L SUCCAR1, J WONG1, K TAYLOR1, A AU1, J ERLICH1, E ZOLTAN1
1University of New South Wales, Department of Nephrology, Prince of Wales Clinical School., Randwick, Sydney, Australia
Aim: To investigate biomarker profiles when ischaemic sAKI is superimposed on sCKD.
Background: sCKD (structural kidney damage without a rise in sCr) modifies diagnosis of nephrotoxin-induced AKI. Renal ischaemia in the presence of pre-existing sCKD may better reflect AKI in Australian adults.
Methods: sCKD was induced in Sprague Dawley rats by dietary supplementation with 0.25% adenine from day 0 to 28 or normal diet in controls. On day 56, sAKI was induced by brief duration renal ischaemic injury insufficient to induce sCr change in normal animals, viz bilateral clamping of the renal arteries for 30 minutes. sCr, urinary biomarkers (kidney injury molecule-1 (KIM-1), monocyte chemotactic protein 1 (MCP-1), clusterin, and interleukin-18 (IL-18)) and histological damage were measured after 1, 2, 3, 7 and 14 days.
Results: During induction of sCKD, urinary biomarker levels increased from day 3 to 21 and returned to baseline by day 56, despite absence of sCr rise. Rats displayed widespread medullary and up to 50% cortical damage. After sAKI in control rats, sCr did not increase and only KIM-1 rose from day 1 to 3 with focal medullary structural damage that recovered by day 7. In sCKD rats, all urinary biomarkers increased from day 1 to 7 post sAKI, and sCr increased continuously until day 14. Severe diffuse structural damage was also present from day 1 after sAKI and persisted until 14 days.
Conclusions: Biomarker profiles are modified after sAKI is superimposed on sCKD. This impacts interpretation of AKI biomarker thresholds since sCKD in Australian adults is likely common and precursory to overt CKD.
Dr Lena Succar is a Postdoctoral Research Fellow at the Prince of Wales Clinical School University of New South Wales, headed by Professor Zoltan Endre. Dr Succar’s research interest is centred on discovery of novel biomarker for early detection and profiling in CKD pathogenesis and progression, particular, in subclinical CKD (Which most likely reflects the adult population) and its modification after AKI.