1. Acute Kidney Injury: Prevention is the Key!
Caribbean Institute of Nephrology
10th Annual Conference on Nephrology & Hypertension
Acute Kidney Injury: Prevention is the Key!
Michael Heung MD MS Associate Chief, Division of Nephrology
University of Michigan
@keepingitrenal

2. Disclosures
I have no relevant financial disclosures or conflicts of interest to report.

3. Outline/Learning Objectives
Describe impact of AKI on overall kidney disease burden
Describe approaches to AKI prevention
Discuss possible paths forward

4. AKI Epidemiology and Outcomes
Meta-analysis of large cohort studies, focusing on those using KDIGO definition for AKI (n=3,585,911)
Pooled incidence 21.6% in hospitalized adults
Mortality rate declined over study period ( )
All-Cause Mortality
Odds of mortality compared to no AKI
Susantitaphong et al, CJASN 2013;8:

5. Pooled AKI incidence rates by world regions
Susantitaphong et al, CJASN 2013;8:

6. AKI as a Pathway to CKD Non-Recovery ESRD Severe AKI Full Recovery
Traditional view:
- AKI could lead to ESRD or CKD directly through non-recovery or partial recovery respectively
- However, “full” renal recovery was considered a fortuitous and benign event
Partial recovery
CKD

7. Long-Term Renal Risk After AKI
Heterogeneity among studies, including definition of AKI
Emphasis on severe AKI
Limited data by AKI severity
Development of CKD:
Pooled HR 8.82
( )
2012 Meta-analysis illustrating the link between AKI and subsequent CKD and ESRD
Key points are on the slide:
Limitations include heterogeneity in how AKI was defined across different studies, plus more emphasis on severe AKI
Many studies used administrative data, so unable to compare by AKI severity
Nonetheless, you can see the significant increased risk for both CKD and ESRD after an episode of AKI
Development of ESRD:
Pooled HR 3.10
( )
Coca et al, KI 2012;81:442-8

8. Dialysis-Requiring AKI
Impact of “Mild” AKI
Analysis of 104,764 hospitalizations in VA (2011)
Relative Risk of CKD 1 Year After Hospitalization
Reference group is no AKI
Adjusted model
This slide brings the conversation back to the connection between AKI and later CKD.
In the VA, we saw a graded increased risk for CKD with worsening severity of AKI. But importantly, even mild (stage 1) AKI was associated with nearly double the risk of developing CKD compared to patients who did not have AKI.
Above are adjusted relative risk ratios from modified Poisson regression. Model included: age, race, sex, pre-admission diabetes and hypertension, sepsis, mechanical ventilation, baseline eGFR.
Stage 1 AKI
Stage 2 AKI
Stage 3 AKI
(no dialysis)
Dialysis-Requiring AKI
Heung et al, AJKD 2016;67:742-52

9. AKI Recovery Pattern Matters
Even transient (“benign”) AKI is associated with increased risk for subsequent CKD
Cause or association – does it matter? Importance of recognition and potential for secondary prevention
Follow-up data from previous slide, now incorporating novel aspect of “recovery pattern”.
Key point is that even mild, transient AKI (i.e. “prerenal azotemia”) appears to be important.
One can argue the causation vs association relationship, but regardless the relationship is there. This argues for increased awareness of longterm risk after AKI and therefore the need for follow-up (which is a segway to the next few slides).
Risk of CKD 1 Year After Discharge
Heung et al, AJKD 2016;67:742-52

10. Updated Paradigm: AKI and Renal Risk
Non-Recovery
ESRD
Primary Prevention
Secondary Prevention
Any AKI
Recovery
Secondary Prevention
Update paradigm: Even AKI with recovery puts patients at risk for longterm CKD and ESRD
Partial recovery
CKD

11. Challenges in Primary Prevention
Balancing nephrotoxin exposure versus clinical need  risk of “renalism”
Community-acquired AKI
Lack of high-level evidence-basis for specific interventions
Lack of nephrology involvement at prevention stage

12. Secondary Prevention
Prevention of mild AKI progressing to more severe AKI
Prevention of development/progression of CKD after AKI recovery
Promoting renal function recovery after severe AKI

