Acute Kidney InjuryFocus on Perioperative Setting

October 10, 2018

Banff, Alberta

Disclosures

Participate in a research group with funding from several sources including industry – funding is at arms length, no overlap with AKI

Disclosures

A lot of the data discussed today is population database derived- methodology varies , definitions vary, and analysis varies. I am aware of the issues but am not an expert in these methodologies.

Objectives

Increase awareness of the importance of AKI events and survivors

Review some aspects of diagnosis and management

Review some emerging processes in diagnosis and management

Mehta RL, et al. Lancet 2015; 385: 2616-2643 Susantitaphong P et al. Clin J Am Soc Nephrol 2013; 8: 1482-1493

RIFLE (2004), AKIN (2007), KD:IGO (2012)

Consensus Definitions for AKI criteria

Stage Serum Creatinine or eGFR Urine Output

RIFLE KD:IGO AKIN

RIFLE KD:IGOAKIN

Risk 1 Increased sCr ≥ 1.5 x baseline or GFR > 25%

Increased sCr 1.5 – 1.9 x baselinewithin prior 7 daysorIncreased sCr x 26.4 µmol/L [0.3 mg/dl]within 48 hours

< 0.5 ml/kg/h ≥ 6 h

Injury 2 Increased sCr ≥ 2 x baseline or GFR > 50% Increased sCr 2–2.9 x from baseline < 0.5 ml/kg/h ≥ 12 h

Failure 3 Increased sCr ≥ 3 x baseline or GFR > 75%, or≥ 354 µmol/L], with an acute ≥ 44 µmol/L

Increased sCr 3 x from baseline, or≥ 354 µmol/L, with an acute ≥ 44 µmol/Lor receiving RRT

< 0.3 ml/kg/h ≥ 24 horanuria ≥ 12 h

Bellomo R, et al. RIFLE. Crit Care 2004; 8(4): R204-12Mehta RL, et al. AKIN. Crit Care 2007; 11: R31-38KDOGI. KD:IGO. Kidney Int 2012; 2(suppl 1):19-36

Minjae K et al Anesthesia & Analgesia 2014; 119(5): 1121-1132

Susantitaphong P et al. Clin J Am Soc Nephrol 2013; 8: 1482-1493

Acute Kidney Injury – a continuum

Definition: “abrupt and sustained decrease in glomerular filtration, urine output, or both.”

Subclinical AKI

does not meet AKI criteria and Biomarker concentration increased AKI

Meets AKI criteria and rapid reversal within 48 hrs up to 7 days (renal recovery)

AKD

Sustained reduced renal function > 7 days CKD

Sustained reduced renal function > 90 days

KDIGO. Kid Int Supplements 2012; 2(Suppl 1): 19-36

Forni LG et al Intensive Care Med (2017) 43:855–866

AKI Outcomes

Dedhia P and Thakar CV. Core Concepts in Acute Kidney Injury. S. S. Waikar et al. (eds.) Springer Science+BusinessMedia, LLC 2018

DeathDeath Death?

KDIGO. Kid Int 2012; 2(Suppl 1): 19-36Ferenbach DA and Bonventre JV. Nephrologie & Therapeutique 2016; 12S: S41–S48Yang Y et al. Pharmacology and Therapeutics 2016;163: 58-73

AKI, Renal Recovery, CKD risk

Pannu N et al Clin J Am Soc Nephrol 2013; 8: 194–202Bucaloui ID et al Kidney Int 2012; 81: 477-485Heung M et al Am J of Kidney Dis 2015; 67(5):742-

No AKI

AKI - R

AKI- NR

Bihorac A et al Annals of Surgery 2009; 249 (5):851-858

Kork F et al Anesthesiology 2015; 123(6): 1301-1311

Summary

Normal kidneys with minimal risk can develop AKI

The more risk factors for AKI, the greater the risk for an AKI event

With AKI there is an increased risk of

Shorterm and longterm mortality,

repeat AKI, hospital readmission,

Incident CKD

progression to CKD and ESRD

CKD is a significant AKI risk factor

AKI Management – Moving to the 5Rs? Hx:

