scholarly journals A Precision Medicine Approach to Biomarker Utilization in Pediatric Sepsis-Associated Acute Kidney Injury

2021 ◽  
Vol 9 ◽  
Author(s):  
James D. Odum ◽  
Hector R. Wong ◽  
Natalja L. Stanski

Sepsis is a leading cause of morbidity and mortality in critically ill children, and acute kidney injury (AKI) is a frequent complication that confers an increased risk for poor outcomes. Despite the documented consequences of sepsis-associated AKI (SA-AKI), no effective disease-modifying therapies have been identified to date. As such, the only treatment options for these patients remain prevention and supportive care, both of which rely on the ability to promptly and accurately identify at risk and affected individuals. To achieve these goals, a variety of biomarkers have been investigated to help augment our currently limited predictive and diagnostic strategies for SA-AKI, however, these have had variable success in pediatric sepsis. In this mini-review, we will briefly outline the current use of biomarkers for SA-AKI, and propose a new framework for biomarker discovery and utilization that considers the individual patient's sepsis inflammatory response. Now recognized to be a key driver in the complex pathophysiology of SA-AKI, understanding the dysregulated host immune response to sepsis is a growing area of research that can and should be leveraged to improve the prediction and diagnosis of SA-AKI, while also potentially identifying novel therapeutic targets. Reframing SA-AKI in this manner – as a direct consequence of the individual patient's sepsis inflammatory response – will facilitate a precision medicine approach to its management, something that is required to move the care of this consequential disorder forward.

2019 ◽  
Vol 8 (3) ◽  
pp. 372 ◽  
Author(s):  
Charat Thongprayoon ◽  
Wisit Kaewput ◽  
Natanong Thamcharoen ◽  
Tarun Bathini ◽  
Kanramon Watthanasuntorn ◽  
...  

Background: The study’s aim was to summarize the incidence and impacts of post-liver transplant (LTx) acute kidney injury (AKI) on outcomes after LTx. Methods: A literature search was performed using the MEDLINE, EMBASE and Cochrane Databases from inception until December 2018 to identify studies assessing the incidence of AKI (using a standard AKI definition) in adult patients undergoing LTx. Effect estimates from the individual studies were derived and consolidated utilizing random-effect, the generic inverse variance approach of DerSimonian and Laird. The protocol for this systematic review is registered with PROSPERO (no. CRD42018100664). Results: Thirty-eight cohort studies, with a total of 13,422 LTx patients, were enrolled. Overall, the pooled estimated incidence rates of post-LTx AKI and severe AKI requiring renal replacement therapy (RRT) were 40.7% (95% CI: 35.4%–46.2%) and 7.7% (95% CI: 5.1%–11.4%), respectively. Meta-regression showed that the year of study did not significantly affect the incidence of post-LTx AKI (p = 0.81). The pooled estimated in-hospital or 30-day mortality, and 1-year mortality rates of patients with post-LTx AKI were 16.5% (95% CI: 10.8%–24.3%) and 31.1% (95% CI: 22.4%–41.5%), respectively. Post-LTx AKI and severe AKI requiring RRT were associated with significantly higher mortality with pooled ORs of 2.96 (95% CI: 2.32–3.77) and 8.15 (95%CI: 4.52–14.69), respectively. Compared to those without post-LTx AKI, recipients with post-LTx AKI had significantly increased risk of liver graft failure and chronic kidney disease with pooled ORs of 3.76 (95% CI: 1.56–9.03) and 2.35 (95% CI: 1.53–3.61), respectively. Conclusion: The overall estimated incidence rates of post-LTx AKI and severe AKI requiring RRT are 40.8% and 7.0%, respectively. There are significant associations of post-LTx AKI with increased mortality and graft failure after transplantation. Furthermore, the incidence of post-LTx AKI has remained stable over the ten years of the study.


