Clinical implications of plasma sADAM10: integrating renal function, histopathology and prognostic outcomes in chronic kidney disease and kidney transplantation

Background: The identification of novel non-invasive biomarkers is crucial for improving the management of chronic kidney disease (CKD) and kidney transplant recipients (KTR). While A Disintegrin and Metalloprotease 10 (ADAM10) is involved in kidney pathology, the clinical relevance of its soluble form, soluble ADAM10 (sADAM10), remains poorly defined. Methods: In this retrospective cohort study, we enrolled 488 participants, including 145 kidney transplant recipients (KTR), 295 patients with chronic kidney disease (CKD), and 48 healthy controls (HC). Plasma sADAM10 was measured by ELISA and evaluated for its correlation with renal function, laboratory parameters, and histopathological findings. Its prognostic value for adverse outcomes was determined using Kaplan-Meier analyses, restricted cubic spline (RCS) Cox regression, and incremental value assessment. Results: Plasma sADAM10 were significantly elevated in biopsy-proven KTR and CKD patients compared to HC. Multivariate analyses revealed cohort-specific independent associations: plasma sADAM10 was independently associated with eGFR in CKD (standardized β = -0.24, P < 0.001), but with neutrophil count in KTR (standardized β = 0.24, P = 0.034). Histopathologically, higher plasma sADAM10 were associated with the severity of interstitial fibrosis and tubular atrophy (IFTA), tubular injury, and interstitial inflammation. RCS analysis demonstrated a significant non-linear association between plasma sADAM10 and post-transplant infection risk (P for non-linearity = 0.029), with plasma sADAM10 providing incremental prognostic value beyond age and eGFR (C-index increase from 0.795 to 0.842; likelihood ratio P = 0.005). In contrast, after adjusting for eGFR and proteinuria, plasma sADAM10 showed no independent association with the composite renal endpoint. For patients with advanced CKD, plasma sADAM10 concentration showed an exponential association with the predicted 5-year risk of kidney failure. Conclusion: Plasma sADAM10 is a context-dependent biomarker with endpoint-specific prognostic value. It shows an independent association with renal dysfunction in CKD and inflammatory activation in KTR, and predicts post-transplant infection risk with incremental value beyond traditional markers. However, its apparent association with renal outcomes is confounded by eGFR. These findings highlight the potential of plasma sADAM10 for infection risk stratification in KTR and warrant further validation in larger cohorts.