Co-morbidities, prior AKI events/CKD, FHx, acute clinical setting,

Medication exposure

Px: Hemodynamic status, infection, sepsis, anemia, hypovolemia, chronic organ dysfunction (Heart, Lung,

Liver), presence of 3rd spacing

Investigations:

urine dipstick/micro, +/- renal U/S, and as indicated

Management Stop Nephrotoxins, renal dose remaining medications

Volume resuscitate, do not volume overload

Serial follow-up; volume status, Cr/eGFR, manage associated complications

Treat hyperglycemia

Consult colleagues as required (Nephro, Cardio, hepatol, ICU)

Ultrasonography should be performed:

when there is no identified cause of acute kidney injury

when pts present with risk factors/symptoms of urinary tract obstruction

when an infected and obstructed kidney is suspected, or when they are at medium or high risk of obstruction based on the risk scoring system

Routine ultrasonography of the urinary tract is not required:

when a non-obstructive cause of the acute kidney injury has been identified

for patients without symptoms of obstruction, without risk factors

when at low risk of urinary tract obstruction based on the risk scoring system

Provincial Clinical Knowledge Topic Acute Kidney Injury, Adult – Inpatient V 2.0 December 2017, page 7

Hospital AKI

Incidence overall 2-23% (more recently 2-9%) (Alberta 20-30%)

Varies with setting – ICU, ward, surgery

ICU 22- 57%

Medical ward (18%)

Incidence of in-hospital (non-ICU/Surgical) AKI likely plateauing (4%)

mortality rates have generally fallen by 50% with and without dialysis

Bellomo R et al. Lancet 2012; 380: 756-766Hoste EA et al. Intensive Care Med 2015; 41: 1411-1423Finlay S et al. Clin Med 2013; 13(3): 233-238Bihorac A, et al. Crit Care Med 2013; 41(11): 2570-2583O’Neal JB et al. Crit Care 2016; 20: 187-195G ME t l A J Kid Di 2016 67(6) 872 880

Perioperative AKI

For general surgery 1-2% (7%)?

Higher risk surgeries:

Cardiac 15%

Trauma 26%

Transplant 71%

Neuro 13%

AKI is associated with higher rates of all postop complications, including CV

Bellomo R et al. Lancet 2012; 380: 756-766Hoste EA et al. Intensive Care Med 2015; 41: 1411-1423Finlay S et al. Clin Med 2013; 13(3): 233-238Bihorac A, et al. Crit Care Med 2013; 41(11): 2570-2583O’Neal JB et al. Crit Care 2016; 20: 187-195Grams ME et al. Am J Kid Dis 2016; 67(6): 872-880 Wang HE et al. Am J Nephrol. 2012;35:349–355

Case #1 - ED

64 yr old male, married, retired handyman, presenting with symptoms of bowel obstruction x 24 hours and 6 month hx of intermittent BRBPR) with progressive constipation.

PMHx – HTN, obesity, ex-smoker (age 57, 40+ pk yrs). Retired 7 years ago due to chronic low back pain. Had gained 10 kg since then but loss 5 kg recently. No prior Sx or hospitalizations.

FHx - Only child, mother 84 (T2DM, HTN, Chol, CAD, prior TIA). Father died of lung cancer remotely

Meds – perindopril 4/12.5, aodipine 2.5 mg (took yesterday) NKDA

Case #1-ED

ROS- sedentary, fatigued, denies CV symptoms or syncope, MRC class 2 dyspnea (true?), no obvious OSA, no oral intake last 24 hours

Non-drinker,

Vitals: 115/85 P 95 (reg) afebrile O2sat 93%

PX: conjunctiva pale, distended abdomen(BS ), JVP low, no S3S4, no carotid bruit, prolonged exp phase, no edema, no rash, no nodes, no hepatosplenomegaly

Lab: Cr 98, K 3.9, Na 132, CO2 21, Cl 96 ; Hgb 120, Plt 276, WBC 14, cholestatic liver profile, albumin 38, INR/PTT normal

Case #1

What do you think his risk is high, low, something else?