2017 ◽  
Vol 18 (12) ◽  
pp. e585-e591 ◽  
Author(s):  
Maya R. Holsen ◽  
Calvin J. Meaney ◽  
Amanda B. Hassinger ◽  
Nicholas M. Fusco

Kidney360 ◽  
2021 ◽  
pp. 10.34067/KID.0004542021
Author(s):  
Erin K Stenson ◽  
Zhiying You ◽  
Ron Reeder ◽  
Jesse Norris ◽  
Halden F. Scott ◽  
...  

Background:Critically ill children with acute kidney injury (AKI) suffer from high morbidity and mortality rates, and lack treatment options. Emerging evidence implicates the role of complement activation in AKI pathogenesis, which could potentially be treated with complement inhibitors. The purpose of this study is to evaluate the association between complement activation fragments and severity of AKI in critically ill children. Methods:A biorepository of critically ill children from a prior multi-site study was leveraged to identify children with stage 3 AKI and matched to patients without AKI based on PELOD-2 (illness severity) scores. Specimens were analyzed for plasma and urine complement activation fragments of factor B, C3a, C4a, and sC5b-9. The primary outcomes were MAKE30 and severe AKI rates. Results:14 patients with stage 3 AKI (5 requiring renal replacement therapy [RRT]) were matched to 14 patients without AKI. Urine factor Ba and plasma C4a levels increased stepwise as severity of AKI increased, from no AKI to stage 3 AKI, to stage 3 AKI with RRT need. Plasma C4a levels were independently associated with increased risk of MAKE30 outcomes (OR 3.2; IQR 1.1-8.9), and urine Ba and plasma Bb, C4a, and C3a were independently associated with risk of severe stage 2-3 AKI on day 3 of admission. Conclusions:Multiple complement fragments increase as magnitude of AKI severity increases. Very high levels of urine Ba or plasma C4a may identify patients at risk for severe AKI, hemodialysis, and MAKE30 outcomes. The fragments may be useful as a functional biomarker of complement activation and may identify those patients to study complement inhibition to treat or prevent AKI in critically ill children. These findings suggest the need for further specific investigations of the role of complement activation in critically ill children at risk of AKI.


Nephron ◽  
2020 ◽  
Vol 144 (12) ◽  
pp. 650-654
Author(s):  
Luca Bordoni ◽  
Donato Sardella ◽  
Ina Maria Schiessl

Acute kidney injury (AKI) is associated with an increased risk of CKD. Injury-induced multifaceted renal cell-to-cell crosstalk can either lead to successful self-repair or chronic fibrosis and inflammation. In this mini-review, we will discuss critical renal cell types acting as victims or executioners in AKI pathology and introduce intravital imaging as a powerful technique to further dissect these cell-to-cell interactions.


Author(s):  
John R. Prowle ◽  
Lui G. Forni ◽  
Max Bell ◽  
Michelle S. Chew ◽  
Mark Edwards ◽  
...  

AbstractPostoperative acute kidney injury (PO-AKI) is a common complication of major surgery that is strongly associated with short-term surgical complications and long-term adverse outcomes, including increased risk of chronic kidney disease, cardiovascular events and death. Risk factors for PO-AKI include older age and comorbid diseases such as chronic kidney disease and diabetes mellitus. PO-AKI is best defined as AKI occurring within 7 days of an operative intervention using the Kidney Disease Improving Global Outcomes (KDIGO) definition of AKI; however, additional prognostic information may be gained from detailed clinical assessment and other diagnostic investigations in the form of a focused kidney health assessment (KHA). Prevention of PO-AKI is largely based on identification of high baseline risk, monitoring and reduction of nephrotoxic insults, whereas treatment involves the application of a bundle of interventions to avoid secondary kidney injury and mitigate the severity of AKI. As PO-AKI is strongly associated with long-term adverse outcomes, some form of follow-up KHA is essential; however, the form and location of this will be dictated by the nature and severity of the AKI. In this Consensus Statement, we provide graded recommendations for AKI after non-cardiac surgery and highlight priorities for future research.


