Urine NGAL in the critically ill



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Urine NGAL in the critically ill preliminary results of the FINNAKI study Sara Nisula Intensive Care Units, Division of Anaesthesia and Intensive Care Medicine, Helsinki University Central Hospital, Helsinki, Finland

Background Neutrophil gelatinase-associated lipocalin (NGAL) Excellent predictor of AKI in isolated cohorts (cardiac surgery, children) Performance varies in critically ill populations Appears to be useful in prediction of the initiation of RRT Accuracy in mortality prediction? Haase M, Bellomo R, Devarajan P et al. Meta-analysis Am J Kidney Dis. 2009

1.Half (1.9. 1.12.2011) 1063 patients U-NGAL not analyzed 487 No AKI (62.7%) 90-day mortality 14.6 % 3494 Admissions 1840 patients 777 patients 290 AKI (37.3%) 90-day mortality 26.2 % 1654 Excluded 89 <18 years 15 Previously in study with RRT 755 Elective admission < 24h 33 On chronic RRT 15 Organ donor 1 Initiation of chronic RRT 89 Declined 20 Foreigner 81 No consent 14 > 5 days in study already 415 Intermediate care 72 Other/unknown 7 Transfers 48 Readmissions 145 AKIN stage 1 (18.7%) 90-day mortality 24.1 % 56 AKIN stage 2 (7.2%) 90-day mortality 23.2 % 89 AKIN stage 3 (11.5%) 90-day mortality 31.5 % 61 RRT (7.8%) 90-day mortality 31.1 %

Method NGAL Rapid ELISA kit (Bioporto diagnostics) www.bioporto.com Dr Runkuan Yang, Tampere University Hospital

Aim & hypothesis AIM: Test U-NGAL s power in predicting AKI, RRT and 90-day mortality in a mixed ICU setting HYPOTHESIS U-NGAL has additional value in predicting AKI, RRT and 90-day mortality in a mixed ICU setting

Evolution of U-NGALU over time Log N=731 N=688 N=596 N=527 N=448 N=348 N=187 (all AKIN stages) U-NGAL (ng/ml) p < 0.001 in all timepoints

Evolution of U-NGAL over time Log Patients with samples from all 7 timepoints * * * * p < 0.01

U-NGAL between groups All U-NGAL samples N=3525 (777 patients) U-NGAL, median (IQR) No AKI 29.1 (10.0 84.2) AKI 91.5 (25.2 487.6) P < 0.001 No RRT 37.1 (12.4 125.3) RRT 607.8 (124.4 1000.0) < 0.001 90-day survivor 38.3 (12.4 148.2) 90-day non-survivor 67.5 (22.7 306.8) < 0.001

U-NGAL between groups Highest U-NGAL from first 24 hours (N=777) U-NGAL median (IQR) No AKI 53.8 ( 18.1 178.3) AKI 228.2 (58.6 1000.0) P < 0.001 No RRT 72.2 (24.4. 291.6) RRT 1000.0 (284.8 1000.0) < 0.001 90-day survivor 70.6 (23.5 316.4) 90-day non-survivor 139.7 (45.2 661.7) < 0.001

U-NGAL in prediction of AKI N=777 AUC= 0.699 (0.661-0.737)

U-NGAL in prediction of RRT N=777 AUC= 0.794 (0.734 0.854)

U-NGAL in prediction of 90-day mortality N=777 AUC= 0.603 (0.554 0.654)

U-NGAL in prediction of AKI, RRT and 90-day mortality Highest U-NGAL during first 24 hours (N=777) AUC Cut off (ng/ml) LR+ AKI 0.699 (0.661-0.737) 111.2 2.0 (1.7 2.3) RRT 0.794 (0.734 0.854) 376.5 3.5 (2.9 4.4) 90-day mortality 0.603 (0.554 0.654) 81.2 1.5 (1.3 1.7)

U-NGAL in prediction of AKI, RRT and 90-day mortality Highest U-NGAL during 5 days N=152 AUC Cut off (ng/ml) LR+ AKI 0.719 (0.638 0.800) 175.6 2.01 (1.43 2.84) RRT 0.805 (0.716 0.895) 292.4 2.45 (1.90 3.17) 90-day mortality 0.430 (0.204 0.532) 39.3 Not valid

Independent predictive value of U-NGAL for RRT RRT OR 95% CI p SAPS II age (per 1 point) 1.043 1.020 1.070 <0.001 Highest U-NGAL 24h (per 1 ng/ml) 1.002 1.001 1.003 <0.001