What are his risk factors for AKI?

What to do preop? Investigations

interventions

AKI Risk Factors

Hypovolemia

Hypoalbuminemia

Advanced age >60, >75

Female

Black

Prior AKI

CKD (with or without proteinuria)

DM

CHFrEF (35% cardiac Sx) (50% CIN)

COPD

Cirrhosis

Hypotension

MM

CTD

Cancer

Sepsis

CIN

Drugs

General Sx

ContrastCardiac Sx

Community AKI

Wilson T et al. Nephrol Dial Transplant (2016) 31: 231–240

Comparison of 3 perioperative AKI evaluations

Biteker M et al 2014 Bell S et al 2015 Keterpal S et al 2009

N = 1200 prospective single acute care facility2010-2012

N = 10,615 (6220 development cohort, 4395 validation cohort)

N = 15,102 from 65,043 cs retrospective single acute care facility 2003-2006

AKI 6.7% N = 80 AKI 10.8 and 6.7 % AKI 0.8% N = 121

Age Age Age

RCRI Male Sex Male

DM DM DM

ASA ASA CHF

NSAID/Cox-2 Renal insufficiency

Total #of drugs Intraperitoneal Sx

ACEI/ARB Ascites

Emergency Sx

Biteker M et al Am J of Surgery 2014; 207(1): 53-59Keterpal S et al Anesthesiology 2007; 107: 892-902Bell S et al BMJ 2015;351:h5639

Our patient

Age Male ACE-I Hypovolemic Intraperitoneal Sx Emergency Sx?

What we added: HgbA1C 6.3% Urine dispstick +1; ACR 22 Urinalysis

James MT et al Am J of Kidney Dis 2015 66(4): 602-612

Dipstick

ACR

Neg <10

Trace 10-29

+1 30-299

+2 300-999

≥ +3 ≥ 1000

Partridge JS et al Age and Ageing 2012; 41: 142–147

TJA Silva Clinics(Sao Paulo)2009 Jul; 64(7): 613–618

Preop NT-proBNP

Meas perioperative High-sensitivity TNT, TNI, CK-MB, and NT-proBNP in AKI high risk CV pts:

≥ 1 of emergency surgery, preop sCr >177 mmol/L, ejection fraction ≤35% or less or grade 3 or 4 left ventricular dysfunction, age > 70, diabetes mellitus, concomitant CABG and valve surgery, or repeat revascularization surgery.

NT-proBNP had the best prediction rate for postop AKI and 1 yr mortality.

Belley-Cote EP et al Journal of Thoracic and Cardiovascular Surgery 2016; 152(1): 245-251

Preop risk factors – be proactive

AKI risk assessment tools have not been externally validated and most have been focused on identifying severe AKI.

The largest group of AKI pts Stage 1, may be under appreciated and misdiagnosed

Post op AKI has significant short and longterm consequences on par with perioperative MIs

Identifying the AKI risk pt preop may help reduce postop incidence +/or severity, LOS and readmission rates.

Preoperatively linking AKI risk assessment to risk reducing measures intra and post op requires communication and team work

Risk factors for AKI, MI, and frailty overlap in the elderly

Consider the usefulness of preop ACR , +/- your NT-proBNP level in the right patient

Intra-op

Hypotension

Anemia, Transfusion PRBCs

Protective measures

Intraop Hypotension and Risk of AKI

Time, MAP, BP sys thresholds

Valmasi

Accumulative time > 90 min at ≥ 20% drop from preop sys BP

If > 50% below preop sys BP for ≥ 5 min incr risk AKI/MI

Sun (retrospective)

