Liberation from renal replacement therapy and early initiation to be supported by the kidney function biomarker Proenkephalin A 119-159 (penKid)

• PenKid identified as a promising kidney function biomarker to support future precision medicine approaches for RRT-dependent AKI.
• A post-hoc analysis of the ELAIN trial indicates that penKid could enable the assessment of kidney function under RRT and guide early and successful liberation of treatment.
• For the risk stratification of AKI patients, penKid may be a useful biomarker in identifying the need for timely RRT initiation.

Hennigsdorf, Germany, December 15, 2022 - The diagnostic company SphingoTec GmbH (SphingoTec) announces first data on the kidney function biomarker penKid as a promising tool in supporting early initiation and liberation from RRT (1). Although RRT remains a pivotal measure in treating AKI complications, it is also associated with significant risks and its duration should be restricted to a minimum. The current findings show that penKid has the potential to reveal unprecedented insights on the underlying kidney function prior and during ongoing RRT, facilitating an early and successful termination of treatment. This may support timely risk stratification and individualization of treatment pathways.

To allow kidney recovery in critically ill patients with AKI, RRT remains the key rescue therapy. However, no precise prediction tools are currently available to determine RRT liberation, although 5 - 13% of AKI patients have a high need for RRT (2,3). Due to scarcely available options, discontinuation of RRT relies on expert-based recommendations or clinical judgment based on controversial indications such as urine output. And yet, early discontinuation of RRT would not only be beneficial for the patient but also support the allocation of limited intensive care resources, thereby helping to reduce costs of unnecessarily long periods of RRT or unsuccessful termination with subsequent need for re-initiation of RRT (4).

The current analysis has demonstrated that penKid could be a competent marker to monitor kidney function during ongoing RRT (1). Low penKid values during RRT were associated with earlier and successful liberation from RRT, compared to the group presenting high penKid levels. As a consequence, penKid could support clinicians identify those patients with sufficient kidney recovery, suitable for RRT liberation. In addition, at the time point of AKI diagnosis, measuring penKid values could allow the identification of patients who may benefit from early RRT initiation. Supplementary data suggest that prompt intervention may result in shorter RRT duration. 

The results of this study are complemented by previous scientific evidence showing that penKid mirrors real-time glomerular filtration rate (GFR) even in non-stable settings (5). Furthermore, penKid is unaffected by non-renal factors such as inflammation, common comorbidities, and gender (6,7,8), making it a suitable biomarker, especially for critically ill patients.

Deborah Bergmann, Director of Marketing and Sales at SphingoTec commented, “The implications of the current findings are of great significance for future individualized approaches in managing RRT-dependent AKI. For the first time, scientists identified a biomarker that has the potential to shed light on clinically hidden developments in patients undergoing RRT, a highly challenging stage. This may benefit patients’ health on short and long term, as well as support healthcare providers reduce costs and better assign resources.”

References:

1. von Groote T et al. Proenkephalin A 119–159 predicts early and successful liberation from renal replacement therapy in critically ill patients with acute kidney injury: a post hoc analysis of the ELAIN trial. Crit Care 26, 333 (2022). https://doi.org/10.1186/s13054-022-04217-4
2. Hoste EA, Bagshaw SM, Bellomo R, et al. Epidemiology of acute kidney injury in critically ill patients: the multinational AKI-EPI study. Intensive Care Med 2015;41:1411–23.
3. Uchino S, Kellum JA, Bellomo R, Doig GS, Morimatsu H, Morgera S, et al. Acute renal failure in critically ill patients: a multinational, multicenter study. JAMA. 2005;294:813–8.
4. Korkeila M, Ruokonen E, Takala J. Costs of care, long-term prognosis and quality of life in patients requiring renal replacement therapy during intensive care. Intensive Care Med. 2000;26:1824-1831.
5. Beunders R, van Groenendael R, Leijte G, Kox M, Pickkers P. Proenkephalin compared to conventional methods to assess kidney function in critically ill sepsis patients. Shock. 2020 Jan;1
6. Beunders et al. (2017), Proenkephalin (PENK) as a novel biomarker for kidney function, JALM, DOI: 10.1373/jalm.2017.023598
7. Caironi P, Latini R, Struck J, Hartmann O, Bergmann A, Bellato V, et al. Circulating proenkephalin, acute kidney injury, and its improvement in patients with severe sepsis or shock. Clin Chem. 2018;64((9)):1361–9.
8. Donato LJ, Meeusen JW, Lieske JC, Bergmann D, Sparwaßer A, Jaffe AS. Analytical performance of an immunoassay to measure proenkephalin. Clin Biochem. 2018 Aug;58:72–7.