Two subphenotypes of septic acute kidney injury are associated with different 90-day mortality and renal recovery

Renske Wiersema, Sakari Jukarainen, Suvi T Vaara, Meri Poukkanen, Päivi Lakkisto, Hector Wong, Adam Linder, Iwan C C van der Horst, Ville Pettilä, Renske Wiersema, Sakari Jukarainen, Suvi T Vaara, Meri Poukkanen, Päivi Lakkisto, Hector Wong, Adam Linder, Iwan C C van der Horst, Ville Pettilä

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.

Keywords: Acute kidney injury; LCA; Mortality; Renal recovery; Sepsis; Subphenotypes.

Conflict of interest statement

A.L. is listed as of the inventors on a patent on the use of HBP as a diagnostic tool in sepsis filed by Hansa Medical AB. All other authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Combined graphs of variable distribution in different sub-phenotypes. Description: variables names with an asterisk were plotted as either natural log or square root transformed. BMI, body mass index; MAP, mean arterial pressure; WBC, white blood cell count; CRP, C-reactive protein; Ela, neutrophil elastase 2; MMP8, matrix metalloproteinase 8; FGF13, fibroblast growth factor 13; OLFM4, olfactomedin 4; PRTN3, proteinase 3; sTM, soluble thrombomodulin; SDC1, syndecan-1; VAP1, vascular adhesion protein 1; Ang2, angiotensin 2; IL-6, interleukin-6; HBP, heparin-binding protein
Fig. 2
Fig. 2
Comparison of class-defining variables by class. Description: variables names with an asterisk were plotted as either natural log or square root transformed. Every variable was standardized to a mean of 0 and SD of 1. Group means of standardized values are shown by class. The distance between the lines corresponds to the standardized mean difference between groups. BMI, body mass index; MAP, mean arterial pressure; WBC, white blood cell count; CRP, C-reactive protein; Ela, neutrophil elastase 2; MMP8, matrix metalloproteinase 8; FGF13, fibroblast growth factor 13; OLFM4, olfactomedin 4; PRTN3, proteinase 3; sTM, soluble thrombomodulin; SDC1, syndecan-1; VAP1, vascular adhesion protein 1; Ang2, angiotensin 2; IL-6, interleukin-6; HBP, heparin-binding protein

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Source: PubMed

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