Une promenade dans l'épidémiologie de l'insuffisance rénale aiguë en quatre étapes

Une promenade dans l'épidémiologie de l'insuffisance rénale aiguë en quatre étapes Fernando Liaño Hospital Universitario Ramón y Cajal Madrid, España Genéve, 14-12-2012

Une promenade dans l'épidémiologie de l'insuffisance rénale aiguë en quatre étapes: Préambule Histoire L'épidémiologie dans l'unité de soins intensifs Un appel de réveil

AKI epidemiology runs fast Hsu RK et al. In 2012 stated: Our findings are consistent with and extend on older studies showing an increase in disease (AKI) incidence in the United States over time 7,8 7.-Hsu CY et al.kidney Int 2007 8.- Waikar SS et al. J Am Soc Nephrol 2006 Hsu RK et al. J Am Soc Nephrol 2013. doi: 10.1681/ASN.2012080800

Une promenade dans l'épidémiologie de l'insuffisance rénale aiguë en quatre étapes: Préambule Histoire L'épidémiologie dans l'unité de soins intensifs Un appel de réveil

Clinical & epidemiological cornerstones in ARF/AKI 2007 2005 2004 2000 1990's 1990 1985 1977 1973 1951 1941 1917 War nephritis (Weldon) Crush syndrome (Bywaters) 1st Acute dialysis (Kolf) APACHE II (Knaus) RRT 1st CAVHF Dosification (Kramer) (Ronco, Schiffl) Isolated UF (Bergström) Definition & standardization RIFLE (Bellomo) Long-term outcomes (Schiffel/liaño) Biomarkers (Mishra)

Clinical & epidemiological cornerstones in ARF/AKI 2007 2005 2004 2000 AKI (Bellomo) 1990's 1990 1985 1977 1973 1951 1941 1917 War nephritis (Weldon) ARF (Smith) Crush syndrome (Bywaters) 1st Acute dialysis (Kolf) APACHE II (Knaus) RRT 1st CAVHF Dosification (Kramer) (Ronco, Schiffl) Isolated UF (Bergström) Definition & standardization RIFLE (Bellomo) Long-term outcomes (Schiffel/liaño) Biomarkers (Mishra)

Clinical & epidemiological cornerstones in ARF/AKI Beginning of the cohort studies 2007 2005 2004 2000 AKI (Bellomo) 1990's 1990 1985 1977 1973 1951 1941 1917 War nephritis (Weldon) ARF (Smith) Crush syndrome (Bywaters) 1st Acute dialysis (Kolf) APACHE II (Knaus) RRT 1st CAVHF Dosification (Kramer) (Ronco, Schiffl) Isolated UF (Bergström) Definition & standardization RIFLE (Bellomo) Long-term outcomes (Schiffel/liaño) Biomarkers (Mishra)

Clinical & epidemiological cornerstones in ARF/AKI Beginning of the cohort studies 2007 2005 2004 2000 1st Epidemio. Study AKI (Bellomo) 1990's 1990 1985 1977 1973 1951 1941 1917 War nephritis (Weldon) ARF (Smith) Crush syndrome (Bywaters) (Eliahou) 1st Acute dialysis (Kolf) 1st CAVHF (Kramer) Isolated UF (Bergström) APACHE II (Knaus) RRT Dosification (Ronco, Schiffl) Definition & standardization RIFLE (Bellomo) Long-term outcomes (Schiffel/liaño) Biomarkers (Mishra)

Clinical & epidemiological cornerstones in ARF/AKI 2007 2005 2004 2000 Beginning of the cohort studies 1st Epidemio. 1st Chapter Epidemio. Study AKI (Bellomo) 1990's 1990 1985 1977 1973 1951 1941 1917 War nephritis (Weldon) ARF (Smith) Crush syndrome (Bywaters) (Kleinknecht) (Eliahou) 1st Acute dialysis (Kolf) 1st CAVHF (Kramer) Isolated UF (Bergström) APACHE II (Knaus) RRT Dosification (Ronco, Schiffl) Definition & standardization RIFLE (Bellomo) Long-term outcomes (Schiffel/liaño) Biomarkers (Mishra)

