Poster Title Acute Kidney Injury (AKI) biomarkers increased in pre-renal AKI. Although the concept of “ pre-renal azotaemia ” is ingrained into clinical practice, the distinction between pre-renal AKI when used to classify a group of causes of AKI leading to renal underperfusion and pre-renal AKI as a distinct and unique type of functional AKI (usually due to one of the pre-renal causes) has been a source of confusion and controversy. The distinction between the entities is potentially important because correction of “ pre-renal factors ” causing renal underperfusion may reverse pre-renal AKI, while neglecting these may lead to AKI becoming irreversible. Kidney injury biomarkers afford the opportunity to investigate if patients classified as having pre-renal AKI on the basis of retained tubular function or brief duration of AKI nevertheless demonstrate evidence of injury. HYPOTHESIS RESULTS Similarly, CysC, NGAL, and IL-18 concentrations were greater in pre-renal AKI-FEurea compared with Control (Table 1). In the cohort of patients in both pre-renal AKI-FENa and pre-renal AKI- FEurea groups only urinary NGAL and CysC were greater than Controls (p<0.01 and p<0.05 respectively, Table 1). No patients for whom AKI was transient (less than 48 hours) needed dialysis, while 15.8% (n=19) of patients in AKI 48 required renal replacement therapy. CONCLUSION METHODS This may not seem very important, I know. But it is! So, I’m bothering telling you so. Dr Suess, The Sleep Book. Printed byChristchurchKidneyResearchGroup Pre-renal AKI is reversible because injury is less severe not because it is a unique physiological response to hypoperfusion. INTRODUCTION. Table 1. Median (IQR) urinary biomarker concentrations in pre-renal AKI and AKI 48 Acknowledgments The EARLYARF study was supported by Health Research Council of New Zealand grant 05/131. Maryam Nejat was supported by a University of Otago Post-Graduate Scholarship. The dedication of John Dean, Jill Robinson, Robyn Hutchison and nursing staff of Canterbury and Dunedin hospitals and the Canterbury Health Laboratory is gratefully acknowledged. Figure 3. Effect of pre-renal AKI- FENa and AKI 48 on urinary biomarker concentration. Post-hoc LSD: different from Control (*p<0.05, **p<0.01, ***p<0.001); AKI 24-48, or AKI 48 versus AKI 24 (#p<0.05, ##p<0.01, ###p<0.001), AKI versus AKI 48 ( Øp ≤0.05, ØØp <0.01). Pre-renal AKI- FENa, AKI 48, and duration of AKI versus concentration of urinary CysC (A), NGAL (B), GGT (C), IL-18 (D), and KIM-1 (E). The median is indicated by a horizontal line within the boxes. The boxes show the inter-quartile range and the whiskers the 10 th - 90 th percentile Significance is versus Control in each case. REFERENCE 1. Endre ZH, Walker RJ, Pickering JW, et al. Early intervention with erythropoietin does not affect the outcome of acute kidney injury (the EARLYARF trial). Kidney Int 2010;77: Figure 2. Effect of duration of AKI on urinary biomarker concentration. Post-hoc least significant difference (LSD) analysis: difference from Control (*p<0.05, **p<0.01, ***p<0.001); AKI 24-48, or AKI 48 v. AKI 24 (#p<0.05, ##p<0.01, ### p<0.001), AKI v. AKI 48 (Øp≤0.05, ØØp<0.01). 1. University of Otago, New Zealand, 2. Cincinnati Children’s Hospital Medical Centre, USA, 3. Harvard Medical School, USA, 4. University of Colorado, USA. Maryam Nejat 1, John W Pickering 1, Prasad Devarajan 2, Joseph V Bonventre 3, Charles L Edelstein 4, Zolt á n H Endre 1 Figure 1. Patients in each group. Urinary CysC, NGAL, IL-18, GGT, and KIM-1 all increased with increasing duration of AKI (p<0.001) (Figure 2). The CysC, NGAL, IL-18, and KIM- 1 concentrations were greater in pre- renal AKI-FENa compared with Control, but were lower than AKI 48 (p<0.05, Table 1 and Figure 3). Five urinary biomarkers of injury, cystatin C (CysC), neutrophil gelatinase-associated lipocalin (NGAL),  -glutamyl transpeptidase (GGT), Interleukin-18 (IL-18) and Kidney Injury Molecule-1 (KIM- 1), were measured at three time points over the first 24 hours of admission of 529 patients from the EARLY ARF 1 trial in two general intensive care units. Plasma and urinary sodium and urea were measured on entry and FENa and FEurea were calculated. The maximum 0 to 24 hr biomarker concentration indexed to urinary creatinine was analysed. AKI was defined as an increase in plasma creatinine above baseline of ≥0.3 mg/dl within 48 hours. Pre-renal status on admission was defined by a low FENa or FEurea or both. Pre-renal AKI-FENa and pre-renal AKI-FEurea were defined as recovery within 48 hours with FENa <1 or FEurea <35 respectively. Patients were stratified according to duration of AKI: (i) recovery within 24 hours (AKI 24), (ii) recovery between 24 and 48 hours (AKI 24-48), (iii) no recovery within 48 hours or renal replacement therapy (AKI 48). Patients with no AKI within 48 hours served as controls. Differences between the distributions were assessed by ANOVA and the Mann-Whitney U test. Urinary biomarkers of injury increased in concentration with duration of AKI regardless of whether there was preservation of tubular function. This suggests that pre-renal AKI is a mild form of structural AKI rather than a unique functional form of AKI. Early return of renal function, as demonstrated by a decrease in creatinine, probably represents recovery not reversibility of a unique functional or physiological form of AKI.