis Moral + legal issues

41 Hypotension Potential risks of RRT: Arrhythmia Membrane bioincompatibility Vascular acces + Anticoagulation Possibly may delay renal recovery and increase risk of CKD?

42 Preferred sites for vascular access; 1 Right internal jugular 2 femoral 3 Left internal jugular 4 Lastly dominant subclavian KDIGO Clinical Practice Guideline for Acute Kidney Injury. Kidney inter., Suppl. 2012; 2: 1 138

43 When should dialysis be started? Individualized to patient needs with 2 goals: 1 Maintaining homeostasis without new insults 2 Allowing supportive measures (nutrition, medication) until renal function improves 3 basic groups a Solute indications (better outcome) b Volume indications (worse outcome) c Both (worst outcome)

44 When should dialysis be started? Clinical judgment based on experience Predicting the immediate future course Trend of the patient progress Immediately (life threatening indications): refractory hyperkalemia, pulmonary edema and acidosis or complications of uremia Convenient timing : symptomatic uremia Biochemical values

45 Starting RRT Early v/s Late (meta analysis) CRRT IHD? fluid Combined RRT Renal Failure, 34(3): , (2012)

46 Impact of fluid overload at initiation of dialysis Bouchard J, et al. Kidney Int 2009; 76:

47 KDIGO 5.1.1: Initiate RRT emergently when life-threatening changes in fluid, electrolyte, and acid-base balance exist (Not Graded) 5.1.2: Consider the broad clinical context, the presence of conditions that can be modified with RRT, and trends of laboratory tests rather than single BUN and creatinine thresholds alone when making the decision to start RRT (Not Graded) KDIGO Clinical Practice Guideline for Acute Kidney Injury. Kidney inter., Suppl. 2012; 2: 1 138

48 How should the patient be dialyzed? Individualized according to patient needs and local facilities Factors to be taken into account: hemodynamic stability brain injury or brain edema bleeding tendency catabolic / nutritional state Cost facilities available developing world (acute peritoneal dialysis)

49 Gabriel DP, Caramori JT, Martim LC et al, Kidney International (2008) 73, S87 S93 High volume PD v/s Daily HD 154 AKI patients requiring dialysis included in a RCT comparing HVPD (36-44L/d) with 3h hemodialysis sessions 6x/ week

50 Modality of renal replacement therapy.numerous issues related to study design, conduct, and quality that dispute the validity and question any inferences that can be drawn from these trials Gabriel DP, et al. Kidney Int 2008; 73:S87-S93

51 KDIGO 5.6.1: Use continuous and intermittent RRT as complementary therapies in AKI patients. (Not Graded) 5.6.2: We suggest using CRRT, rather than standard intermittent RRT, for hemodynamically unstable patients. (2B) 5.6.3: We suggest using CRRT, rather than intermittent RRT, for AKI patients with acute brain injury or other causes of increased intracranial pressure or generalized brain edema. (2B) KDIGO Clinical Practice Guideline for Acute Kidney Injury. Kidney inter., Suppl. 2012; 2: 1 138

52 Dialysis dose Survival CRRT: 20-25ml/kg/h IHD: Weekly Kt/V = 3,9 Dialysis dose Am J Kidney Dis. 2012;59(4):

53 When should dialysis be stopped? When the medical aid fails?. Part of DNR / withdrawal (futile) ASN guidelines* Recovery (initial indication resolved) urine volume (> 1-2L / day without diuretics) creat < 500 mol/l and urea < 30mmol/L *AJKD V37, no pp

54 Prognosis after AKI Meta-analysis of 13 studies (11 with > 3000 patients) Identified AKI as an independent risk factor for CKD, ESRD, Death and other important nonrenal outcomes CKD (HR=8,8) ESRD (HR=3,1) Death (HR=2) Steven G. C, Swathi S, Chirag R. P Kidney International (2012) 81,

55 Prognosis after AKI 41,327 adult patients in Ontario with acute kidney injury who did not require in-hospital dialysis, and who survived free of dialysis 30 days after discharge were compared to patients without acute kidney injury during their index hospitalization Hazard ratio=2.70, 95% CI The American Journal of Medicine (2012) 125,

56 Follow- up after AKI At 3 months decide how they need to be managed according to the KDOQI CKD guidelines. Remember the additional risk of CKD even if they have recovered renal function