Kidney Volume as a Predictor and Modifier of Acute Kidney Injury with Renin-Angiotensin System Inhibitors

KEY POINTS: Small kidney volume was associated with a higher proportion of glomerulosclerosis independent of eGFR. Renin-angiotensin system inhibitors were associated with a higher incidence of AKI after cardiovascular surgery only among those with small kidney volume. Small kidneys for GFR may represent less viable nephrons and compensatory hyperfiltration. BACKGROUND: Reduced nephron number has been reported to be an independent risk factor for AKI. We aimed to investigate the clinical implications of kidney volume or age as a candidate surrogate marker of nephron number in predicting AKI after cardiovascular (CV) surgery. METHODS: A single-center retrospective cohort study and a cross-sectional study were conducted. The cohort study enrolled adults (age 18 years or older) who underwent CV surgery from 2012 to 2020 at a university hospital. The association of height-adjusted total kidney volume (htTKV) with postoperative AKI and an effect modification by htTKV for the association of renin-angiotensin system inhibitors (RASi) with AKI were assessed by logistic regression analyses. HtTKV was measured by the SYNAPSE VINCENT image analysis system. The cross-sectional study enrolled adults who underwent kidney biopsy from 2014 to 2023, with diagnoses of IgA nephropathy, nephrosclerosis, or minor glomerular abnormalities. The associations of htTKV with histopathological lesions were examined. RESULTS: Among 518 participants who underwent CV surgery, 177 developed AKI. Lower htTKV and higher eGFR per TKV, but not older age, were associated with AKI independent of eGFR (odds ratio of 1.48; 95% confidence interval, 1.05 to 1.92 per one-SD decrement of htTKV). The use of RASi was associated with a significantly higher incidence of AKI at htTKV lower than 100 ml/m 2 ( P for interaction 0.001). Such effect modification was not found for age. Among 136 participants with kidney biopsies, htTKV of 100 ml/m 2 or less was associated with a higher proportion of glomerular sclerosis independent of eGFR. CONCLUSIONS: We speculate that RAS activation might maintain eGFR by glomerular hyperfiltration in patients with low htTKV. Observed higher incidence of postoperative AKI among RASi users with smaller htTKV for eGFR supports this hypothesis. Withholding RASi before CV surgery might prevent AKI among those with htTKV of 100 ml/m 2 or less.