13. “PrevAKI” Study
72hrs post-op
Meersch (2017): Single-center RCT (n=276) of pts undergoing cardiac surgery identified as high risk by [TIMP-2*IGFBP7] >0.3 at 4hrs post-CPB
Randomized to usual care versus “bundled care”
2 reasons to bring this up:
First study to show potential impact difference of biomarkers for AKI  how to incorporate into practice, perhaps?
Example of protocolized management having clinical benefit
Akin to what’s been shown in sepsis?
Meersch, Int Care Med 2017, epub Jan 21

14. PrevAKI “Bundle” Avoidance of nephrotoxins
Attempt to avoid radiocontrast
Discontinuation of ACEI/ARB for 48hrs post-op
Close monitoring of SCr and UOP
Avoidance of hyperglycemia
Close hemodynamic monitoring
Draw analogy to impact of bundling on sepsis outcomes (EGDT)
Meersch, Int Care Med 2017, epub Jan 21

15. BigpAK Study
Gocze (2017): Single-center RCT in patients undergoing major (>4hr) non-cardiac surgery (n=121)
High risk cohort ([TIMP2*IGFBP7]>0.3)
Any AKI
Stage 2/3 AKI
ICU LOS
P=0.035
48.0%
27.1%
19.7%
6.7%
Gocze Ann Surg 2017, epub Aug 29

16. BigpAK “Bundle”
Emphasis on volume therapy (balanced solutions) based on CVP<10 and evidence of fluid-responsiveness (SVV>10%, IVC<2cm, response to passive leg raise, response to 200mL fluid challenge)
Target MAP >65mmHg
Key difference: Nephrology consultation at time of randomization
Monitoring of nephrotoxins, medication adjustment
My new favorite study!
- Proof that nephrologists change outcomes???

17. Preventing Progression to CKD
Recognition of AKI as a prolonged inflammatory state
Bao (2014): Use of lithium to promote renal recovery post-AKI in micr models
Inhibitor of glycogen synthase kinase 3ß
Bao JASN 2014;25:

18. Retrospective cohort of AKI patients requiring
outpatient dialysis (n=100)
At 90 days follow-up: 43% recovered off-RRT, 48% ESRD N=
N =
Hemodial Int 2017; epub Mar 13

19. Predictors of Renal Recovery
Variable
Recovery (n=43)
Non-Recovery (n=57)
P-value
Diabetes Mellitus
25.6%
43.9%
0.059
CHF
42.1%
0.086
Charlson index
2.3 (1.7)
3.1 (1.8)
0.041
Baseline eGFR
73.6 (28.8)
51.6 (28.6)
<0.001
Initial RRT modality CRRT
48.8%
15.8%
UOP at discharge
684 (733)
279 (416)
0.002
No differences in laboratory parameters (Cr, BUN, albumin) at time of admission or RRT initiation
No differences in duration of inpatient RRT requirement
No differences in fluid overload

20. Outpatient Hemodialysis Care
Focusing on 1st week of outpatient dialysis:
Variable
Recovery (n=43)
Non-Recovery (n=57)
P-value
Total fluid removal (L)
4.1 (2.9)
5.3 (2.7)
0.037
Ultrafiltration rate (mL/kg/hr)
4.7 (3.2)
6.0 (3.2)
0.041
Hypotension
(>3 episodes of SBP<90)
9.3%
24.6%
0.049

21. What About Peritoneal Dialysis?
Potential advantages:
Preservation of residual renal function/promotion of renal recovery
Avoidance of catheter-related bloodstream infections
Less inflammation and hemodynamic instability compared to standard HD
Moist (JASN 2000): In new ESRD patients, compared to HD, PD associated with lower loss of residual renal function (adj OR 0.35, p=0.0001)

22. Potential Role of PD?
Theoretical benefit over HD for renal function recovery
At present, not enough evidence to clearly support a role
Testable hypothesis: Early conversion to PD around hospital discharge may increase likelihood of renal function recovery
Compared to standard IHD?
Compared to daily extended HD?
Potential pitfalls:
Training of an acute patient population
New urgent start PD programs, or assisted PD
Follow-up and monitoring of recovery
Metabolic effects (glucose)
Peritonitis risk (fluid overload)

23. Summary
AKI occurs commonly among hospitalized patients, and contributes significantly to overall kidney disease burden
At present, prevention of AKI remains the best approach to curbing the impact of this syndrome
Primary
Secondary

24. Thank you!