Assessing GFR With Proenkephalin

Remi Beunders; Leslie J Donato; Roger van Groenendael; Birte Arlt; Cristiane Carvalho-Wodarz; Janin Schulte; Anton Cc Coolen; John C Lieske; Jeffrey W Meeusen; Allan S Jaffe; Peter Pickkers

doi:10.1016/j.ekir.2023.08.006

Assessing GFR With Proenkephalin

Kidney Int Rep. 2023 Aug 19;8(11):2345-2355. doi: 10.1016/j.ekir.2023.08.006. eCollection 2023 Nov.

Authors

Remi Beunders^{1

2}, Leslie J Donato³, Roger van Groenendael^{1

2

4}, Birte Arlt⁵, Cristiane Carvalho-Wodarz⁵, Janin Schulte⁵, Anton Cc Coolen^{6

7}, John C Lieske^{3

8}, Jeffrey W Meeusen³, Allan S Jaffe^{3

9}, Peter Pickkers^{1

2}

Affiliations

¹ Department of Intensive Care Medicine, Radboud University Medical Center, Nijmegen, The Netherlands.
² Radboud Institute for Molecular Life Sciences (RIMLS), Radboud University Medical Center, Nijmegen, The Netherlands.
³ Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA.
⁴ Department of Anesthesiology, Pain and Palliative Medicine, Radboud University Medical Center, Nijmegen, The Netherlands.
⁵ SphingoTec GmbH, Hennigsdorf, Germany.
⁶ Department of Biophysics, Donders Institute, Radboud University, Nijmegen, The Netherlands.
⁷ Saddle Point Science Europe BV, Nijmegen, The Netherlands.
⁸ Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota, USA.
⁹ Department of Cardiology, Mayo Clinic, Rochester, USA.

Abstract

Introduction: In clinical practice, kidney (dys)function is monitored through creatinine-based estimations of glomerular filtration rate (eGFR: Modification of Diet in Renal Disease [MDRD], Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI]). Creatinine is recognized as a late and insensitive biomarker of glomerular filtration rate (GFR). The novel biomarker proenkephalin (PENK) may overcome these limitations, but no PENK-based equation for eGFR is currently available. Therefore, we developed and validated a PENK-based equation to assess GFR.

Methods: In this international multicenter study in 1354 stable and critically ill patients, GFR was measured (mGFR) through iohexol or iothalamate clearance. A generalized linear model with sigmoidal nonlinear transfer function was used for equation development in the block-randomized development set. Covariates were selected in a data-driven fashion. The novel equation was assessed for bias, precision (mean ± SD), and accuracy (eGFR percentage within ±30% of mGFR, P30) in the validation set and compared with MDRD and CKD-EPI.

Results: Median mGFR was 61 [44-81] ml/min per 1.73 m². In order of importance, PENK, creatinine, and age were included, and sex or race did not improve performance. The PENK-based equation mean ± SD bias of the mGFR was 0.5 ± 15 ml/min per 1.73 m², significantly less compared with MDRD (8 ± 17, P < 0.001) and 2009 CKD-EPI (5 ± 17, P < 0.001), not reaching statistical significance compared with 2021 CKD-EPI (1.3 ± 16, P = 0.06). The P30 accuracy of the PENK-based equation was 83%, significantly higher compared with MDRD (68%, P < 0.001) and 2009 CKD-EPI (76%, P < 0.001), similar to 2021 CKD-EPI (80%, P = 0.13).

Conclusion: Overall, the PENK-based equation to assess eGFR performed better than most creatinine-based equations without using sex or race.

Keywords: acute kidney injury; creatinine; estimated glomerular filtration rate; gold standard; kidney function; proenkephalin.