aki to ckd epidemiology and predictive models lakhmir s. chawla, md
TRANSCRIPT
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AKI to CKD Epidemiology and Predictive Models
Lakhmir S. Chawla, MD
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Overview
• Background• Clinical Epidemiology• Mechanism of Post-AKI to CKD Progression• Trial Design
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Study’s Conclusion
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Coca et al, Kidney International, 2011
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CKD
CON
ARF
ATN
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AKI Progression to CKDPediatrics
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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
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.
Figure Legend:
49 studies, 3,476 patients
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• 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
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PICU Study
• 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
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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
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AKIDe novo and ACRF
10-15% Mortality
AKI Survivors Round I
10% ESRD
AKI SurvivorsRound IIAKI SurvivorsRound II
20% CKD 4
AKI SurvivorsRound IIIAKI SurvivorsRound III
0 30d 60-90d 24 mo > 3 yrs
2 million 1.7 million
1.5 million
300K170K
300K
1 Billion
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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
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Wynn, Nature Med, 2010
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Bechtel, Nature Medicine 16, 544–550 (2010) 5 azacytidine
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Acute Kidney Injury
Normal Repair and Recovery
Moderate Injury Severe Injury
Cell Cycle Arrest
TGF-Beta1 Predominates
Epigenetic Modification
Sustained Myofibroblast Activation
Interstitial Fibrosis
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.
Spurgeon K R et al. Am J Physiol Renal Physiol 2005;288:F568-F577
©2005 by American Physiological Society
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*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
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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?
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Derivation Cohort – 5,351 -> Hospitalized patients with ATN or ARF, without CKDValidation Cohort - 11,589 -> Hospitalized patients with MI or Pneumonia and AKI - RIF
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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
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One Year Survivors of AKI
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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)
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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
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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, anti-
inflammatory agents,