Sepsis is a life-threatening organ dysfunction caused by a dysregulated host-response to infections. Osteopontin (OPN) is an extracellular matrix protein involved in the inflammatory response. Our aim was to evaluate the diagnostic and prognostic performance in sepsis of a single OPN determination in the Emergency Department (ED). We conducted a single-centre prospective observational study in an Italian ED where we enrolled 102 consecutive patients presenting with suspected infection and qSOFA ≥ 2. OPN plasma concentration was found to be an independent predictor of sepsis (OR = 1.020, 95% CI 1.002–1.039, p = 0.031) and the diagnostic receiver operating characteristic (ROC) curve resulted in an area under the curve (AUC) of 0.878. OPN levels were positively correlated to plasma creatinine (r = 0.401 with p = 0.0001), but this relation was not explained by the development of acute kidney injury (AKI), since no difference was found in OPN concentration between AKI and non-AKI patients. The analysis of 30-days mortality showed no significant difference in OPN levels between alive and dead patients (p = 0.482). In conclusion, a single determination of OPN concentration helped to identify patients with sepsis in the ED, but it was not able to predict poor prognosis in our cohort of patients.

Sepsis is the most common cause of acute kidney injury (AKI) in critically ill patients. Four phenotypes (α, β, γ, δ) for sepsis, which have different outcomes and responses to treatment, were described using routine clinical data in the electronic health record. Do the frequencies of AKI, acute kidney disease (AKD), chronic kidney disease (CKD), and AKI on CKD differ by sepsis phenotype? This was a secondary analysis of a randomized clinical trial of early resuscitation, including patients with septic shock at 31 sites. After excluding patients with end-stage kidney disease and missing data, we determined frequencies of the following clinical outcomes: AKI (defined within 24 h as Kidney Disease: Improving Global Outcomes stages 2 or 3 or stage 1 with tissue inhibitor of metalloproteinases-2 × insulin-like growth factor binding protein 7 value of > 2.0), CKD, and AKD (persistence of AKI at any stage on day 7 after enrollment) across four phenotypes. We performed multivariable logistic regression to assess the risk-adjusted association between development of AKI and AKD and phenotype. Among 1,090 eligible patients, 543 patients (50%) had AKI. Across phenotypes, the frequencies of AKI varied, being highest in the δ and β phenotypes (78% and 71%, respectively) and the lowest in the α phenotype (26%; P < .001). AKD occurred most often in the δ phenotype (41%) and least often in the α phenotype (8%; P < .001). The highest frequencies of CKD and of AKI on CKD were found in the β phenotype (53% and 38% respectively; P < .001 for both). In the multivariable logistic regression models (α phenotype as reference), δ phenotype showed the strongest association with AKI (OR, 12.33; 95% CI, 7.81-19.47; P < .001) and AKD (OR, 9.18; 95% CI, 5.44-15.51; P < .001). The rates of AKI and AKD differed across clinical sepsis phenotypes and are more common among patients with phenotypes β and δ. Phenotype β showed a higher level of underlying CKD that predisposed patients to new AKI. The α and γ phenotypes showed lower frequencies of AKI and less progression to AKD.

In the perioperative setting, acute kidney injury (AKI) is a frequent complication, and AKI itself is associated with adverse outcomes such as higher risk of chronic kidney disease and mortality. Various risk factors are associated with perioperative AKI, and identifying them is crucial to early interventions addressing modifiable risk and increasing monitoring for nonmodifiable risk. Different mechanisms are involved in the development of postoperative AKI, frequently picturing a multifactorial etiology. For these reasons, no single renoprotective strategy will be effective for all surgical patients, and efforts have been attempted to prevent kidney injury in different ways. Some renoprotective strategies and treatments have proven to be useful, some are no longer recommended because they are ineffective or even harmful, and some strategies are still under investigation to identify the best timing, setting, and patients for whom they could be beneficial. With this review, we aim to provide an overview of recent findings from studies examining epidemiology, risk factors, and mechanisms of perioperative AKI, as well as different renoprotective strategies and treatments presented in the literature.

