Urinary Biomarkers of AKI and Mortality 3 Years after Cardiac Surgery

Urinary biomarkers of AKI provide prognostic value for in-hospital outcomes, but little is known about their association with longer-term mortality after surgery. We sought to assess the association between kidney injury biomarkers and all-cause mortality in an international, multicenter, prospective long-term follow-up study from six clinical centers in the United States and Canada composed of 1199 adults who underwent cardiac surgery between 2007 and 2009 and were enrolled in the Translational Research in Biomarker Endpoints in AKI cohort. On postoperative days 1–3, we measured the following five urinary biomarkers: neutrophil gelatinase-associated lipocalin, IL-18, kidney injury molecule-1 (KIM-1), liver fatty acid binding protein, and albumin. During a median follow-up of 3.0 years (interquartile range, 2.2–3.6 years), 139 participants died (55 deaths per 1000 person-years). Among patients with clinical AKI, the highest tertiles of peak urinary neutrophil gelatinase-associated lipocalin, IL-18, KIM-1, liver fatty acid binding protein, and albumin associated independently with a 2.0- to 3.2-fold increased risk for mortality compared with the lowest tertiles. In patients without clinical AKI, the highest tertiles of peak IL-18 and KIM-1 also associated independently with long-term mortality (adjusted hazard ratios [95% confidence intervals] of 1.2 [1.0 to 1.5] and 1.8 [1.4 to 2.3] for IL-18 and KIM-1, respectively), and yielded continuous net reclassification improvements of 0.26 and 0.37, respectively, for the prediction of 3-year mortality. In conclusion, urinary biomarkers of kidney injury, particularly IL-18 and KIM-1, in the immediate postoperative period provide additional prognostic information for 3-year mortality risk in patients with and without clinical AKI.In many studies, the development of AKI, defined by acute changes in serum creatinine, associates with a higher risk of long-term mortality.^1,2 Acute changes in serum creatinine, however, may not fully reflect the severity of kidney injury due to the influence of age, sex, muscle mass, changes in hydration, nutritional status, and medications on creatinine kinetics. Moreover, serum creatinine may abruptly rise in hospitalized settings due to functional processes such as altered hemodynamics, without any true nephron damage. Several urinary biomarkers of structural kidney injury have been investigated in human cohorts in an effort to identify AKI earlier, improve the diagnosis of AKI, and to aid in risk stratification.³ It is largely unknown, however, whether kidney injury biomarkers associate with long-term outcomes, including mortality, and whether these biomarkers add useful prognostic information beyond the standard measure to detect AKI (e.g., peak change in serum creatinine). Some data suggest that “subclinical AKI,” as evidenced by elevations in urinary kidney injury biomarkers in the absence of a rise in serum creatinine, associates with worse in-hospital clinical outcomes.⁴ Few studies have examined whether kidney injury biomarkers associate with long-term mortality after hospital discharge.⁵To address the current knowledge gaps, we conducted this study to characterize the association between kidney injury biomarkers and long-term mortality and to assess whether these biomarkers provide any incremental prognostic information for long-term mortality beyond that of serum creatinine changes and other clinical variables.     

The serotonin-N-acetylserotonin–melatonin pathway as a biomarker for autism spectrum disorders

Elevated whole-blood serotonin and decreased plasma melatonin (a circadian synchronizer hormone that derives from serotonin) have been reported independently in patients with autism spectrum disorders (ASDs). Here, we explored, in parallel, serotonin, melatonin and the intermediate N-acetylserotonin (NAS) in a large cohort of patients with ASD and their relatives. We then investigated the clinical correlates of these biochemical parameters. Whole-blood serotonin, platelet NAS and plasma melatonin were assessed in 278 patients with ASD, their 506 first-degree relatives (129 unaffected siblings, 199 mothers and 178 fathers) and 416 sex- and age-matched controls. We confirmed the previously reported hyperserotonemia in ASD (40% (35–46%) of patients), as well as the deficit in melatonin (51% (45–57%)), taking as a threshold the 95th or 5th percentile of the control group, respectively. In addition, this study reveals an increase of NAS (47% (41–54%) of patients) in platelets, pointing to a disruption of the serotonin-NAS–melatonin pathway in ASD. Biochemical impairments were also observed in the first-degree relatives of patients. A score combining impairments of serotonin, NAS and melatonin distinguished between patients and controls with a sensitivity of 80% and a specificity of 85%. In patients the melatonin deficit was only significantly associated with insomnia. Impairments of melatonin synthesis in ASD may be linked with decreased 14-3-3 proteins. Although ASDs are highly heterogeneous, disruption of the serotonin-NAS–melatonin pathway is a very frequent trait in patients and may represent a useful biomarker for a large subgroup of individuals with ASD.     

