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

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Presentation on theme: "AKI to CKD Epidemiology and Predictive Models Lakhmir S. Chawla, MD."— 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 Studys Conclusion

4 Coca et al, Kidney International, 2011



7 AKI Progression to CKD Pediatrics

8 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



11 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 12-18 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 Childrens prospective study AKI defined by AKIN criteria CKD = < 60 ml/min/1.73m 2 CKD risk – 60 to 90 ml/min/1.73m 2 OR – > 150 ml/min/1.73m 2 Microalbuminuria BP > 95 th 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 De novo and ACRF 10-15% Mortality AKI Survivors Round I 10% ESRD AKI Survivors Round II AKI Survivors Round II 20% CKD 4 AKI Survivors Round III AKI Survivors Round III 030d60-90d 24 mo > 3 yrs 2 million 1.7 million 1.5 million 300K 170K 300K 1 Billion

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 Normal Repair and Recovery Moderate InjurySevere Injury 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 dont 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 - 11,589 -> Hospitalized patients with MI or Pneumonia and AKI - RIF


28 Derivation CohortValidation Cohort Model 1 - FullC = 0.82, p < 0.0001C = 0.81, p < 0.0001 Model 2 - AbbreviatedC = 0.81, p < 0.0001 Model 3 – Sentinel EventsC = 0.77, p < 0.0001C =0.82, p < 0.0001


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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