Caring for the AKI Survivor: What is Required?

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Caring for the AKI Survivor: What is Required? Ron Wald, MDCM MPH FRCPC Division of Nephrology St. Michael s Hospital and University of Toronto February 28, 2019

A patient in your ICU 65M with DM, HTN, COPD admitted for septic shock in context of urosepsis ventilation and pressors required oliguric, scr 5.1 mg/dl (baseline scr 1.0 mg/dl) CRRT is started

Course in hospital After 5 days on CRRT, urine output shows progressive improvement CRRT withdrawn scr stabilizes at 200 2.2 mg/dl with no requirement for dialysis x 5 days patient ready for discharge to the ward 10 days later, discharged to Rehab, serum creatinine 1.6 mg/dl

Questions for consideration What is the likelihood that this patient will return to his pre-morbid level of kidney function? When should kidney function be rechecked? What are the risks that this patient faces in the coming weeks and months?

Objectives To review kidney and non-kidney outcomes of relevance to AKI survivors To review interventions designed to improve outcomes for AKI survivors To discuss recent research on the prediction of adverse kidney outcomes among AKI survivors

Threats affecting AKI survivors CKD- de novo/progressive Recurrent AKI Rehospitalization Cardiovascular health Medication errors Quality of life

Reversible AKI and the risk of CKD Cohort study in a large health provider in Pennsylvania, 2004-2007 Identified 1,997 patients admitted to hospital with AKI (50% increase in scr) who also: Had no evidence of egfr < 60 or urinary abnormalities in preceding year Survived to 90 days following discharge Recovered > 90% of baseline GFR Bucaloiu KI 2012

AKI and de novo CKD AKI (n=1610) No AKI (n=3652) Age 63.0 (52.0, 74.0) 63.0 (51.0, 73.0) ICU, % 9.7 7.3 Baseline egfr 97.2 (86.4,110.0) DM 28.9 26.7 HTN 57.7 55.8 CAD 22.7 21.4 97.0 (86.1, 109.7) Bucaloiu KI 2012

Time to CKD by AKI Status RR for CKD 2.14 (95% CI,1.96-2.43) Bucaloiu KI 2012

The risk of chronic dialysis in survivors of AKI-D in Canada Risk of chronic dialysis Adjusted HR: 3.22 (2.70-3.86) (n=3769) (n=13,598)

Recurrent AKI in the US VA Median time to recurrent AKI 64 d ~60% of events occurred within 90 d Key risk factors: Older age Comorbidities (CKD, DM, CAD, dementia) Index hospitalization dx (HF, malignancy, volume depletion) Receipt of chemotherapy Siew et al, JASN 2015

AKI survivors are at higher risk of 30-day all-cause rehospitalization ahr=1.53 (1.50-1.57) Silver et al Am J Med 2016

Are there non kidney-related outcomes that we need to worry about?

AKI and the risk of major adverse cardiovascular events AKI MI MI + AKI Chawla et al CJASN 2014

The risk of heart failure following AKI 1.2M admissions to VA hospitals 150,000 with AKI (mostly stage 1) Matched 1:1 with hospitalized patients who did not experience AKI No patient had pre-existing heart failure Primary outcome: incident heart failure defined as hospitalization with HF or 2 ambulatory visits for HF, within 2 years of index hospitalization Bansal et al AJKD 2018

The risk of heart failure following AKI HR 1.23 (95% CI 1.19-1.27)

Cardiovascular health following AKI AKI is a risk factor for de novo hypertension 43,611 normotensive patients hospitalized between 2008-2011 An episode of AKI was independently associated with a diagnosis of hypertension (aor 1.22, 95% CI 1.12-1.33) with risk higher in greater AKI severity Hsu JASN 2015

Quality of life following AKI-D troubling data from the ATN trial 415 participants who survived to Day 60 Health utility measured in 8 domains* on scale of 0 (~ death) to 1 (perfect health) 27% had health utility index of 0 (ie, equal to or worse than death) *vision, hearing, speech, ambulation, dexterity, emotion, cognition, and pain Johansen et al, CJASN 2010

To summarize AKI is associated with a myriad of bad outcomes including CKD Recurrent AKI and rehospitalization CVD Heart failure Poor HRQoL Are these relationships causal? Does causality matter?

Objectives To review kidney and non-kidney outcomes of relevance to AKI survivors To review interventions that may improve outcomes for AKI survivors To discuss recent research on the prediction of adverse kidney outcomes among AKI survivors

RAAS blockade after AKI Brar et al JAMA Int Med 2018

RAAS blockade after AKI Central research question: Does the prescription of an ACEi or ARB within 6 months after discharge improve survival in AKI survivors? 46,253 Albertans hospitalized with AKI between July 1, 2008- March 31, 2013 who survived to discharge 9456 ACEi/ARB recipients matched 1:1 to those who did not receive a ACEi/ARB rx

RAAS blockade after AKI

Given the complexity of AKI survivors, can enhanced processes of care improve patients outcomes?

