Mr Vincent Go1, Dr Amy Au2, Dr Jonathan Erlich2, Prof. Zoltan Endre2, Dr Camila Eleuterio Rodrigues3
1Faculty of Medicine and Health, University Of New South Wales, , Australia, 2Department of Nephrology, Prince of Wales Hospital, , Australia, 3Hospital das Clinicas da FMUSP, , Brazil
Biography:
Vincent is a fourth-year medical student at the University of New South Wales. With an interest in nephrology, his current research is focused on “Mitochondrial Damage Biomarkers Associated with Calcineurin-Inhibitor Nephrotoxicity Following Kidney Transplantation”.
Aim:
To investigate if tubular injury caused by calcineurin-inhibitor (CNI) nephrotoxicity measured by urine and plasma biomarkers are detectable before creatinine-based functional change.
Background:
Tacrolimus is the main CNI as part of post-transplant immunosuppression regimens and its use increases each year alongside the increasing rates of kidney transplantation. Nephrotoxic effects of tacrolimus are often identified late by serum creatinine (SCr) or biopsy (current method of determining allograft outcomes). Therefore, identifying subclinical acute kidney injury (AKI) by novel functional marker, plasma Cystatin-C (CysC) and damage biomarker, urinary Kidney-Injury-Molecule-1 (KIM-1) helps determine early allograft damage or rejection. KIM-1 is the FDA approved biomarker for renal drug toxicity.
Methods:
Prospective observational cohort study of 67 patients undergoing kidney transplantation at the Prince of Wales Hospital had daily urine and blood samples collected pre-surgery until 30 days post-surgery. Samples were assayed for SCr, CysC and KIM-1, which was normalised by urinary creatinine (UCr). AKI was defined by biomarker levels ≥ 50% of the preceding 7 days.
Results:
SCr detected 8 AKI episodes (median data points per patient = 16, IQR: 14-20) whilst CysC detected 15 AKI episodes (median data points per patient = 11, IQR: 5-15) and KIM-1/UCr detected 39 AKI episodes (median data points per patient = 13.5, IQR: 10.75-18) between Day 6 to 30. In a subset of 8 patients, 75% had elevations of tacrolimus precede changes to urinary KIM-1, which were not mirrored by changes in SCr.
Conclusions: CysC and KIM-1 can detect tacrolimus-induced AKI episodes more effectively than current measures of SCr in post-transplant patients.
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