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New biomarkers useful for preventing, managing acute kidney injury

JAMA Network Open
Reuters Health - 07/10/2020 - New biomarkers can be used in combination with clinical information to improve the prevention and management of acute kidney injury (AKI), according to a consensus report from the Acute Disease Quality Initiative (ADQI).

"Significant progress has already been made in the field of AKI biomarkers, which has resulted in a better understanding of the pathophysiology of AKI and improved outcomes with biomarker-guided management," said Dr. Marlies Ostermann of King's College London, Guy's and St. Thomas' Hospital.

"The prospect of clearer identification of high-risk patients and different AKI sub-phenotypes and the utilization of appropriately selected biomarkers in routine clinical will support individualized patient-centered care for patients with AKI," she told Reuters Health by email.

Dr. Ostermann and colleagues in the ADQI met in 2019 to review available evidence on new AKI biomarkers and develop recommendations regarding AKI risk assessment, prediction, prevention, diagnosis, management, and kidney recovery. Their review included 22 putative biomarkers of AKI, ranging from enzymes on proximal tubular cells to pro-inflammatory cytokines.

The new report, in JAMA Network Open, includes 11 consensus statements arising from the meeting.

Among other recommendations, the authors encourage using validated biomarkers, such as tissue inhibitor of metalloproteinases 2 (TIMP-2) and insulin-like growth-factor-binding protein 7 (IGFBP7), to identify patient populations for whom preventive interventions have been shown to improve outcomes.

Clinical assessment and validated biomarkers should be combined, they add, to triage patients and optimize the timing and type of interventions designed to improve processes of care and patient outcomes.

A combination of damage and functional biomarkers, along with clinical information, should be used to improve the diagnostic accuracy of AKI, to recognize the different pathophysiological processes, to discriminate AKI etiology, and to assess AKI severity.

These recommendations have the highest potential to improve the management and outcome of patients with AKI, according to Dr. Ostermann.

The authors also suggest that the inclusion of biomarker data with clinical assessments can be used to identify patients who will need kidney-replacement therapy and to facilitate the optimal timing of its initiation.

Some may regard this recommendation as controversial. "Optimal timing of kidney-replacement therapy remains challenging," Dr. Ostermann said. "It is our hope that new biomarkers will assist with the decision-making process, but more research is necessary to identify these markers and to investigate their role in clinical practice."

"In the absence of a therapy for AKI, we would like to emphasize the urgent need for individualized management based on risk profile and AKI sub-phenotype," she added. "The integration of appropriately selected AKI biomarkers can support clinical management as well as the identification of novel drug therapies. It is very likely that initial costs will be offset by improved patient outcomes and reduced long-term healthcare costs."

Dr. Zoltan H. Endre of Prince of Wales Hospital and the University of New South Wales, in Sydney, Australia, who recently reviewed biomarkers in AKI, told Reuters Health by email, "While consensus functional definitions of AKI embodied in the current definition of AKI have advanced the field, allowing comparison of outcomes at different degrees of severity, they have never allowed early intervention and are unlikely ever to do so, because these rely on function and kidney changes in function that must follow other events, such as cell damage."

"While more research is always necessary, it is clearly time to incorporate damage as well as functional biomarkers into the basic definition of AKI and to implement this as soon as possible in the many well-defined patients at high risk of AKI," said Dr. Endre, who was not involved with the new report. "On the other hand, mass screening with damage biomarkers is not recommended."

Dr. Endre added, "Equipoise or a high pre-test probability is needed to make the initial incorporation of damage biomarkers cost-effective and provide the less-converted with an opportunity to understand the use of such biomarkers in clinical context."

The paper also includes a proposed new definition of AKI, a refined staging system for the diagnosis of AKI, and more than a dozen recommendations for future research.

By Will Boggs MD

SOURCE: https://bit.ly/2SvUW8h JAMA Network Open, online October 6, 2020.

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