Browsing by Subject "Acute kidney injury"

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  • CardShock Investigators; Jäntti, Toni; Tarvasmäki, Tuukka; Harjola, Veli-Pekka; Pulkki, Kari; Turkia, Heidi; Sabell, Tuija; Tolppanen, Heli; Jurkko, Raija; Hongisto, Mari; Kataja, Anu; Sionis, Alessandro; Silva-Cardoso, Jose; Banaszewski, Marek; DiSomma, Salvatore; Mebazaa, Alexandre; Haapio, Mikko; Lassus, Johan (2021)
    Background: Acute kidney injury (AKI) is a frequent form of organ injury in cardiogenic shock. However, data on AKI markers such as plasma proenkephalin (P-PENK) and neutrophil gelatinase-associated lipocalin (P-NGAL) in cardiogenic shock populations are lacking. The objective of this study was to assess the ability of P-PENK and P-NGAL to predict acute kidney injury and mortality in cardiogenic shock. Results: P-PENK and P-NGAL were measured at different time points between baseline and 48 h in 154 patients from the prospective CardShock study. The outcomes assessed were AKI defined by an increase in creatinine within 48 h and all-cause 90-day mortality. Mean age was 66 years and 26% were women. Baseline levels of P-PENK and P-NGAL (median [interquartile range]) were 99 (71-150) pmol/mL and 138 (84-214) ng/mL. P-PENK > 84.8 pmol/mL and P-NGAL > 104 ng/mL at baseline were identified as optimal cut-offs for AKI prediction and independently associated with AKI (adjusted HRs 2.2 [95% CI 1.1-4.4, p = 0.03] and 2.8 [95% CI 1.2-6.5, p = 0.01], respectively). P-PENK and P-NGAL levels at baseline were also associated with 90-day mortality. For patients with oliguria <0.5 mL/kg/h for > 6 h before study enrollment, 90-day mortality differed significantly between patients with low and high P-PENK/P-NGAL at baseline (5% vs. 68%, p <0.001). However, the biomarkers provided best discrimination for mortality when measured at 24 h. Identified cut-offs of P-PENK24h > 105.7 pmol/L and P-NGAL(24h) > 151 ng/mL had unadjusted hazard ratios of 5.6 (95% CI 3.1-10.7, p <0.001) and 5.2 (95% CI 2.8-9.8, p <0.001) for 90-day mortality. The association remained significant despite adjustments with AKI and two risk scores for mortality in cardiogenic shock. Conclusions: High levels of P-PENK and P-NGAL at baseline were independently associated with AKI in cardiogenic shock patients. Furthermore, oliguria before study inclusion was associated with worse outcomes only if combined with high baseline levels of P-PENK or P-NGAL. High levels of both P-PENK and P-NGAL at 24 h were found to be strong and independent predictors of 90-day mortality.
  • Forni, L. G.; Darmon, M.; Ostermann, M.; Oudemans-van Straaten, H. M.; Pettilä, Ville; Prowle, J. R.; Schetz, M.; Joannidis, M. (2017)
    Acute kidney injury (AKI) is a frequent complication of critical illness and carries a significant risk of short-and long-term mortality, chronic kidney disease (CKD) and cardiovascular events. The degree of renal recovery from AKI may substantially affect these long-term endpoints. Therefore maximising recovery of renal function should be the goal of any AKI prevention and treatment strategy. Defining renal recovery is far from straightforward due in part to the limitations of the tests available to assess renal function. Here, we discuss common pitfalls in the evaluation of renal recovery and provide suggestions for improved assessment in the future. We review the epidemiology of renal recovery and of the association between AKI and the development of CKD. Finally, we stress the importance of post-discharge follow-up of AKI patients and make suggestions for its incorporation into clinical practice. Summary key points are that risk factors for non-recovery of AKI are age, CKD, comorbidity, higher severity of AKI and acute disease scores. Second, AKI and CKD are mutually related and seem to have a common denominator. Third, despite its limitations full recovery of AKI may best be defined as the absence of AKI criteria, and partial recovery as a fall in AKI stage. Fourth, after an episode of AKI, serial follow-up measurements of serum creatinine and proteinuria are warranted to diagnose renal impairment and prevent further progression. Measures to promote recovery are similar to those preventing renal harm. Specific interventions promoting repair are still experimental.
