AKI to CKD
Epidemiology and Predictive Models
Lakhmir S. Chawla, MD
Overview
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•
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Background
Clinical Epidemiology
Mechanism of Post-AKI to CKD Progression
Trial Design
Study’s Conclusion
Coca et al, Kidney International, 2011
90
CON
Mean eGFR (ml/min/1.73m2)
80
70
ARF
60
ATN
50
CKD
40
30
20
1-yr Pre
0-30 days
1-3 mos. post
Time Period
3-12 mos. post
1-5 yrs post
AKI Progression to CKD
Pediatrics
49 studies, 3,476 patients
From: Long-term Renal Prognosis of Diarrhea-Associated Hemolytic Uremic Syndrome: A Systematic Review,
Meta-analysis, and Meta-regression
JAMA. 2003;290(10):1360-1370. doi:10.1001/jama.290.10.1360
Figure Legend:
These studies had a higher proportion of patients with death or permanentend-stage renal disease (ESRD) at follow-up, explaining
10% of the between-studyvariability (P = .02), and a higher proportion ofpatients with a glomerular filtration rate (GFR) lower than 80
mL/min per1.73 m2, hypertension, or proteinuria at last follow-up, explaining15% of the between-study variability (P<.001).The area
of each circle is proportional to the number of patients in eachstudy. Curves are best-fit lines from meta-regression. See "Methods"
section.
• 15/29 (59%) had at least one sign of renal
injury (hyperfiltration, decr. GFR, or HTN)
• Most conservative estimate
– 15/126 (11.9%)
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Fifty-two patients requiring RRT for AKI
Thirteen available for 12-18 year follow-up
9/13 had one sign/symptom of CKD
Majority of patients in both studies
unavailable for follow-up
PICU Study
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•
•
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BC Children’s prospective study
AKI defined by AKIN criteria
CKD = < 60 ml/min/1.73m2
CKD risk
– 60 to 90 ml/min/1.73m2 OR
– > 150 ml/min/1.73m2
• Microalbuminuria
• BP > 95th percentile
Summary
• De novo AKI is associated with Incident CKD
and ESRD
• Precise estimates of the incidence of CKD
progression after AKI in children are lacking
due to incomplete follow up
• Children who survive an episode of AKI
requiring RRT deserve long-term follow up
1 Billion
0
30d
2 million
60-90d
1.7
million
AKI
AKI Survivors
Round I
De novo and ACRF
24 mo
> 3 yrs
1.5
million
AKI Survivors
Round II
AKI Survivors
Round III
300K
170K
10-15% Mortality
10% ESRD
300K
20% CKD 4
How does AKI progress to CKD?
• Host Predisposition: genetics / co-morbidities
• Nephron loss followed by glomerular
hypertrophy
• Fibrosis and Maladaptive repair
• Vascular drop out as a consequence of
endothelial injury
Wynn, Nature Med, 2010
Bechtel, Nature Medicine 16, 544–550 (2010)
5 azacytidine
Acute Kidney Injury
Moderate Injury
Severe Injury
Normal Repair and
Recovery
Cell Cycle Arrest
TGF-Beta1
Predominates
Epigenetic Modification
Sustained Myofibroblast Activation
Interstitial Fibrosis
.
Spurgeon K R et al. Am J Physiol Renal Physiol
2005;288:F568-F577
©2005 by American Physiological Society
*Post-AKI vascular density does NOT return to normal
*VEGF 121 given early after AKI preserves vascular density
*High Na diet promotes fibrosis and progression to CKD
Can We Intervene?
• So what?
• Just like all AKI, if we don’t dialyze it now, we
will have to dialyze it later
• Identification of patients at risk
• What are the risk factors?
Derivation Cohort – 5,351 -> Hospitalized patients with ATN or ARF, without CKD
Validation Cohort - 11,589 -> Hospitalized patients with MI or Pneumonia and AKI - RIF
Derivation Cohort
Validation Cohort
Model 1 - Full
C = 0.82, p < 0.0001
C = 0.81, p < 0.0001
Model 2 - Abbreviated
C = 0.81, p < 0.0001
C = 0.81, p < 0.0001
Model 3 – Sentinel Events
C = 0.77, p < 0.0001
C =0.82, p < 0.0001
One Year Survivors of AKI
Interventions
• Nephrologist (CKD clinic) See the patient?
– HTN control
– ACEi
– Low protein diet
• TGF-Beta inhibition
• VEGF promotion (early post-AKI)
• p53 inhibition (early post-AKI)
Summary
• Severity of AKI is associated with CKD
progression in AKI survivors
• Decreased concentration of serum albumin is
associated with progression to CKD
– Likely a marker if increased inflammation
• Breaking the vicious cycle of AKI to CKD to AKI
to ESRD could have significant impacts on
disease burden
Future Directions
• Beta-blocker for MI allegory
• Primary prevention study in AKI survivors to
prevent progression to CKD
• Identify patients at risk
• Enroll, randomize
• 2 x 2 factorial design
• Interventions: BP control, RAAS inhibition, antiinflammatory agents,