How can we address these simultaneous threats to AKI survivors? One possible solution: nephrologist-led structured follow-up addresses the inadequate follow-up accorded to AKI survivors recognizes the unique complexity and dynamic nature of this population rooted in data from HF, CAD and COPD populations

Nephrology Follow-Up for AKI-D Survivors HR 0.76 (95% CI: 0.62-0.93) Seeing a nephrologist within 90 days of discharge associated with a 25% reduction in mortality Harel et al Kidney Int 2013

The SMH AKI Follow-Up Clinic initiated at St. Michael s Hospital, Toronto in September 2013 goal was to fill a perceived gap in the care provided to AKI survivors

Overview of the SMH AKI Follow-up Clinic Slide courtesy of S. Silver

What do we do in the AKI Follow-Up Clinic? BP and albuminuria control cardiovascular prevention as appropriate medication reconciliation sick day medication counselling facilitation of referrals patient and primary care MD education

Does any of this work? Nephrologist Follow-up versus USual care after an acute kidney Injury hospitalization (FUSION): A randomized controlled trial Clinicaltrials.gov NCT02483039 4-site RCT, envisioned as a vanguard phase for a definitive clinical trial

Research Question Does follow-up with a nephrologist in an AKI Follow-up Clinic within 30-days after a hospitalization complicated by AKI reduce the number of major adverse kidney events at one year compared to patients who do not receive follow-up in an AKI Follow-up Clinic?

Eligibility Criteria Inclusion Criteria Age 18 years Kidney Disease Improving Global Outcomes stage 2 AKI and above (including need for dialysis) Exclusion Criteria Kidney transplant recipients Outpatient baseline egfr under 30mL/min/1.73m 2 Patients with a persistent requirement for dialysis Clinical diagnosis or suspicion of: glomerulonephritis, vasculitis, HUS, PCKD, myeloma cast nephropathy Pregnancy Residence at a nursing home facility Palliation as primary goal of care Previously established and ongoing nephrology follow-up

Intervention Group Nephrologist visit within 30-days of hospital discharge with further appointments at the discretion of the nephrologist Standardized assessment forms provided to help direct care Routine bloodwork at least every 3 months for 12 months AKI Follow-up Clinic discharge at one year post-randomization

Usual Care Group Patient letter outlining AKI diagnosis and followup recommendations Telephone calls by study staff at 3, 6, and 9 months post-randomization Optional nephrology visit at 12 months to act as end-of-study visit participants may still be referred to a nephrologist by their healthcare provider, but they will be triaged as any other nephrology referral

Primary Outcome: Major Adverse Kidney Events (MAKE) at 1 Year Composite outcome: Death Chronic dialysis CKD progression Incident CKD = first time egfr is under 60mL/min/1.73m 2 and stays below this value for 3 months Progressive CKD = 25% egfr decrease from known baseline that is <60mL/min/1.73m 2 and the egfr stays below this value for 3 months

FUSION Pilot Results: Feasibility 269 eligible patients approached to participate 71 recruited Possible factors highlighting poor participation rates: limited appreciation of AKI in context of a complex stay in hospital too many MD appointments distance from SMH

FUSION: Baseline characteristics AKI Clinic (n=34) Age 64 (10) 66 (11) Female Sex 29% 32% ICU 44% 49% Usual Care (n=37) LOS 12 (7-21) days 16 (10-22) days Stage 2 32% 46% Stage 3 68% 54% Baseline egfr 79 (23) 73 (22) Discharge egfr 55 (23) 59 (27) Silver SA et al, unpublished data

Alternative approaches to ensure better post-aki care Reduce dependence on return hospital visits Telehealth, home BP checks, PoC monitoring Engage nurse navigators to carry out a multidisciplinary intervention Target the intervention to patients at the highest risk

Objectives To review kidney and non-kidney outcomes of relevance to AKI survivors To review interventions that may improve outcomes for AKI survivors To discuss recent research on the prediction of adverse kidney outcomes among AKI survivors

Are there some patients who are destined for a higher likelihood of kidney non-recovery? James et al JAMA 2017

Prediction of advanced Patient population: CKD after AKI hospitalized with AKI between 2004-2014 pre-existing egfr > 45 ml/min/1.73 m 2 survived for > 30 days following discharge 9973 patients in Alberta and 2761 in Ontario Outcome: egfr < 30 ml/min/1.73 m 2 or need for maintenance dialysis between 30 days and 1 year after hospital discharge James et al JAMA 2017

Prediction of advanced CKD after AKI

This area is receiving increasing attention

Care of the AKI survivor: Final points the AKI survivor is a vulnerable patient who remains susceptible to numerous risks well after acute illness has resolved post-discharge follow-up represents an opportunity to close an important healthcare gap patient selection and the nature of the interventions/follow-up are controversial new tools may help focus post-aki care to those most likely to derive benefit

Acknowledgements Funding: AFP Innovation Program (SMH and Sunnybrook) Sam Silver Ziv Harel Neill Adhikari, Ali Zahirieh Adic Perez-Sanchez Abhi Kitchlu, Dan Blum ICES Kidney Dialysis Transplantation Program

Caring for the AKI Survivor: What is Required? Ron Wald, MDCM MPH FRCPC Division of Nephrology St. Michael s Hospital and University of Toronto February 28, 2019