  • REVERSE-AKI Study Team; Vaara, Suvi T.; Ostermann, Marlies; Bitker, Laurent; Pettilä, Ville (2021)
    Purpose We compared a restrictive fluid management strategy to usual care among critically ill patients with acute kidney injury (AKI) who had received initial fluid resuscitation. Methods This multicenter feasibility trial randomized 100 AKI patients 1:1 in seven ICUs in Europe and Australia. Restrictive fluid management included targeting negative or neutral daily fluid balance by minimizing fluid input and/or enhancing urine output with diuretics administered at the discretion of the clinician. Fluid boluses were administered as clinically indicated. The primary endpoint was cumulative fluid balance 72 h from randomization. Results Mean (SD) cumulative fluid balance at 72 h from randomization was - 1080 mL (2003 mL) in the restrictive fluid management arm and 61 mL (3131 mL) in the usual care arm, mean difference (95% CI) - 1148 mL (- 2200 to - 96) mL, P = 0.033. Median [IQR] duration of AKI was 2 [1-3] and 3 [2-7] days, respectively (median difference - 1.0 [- 3.0 to 0.0], P = 0.071). Altogether, 6 out of 46 (13%) patients in the restrictive fluid management arm and 15 out of 50 (30%) in the usual care arm received renal replacement therapy (RR 0.42; 95% CI 0.16-0.91), P = 0.043. Cumulative fluid balance at 24 h and 7 days was lower in the restrictive fluid management arm. The dose of diuretics was not different between the groups. Adverse events occurred more frequently in the usual care arm. Conclusions In critically ill patients with AKI, a restrictive fluid management regimen resulted in lower cumulative fluid balance and less adverse events compared to usual care. Larger trials of this intervention are justified.
  • Strand, Kristian; Søreide, Eldar; Kirkegaard, Hans; Taccone, Fabio Silvio; Grejs, Anders Morten; Duez, Christophe Henri Valdemar; Jeppesen, Anni Nørgaard; Storm, Christian; Rasmussen, Bodil Steen; Laitio, Timo; Hassager, Christian; Toome, Valdo; Hästbacka, Johanna; Skrifvars, Markus B (2020)
    Background Acute kidney injury (AKI) is common after cardiac arrest and targeted temperature management (TTM). The impact of different lengths of cooling on the development of AKI has not been well studied. In this study of patients included in a randomised controlled trial of TTM at 33°C for 24 versus 48hours after cardiac arrest (TTH48 trial), we examined the influence of prolonged TTM on AKI and the incidence and factors associated with the development of AKI. We also examined the impact of AKI on survival. Methods This study was a sub-study of the TTH48 trial, which included patients cooled to 33±1˚C after out-of-hospital cardiac arrest for 24 versus 48hours. AKI was classified according to the KDIGO AKI criteria based on serum creatinine and urine output collected until ICU discharge for a maximum of seven days. Survival was followed for up to six months. The association of admission factors on AKI was analysed with multivariate analysis and the association of AKI on mortality was analysed with Cox regression using the time to AKI as a time-dependent covariate. Results Of the 349 patients included in the study, 159 (45.5%) developed AKI. There was no significant difference in the incidence, severity or time to AKI between the 24- and 48-hour groups. Serum creatinine values had significantly different trajectories for the two groups with a sharp rise occurring during rewarming. Age, time to return of spontaneous circulation, serum creatinine at admission and body mass index were independent predictors of AKI. Patients with AKI had a higher mortality than patients without AKI (hospital mortality 36.5% vs 12.5%, p
  • Passov, Arie; Petäjä, Liisa; Pihlajoki, Marjut; Salminen, Ulla-Stina; Suojaranta, Raili; Vento, Antti; Andersson, Sture; Pettilä, Ville; Schramko, Alexey; Pesonen, Eero (BioMed Central, 2019)