1990

Clinical & epidemiological cornerstones in ARF/AKI 2007 2005 2004 2000 1990's 1990 1985 1977 1973 1951 1941 1917 War nephritis (Weldon) Beginning of the cohort studies 1st Epidemio. Study ARF (Smith) Crush syndrome (Bywaters) 1st Epidemio. Chapter 1st Acute dialysis (Kolf) Multicentre studies (Kleinknecht) (Eliahou) (Feest, Liaño, Brivet) 1st CAVHF (Kramer) Isolated UF (Bergström) AKI APACHE II (Knaus) (Bellomo) RRT Dosification (Ronco, Schiffl) Definition & standardization RIFLE (Bellomo) Long-term outcomes (Schiffel/liaño) Biomarkers (Mishra)

Clinical & epidemiological cornerstones in ARF/AKI 2007 2005 2004 2000 1990's 1990 1985 1977 1973 1951 1941 1917 War nephritis (Weldon) Beginning of the cohort studies 1st Epidemio. Study ARF (Smith) Crush syndrome (Bywaters) 1st Epidemio. Chapter 1st Acute dialysis (Kolf) Multicentre studies (Kleinknecht) (Eliahou) 1st Use of administrative databases (Feest, Liaño, Brivet) 1st CAVHF (Kramer) Isolated UF (Bergström) AKI APACHE II (Knaus) (Liangos, Waikar, Xue) (Bellomo) RRT Dosification (Ronco, Schiffl) Definition & standardization RIFLE (Bellomo) Long-term outcomes (Schiffel/liaño) Biomarkers (Mishra)

Clinical & epidemiological cornerstones in ARF/AKI 2007 2005 2004 2000 1990's 1990 1985 1977 1973 1951 1941 1917 War nephritis (Weldon) Beginning of the cohort studies 1st Epidemio. Study ARF (Smith) Crush syndrome (Bywaters) 1st Epidemio. Chapter 1st Acute dialysis (Kolf) Multicentre studies (Kleinknecht) (Eliahou) Epidemiological Population-Based Use of RIFLE 1st Use of administrative databases (Feest, Liaño, Brivet) 1st CAVHF (Kramer) Isolated UF (Bergström) AKI APACHE II (Knaus) (Bellomo) RRT Dosification (Ronco, Schiffl) (Ali) (Liangos, Waikar, Xue) Definition & standardization RIFLE (Bellomo) Long-term outcomes (Schiffel/liaño) Biomarkers (Mishra)

Clinical & epidemiological cornerstones in ARF/AKI 2007 2005 2004 2000 1990's 1990 1985 1977 1973 1951 1941 1917 War nephritis (Weldon) Beginning of the cohort studies 1st Epidemio. Study ARF (Smith) Crush syndrome (Bywaters) 1st Epidemio. Chapter 1st Acute dialysis (Kolf) Multicentre studies (Kleinknecht) (Eliahou) Epidemiological Population-Based Use of RIFLE 1st Use of administrative databases (Feest, Liaño, Brivet) 1st CAVHF (Kramer) Isolated UF (Bergström) AKI APACHE II (Knaus) (Bellomo) RRT Dosification (Ronco, Schiffl) (Ali) (Liangos, Waikar, Xue) Definition & standardization RIFLE (Bellomo) Long-term outcomes (Schiffel/liaño) Biomarkers (Mishra) Search for new issues

Une promenade dans l'épidémiologie de l'insuffisance rénale aiguë en quatre étapes: Préambule Histoire L'épidémiologie dans l'unité de soins intensifs Un appel de réveil

Epidemiology of AKI in the ICU setting Incidence and mortality Time of development Etiology Early outcome Late outcome

