Common Inflammation-Related Candidate Gene Variants and Acute Kidney Injury in 2647 Critically Ill Finnish Patients

Acute kidney injury (AKI) is a syndrome with high incidence among the critically ill. Because the clinical variables and currently used biomarkers have failed to predict the individual susceptibility to AKI, candidate gene variants for the trait have been studied. Studies about genetic predisposition to AKI have been mainly underpowered and of moderate quality. We report the association study of 27 genetic variants in a cohort of Finnish critically ill patients, focusing on the replication of associations detected with variants in genes related to inflammation, cell survival, or circulation. In this prospective, observational Finnish Acute Kidney Injury (FINNAKI) study, 2647 patients without chronic kidney disease were genotyped. We defined AKI according to Kidney Disease: Improving Global Outcomes (KDIGO) criteria. We compared severe AKI (Stages 2 and 3, n = 625) to controls (Stage 0, n = 1582). For genotyping we used iPLEXTM Assay (Agena Bioscience). We performed the association analyses with PLINK software, using an additive genetic model in logistic regression. Despite the numerous, although contradictory, studies about association between polymorphisms rs1800629 in TNFA and rs1800896 in IL10 and AKI, we found no association (odds ratios 1.06 (95% CI 0.89–1.28, p = 0.51) and 0.92 (95% CI 0.80–1.05, p = 0.20), respectively). Adjusting for confounders did not change the results. To conclude, we could not confirm the associations reported in previous studies in a cohort of critically ill patients

Heparin-binding protein (HBP) improves prediction of sepsis-related acute kidney injury

Background: Sepsis-related acute kidney injury (AKI) accounts for major morbidity and mortality among the critically ill. Heparin-binding protein (HBP) is a promising biomarker in predicting development and prognosis of severe sepsis and septic shock that has recently been proposed to be involved in the pathophysiology of AKI. The objective of this study was to investigate the added predictive value of measuring plasma HBP on admission to the intensive care unit (ICU) regarding the development of septic AKI. Methods: We included 601 patients with severe sepsis or septic shock from the prospective, observational FINNAKI study conducted in seventeen Finnish ICUs during a 5-month period (1 September 2011–1 February 2012). The main outcome measure was the development of KDIGO AKI stages 2–3 from 12 h after admission up to 5 days. Statistical analysis for the primary endpoint included construction of a clinical risk model, area under the receiver operating curve (ROC area), category-free net reclassification index (cfNRI) and integrated discrimination improvement (IDI) with 95% confidence intervals (95% CI). Results: Out of 511 eligible patients, 101 (20%) reached the primary endpoint. The addition of plasma HBP to a clinical risk model significantly increased ROC area (0.82 vs. 0.78, p = 0.03) and risk classification scores: cfNRI 62.0% (95% CI 40.5–82.4%) and IDI 0.053 (95% CI 0.029–0.075). Conclusions: Plasma HBP adds predictive value to known clinical risk factors in septic AKI. Further studies are warranted to compare the predictive performance of plasma HBP to other novel AKI biomarkers

Heparin-binding protein (HBP) improves prediction of sepsis-related acute kidney injury

Background: Sepsis-related acute kidney injury (AKI) accounts for major morbidity and mortality among the critically ill. Heparin-binding protein (HBP) is a promising biomarker in predicting development and prognosis of severe sepsis and septic shock that has recently been proposed to be involved in the pathophysiology of AKI. The objective of this study was to investigate the added predictive value of measuring plasma HBP on admission to the intensive care unit (ICU) regarding the development of septic AKI. Methods: We included 601 patients with severe sepsis or septic shock from the prospective, observational FINNAKI study conducted in seventeen Finnish ICUs during a 5-month period (1 September 2011–1 February 2012). The main outcome measure was the development of KDIGO AKI stages 2–3 from 12 h after admission up to 5 days. Statistical analysis for the primary endpoint included construction of a clinical risk model, area under the receiver operating curve (ROC area), category-free net reclassification index (cfNRI) and integrated discrimination improvement (IDI) with 95% confidence intervals (95% CI). Results: Out of 511 eligible patients, 101 (20%) reached the primary endpoint. The addition of plasma HBP to a clinical risk model significantly increased ROC area (0.82 vs. 0.78, p = 0.03) and risk classification scores: cfNRI 62.0% (95% CI 40.5–82.4%) and IDI 0.053 (95% CI 0.029–0.075). Conclusions: Plasma HBP adds predictive value to known clinical risk factors in septic AKI. Further studies are warranted to compare the predictive performance of plasma HBP to other novel AKI biomarkers

Association of endothelial and glycocalyx injury biomarkers with fluid administration, development of acute kidney injury, and 90-day mortality:data from the FINNAKI observational study

Abstract Background: Injury to endothelium and glycocalyx predisposes to vascular leak, which may subsequently lead to increased fluid requirements and worse outcomes. In this post hoc study of the prospective multicenter observational Finnish Acute Kidney Injury (FINNAKI) cohort study conducted in 17 Finnish intensive care units, we studied the association of Syndecan-1 (SDC-1), Angiopoetin-2 (Ang-2), soluble thrombomodulin (sTM), vascular adhesion protein-1 (VAP-1) and interleukin-6 (IL-6) with fluid administration and balance among septic critical care patients and their association with development of acute kidney injury (AKI) and 90-day mortality. Results: SDC-1, Ang-2, sTM, VAP-1 and IL-6 levels were measured at ICU admission from 619 patients with sepsis. VAP-1 decreased (p < 0.001) and IL-6 increased (p < 0.001) with increasing amounts of administered fluid, but other biomarkers did not show differences according to fluid administration. In linear regression models adjusted for IL-6, only VAP-1 was significantly associated with fluid administration on day 1 (p < 0.001) and the cumulative fluid balance on day 5/ICU discharge (p = 0.001). Of 415 patients admitted without AKI, altogether 112 patients (27.0%) developed AKI > 12 h from ICU admission (AKI>12 h). They had higher sTM levels than patients without AKI, and after multivariable adjustment log, sTM level was associated with AKI>12 h with OR (95% CI) of 12.71 (2.96–54.67), p = 0.001). Ninety-day non-survivors (n = 180; 29.1%) had higher SDC-1 and sTM levels compared to survivors. After adjustment for known confounders, log SDC-1 (OR [95% CI] 2.13 [1.31–3.49], p = 0.002), log sTM (OR [95% CI] 7.35 [2.29–23.57], p < 0.001), and log Ang-2 (OR [95% CI] 2.47 [1.44–4.14], p = 0.001) associated with an increased risk for 90-day mortality. Finally, patients who had high levels of all three markers, namely, SDC-1, Ang-2 and sTM, had an adjusted OR of 5.61 (95% CI 2.67–11.79; p < 0.001) for 90-day mortality. Conclusions: VAP-1 and IL-6 associated with fluid administration on the first ICU day. After adjusting for confounders, sTM was associated with development of AKI after 12 h from ICU admission. SDC-1, Ang-2 and sTM were independently associated with an increased risk for 90-day mortality

ESICM LIVES 2016: part two : Milan, Italy. 1-5 October 2016.

Meeting abstrac