    Abstract Background Acute kidney injury (AKI) is common after heart surgery. Neutrophil gelatinase-associated lipocalin (NGAL) is produced in injured kidney. NGAL has been used as an early plasma biomarker for AKI in patients undergoing heart surgery. Neutrophils contain all isoforms (25-kDa, 45-kDa and 145-kDa) but the kidney produces almost exclusively the 25-kDa isoform of NGAL. We investigated first, whether there is association between NGAL and neutrophil activation, and second whether activated neutrophils are a significant source of circulating NGAL in plasma in patients undergoing cardiac surgery. Methods Two separate patient cohorts were studied: 1) the “kinetic cohort” (n = 29) and 2) the “FINNAKI cohort” (n = 306). As NGAL is strictly co-localized with lactoferrin in neutrophils, NGAL and lactoferrin were measured with enzyme-linked immunosorbent assay in all patients. In sixty-one patients of the “FINNAKI cohort” Western blot was used to separate NGAL isoforms according to their molecular size. Mann-Whitney U, Kruskal-Wallis H, Pearson’s and Spearman’s tests were used as appropriate. Results There was strong intraoperative association between NGAL and lactoferrin at all four time-points in the “kinetic cohort”. In the “FINNAKI cohort”, NGAL and lactoferrin concentrations correlated preoperatively (R = 0.59, p < 0.001) and at admission to the intensive care unit (R = 0.69, p < 0.001). At admission to intensive care unit, concentrations of NGAL and lactoferrin were higher in AKI than in non-AKI patients (NGAL: p < 0.001; lactoferrin: p < 0.029). In Western blot analyses, neutrophil specific 45-kDa isoform (median 41% [IQR 33.3–53.1]) and mostly neutrophil derived 145-kDa isoform (median 53.5% [IQR 44.0–64.9%]) together represented over 90% of total NGAL in plasma. Potentially kidney derived NGAL isoform (25-kDa) accounted for only 0.9% (IQR 0.3 – 3.0%) of total NGAL in plasma. There were no statistically significant differences in the distribution of NGAL isomers between AKI and non-AKI patients. Conclusions Plasma NGAL during cardiac surgery is associated with neutrophil activation. Based on molecular size, the majority of circulating NGAL is derived from neutrophils. Neutrophil activation is a confounding factor when interpreting increased plasma NGAL in cardiac surgery.
  • Passov, Arie; Petäjä, Liisa; Pihlajoki, Marjut; Salminen, Ulla-Stina; Suojaranta, Raili; Vento, Antti; Andersson, Sture; Pettilä, Ville; Schramko, Alexey; Pesonen, Eero (2019)
    Background: Acute kidney injury (AKI) is common after heart surgery. Neutrophil gelatinase-associated lipocalin (NGAL) is produced in injured kidney. NGAL has been used as an early plasma biomarker for AKI in patients undergoing heart surgery. Neutrophils contain all isoforms (25-kDa, 45-kDa and 145-kDa) but the kidney produces almost exclusively the 25-kDa isoform of NGAL. We investigated first, whether there is association between NGAL and neutrophil activation, and second whether activated neutrophils are a significant source of circulating NGAL in plasma in patients undergoing cardiac surgery. Methods: Two separate patient cohorts were studied: 1) the "kinetic cohort" (n = 29) and 2) the "FINNAKI cohort" (n = 306). As NGAL is strictly co-localized with lactoferrin in neutrophils, NGAL and lactoferrin were measured with enzyme-linked immunosorbent assay in all patients. In sixty-one patients of the "FINNAKI cohort" Western blot was used to separate NGAL isoforms according to their molecular size. Mann-Whitney U, Kruskal-Wallis H, Pearson's and Spearman's tests were used as appropriate. Results: There was strong intraoperative association between NGAL and lactoferrin at all four time-points in the "kinetic cohort". In the "FINNAKI cohort", NGAL and lactoferrin concentrations correlated preoperatively (R = 0.59, p <0.001) and at admission to the intensive care unit (R = 0.69, p <0.001). At admission to intensive care unit, concentrations of NGAL and lactoferrin were higher in AKI than in non-AKI patients (NGAL: p <0.001; lactoferrin: p <0.029). In Western blot analyses, neutrophil specific 45-kDa isoform (median 41% [IQR 33.3-53.1]) and mostly neutrophil derived 145-kDa isoform (median 53.5% [IQR 44.0-64.9%]) together represented over 90% of total NGAL in plasma. Potentially kidney derived NGAL isoform (25-kDa) accounted for only 0.9% (IQR 0.3 - 3.0%) of total NGAL in plasma. There were no statistically significant differences in the distribution of NGAL isomers between AKI and non-AKI patients. Conclusions: Plasma NGAL during cardiac surgery is associated with neutrophil activation. Based on molecular size, the majority of circulating NGAL is derived from neutrophils. Neutrophil activation is a confounding factor when interpreting increased plasma NGAL in cardiac surgery.
