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. 2024 Jan 19;17(1):sfae004.
doi: 10.1093/ckj/sfae004. eCollection 2024 Jan.

Cystatin C or creatinine for pre-operative assessment of kidney function and risk of post-operative acute kidney injury: a secondary analysis of the METS cohort study

John R Prowle  1   2 , Bernard Croal  3 , Thomas E F Abbott  1   2 , Brian H Cuthbertson  4   5   6 , Duminda N Wijeysundera  4   7   8 ; METS study investigators
Collaborators, Affiliations

Cystatin C or creatinine for pre-operative assessment of kidney function and risk of post-operative acute kidney injury: a secondary analysis of the METS cohort study

John R Prowle et al. Clin Kidney J. .

Abstract

Background: Post-operative acute kidney injury (PO-AKI) is a common surgical complication consistently associated with subsequent morbidity and mortality. Prior kidney dysfunction is a major risk factor for PO-AKI, however it is unclear whether serum creatinine, the conventional kidney function marker, is optimal in this population. Serum cystatin C is a kidney function marker less affected by body composition and might provide better prognostic information in surgical patients.

Methods: This was a pre-defined, secondary analysis of a multi-centre prospective cohort study of pre-operative functional capacity. Participants were aged ≥40 years, undergoing non-cardiac surgery. We assessed the association of pre-operative estimated glomerular filtration rate (eGFR) calculated using both serum creatinine and serum cystatin C with PO-AKI within 3 days after surgery, defined by KDIGO creatinine changes. The adjusted analysis accounted for established AKI risk factors.

Results: A total of 1347 participants were included (median age 65 years, interquartile range 56-71), of whom 775 (58%) were male. A total of 82/1347 (6%) patients developed PO-AKI. These patients were older, had higher prevalence of cardiovascular disease and related medication, were more likely to have intra-abdominal procedures, had more intraoperative transfusion, and were more likely to be dead at 1 year after surgery 6/82 (7.3%) vs 33/1265 (2.7%) (P = .038). Pre-operative eGFR was lower in AKI than non-AKI patients using both creatinine and cystatin C. When both measurements were considered in a single age- and sex-adjusted model, eGFR-Cysc was strongly associated with PO-AKI, with increasing risk of AKI as eGFR-Cysc decreased below 90, while eGFR-Cr was no longer significantly associated.

Conclusions: Data from over 1000 prospectively recruited surgical patients confirms pre-operative kidney function as major risk factor for PO-AKI. Of the kidney function markers available, compared with creatinine, cystatin C had greater strength of association with PO-AKI and merits further assessment in pre-operative assessment of surgical risk.

Keywords: AKI; creatinine; cystatin C; prognosis; surgery.

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Conflict of interest statement

J.R.P. has received honoraria from Paion Ltd, Baxter Inc., Biomerieux SA and Nikkiso Europe GmbH; he is a scientific advisor for Mission Therapeutics Ltd, Jafron Biomedical Co. Ltd and Nephrolyx GmbH, and serves on a Data Monitoring and Safety Board for Novartis Inc.; he is a specialty editor for the Clinical Kidney Journal and Blood Purification. B.H.C. and D.N.W. are supported in part by Merit Awards from the Department of Anesthesiology and Pain Medicine at the University of Toronto. D.N.W. is supported in part by the Endowed Chair in Translational Anesthesiology Research at St Michael's Hospital and the University of Toronto. D.N.W. has received honoraria from Edwards Lifesciences within the last 5 years and is a member of the Scientific Advisory Board for Surgical Safety Technologies Inc. T.E.F.A. is an NIHR Clinical Lecturer, an editor of the British Journal of Anaesthesia, has received research funding from the Medical Research Council, the National Institute of Academic Anaesthesia and Barts Charity, and has received consultancy fees from MSD and Edwards Life Sciences unrelated to this work. All other authors report no financial relationships with any organizations that might have an interest in the submitted work in the previous 3 years, and no other relationships or activities that could appear to have influenced the submitted work.

Figures

Figure 1:
Figure 1:
Patient flow diagram showing the number of cases included in the analysis.
Figure 2:
Figure 2:
Pre-operative creatinine (A) and cystatin C (B) by AKI outcome. Wilcoxon Rank Sum Test.
Figure 3:
Figure 3:
Pre-operative eGFR-Cr and eGFR-Cysc by AKI outcome. Wilcoxon Rank Sum Test.
Figure 4:
Figure 4:
Age- and sex-adjusted probability of AKI by baseline creatinine (upper panels) or cystatin C (lower panels) estimates of GFR (in mL/min/1.73 m2) in logistic regression modelling treating eGFR as a non-linear covariate fitted to a restricted cubic spline. Three side-by-side panels show modelling of AKI for the 25th, 50th and 75th centiles of age (51, 65 and 76 years, respectively) For eGFR-Cr a U-shaped relationship with increasing risk at low and high eGFR is apparent, for eGFR-Cysc the relationship is J-shaped with highest risk with lower eGFR below 90.
Figure 5:
Figure 5:
Age- and sex-adjusted probability of AKI by baseline creatinine and cystatin C estimates of GFR in logistic regression modelling including both eGFR measures (in mL/min/1.73 m2) as non-linear covariates fitted to restricted cubic splines. Three side-by-side panels show modelling of AKI for the 25th, 50th and 75th centiles of age (51, 65 and 76 years, respectively). In this model eGFR-Cr was not significantly associated with risk of AKI while eGFR-Cysc remained strongly associated. Note lines for eGFR creatinine of 45 and 75 in blue and green are closely overlapped.
Figure 6:
Figure 6:
Pre-operative creatinine:cystatin C ratio and mobility and survival status at 1 year after surgery. Within each gender worse, functional outcome is associated with progressively lower creatinine:cystatin C ratio, a putative index of skeletal muscle mass. Notches approximate the 95% confidence interval for that median. Wilcoxon Rank Sum Test.
Figure 7:
Figure 7:
Logistic regression for multivariable logistic regression for the presence of impaired mobility (death or bedbound, some impairment of mobility) at 1 year. Creatinine:cystatin C ratio pre-operatively remained a very significant association of the adverse mobility outcome even after accounting for gender, age, BMI and baseline mobility status. Predictions are shown for median age of 65 years and BMI of 25 kg/m2. Creatinine:cystatin C ratio is based on creatinine in µmol/L and cystatin C in mg/dL.
See this image and copyright information in PMC

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