U-NGAL in patients with no sepsis Patients with no sepsis at admission (N=562) AKI 189 (33.6%) RRT 37 (6.6%) 90-day mortality 88 (15.7%)

U-NGAL in patients with no sepsis (N=562 patients) U-NGAL (all) median (IQR) p U-NGAL (highest first 24h) median (IQR) p No AKI 22.6 (10.0 55.9) < 0.001 40.8 (15.4 109.3) AKI 56.4 (17.1-195.8) 126.1 (33.6 538.4 ) < 0.001 No RRT 27.7 (10.0 72.3) < 0.001 48.1 (17.6 160.8) RRT 284.8 (67.9 1000.0) 602.5 (129.7 1000.0) < 0.001 90-day survivor 29.3 (10.0 83.4) < 0.001 49.9 (17.5 172.3) 90-day non-survivor 42.7 (15.3 125.7) 96.0 (33.4 293.6) 0.010

U-NGAL in patients with no sepsis AKI RRT Highest U-NGAL during first 24 hours (N=561) AUC= 0.674 (0.627 0.722) AUC= 0.790 (0.708 0.872)

U-NGAL in patients with no sepsis 90-day mortality Highest U-NGAL during first 24 hours (N=561) AUC= 0.586 (0.524 0.648)

Conclusions Urine NGAL predicted AKI adequately (AUC 0.699) RRT well (AUC 0.794) 90-day mortality inadequately (AUC 0.603) No better in patients with no sepsis

Study Group Central Finland Central Hospital: Raili Laru-Sompa, Anni Pulkkinen, Minna Saarelainen, Mikko Reilama, Sinikka Tolmunen, Ulla Rantalainen, Marja Miettinen East Savo Central Hospital: Markku Suvela, Katrine Pesola, Pekka Saastamoinen, Sirpa Kauppinen Helsinki University Central Hospital: Ville Pettilä, Kirsi-Maija Kaukonen, Anna-Maija Korhonen, Sara Nisula, Suvi Vaara, Raili Suojaranta-Ylinen, Leena Mildh, Mikko Haapio, Laura Nurminen, Sari Sutinen, Leena Pettilä, Helinä Laitinen, Heidi Syrjä, Kirsi Henttonen, Elina Lappi, Hillevi Boman Jorvi Central Hospital: Tero Varpula, Päivi Porkka, Mirka Sivula Mira Rahkonen, Anne Tsurkka, Taina Nieminen, Niina Prittinen. Kanta-Häme Central hospital: Ari Alaspää, Hanna Juntunen, Teija Sanisalo Kuopio University Hospital: Ilkka Parviainen, Ari Uusaro, Esko Ruokonen, Stepani Bendel, Niina Rissanen, Maarit Lång, Sari Rahikainen, Saija Rissanen, Merja Ahonen, Elina Halonen, Eija Vaskelainen Lapland Central Hospital: Meri Poukkanen, Esa Lintula, Sirpa Suominen Länsi Pohja Central Hospital: Jorma Heikkinen, Timo Lavander, Kirsi Heinonen, Anne-Mari Juopperi, Middle Ostrobothnia Central Hospital: Tadeusz Kaminski, Fiia Gäddnäs, Tuija Kuusela, Jane Roiko North Karelia Central Hospital: Sari Karlsson, Matti Reinikainen, Tero Surakka, Helena Jyrkönen, Tanja Eiserbeck, Jaana Kallinen Satakunta Hospital district: Vesa Lund, Päivi Tuominen, Pauliina Perkola, Riikka Tuominen, Marika Hietaranta, Satu Johansson South Karelia Central Hospital: Seppo Hovilehto, Anne Kirsi, Pekka Tiainen, Tuija Myllärinen, Pirjo Leino, Anne Toropainen Tampere University Hospital: Anne Kuitunen, Jyrki Tenhunen, Ilona Leppänen, Markus Levoranta, Sanna Hoppu, Jukka Sauranen, Atte Kukkurainen, Samuli Kortelainen, Simo Varila Turku University Hospital: Outi Inkinen, Niina Koivuviita, Jutta Kotamäki, Anu Laine Oulu University Hospital: Tero Ala-Kokko, Jouko Laurila, Sinikka Sälkiö Vaasa Central Hospital: Simo-Pekka Koivisto, Raku Hautamäki, Maria Skinnar

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