  • Virkkala, Tiia (Helsingfors universitet, 2017)
    Hemolyyttis-ureeminen oireyhtymä (HUS) on tromboottinen mikroangiopatia, jonka diagnostisiin kriteereihin kuuluvat hemolyyttinen anemia, trombosytopenia ja munuaisten vajaatoiminta. Lapsilla sen yleisin aiheuttaja on enterohemorraginen Escherichia coli (EHEC), ja se on yksi tärkeimmistä akuutin munuaisten vajaatoiminnan aiheuttajista lapsilla. Tämän tutkimuksen tavoitteena oli selvittää suomalaisten HUS-potilaiden taudinkuvaa, löydöksiä sekä lyhyen ja pitkän aikavälin ennustetta. Tutkimusta varten analysoitiin takautuvasti kaikki Helsingin yliopistollisen keskussairaalan Lastenklinikalla vuosina 2005-2016 hoidetut HUS-potilaat. Potilaita oli yhteensä 33, ja heistä suurimmalla osalla todettiin EHEC-infektio. Yleisimmät oireet olivat gastroenteriittioireet, neurologiset oireet ja munuaistoiminnan häiriöt. HUS:n hoito on oireenmukaista painottuen etenkin mahdollisen akuutin munuaisvaurion hoitoon, ja suurin osa potilaistamme vaatikin dialyysihoitoa. Tutkimuksemme mukaan HUS:n ennuste Suomessa on hyvä. Yksikään potilas ei kuollut tautiinsa seurannan aikana. 24,2 prosentille potilaista jäi jokin pitkäaikaishaitta, ja heistä kahdelle (6,06 %) kehittyi munuaissiirrännäistä vaativa munuaisten krooninen vajaatoiminta. Tämän tutkimuksen perusteella ei voida päätellä mahdollisia huonoa ennustetta ennustavia tekijöitä.
  • Helanterä, Ilkka; Koljonen, Virve; Finne, Patrik; Tukiainen, Erkki; Gissler, Mika (2016)
    Objective: Acute kidney injury (AKI) commonly complicates burn. Recently, AKI has been suggested to be causally related to chronic end-stage renal disease (ESRD), but controversial data also exist. Our aim was to study the risk of ESRD after burn in a nationwide analysis. Methods: All burn patients undergoing hospitalization between 1998 and 2011 were identified from the National Hospital Discharge Register, and the data were linked with the Finnish Registry for Kidney Diseases, which includes all individuals receiving chronic renal replacement therapy (RRT) in Finland. Results: Altogether 41,179 adults were treated at hospitals for burns in Finland between 1998 and 2011. Of these, 86 had a diagnosis of AKI related to the burn. Forty-three burn survivors had ESRD and RRT initiated related to or after the burn. The overall risk for ESRD after burn was increased (standardized incidence ratio, SIR, 2.40, 95% CI 1.73-3.23) compared with the Finnish population. Standardized incidence ratio was 3.11 (95% CI 1.66-5.32) in women and 1.89 (95% CI 1.27-2.69) in men. Of these 43 patients, 38 had a specific non-burn-related diagnosis of ESRD identified in the registry, and ESRD was deemed unlikely to be directly related to the burn. In five patients, the diagnosis of ESRD was unknown cause of renal failure, and causality of the burn with ESRD was evaluated as plausible. Conclusion: In conclusion, a significantly increased risk of ESRD was recorded after a severe burn. Our results do not support increased incidence of ESRD solely as a consequence of AKI due to burn, but burn may increase the risk of ESRD in patients with pre-existing chronic kidney disease. (C) 2015 Elsevier Ltd and ISBI. All rights reserved.