Patients Initial Hospital Location Gynaecology ICU Nephrology 1% 27% 13% 34% Medical Dpts. 2% Traumatology 23% Surgical Dpts. Liaño F et al. Kidney Int 1996; 50:811-818

AKI in critically-ill patients: Multicentre prospective studies PATIENTS ADMITTED IN 54 ICU: 29,269 (Multinational) WITH AKI: 1,738 ICU Incidence: 5.7 % PATIENTS ADMITTED IN 43 ICU: 15,714 (National - Spain) WITH AKI: 901 ICI Incidence: 5.7 % Uchino et al. JAMA 2005; 294: 813-818 Herrera et al. Med Intensiva 2006; 30:260-267

Incidence of AKI according to age during a decade in Australia Age in years Median age: 64.1 (49-74) Bagshaw SM et al. Critical Care 2007; 11:R68

Incidence (%) Effect of the level of serum creatinine concentration in AKI diagnosis in a series of 9,210 patients admitted to Brigham and Women s Hospital 18 16 14 12 10 8 6 4 N= 1564 N = 885 N = 246 N = 105 2 0 0.3-0.4 0.5-0.9 1.0-1.9 > 2.0 SCr in mg/dl Chertow G et al. J Am Soc Nephrol 16: 3365-3379, 2005

a ICU Incidence of early AKI in the same setting (ANZICS Database) varies with definition PATIENTS ADMITTED IN 20 ICU: 91,254 1996-2005 Criteria: SCr>1.5 mg/dl AKI 4,754 Incidence: 5.2 % b PATIENTS ADMITTED IN 57 ICU: 120,123 2000-2005 Criteria: RIFLE AKI 43,395 Incidence: 36.0 % a) Bagshaw SM et al. Critical Care 2007; 11:R68 b) Bagshaw SM et al. Critical Care 2008; 12:R47

Mortality (%) Declining Fracaso renal mortality in patients with acute renal failure, agudo 1988 to 2002. Waikar SS et al. J Am Soc Nephrol 2006; 17: 1143-1150 45 40 35 30 25 20 15 10 ARF with dialysis ARF 5 0 1988 1989 1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 Incidence: 1988 610/1,000,000 inhabitants 2002 2880/1,000,000 h

Mortality (%) Declining Fracaso renal mortality in patients with acute renal failure, agudo 1988 to 2002. Waikar SS et al. J Am Soc Nephrol 2006; 17: 1143-1150 45 40 35 30 25 20 15 10 5 0 1988 ARF with dialysis ARF 1989 1990 Incidence: 1988 1991 1992 1993 1994 1995 1996 610/1,000,000 inhabitants 1997 1998 1999 2002 2880/1,000,000 h Δ 10 % YEARLY 2000 2001 2002

Incidence of dialysis-requiring AKI Hsu RK et al. J Am Soc Nephrol 2013. doi: 10.1681/ASN.2012080800

Incidence of dialysis-requiring AKI Δ 10 % YEARLY Hsu RK et al. J Am Soc Nephrol 2013. doi: 10.1681/ASN.2012080800

Mortality (%) Mortality rate during a decade for early AKI in a cohort of Australian ICUs Year AKI No AKI Bagshaw SM et al. Critical Care 2007; 11:R68

Epidemiology of AKI in the ICU setting Incidence Time of development Etiology Early outcome Late outcome

AKI can develop in: Community ICU Hospital Ward

AKI can develop in: Community Late AKI ICU Hospital Ward Early AKI

ICU Incidence of AKI using RIFLE criteria Hoste EAJ et al Critical Care 2006; 10: R73

ICU Incidence of AKI using RIFLE criteria Early AKI 22% Hoste EAJ et al Critical Care 2006; 10: R73 Late AKI 45%

ICU Incidence of AKI using RIFLE criteria Early AKI 22% 67 % Hoste EAJ et al Critical Care 2006; 10: R73 Late AKI 45%

