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ACUTE KIDNEY INJURY IN 2018

The handwriting is on the wall: there will soon be a drug for AKI

Nature Reviews Nephrology volume 15, pages 65–66 (2019)Cite this article

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With many failures, a sense of helplessness has overshadowed the field of acute kidney injury (AKI). Publications in 2018 offer new hope: better drug targets, better end points and improved understanding of conditions that cause AKI and its complications bring promise that a drug will soon be available.

Key advances

  • The risk of acute kidney injury (AKI) and adverse kidney events in hospitalized patients can be reduced by using physiological solutions instead of saline for intravenous fluid therapy1,2.

  • Strategies for the enrichment and subcategorization of patients with AKI who are most likely to benefit from specific treatments are now available5,8.

  • New mechanisms and related drug targets, most notably related to mitochondrial dysfunction, have transformed the therapeutic landscape of AKI7,8,9.

  • End points for use in trials of AKI therapies are now well defined1,2,5,10.

Acute kidney injury (AKI) is an intractable problem; it affects 10–15% of patients admitted to hospital, with as many as 100 million cases occurring worldwide annually. In the past, it has been a field without much optimism; pioneering work1,2 has shown that about 50% of patients who develop stage 2 or 3 AKI3 do not recover renal function, at least not within 30 days of AKI onset, and that the overall combined rates of death, dialysis and/or persistent renal dysfunction are about 5% for hospitalized patients2 and 15% for those in intensive care units1. Just as importantly though, we now know that the risk of adverse kidney outcomes can be modified1,2 with a remarkably simple intervention — that is, by reducing the use of saline in favour of more physiological fluids. Although this approach is hardly a cure, two trials observed an absolute risk reduction of 1%, which could save thousands of lives.

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Fig. 1: Reasons for optimism in AKI therapeutics.

References

  1. Semler, M. W. et al. Balanced crystalloids versus saline in critically ill adults. N. Engl. J. Med. 378, 829–839 (2018).

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  8. Poyan Mehr, A. et al. De novo NAD+ biosynthetic impairment in acute kidney injury in humans. Nat. Med. 24, 1351–1359 (2018).

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Author information

Authors and Affiliations

  1. Center for Critical Care Nephrology, University of Pittsburgh, Pittsburgh, PA, USA

    John A. Kellum & Dana Y. Fuhrman

  2. Department of Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA, USA

    John A. Kellum & Dana Y. Fuhrman

  3. Children’s Hospital of Pittsburgh, Pittsburgh, PA, USA

    Dana Y. Fuhrman

Authors
  1. John A. Kellum
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  2. Dana Y. Fuhrman
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Corresponding author

Correspondence to John A. Kellum.

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Competing interests

J.A.K. has received grant support and consulting fees from Astute Medical and TES Pharma. D.Y.F. declares no competing interests.

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Kellum, J.A., Fuhrman, D.Y. The handwriting is on the wall: there will soon be a drug for AKI. Nat Rev Nephrol 15, 65–66 (2019). https://doi.org/10.1038/s41581-018-0095-2

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