  • Mildh, Henriikka; Pettilä, Ville; Korhonen, Anna-Maija; Karlsson, Sari; Ala-Kokko, Tero; Reinikainen, Matti; Vaara, Suvi; FINNAKI Study Grp (2016)
    Background: The role of an episode of acute kidney injury (AKI) in long-term mortality among initial survivors of critical illness is controversial. We aimed to determine whether AKI is independently associated with decreased survival at 3 years among 30-day survivors of intensive care. Results: We included 2336 30-day survivors of intensive care enrolled in the FINNAKI study conducted in seventeen medical-surgical ICUs in Finland during a 5-month period in 2011-2012. The incidence of AKI, defined by the Kidney Disease: Improving Global Outcomes criteria, was 34.6%, and 192 (8.3%) commenced RRT. The 3-year mortality among AKI patients was 23.5% (95% CI 20.6-26.4%) compared to 18.9% (17.0-20.9%) of patients without AKI, p = 0.01. However, after adjustments using Cox proportional hazards regression, AKI was not associated with decreased 3-year survival (HR 1.05; CI 95% 0.86-1.27), whereas advanced age, poor pre-morbid functional performance, and presence of several comorbidities were. Additionally, we matched AKI patients to non-AKI patients 1: 1 according to age, gender, presence of severe sepsis, and a propensity score to develop AKI. In the well-balanced matched cohort, 3-year mortality among AKI patients was 136 of 662 (20.5%; 17.5-23.6%) and among matched non-AKI patients 143 of 662 (21.6%; 18.5-24.7%), p = 0.687. Neither AKI nor RRT was associated with decreased survival at 3 years in the sensitivity analyses that excluded patients (1) with chronic kidney disease, (2) with AKI not commenced renal replacement therapy (RRT), and (3) with estimated pre-admission creatinine, chronic kidney disease, or AKI stage 1. Conclusion: AKI was not an independent risk factor for 3-year mortality among 30-day survivors. Increased 3-year mortality among patients with AKI who survive critical illness may not be related to AKI per se, but rather to advanced age and pre-existing comorbidities.
  • Mildh, Henriikka; Pettilä, Ville; Korhonen, Anna-Maija; Karlsson, Sari; Ala-Kokko, Tero; Reinikainen, Matti; Vaara, Suvi T (Springer Paris, 2016)
    Abstract Background The role of an episode of acute kidney injury (AKI) in long-term mortality among initial survivors of critical illness is controversial. We aimed to determine whether AKI is independently associated with decreased survival at 3 years among 30-day survivors of intensive care. Results We included 2336 30-day survivors of intensive care enrolled in the FINNAKI study conducted in seventeen medical–surgical ICUs in Finland during a 5-month period in 2011–2012. The incidence of AKI, defined by the Kidney Disease: Improving Global Outcomes criteria, was 34.6%, and 192 (8.3%) commenced RRT. The 3-year mortality among AKI patients was 23.5% (95% CI 20.6–26.4%) compared to 18.9% (17.0–20.9%) of patients without AKI, p = 0.01. However, after adjustments using Cox proportional hazards regression, AKI was not associated with decreased 3-year survival (HR 1.05; CI 95% 0.86–1.27), whereas advanced age, poor pre-morbid functional performance, and presence of several comorbidities were. Additionally, we matched AKI patients to non-AKI patients 1:1 according to age, gender, presence of severe sepsis, and a propensity score to develop AKI. In the well-balanced matched cohort, 3-year mortality among AKI patients was 136 of 662 (20.5%; 17.5–23.6%) and among matched non-AKI patients 143 of 662 (21.6%; 18.5–24.7%), p = 0.687. Neither AKI nor RRT was associated with decreased survival at 3 years in the sensitivity analyses that excluded patients (1) with chronic kidney disease, (2) with AKI not commenced renal replacement therapy (RRT), and (3) with estimated pre-admission creatinine, chronic kidney disease, or AKI stage 1. Conclusion AKI was not an independent risk factor for 3-year mortality among 30-day survivors. Increased 3-year mortality among patients with AKI who survive critical illness may not be related to AKI per se, but rather to advanced age and pre-existing comorbidities.
