James F. Doyle

Acute kidney injury: short-term and long-term effects

Acute kidney injury (AKI) is the most common cause of organ dysfunction in critically ill adults, with a single episode of AKI, regardless of stage, carrying a significant morbidity and mortality risk. Since the consensus on AKI nomenclature has been reached, data reflecting outcomes have become more apparent allowing investigation of both short- and long-term outcomes.Classically the short-term effects of AKI can be thought of as those reflecting an acute deterioration in renal function per se. However, the effects of AKI, especially with regard to distant organ function (“organ cross-talk”), are being elucidated as is the increased susceptibility to other conditions. With regards to the long-term effects, the consideration that outcome is a simple binary endpoint of dialysis or not, or survival or not, is overly simplistic, with the reality being much more complex.Also discussed are currently available treatment strategies to mitigate these adverse effects, as they have the potential to improve patient outcome and provide considerable economic health savings. Moving forward, an agreement for defining renal recovery is warranted if we are to assess and extrapolate the efficacy of novel therapies. Future research should focus on targeted therapies assessed by measure of long-term outcomes.

Should we treat pyrexia? And how do we do it?

The concept of pyrexia as a protective physiological response to aid in host defence has been challenged with the awareness of the severe metabolic stress induced by pyrexia. The host response to pyrexia varies, however, according to the disease profile and severity and, as such, the management of pyrexia should differ; for example, temperature control is safe and effective in septic shock but remains controversial in sepsis. From the reported findings discussed in this review, treating pyrexia appears to be beneficial in septic shock, out of hospital cardiac arrest and acute brain injury.Multiple therapeutic options are available for managing pyrexia, with precise targeted temperature management now possible. Notably, the use of pharmacotherapy versus surface cooling has not been shown to be advantageous. The importance of avoiding hypothermia in any treatment strategy is not to be understated.Whilst a great deal of progress has been made regarding optimal temperature management in recent years, further studies will be needed to determine which patients would benefit the most from control of pyrexia and by which means this should be implemented. This narrative review is part of a series on the pathophysiology and management of pyrexia.

Long-Term Follow-up of Acute Kidney Injury

In the general hospital setting, approximately 15% of inpatients sustain an episode of acute kidney injury (AKI) but in the critical care environment this can increase to over 25%. An episode of AKI increases the risk for both future chronic kidney disease and associated cardiovascular complications. Discharge of patients who have suffered a renal insult resulting in AKI should include consideration of longer-term follow-up, which may require nephrology input. This increase in health care burden and economic costs may be quantified and justifies the need to develop robust quality-improvement projects aimed at AKI prevention, identification, and improved management.

Update on sepsis-associated acute kidney injury: emerging targeted therapies

Sepsis-associated acute kidney injury (SA-AKI) is an independent predictor of increased mortality and morbidity. It is essential that further advances in the treatment of sepsis should prioritize targeted therapies in SA-AKI in order to improve these bleak outcomes. As yet, a unique therapy that effectively reduces the impact of acute kidney injury has not been demonstrated. However, the emergence of novel targeted therapies, perhaps in combination, has the possibility of significantly reducing the long-term sequelae of an episode of SA-AKI. In this review, we will focus on the shared etiology of these conditions and how this is managed with targeted therapy and finally the emerging novel therapies that may play an additional role to current treatment strategies.

Goal-directed therapy and acute kidney injury: as good as it gets?

The use of goal-directed therapy as part of an enhanced recovery programme is well established in terms of management of the modern high-risk surgical patient in order to reduce both morbidity and mortality. The mechanisms behind this improvement are debated, but a reduction in the development of post-operative complications including acute kidney injury may be relevant. A recent study examining this relationship has been reported and is discussed here.

The life and work of Harvey Cushing 1869–1939: A pioneer of neurosurgery

Harvey Cushing is well known as being the father of modern neurological surgery and his portrait brands the American Association of Neurological Surgeons. He was the youngest of 10 children and from medical lineage with his father, grandfather and great-grandfather all being general medical practitioners. The details of his life and work are particularly well documented as a result of his obsessive letter writing and record keeping.

Wrong guidelines: how to detect them and what to do in the case of flawed recommendations

Any evidence-based recommendation needs careful assessment of its methodological background as well as of its content trustworthiness, especially given that following it will not necessarily produce the intended clinical outcomes. There are no established instruments to evaluate guidelines for their content, while useful tools assessing the quality of methods followed are well recognised and adopted. We suggest a ‘safety bundle’ considering methodological aspects and content trustworthiness of guidelines, by adopting the GRADE method in a backward fashion. Sharing the critical analysis of the guidelines with patients, including any eventual uncertainty about them, is of key importance in order to avoid the possible adverse effects derived from following the wrong guidelines. Such critical approach is also helpful and beneficial in producing better care pathways, health policy decisions and more relevant and ethical research.

