Association of Urinary Soluble CD163 With Response to Immunosuppressive Therapy and Renal Relapse in IgAN

Introduction: The absence of a dynamic, noninvasive biomarker to monitor intrarenal immunologic activity during and after immunosuppressive therapy limits patient-specific risk stratification and timely treatment decisions in IgA nephropathy (IgAN). The clinical utility of urinary soluble CD163 (sCD163) for predicting response to immunosuppressive therapy and detecting renal relapse remains to be fully elucidated. Methods: This prospective cohort study included 281 patients with IgAN who were at high risk of progression. All the patients received immunosuppressive therapy for a median of 18 months. Urinary sCD163 levels were measured and normalized to creatinine. Treatment response to immunosuppression was defined as a reduction in urinary protein excretion with stable renal function within 12 months of immunosuppression. Relapse was defined as an increase in urinary protein excretion after remission. Results: Baseline urinary sCD163 correlated strongly with glomerular and tubulointerstitial CD163-positive macrophage density on kidney biopsy. Patients in the highest tertile of baseline urinary sCD163 had 8-fold greater odds of treatment response (adjusted odds ratio: 8.04, 95% confidence interval [CI]: 3.88-16.67) than those in the lowest tertile. Adding urinary sCD163 to a clinical-histological model significantly improved the discriminatory ability for treatment response, increasing the area under the receiver operating characteristic curve (AUC) to 0.82. Longitudinal urinary sCD163 was significantly associated with time to relapse, with an adjusted hazard ratio of 1.38 (95% CI: 1.21-1.56). Conclusion: Urinary sCD163 is independently associated with response to immunosuppressive therapy and may serve as a potential biomarker for impending relapse in high-risk IgAN, which could help personalize therapeutic management.