  • Wiersema, Renske; Jukarainen, Sakari; Vaara, Suvi T; Poukkanen, Meri; Lakkisto, Päivi; Wong, Hector; Linder, Adam; van der Horst, Iwan C C; Pettilä, Ville (BioMed Central, 2020)
    Abstract Background The pathophysiology of septic acute kidney injury is inadequately understood. Recently, subphenotypes for sepsis and AKI have been derived. The objective of this study was to assess whether a combination of comorbidities, baseline clinical data, and biomarkers could classify meaningful subphenotypes in septic AKI with different outcomes. Methods We performed a post hoc analysis of the prospective Finnish Acute Kidney Injury (FINNAKI) study cohort. We included patients admitted with sepsis and acute kidney injury during the first 48 h from admission to intensive care (according to Kidney Disease Improving Global Outcome criteria). Primary outcomes were 90-day mortality and renal recovery on day 5. We performed latent class analysis using 30 variables obtained on admission to classify subphenotypes. Second, we used logistic regression to assess the association of derived subphenotypes with 90-day mortality and renal recovery on day 5. Results In total, 301 patients with septic acute kidney injury were included. Based on the latent class analysis, a two-class model was chosen. Subphenotype 1 was assigned to 133 patients (44%) and subphenotype 2 to 168 patients (56%). Increased levels of inflammatory and endothelial injury markers characterized subphenotype 2. At 90 days, 29% of patients in subphenotype 1 and 41% of patients in subphenotype 2 had died. Subphenotype 2 was associated with a lower probability of short-term renal recovery and increased 90-day mortality. Conclusions In this post hoc analysis, we identified two subphenotypes of septic acute kidney injury with different clinical outcomes. Future studies are warranted to validate the suggested subphenotypes of septic acute kidney injury.
  • Wiersema, Renske; Jukarainen, Sakari; Vaara, Suvi T.; Poukkanen, Meri; Lakkisto, Päivi; Wong, Hector; Linder, Adam; van der Horst, Iwan C. C.; Pettilä, Ville (2020)
    Background The pathophysiology of septic acute kidney injury is inadequately understood. Recently, subphenotypes for sepsis and AKI have been derived. The objective of this study was to assess whether a combination of comorbidities, baseline clinical data, and biomarkers could classify meaningful subphenotypes in septic AKI with different outcomes. Methods We performed a post hoc analysis of the prospective Finnish Acute Kidney Injury (FINNAKI) study cohort. We included patients admitted with sepsis and acute kidney injury during the first 48 h from admission to intensive care (according to Kidney Disease Improving Global Outcome criteria). Primary outcomes were 90-day mortality and renal recovery on day 5. We performed latent class analysis using 30 variables obtained on admission to classify subphenotypes. Second, we used logistic regression to assess the association of derived subphenotypes with 90-day mortality and renal recovery on day 5. Results In total, 301 patients with septic acute kidney injury were included. Based on the latent class analysis, a two-class model was chosen. Subphenotype 1 was assigned to 133 patients (44%) and subphenotype 2 to 168 patients (56%). Increased levels of inflammatory and endothelial injury markers characterized subphenotype 2. At 90 days, 29% of patients in subphenotype 1 and 41% of patients in subphenotype 2 had died. Subphenotype 2 was associated with a lower probability of short-term renal recovery and increased 90-day mortality. Conclusions In this post hoc analysis, we identified two subphenotypes of septic acute kidney injury with different clinical outcomes. Future studies are warranted to validate the suggested subphenotypes of septic acute kidney injury.