2021 ◽  
Vol 10 (10) ◽  
pp. 2151
Author(s):  
Rita Pavasini ◽  
Matteo Tebaldi ◽  
Giulia Bugani ◽  
Elisabetta Tonet ◽  
Roberta Campana ◽  
...  

Whether contrast-associated acute kidney injury (CA-AKI) is only a bystander or a risk factor for mortality in older patients undergoing percutaneous coronary intervention (PCI) is not well understood. Data from FRASER (NCT02386124) and HULK (NCT03021044) studies have been analysed. All patients enrolled underwent coronary angiography. The occurrence of CA-AKI was defined based on KDIGO criteria. The primary outcome of the study was to test the relation between CA-AKI and 3-month mortality. Overall, 870 older ACS adults were included in the analysis (mean age 78 ± 5 years; 28% females). CA-AKI occurred in 136 (16%) patients. At 3 months, 13 (9.6%) patients with CA-AKI died as compared with 13 (1.8%) without it (p < 0.001). At multivariable analysis, CA-AKI emerged as independent predictor of 3-month mortality (HR 3.51, 95%CI 1.05–7.01). After 3 months, renal function returned to the baseline value in 78 (63%) with CA-AKI. Those without recovered renal function (n = 45, 37%) showed an increased risk of mortality as compared to recovered renal function and no CA-AKI subgroups (HR 2.01, 95%CI 1.55–2.59, p = 0.009 and HR 2.71, 95%CI 1.45–5.89, p < 0.001, respectively). In conclusion, CA-AKI occurs in a not negligible portion of older MI patients undergoing invasive strategy and it is associated with short-term mortality.


Author(s):  
Andrew M Vekstein ◽  
Babtunde A Yerokun ◽  
Oliver K Jawitz ◽  
Julie W Doberne ◽  
Jatin Anand ◽  
...  

Abstract OBJECTIVES The impact of hypothermic circulatory arrest (HCA) temperature on postoperative acute kidney injury (AKI) has not been evaluated. This study examined the association between circulatory arrest temperatures and AKI in patients undergoing proximal aortic surgery with HCA. METHODS A total of 759 consecutive patients who underwent proximal aortic surgery (ascending ± valve ± root) including arch replacement requiring HCA between July 2005 and December 2016 were identified from a prospectively maintained institutional aortic surgery database. The primary outcome was AKI as defined by Risk, Injury, Failure, Loss, End Stage Renal Disease (ESRD) criteria. The association between minimum nasopharyngeal (NP) and bladder temperatures during HCA and postoperative AKI was assessed, adjusting for patient-level factors using multivariable logistic regression. RESULTS A total of 85% (n = 645) of patients underwent deep hypothermia (14.1–20.0°C), 11% (n = 83) low-moderate hypothermia (20.1–24.0°C) and 4% (n = 31) high-moderate hypothermia (24.1–28.0°C) as classified by NP temperature. When analysed by bladder temperature, 59% (n = 447) underwent deep hypothermia, 22% (n = 170) low-moderate, 16% (n = 118) high-moderate and 3% mild (n = 24) (28.1–34.0°C) hypothermia. The median systemic circulatory arrest time was 17 min. The incidence of AKI did not differ between hypothermia groups, whether analysed using minimum NP or bladder temperature. In the multivariable analysis, the association between degree of hypothermia and AKI remained non-significant whether analysed as a categorical variable (hypothermia group) or as a continuous variable (minimum NP or bladder temperature) (all P &gt; 0.05). CONCLUSIONS In patients undergoing proximal aortic surgery including arch replacement requiring HCA, degree of systemic hypothermia was not associated with the risk of AKI. These data suggest that moderate hypothermia does not confer increased risk of AKI for patients requiring circulatory arrest, although additional prospective data are needed.


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