Epidemiology of AKI in the ICU setting Incidence Time of development Etiology Early outcome Late outcome

TYPE OF AKI Type (%) ICU n = 253 No-ICU n = 495 P ATN 76 37 <0.001 Prerenal 18 28 0.002 Acute-on- 8 15 0.005 Chronic Obstructive 0,8 15 <0.001 ATIN 0 3 <0.001 Acute GN 2 4 0.325 Others 1,2 10 <0.001 Liaño F et al. Kidney Int Suppl 1998; 66:S16-S24

Causes associated with the development of AKI in 1,726 criticallyill patients 50 45 40 35 30 25 20 15 10 5 0 Septic shock Surgery Cardiogenic shock Hypovolemia Drugs HRS Obstructive Others Uchino et al. JAMA 2005; 294: 813-818

Epidemiology of AKI in the ICU setting Incidence Time of development Etiology Early outcome Late outcome

ORIGINAL DISEASE PREVIOUS HEALTH CONDITION KIND AND SEVERITY OF KIDNEY INSULT Baseline SCr Acute response Short-term outcome RECOVERY DEATH

Analysis of the cardiovascular co-morbility in ARF and non-arf cases: an estimation in 29,039,599 hospitalised patients in the USA during 2001 Liangos O et al. Clin J Am Soc Nephrol 1: 43-51, 2006 35 30 25 20 15 10 5 0 * Coronary Dis. * * * * HF CKD HT Diabetes ARF No ARF (558,032) (28,481,567) *, p < 0.0001

HRs for in-hospital Mortality by Baseline CKD and AKI status HR egfr (ml/min/1.7m 2 ) Pannu N et al. Am J Kidney Dis 2011; 58:206-213 40,000 pats.

ORIGINAL DISEASE PREVIOUS HEALTH CONDITION KIND AND SEVERITY OF KIDNEY INSULT Baseline SCr Acute response Short-term outcome RECOVERY DEATH Mortality in ICU: 30-80%

Incidence and outcomes of AKI in intensive care units: A veterans administration study Thakar CV et al. Crit Care Med 2009; 37: 2552-2558 Retrospective observational study in a national cohort of 325,398 pats. Admitted to 191 ICUs (2001-2006). AKI: AKIN classification ICU evaluated by a VA system

Incidence and outcomes of AKI in intensive care units: A veterans administration study Thakar CV et al. Crit Care Med 2009; 37: 2552-2558 326,395 ICU pats (22 %) 71,486 AKI (4.4 %) 3,140 needed RRT. Odds of death by severity of AKI Aki stage Odds ratio 95% CI I 2.23 2.17-2.30 II 6.08 5.74-6.44 III 8.6 8.08-9.15 III -RRT 5.78 5.30-6.31

ORIGINAL DISEASE PREVIOUS HEALTH CONDITION KIND AND SEVERITY OF KIDNEY INSULT Baseline SCr Acute response Length of AKI Short-term outcome RECOVERY DEATH

Mortality rates by magnitude and length of Acute Kidney Injury Coca et al. Kidney Int 2010; 78:926-933 35,302 Postoperative diabetic pats. (non cardiac sur). VA data AKI:18% ICU information not provided

Epidemiology of AKI in the ICU setting Incidence Time of development Etiology Early outcome Late outcome

ORIGINAL DISEASE PREVIOUS HEALTH CONDITION KIND AND SEVERITY OF KIDNEY INSULT Baseline SCr Acute response Short-term outcome DEATH RECOVERY Long-term outcome TOTAL Recov. CKD? DEATH

Cumulative Survival Rate LONG-TERM ATN SURVIVAL CURVES: ICU vs NON-ICU PATIENTS 1 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 0 Non ICU patients p=0.002 ICU patients 1 2 3 4 5 6 7 8 9 1011 1213141516171819202122 Years Liaño F et al. Kidney Int 2007; 71:679-686