  • FINNAKI Study Grp; Hoste, Eric A.; Vaara, Suvi T.; De Loor, Jorien; Haapio, Mikko; Nuytinck, Lieve; Demeyere, Kristel; Pettila, Ville; Meyer, Evelyne (2020)
    Background Acute kidney injury (AKI) is a frequently occurring syndrome in critically ill patients and is associated with worse outcomes. Biomarkers allow early identification and therapy of AKI which may improve outcomes. Urine chitinase 3-like protein 1 (uCHI3L1) was recently identified as a promising urinary biomarker for AKI. In this multicenter study, we evaluated the diagnostic performance for AKI stage 2 or greater of uCHI3L1 in comparison with the urinary cell cycle arrest biomarkers urinary tissue inhibitor of metalloproteinases-2 (TIMP-2)center dot insulin-like growth factor-binding protein 7 (IGFBP7) measured by NephroCheck Risk (R). Methods Post hoc laboratory study of the prospective observational FINNAKI study. Of this cohort, we included patients with stored admission urine samples and availability of serum creatinine at day 1 of admission. Patients who already had AKI stage 2 or 3 at ICU admission were excluded. AKI was defined and staged according to the KDIGO definition and staging system. The primary endpoint was AKI stage 2 or 3 at day 1. Biomarker performance was assessed by the area under the curve of the receiver operating characteristic curve (AUC). We assessed individual performance and different combinations of urine biomarkers. Results Of 660 included patients, 49 (7.4%) had AKI stages 2-3 at day 1. All urine biomarkers were increased at admission in AKI patients. All biomarkers and most combinations had AUCs <0.700. The combination uCHI3L1 center dot TIMP-2 was best with a fair AUC of 0.706 (0.670, 0.718). uCHI3L1 had a positive likelihood ratio (LR) of 2.25 which was comparable to that of the NephroCheck Risk (R) cutoff of 2.0, while the negative LR of 0.53 was comparable to that of the NephroCheck Risk (R) cutoff of 0.3. Conclusions We found that uCHI3L1 and NephroCheck Risk (R) had a comparable diagnostic performance for diagnosis of AKI stage 2 or greater within a 24-h period in this multicenter FINNAKI cohort. In contrast to initial discovery and validation studies, the diagnostic performance was poor. Possible explanations for this observation are differences in patient populations, proportion of emergency admissions, proportion of functional AKI, rate of developing AKI, and observation periods for diagnosis of AKI.
  • Hoste, Eric A; Vaara, Suvi T; De Loor, Jorien; Haapio, Mikko; Nuytinck, Lieve; Demeyere, Kristel; Pettilä, Ville; Meyer, Evelyne (BioMed Central, 2020)
    Abstract Background Acute kidney injury (AKI) is a frequently occurring syndrome in critically ill patients and is associated with worse outcomes. Biomarkers allow early identification and therapy of AKI which may improve outcomes. Urine chitinase 3-like protein 1 (uCHI3L1) was recently identified as a promising urinary biomarker for AKI. In this multicenter study, we evaluated the diagnostic performance for AKI stage 2 or greater of uCHI3L1 in comparison with the urinary cell cycle arrest biomarkers urinary tissue inhibitor of metalloproteinases-2 (TIMP-2)•insulin-like growth factor-binding protein 7 (IGFBP7) measured by NephroCheck Risk®. Methods Post hoc laboratory study of the prospective observational FINNAKI study. Of this cohort, we included patients with stored admission urine samples and availability of serum creatinine at day 1 of admission. Patients who already had AKI stage 2 or 3 at ICU admission were excluded. AKI was defined and staged according to the KDIGO definition and staging system. The primary endpoint was AKI stage 2 or 3 at day 1. Biomarker performance was assessed by the area under the curve of the receiver operating characteristic curve (AUC). We assessed individual performance and different combinations of urine biomarkers. Results Of 660 included patients, 49 (7.4%) had AKI stages 2–3 at day 1. All urine biomarkers were increased at admission in AKI patients. All biomarkers and most combinations had AUCs < 0.700. The combination uCHI3L1•TIMP-2 was best with a fair AUC of 0.706 (0.670, 0.718). uCHI3L1 had a positive likelihood ratio (LR) of 2.25 which was comparable to that of the NephroCheck Risk® cutoff of 2.0, while the negative LR of 0.53 was comparable to that of the NephroCheck Risk® cutoff of 0.3. Conclusions We found that uCHI3L1 and NephroCheck Risk® had a comparable diagnostic performance for diagnosis of AKI stage 2 or greater within a 24-h period in this multicenter FINNAKI cohort. In contrast to initial discovery and validation studies, the diagnostic performance was poor. Possible explanations for this observation are differences in patient populations, proportion of emergency admissions, proportion of functional AKI, rate of developing AKI, and observation periods for diagnosis of AKI.
