1. AKI to CKD Epidemiology and Predictive Models
Lakhmir S. Chawla, MD

2. Overview Background Clinical Epidemiology
Mechanism of Post-AKI to CKD Progression
Trial Design

3. Study’s Conclusion

4. Coca et al, Kidney International, 2011

6. CON
ARF
ATN
CKD
Figure 2b

7. AKI Progression to CKD Pediatrics

8. 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): doi: /jama
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.

11. Most conservative estimate
15/29 (59%) had at least one sign of renal injury (hyperfiltration, decr. GFR, or HTN)
Most conservative estimate
15/126 (11.9%)

12. Fifty-two patients requiring RRT for AKI
Thirteen available for year follow-up
9/13 had one sign/symptom of CKD
Majority of patients in both studies unavailable for follow-up

13. 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

16. 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

17. AKI 2 million 1.7 million 1.5 million 300K 170K 300K 1 Billion
d d mo > 3 yrs
2 million
1.7 million
1.5 million
AKI Survivors
Round II
AKI
De novo and ACRF
AKI Survivors
Round III
AKI Survivors Round I
300K
170K
300K
10-15% Mortality
10% ESRD
20% CKD 4

18. 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

19. Wynn, Nature Med, 2010

20. Bechtel, Nature Medicine 16, 544–550 (2010)
5 azacytidine

21. Acute Kidney Injury Moderate Injury Severe Injury
Normal Repair and Recovery
Cell Cycle Arrest
TGF-Beta1 Predominates
Epigenetic Modification
Sustained Myofibroblast Activation
Interstitial Fibrosis

22. . Spurgeon K R et al. Am J Physiol Renal Physiol 2005;288:F568-F577
©2005 by American Physiological Society

23. *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

25. 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?

26. Derivation Cohort – 5,351 -> Hospitalized patients with ATN or ARF, without CKD
Validation Cohort - 11, > Hospitalized patients with MI or Pneumonia and AKI - RIF

28. Derivation Cohort
Validation Cohort
Model 1 - Full
C = 0.82, p <
C = 0.81, p <
Model 2 - Abbreviated
Model 3 – Sentinel Events
C = 0.77, p <
C =0.82, p <

30. One Year Survivors of AKI

31. 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)

32. 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

33. 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,