KIDNEY FUNCTIONAL RESERVE DETECTS SUBCLINICAL CHRONIC KIDNEY DISEASE AND SUBCLINICAL ACUTE KIDNEY INJURY PREDICTS LONG-TERM KIDNEY OUTCOMES AFTER CARDIAC SURGERY WITH CARDIOPULMONARY BYPASS

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Abstract Title *

KIDNEY FUNCTIONAL RESERVE DETECTS SUBCLINICAL CHRONIC KIDNEY DISEASE AND SUBCLINICAL ACUTE KIDNEY INJURY PREDICTS LONG-TERM KIDNEY OUTCOMES AFTER CARDIAC SURGERY WITH CARDIOPULMONARY BYPASS

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Co-author 1

Camila Eleuterio Rodrigues c.eleuteriorodrigues@unsw.edu.au School of Clinical Medicine, Faculty of Medicine and Health, University of New South Wales Nephrology Sydney Australia * Prince of Wales Hospital Nephrology Sydney Australia Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo Nephrology São Paulo Brazil

Co-author 2

Amy Au yokemooi.au@unsw.edu.au School of Clinical Medicine, Faculty of Medicine and Health, University of New South Wales Nephrology Sydney Australia - Prince of Wales Hospital Nephrology Sydney Australia

Co-author 3

Daniel Rebello d.rebello@student.unsw.edu.au School of Clinical Medicine, Faculty of Medicine and Health, University of New South Wales Faculty of Medicine and Health Sydney Australia -

Co-author 4

Claire Johnston Claire.Johnston1@health.nsw.gov.au Prince of Wales Hospital Nephrology Sydney Australia -

Co-author 5

Maria Maawad Maria.Maawad@health.nsw.gov.au Prince of Wales Hospital Nephrology Sydney Australia -

Co-author 6

Florian Uhle florian.uhle@sphingotec.com SphingoTec GmbH SphingoTec GmbH Hennigsdorf Germany -

Co-author 7

Jonathan Erlich j.erlich@unsw.edu.au School of Clinical Medicine, Faculty of Medicine and Health, University of New South Wales Nephrology Sydney Australia - Prince of Wales Hospital Nephrology Sydney Australia

Co-author 8

Zoltan Endre zoltan.endre@unsw.edu.au School of Clinical Medicine, Faculty of Medicine and Health, University of New South Wales Nephrology Sydney Australia - Prince of Wales Hospital Nephrology Sydney Australia

Co-author 9

Co-author 10

Co-author 11

Co-author 12

Co-author 13

Co-author 14

Co-author 15

Introduction

Acute Kidney Injury (AKI) leads to Chronic Kidney Disease (CKD). Subclinical AKI is associated with increased mortality, but the lack of available biomarkers and thresholds restricts its recognition. Subclinical CKD may progress to overt CKD, but the diagnosis is challenging. In this study we evaluated preoperative kidney functional reserve in patients undergoing cardiac surgery to assess subclinical CKD and postoperative kidney biomarker profiles to determine which predict KDIGO AKI and impact long-term outcomes at 1 year after cardiopulmonary bypass (CPB).

Methods

We assessed 68 adults undergoing cardiac surgery with CPB. In 38 patients (56%) a preoperative Kidney Functional Reserve (KFR) test was performed by measurement of baseline and protein-stimulated function using creatinine clearance (CrCl) and GFRs estimated from plasma cystatin C (CysC) and proenkephalin-A (PENK). Blood and urine samples were collected preoperatively in all participants and postoperative samples were collected at 30 min after the surgery and daily for 3 days. We measured plasma creatinine (pCr) in blood and creatinine (uCr), KIM-1, NGAL and TIMP-2 x IGFBP7 (NC) in urine. KDIGO AKI was defined by pCr and urinary output criteria. At 1 year after the surgery, long-term pCr and urine albumin/creatinine ratio (ACR) were measured.

Results

KDIGO defined cardiac surgery-associated (CS-AKI) developed in 45% (31/68): pCr-based AKI in 4/68, urine output (UO) criteria in 22/68, combined pCr & UO in 5/68. KIM-1 AKI was defined as a maximum postoperative urine KIM-1 value > 4ng/ml and this was found in 64.6% of participants (52.4% of whom developed postoperative KDIGO AKI). NC-AKI was defined as a maximum postoperative urine NC value > 2 (ng/ml)2/1000, which happened in 13.2% of participants (88.9% of whom developed KDIGO AKI). NGAL/uCr at 30 minutes after surgery differentiated those who would later develop postoperative AKI up to day 3 and the best threshold for this was 1.49 ug/mmol uCr (sensitivity: 0.71; specificity: 0.75; accuracy: 0.73). KIM-1 and NC daily values were similar in patients with or without KDIGO AKI.

At 1 year after surgery, 35 out of 68 participants had eGFR measured. Median [IQR] loss of eGFR was 2.8 [-4.5; 12.0] ml/min/1.73m2 and 42.8% of patients with long-term follow-up lost > 5ml/min/1.73m2 at 1 year. Patients with KIM-1 AKI and NC-AKI had a reduction in eGFR at 1 year after surgery, when compared to baseline, but NGAL levels were not associated with long term outcome. Urine KIM-1 levels were especially associated with a reduction in long-term eGFR, as 30% of patients with high loss of kidney function developed KIM-1 AKI but no KDIGO AKI.

Preoperative CrCl-KFR predicted postoperative KDIGO AKI; this mainly reflected reserve tubular, not reserve glomerular function. CysC- and PENK-KFR represented the glomerular component of kidney reserve and did not predict post-operative AKI but did predict the reduction in long-term eGFR. PENK-KFR was also associated with higher ACR at 1 year.

Conclusion

Urine KIM-1 and NC detected subclinical AKI. Postoperative urine NGAL predicted KDIGO AKI. CrCl-KFR detected tubular reserve and predicted postoperative KDIGO AKI. CysC- and PENK-KFR detected subclinical CKD and predicted long-term postoperative loss of kidney function.

The content in this abstract was submitted for CRRT-AKI 2026 meeting.

Funded by FAPESP, Prince of Wales and Lewis Foundation

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