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AKI to CKD Epidemiology and Predictive Models

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Presentation on theme: "AKI to CKD Epidemiology and Predictive Models"— Presentation transcript:

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,

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