FACTORS ASSOCIATED WITH LONG-TERM MORTALITY IN ATN: Reference Value Regresion Coefficient p Relative Risk Confidence Interval AGE 0.05 0.000 1.05 1.03-1.07 Co-morbid Factors Absent 1.40 0.009 4.08 1.42-11.7 Type of admission: Surgical Medical -0.68 0.002 0.50 0.33-0.78 Non-Oliguric ARF Oliguric ARF -0.69 0.005 0.50 0.31-0.80 ATN: LONG-TERM OUTCOME

Risk of Chronic Dialysis and All-Cause of Mortality in AKI-dialysed patients and matched patients without AKI Wald et al. JAMA 2009; 302: 1179

Risk of Chronic Dialysis and All-Causes of Mortality in AKI-dialysed patients and matched patients without AKI Wald et al. JAMA 2009; 302: 1179

Rate ratios of mortality and ESRD following AKI: Lancet 2010; 376:2096-2103 Mortality ESRD or doubling SCr RR (95 %CI) of AKI patients RR (95 %CI) of patients w/o AKI 900,000 patients

Une promenade dans l'épidémiologie de l'insuffisance rénale aiguë en quatre étapes: Préambule Histoire L'épidémiologie dans l'unité de soins intensifs Un appel de réveil

? AKI CKD Chronic RRT

From AKI to ESKD: could this hypothesis be true? AKI Recovery Recovery ESKD Chronic Dialysis Death Death Death

From AKI to ESKD: could this hypothesis be true? Recovery Recovery Chronic Dialysis AKI ESKD Death 50% Death Death 100% At discharge Alive 50 % Follow-up: 5 yr With CKD: range 14-61 (%) Alive: 50-70 % of survivors Follow-up: 5 yr On RRT 1% of survivors With data from : Ponte B et al. NDT 2008; 23 3859 & Schiffl H et al. NDT 2008; 23: 2235

Kidney Int 2012; 81:477-485 Methods: Propensity score-matched cohort. retrospective analysis Pennsylvania. (2004-2007) Populations: Patients dicharged alive 30,207 Reversible AKI: 1,997. (Critical Care: 18%) Length of AKI: 24 h: 75% Matched: 1,610 AKI vs 3,652 control pats. Excluded: egfr 60 ml/min/1.73 m 2 Hematuria and /or proteinuria

Kidney Int 2012; 81:477-485 Long-term survival Cumulative incidence of CKD Adjusted risk of mortality: HR 1.18 (CI 95%; 0.9-1.46) Risk of de novo CKD: HR 1.91 (CI 95%; 1.75-2.09)

CKD and Long-term AKI outcome Triverio PA et al. Nephrol Dial Transplant 2009; 24: 2186-89

ATN LONG-TERM OUTCOME: Causes of Mortality during the follow-up Cause of ATN admission 59.3 Cardiac 16,3 Neurological 8,1 Respiratory Insufficiency 7 7 Infection 4,6 Hepatic failure Other causes 17,4 Unknown 9,5 0 10 20 30 40 50 60 % Liaño F et al. Kidney Int 2007; 71:679-686

Une promenade dans l'épidémiologie de l'insuffisance rénale aiguë en quatre étapes Summary I The different epidemiological approaches, cohort, multicentre, population-based and administrative databases provide complementary information Serum creatinine is the main tool used in the epidemiological studies

Summary II Une promenade dans l'épidémiologie de l'insuffisance rénale aiguë en quatre étapes Incidence of AKI in the ICU is high and higher than in other settings Incidence rates vary according to the definition used Mortality remains high even though a trend to decrease has been observed AKI is more frequent among older patients

Une promenade dans l'épidémiologie de l'insuffisance rénale aiguë en quatre étapes Summary III CKD and other comorbidities contribute to development of AKI AKI seems to facilitate progression to CKD and death Comorbidities also influence long-term outcome and could be behind the progression to CKD and death

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