Effect of renal angioembolization on post-traumatic acute kidney injury after high-grade renal trauma: A comparative study of 52 consecutive cases

Background

Acute kidney injury (AKI) is associated with unfavourable outcomes and higher mortality after trauma. Renal angioembolization (RAE) has proved efficiency in the management of high-grade renal trauma (HGRT), but inevitably expose to unavoidable ischaemic areas or contrast medium nephrotoxicity which may impair renal function in the following hours. The aim of this study was to assess the potential acute impact of RAE on renal function in a consecutive series of HGRTs treated nonoperatively.

Materials and methods

Of 101 cases of renal trauma admitted to our Regional Trauma Center between January 2005 and January 2010, 52 cases of HGRT were treated nonoperatively; they were retrospectively classified into 2 groups according to whether RAE was used. Incidence and progression of AKI (RIFLE classification), maximum increase in serum creatinine (SCr), level since admission and recovery of renal function at discharge were compared between the groups. Multivariable analysis was performed to determine the role of RAE as an independent risk factor of AKI.

Results

RAE was performed in 10 patients within the first 48 h. The RAE and no RAE groups were comparable in terms of severity score, renal injury grade, and level of SCr on admission. AKI incidence (RIFLE score Risk or worse) after 48 and 96 h was 33% and 10%, respectively and did not differ significantly between groups at 48 h (p = 1.00) or 96 h (p = 1.00). The median maximum increase in SCr was significantly higher in no RAE than RAE group (30.4% vs. 6.9%, p = 0.04). RAE was not found to be a significant variable in a multiple linear regression analysis predicting maximum SCr rise (p = 0.34). SCr at discharge was >120% of baseline in only 5 patients, with no difference according to RAE (p = 0.24).

Conclusion

In a population of nonoperatively treated HGRT, the incidence of AKI decreased from almost 30% to 10% at 48 h and 96 h. RAE proceeding did not seem to affect significantly the occurrence and course of AKI or renal recovery. The decision to use RAE should probably not be restricted by fear of worsening renal function.     

Inflammatory Biomarkers and Bladder Cancer Prognosis: A Systematic Review

Context

Host immune response has an impact on tumour development and progression. There is interest in the use of inflammatory biomarkers (InfBMs) in cancer care. Although several studies assessing the potential prognostic value of InfBMs in cancer have been published in the past decades, they have had no impact on the management of patients with urothelial bladder carcinoma (UBC).

Objective

To review and summarise the scientific literature on the prognostic value of tumour, serum, urine, and germline DNA InfBMs on UBC.

Evidence acquisition

A systematic review of the literature was performed searching the Medline and Embase databases for original articles published between January 1975 and November 2013. The main inclusion criterion was the provision of a survival analysis (Kaplan-Meier and/or Cox) according to the Reporting Recommendations for Tumor Marker Prognostic Studies guidelines for the assessment of prognostic markers. We focused on markers assessed at least twice in the literature. Findings are reported following Preferred Reporting Items for Systematic Reviews and Meta-analysis guidelines.

Evidence synthesis

Overall, 34 publications, mostly retrospective, fulfilled the main inclusion criterion. Main limitations of these studies were missing relevant information about design or analysis and heterogeneous methodology used. Inflammatory cells, costimulatory molecules in tumour cells, and serum cytokines showed prognostic significance, mainly in univariable analyses. High C-reactive protein values were consistently reported as an independent prognostic factor for mortality in invasive UBC.

Conclusions

There is a dearth of studies on InfBMs in UBC compared with other tumour types. Evidence suggests that InfBMs may have an impact on the management of patients with UBC. Currently, methodological drawbacks of the studies limit the translational potential of results.

Patient summary

In this review, we analysed studies evaluating the impact of inflammatory response on bladder cancer progression. Despite methodological limitations, some inflammatory biomarkers should be further analysed because they hold promise to improve patient care.