Full Papers; Authors: M. Bellan, M. Quaglia, A. Nerviani, D. Mauro, M. Lewis, F. Goegan, A. Gibbin, S. Pagani, L. Salmi, L. Molinari, L.M. Castello, G.C. Avanzi, V. Cantaluppi, M. Pirisi, P.P. Sainaghi, C. Pitzalis

OBJECTIVES: To describe study design considerations and to simulate a trial of biomarker-guided sepsis management aimed to reduce acute kidney injury (acute kidney injury). Tissue inhibitor of metalloproteinases-2 and insulin-like growth factor-binding protein 7, urinary biomarkers of cell-cycle arrest, and indicators of kidney stress can detect acute kidney injury before clinical manifestations. We sought to determine the event rates for acute kidney injury as a function of serial measurements of urinary (tissue inhibitor of metalloproteinases-2)•(insulin-like growth factor-binding protein 7) in patients at risk of sepsis-associated acute kidney injury, so that an escalating series of kidney-sparing sepsis bundles based on international guidelines could be applied. DESIGN: We described the study protocol of “Limiting acute kidney injury Progression In Sepsis,” a phase 4, multicenter, adaptive, randomized controlled trial. We performed simulations to estimate the rates for the trial’s primary endpoint using patient-level data from two previous studies (Sapphire and Protocolized Care for Early Septic Shock). SETTING: Academic and community ICUs. PATIENTS: Critically ill patients with sepsis or septic shock, without evidence of stage 2/3 acute kidney injury at enrollment. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Our primary endpoint is progression of two or more stages of acute kidney injury, death, or dialysis within 72 hours after enrollment. In the Sapphire simulation, 45 of 203 patients (22%) with sepsis met the endpoint. In Protocolized Care for Early Septic Shock, 144 of 607 patients (24%) with septic shock met the endpoint. In both simulations, (tissue inhibitor of metalloproteinases-2)•(insulin-like growth factor-binding protein 7) patterns, suggested by Limiting acute kidney injury Progression In Sepsis protocol, stratified the risk for the endpoint from 6% (three negative tests) to 41% (for patients eligible for the highest level of kidney-sparing sepsis bundle) in Sapphire, and 14% (two negative tests) to 46% (for the highest level of kidney-sparing sepsis bundle) in Protocolized Care for Early Septic Shock. CONCLUSIONS: Findings of our Limiting acute kidney injury Progression In Sepsis trial simulation confirmed that (tissue inhibitor of metalloproteinases-2)•(insulin-like growth factor-binding protein 7) could identify patients with different rates of progression to moderate/severe acute kidney injury, death, or dialysis in 72 hours. The Limiting acute kidney injury Progression In Sepsis protocol algorithm is therefore feasible in terms of identifying suitably high-risk individuals for kidney-sparing sepsis bundle.

Aim: Plasma Gas6 was tested as an alternative to Baveno VI criteria (liver stiffness 150 × 109/l) in an endoscopy-sparing strategy. Methods: A total of 160 patients with chronic hepatitis C and advanced fibrosis/cirrhosis underwent, on the same occasion, liver elastography, upper endoscopy, a platelet count and serum Gas6 measurement. Results: A total of 74/160 (46%) patients had esophageal varices, that were small (diameter <5 mm) in 57/160 (34%) and large in 17/160 (11%) cases. A total of 34/160 (21%) patients satisfied Baveno VI criteria, according to which screening for esophageal varices could have been omitted; 1/34 had large varices (sensitivity 94%). A plasma Gas6 value <45 ng/ml, detected in 34/160 (21%) patients, was also 94% sensitive. Conclusion: Plasma Gas6 might represent a feasible alternative to Baveno VI criteria when transient elastography is unavailable/unsuccessful.