  • FINNAKI Study Grp; Törnblom, Sanna; Nisula, Sara; Petäjä, Liisa; Vaara, Suvi T.; Haapio, Mikko; Pesonen, Eero; Pettilä, Ville (2020)
    Background: Neutrophil gelatinase-associated lipocalin (NGAL) is released from kidney tubular cells under stress as well as from neutrophils during inflammation. It has been suggested as a biomarker for acute kidney injury (AKI) in critically ill patients with sepsis. To evaluate clinical usefulness of urine NGAL (uNGAL), we post-hoc applied recently introduced statistical methods to a sub-cohort of septic patients from the prospective observational Finnish Acute Kidney Injury (FINNAKI) study. Accordingly, in 484 adult intensive care unit patients with sepsis by Sepsis-3 criteria, we calculated areas under the receiver operating characteristic curves (AUCs) for the first available uNGAL to assess discrimination for four outcomes: AKI defined by Kidney Disease: Improving Global Outcomes (KDIGO) criteria, severe (KDIGO 2-3) AKI, and renal replacement therapy (RRT) during the first 3 days of intensive care, and mortality at day 90. We constructed clinical prediction models for the outcomes and used risk assessment plots and decision curve analysis with predefined threshold probabilities to test whether adding uNGAL to the models improved reclassification or decision making in clinical practice. Results: Incidences of AKI, severe AKI, RRT, and mortality were 44.8% (217/484), 27.7% (134/484), 9.5% (46/484), and 28.1% (136/484). Corresponding AUCs for uNGAL were 0.690, 0.728, 0.769, and 0.600. Adding uNGAL to the clinical prediction models improved discrimination of AKI, severe AKI, and RRT. However, the net benefits for the new models were only 1.4% (severe AKI and RRT) to 2.5% (AKI), and the number of patients needed to be tested per one extra true-positive varied from 40 (AKI) to 74 (RRT) at the predefined threshold probabilities. Conclusions: The results of the recommended new statistical methods do not support the use of uNGAL in critically ill septic patients to predict AKI or clinical outcomes.
  • Törnblom, Sanna; Nisula, Sara; Petäjä, Liisa; Vaara, Suvi T; Haapio, Mikko; Pesonen, Eero; Pettilä, Ville (Springer International Publishing, 2020)
    Abstract Background Neutrophil gelatinase-associated lipocalin (NGAL) is released from kidney tubular cells under stress as well as from neutrophils during inflammation. It has been suggested as a biomarker for acute kidney injury (AKI) in critically ill patients with sepsis. To evaluate clinical usefulness of urine NGAL (uNGAL), we post-hoc applied recently introduced statistical methods to a sub-cohort of septic patients from the prospective observational Finnish Acute Kidney Injury (FINNAKI) study. Accordingly, in 484 adult intensive care unit patients with sepsis by Sepsis-3 criteria, we calculated areas under the receiver operating characteristic curves (AUCs) for the first available uNGAL to assess discrimination for four outcomes: AKI defined by Kidney Disease: Improving Global Outcomes (KDIGO) criteria, severe (KDIGO 2–3) AKI, and renal replacement therapy (RRT) during the first 3 days of intensive care, and mortality at day 90. We constructed clinical prediction models for the outcomes and used risk assessment plots and decision curve analysis with predefined threshold probabilities to test whether adding uNGAL to the models improved reclassification or decision making in clinical practice. Results Incidences of AKI, severe AKI, RRT, and mortality were 44.8% (217/484), 27.7% (134/484), 9.5% (46/484), and 28.1% (136/484). Corresponding AUCs for uNGAL were 0.690, 0.728, 0.769, and 0.600. Adding uNGAL to the clinical prediction models improved discrimination of AKI, severe AKI, and RRT. However, the net benefits for the new models were only 1.4% (severe AKI and RRT) to 2.5% (AKI), and the number of patients needed to be tested per one extra true-positive varied from 40 (AKI) to 74 (RRT) at the predefined threshold probabilities. Conclusions The results of the recommended new statistical methods do not support the use of uNGAL in critically ill septic patients to predict AKI or clinical outcomes.