MAP < 60 for > 20 min; MAP < 55 for 10 min

Walsh

MAP < 55 incr AKI/MI

< 55 for 1-5 6-10 11-20 AKI HR 1.18; > 20 min HR 1.51

Sun YS et al Anesthesiology 2015; 123: 515-523Salmasi V et al Anesthesiology 2017; 126: 47-65Walsh M et al Anesthesiology 2013; 119(3): 507-515Hallqvist L et al Eur J Anesthesia 2018;35: 273-279

Hgb

Preop anemia ≤ 80 assoc with post AKI risk

PRBCs during and after cardiac Sx (TAVI)(CABG) increase AKI risk

Also increases IL-18 and NGAL levels post op (≥ 2 units)

No evidence for protective medications or “ischemic preconditioning”

Thongprayoon C et al World J Nephrol 2016; 5(5): 82-88Tewari P et al J Cardiothoracic Surgery2015; 10(Suppl1): A168

Biomarkers More than 50, urine and/or serum

No funding for NGAL in Calgary

Intended to find the sub-clinical AKI, restratify AKI and understand it’s natural Hx.

More likely cost effective in the ICU

Molitoris BA and Reilly E, Semin Nephrol 2016; 36(1): 31-41

Forni LG et al Intensive Care Med (2017) 43:855–866

Ortega LM and Heung M Nefrologia 2018; 38(4): 361-367

The 5 Rs

Risk

Recognition

Response

Recovery

Rehabilitation

Ebah L et al BMJ Quality Improvement Reports 2017;6:u219176.w7476.

Ebah L et al BMJ Quality Improvement Reports 2017;6:u219176.w7476.

Outcomes: 2015 to date

31% reduction new AKI

23% reduction in LOS

40% reduction in time to AKI recovery

10% reduction in AKI deaths

Ebah L et al BMJ Quality Improvement Reports 2017;6:u219176.w7476.

Summary

Clinical approaches to Dx and manage AKI at risk pts will

Continue to evolve along pt “care bundles”

Be more multi-disciplinary than present

Introduce new technologies and types of information into the clinical spaces

Require more cooperation and teamwork in the spirit of proactiveness

For now

If you haven’t been, focus preop more specifically on perioperative AKI risk

Discuss ways to improve Dx and management with your colleagues

Ensure appropriate follow up

Case#1- on the ward

Day 1 post op

u/o down overnight, 300 ml over 10 hrs

IV running NS 150 hr for the last hr, overnight IV went interstitial

Clinically hypovolemic

Foley catheter in situ

sCr 155

What do you think is going on?

What are you going to do?

Alberta AKI QI project

E-alerts (KDIGO stage 1, 2, 3)

Clinical pathway based on pre-intra- and post- renal evaluation for AKI and initial response

Order sets – diet, monitoring laboratory (focus on day 2 & 3), diagnostic imaging and fluid therapies

Disposition planning

Rural considerations

Minjae K et al Anesthesia & Analgesia 2014; 119(5): 1121-1132

Support AKI Outcome measures

When to involve Nephrology?

A possible diagnosis that may need specialist treatment (eg., presence of proteinuria or hematuria on urinalysis can suggest kidney vasculitis or glomerulonephritis; white blood cell casts can suggest tubulointerstitial nephritis; anemia, hypercalcemia, and fractures can suggest multiple myeloma)

* Acute kidney injury of unclear etiology (no pre-renal or post-renal cause identified)

* Progressive AKI despite correction of pre-renal/post-renal factors

* A kidney transplant

* Pre-existing advanced chronic kidney disease, eGFR less than 30mL/min/1.73m2

* Complications associated with AKI which may require renal replacement therapy:

o Hyperkalemia refractory to medical therapy

o Metabolic acidosis refractory to medical therapy

o Symptoms or complications of uremia (pericarditis, encephalopathy)

o Fluid overload causing respiratory compromise (pulmonary edema)

Discharge

Calculate the pt’s “Advanced CKD after AKI Risk Index”

Refer to nephrology, as necessary