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An Assessment of Urinary Biomarkers in a Series of Declined Human Kidneys Measured During Ex Vivo Normothermic Kidney Perfusion

Hosgood, Sarah A. PhD1,2; Nicholson, Michael L. DSc1,2

doi: 10.1097/TP.0000000000001504
Original Clinical Science-General

Background: The measurement of urinary biomarkers during ex vivo normothermic kidney perfusion (EVKP) may aid in the assessment of a kidney prior to transplantation. This study measured levels of neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1) and endothelin-1 (ET-1) during EVKP in a series of discarded human kidneys.

Methods: Fifty-six kidneys from deceased donors were recruited into the study. Each kidney underwent 60 minutes of EVKP and was scored based on the macroscopic appearance, renal blood flow and urine output. The scores ranged from 1 (least injury) to 5 (most severe). Levels of oxygen consumption, extraction, creatinine fall and fractional excretion of sodium were measured during perfusion. Urinary levels of NGAL, KIM-1, and ET-1 were measured after EVKP.

Results: Thirty-eight kidneys had an EVKP score of 1 or 2, 8 a score of 3 and 10 a score of 4 or 5. During EVKP lower levels of oxygen consumption, higher oxygen extraction, a lower decrement of serum creatinine, and higher levels of NGAL and ET-1 were associated with a higher EVKP score (P < 0.05). These parameters were also associated with a raised creatinine level in the donor before organ retrieval. Levels of KIM-1 were not associated with the perfusion parameters (P = 0.649) or renal function in the donor (R2 = 0.02458: P = 0.271).

Conclusions: The measurement of urinary biomarkers, particularly NGAL in combination with functional perfusion parameters and the EVKP score provides an informative measure of kidney quality which may aid the decision to transplant the kidney.

This study of the measurement of neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1) and endothelin-1 (ET-1) during ex-vivo normothermic kidney perfusion of 56 discarded kidneys shows that NGAL with functional perfusion parameters and the EVKP score could assist in determining which kidneys are usable.

1 Department of Surgery, Addenbrooke's Hospital, University of Cambridge, Cambridge, United Kingdom.

2 Department Infection, Immunity and Inflammation, Transplant Group, University of Leicester, Leicester General Hospital, United Kingdom.

Received 20 June 2016. Revision received 27 August 2016.

Accepted 2 September 2016.

This study was supported by Kidney Research UK. The research was also funded by the National Institute for Health Research Blood and Transplant Research Unit (NIHR BTRU) in Organ Donation and Transplantation at the University of Cambridge in collaboration with Newcastle University and in partnership with NHS Blood and Transplant (NHSBT). The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR, the Department of Health or NHSBT.

The authors declare no conflict of interest.

S.A.H. designed the study, carried out the perfusion, wrote and reviewed the article. M.L.N. designed the study and reviewed the article.

Correspondence: Sarah A Hosgood, PhD, Department of Surgery, University of Cambridge, Addenbrooke's Hospital, Level 9 PO BOX 202, Hill's Road, Cambridge, CB2 OQQ, United Kingdom. (sh744@cam.ac.uk).

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