Vitamin D levels in critically ill patients with acute kidney injury: a protocol for a prospective cohort study (VID-AKI)

Introduction Acute kidney injury (AKI) affects more than 50% of critically ill patients. The formation of calcitriol, the active vitamin D metabolite, from the main inactive circulating form, 25-hydroxyvitamin D (25(OH)D), occurs primarily in the proximal renal tubules. This results in a theoretical basis for reduction in levels of calcitriol over the course of an AKI. Vitamin D deficiency is highly prevalent in critically ill adults, and has been associated with increased rates of sepsis, longer hospital stays and increased mortality. The primary objective of this study is to perform serial measurements of 25(OH)D and calcitriol (1,25(OH)2D), as well as parathyroid hormone (PTH) and fibroblast growth factor 23 (FGF23) levels, in critically ill adult patients with and without AKI, and to determine whether patients with AKI have significantly lower vitamin D metabolite concentrations. The secondary objectives are to describe dynamic changes in vitamin D metabolites, PTH and FGF23 during critical illness; to compare vitamin D metabolite concentrations in patients with AKI with and without renal replacement therapy; and to investigate whether there is an association between vitamin D status and outcomes. Methods and analysis 230 general adult intensive care patients will be recruited. The AKI arm will include 115 critically ill patients with AKI Kidney Disease Improving Global Outcome stage II or stage III. The comparison group will include 115 patients who require cardiovascular or respiratory support, but who do not have AKI. Serial measurements of vitamin D metabolites and associated hormones will be taken on prespecified days. Patients will be recruited from two large teaching Trusts in England. Data will be analysed using standard statistical methods. Ethics and dissemination Ethical approval was obtained. Upon completion, the study team will submit the study report for publication in a peer-reviewed scientific journal and for conference presentation. Trial registration number NCT02869919; Pre-results.

Acute Kidney Injury Biomarkers: What Do They Tell Us?

The definition of acute kidney injury (AKI) is now well established and encompasses changes in both the urine output and the serum creatinine (SCr) over time. Many studies to date have concentrated solely on the SCr criteria, as this is relatively easy to monitor, given that accurate urine output is rarely measured outside critical care areas. However, many studies have emphasised the inadequacies of SCr in highlighting potential renal injury in a timely fashion. These limitations reflect not only acute changes in creatinine metabolism in the critically ill but also the kinetics of creatinine generation that may hinder early recognition of AKI. In turn, this may prevent judicious intervention promoting the misconception that little can be done for patients with this devastating condition except treating the consequences. Such observations have led to much research focused on identifying early indicators of AKI that may enable early treatment and hopefully lead to improved outcomes. This explains in part the reasoning behind the interest in biomarkers of AKI and which may see them develop a role as part of established clinical tool(s) in both the assessment of severity of AKI and the potential to assess recovery. However, much of the effort behind biomarker research has focused on the ability of such candidate molecules to predict AKI as defined by the imperfect gold standards used currently. It may be that the presence of renal biomarkers associated with renal stress or injury in isolation dictates poor outcomes and as such may provide diagnostic certainty in their own right.

Association between intravascular thermoregulation devices and the development of venous thrombo-embolic phenomenon

Intravascular thermoregulation devices (ITDs) have proved effective for achieving targeted temperature management in critically ill patients. Previous reports, however, have suggested an association between ITDs and venous thrombo-embolic phenomenon (VTE). Our local quality improvement initiative explored this possible association. All patients with ITDs (Thermoguard XP temperature management system) inserted over a two-year period in our 28-bed intensive care unit (ICU) were identified retrospectively from a departmental record of procedures. Of twenty-five patients who received ITDs, review of medical notes, discharge summaries, and imaging revealed that three had subsequent radiological evidence of VTE. Of these, one had the ITD inserted to achieve therapeutic hypothermia (target 33 ) and the others, for the prevention of pyrexia (target 37.5–38 ). In all three patients, ITDs were sited in femoral veins, under ultrasound without peri-procedural complications. In one patient, the VTE was clinically apparent and confirmed with Doppler; in the other two patients, VTE were incidental findings on ECHO and CT. Thrombi were local to the site of ITD placement in the femoral vein in one patient and involved the inferior vena cavae of the other two. One patient later had incidental CT evidence of pulmonary embolism. Other risk factors for VTE included critical illness, reduced mobility, mechanical ventilation, obesity and medications, namely the combined oral contraceptive pill and antipsychotics. All three patients received prophylactic mechanical treatment against VTE, but pharmacological prophylaxis was held in one case due to bleeding risk. Critically, we note that two of the three cases had ITDs in situ for more than 72 h, longer than the manufacturer’s recommendation, and one of these had a combination of ITD and haemofiltration vascular access catheter in the same site for over a week. Review of hospital outcomes demonstrated that all three survived admission and were either discharged home or transferred to another unit for rehabilitation. Our finding that at least 12% of our ICU patients managed with ITDs over a two-year period had radiological evidence of VTE compares to a similar frequency of 12.7% (CI: 12.7%; 95% CI: 8.7–17.5%) reported for all ICU patients screened for thrombosis in a meta-analysis of seven studies (n1⁄4 1783). We stress, however, that our reported figure represents the minimum frequency, given that we did not routinely screen our patients and noting that two of the three cases were asymptomatic for VTE. The mechanism of a potential association between ITDs and VTE remain to be clarified, and further investigation is warranted with screening in larger patient groups and comparative studies involving other intravascular devices. Our observation nonetheless highlights the importance of timely removal of ITDs and justifies a high index of clinical suspicion for VTE occurrence, particularly as VTE has been linked to key outcomes including duration of ICU and hospital stay and hospital mortality. In addition, given that targeted temperature management with the newer (gel-based) surface cooling devices is equally efficacious, there may be a justified move away from the use of ITDs in the future.