Racial Differences in Dysregulation of the Renin-Angiotensin-aldosterone System in Patients with Prurigo Nodularis

Background: There are limited data characterizing the association between renal disease and prurigo no-dularis (PN). Objective: To characterize the association and describe mechanistic disease linkages between PN and renal comorbidities. Methods: We conducted a cross-sectional analysis of renal comorbidities in PN using TriNetX, a global health research network providing access to medical records. Epidemiological findings provided the basis for translational studies on plasma and skin biopsy samples from PN patients stratified by race. Results: PN was associated with stages 1-5 of chronic kidney disease (CKD), end-stage renal disease, ne-phritic syndrome, nephrotic syndrome, glomerular disease, and tubulointerstitial disease, but the asso-ciations were significantly stronger in black patients. Compared to controls, CKD progression was faster (HR 2.88, 95% CI: 1.01-8.26) only in black PN (10-year survival: 63.5% black vs. 85.5% white). Circulating plasma angiotensinogen levels were dysregulated (P < 0.001) only in black PN patients. Cutaneous transcriptomic analysis of genes related to the renin-angiotensin-aldosterone system (RAAS) revealed considerable dys-regulation in PN lesions with greater dysregulation in black patients. Conclusions: Significant dysregulation of the cutaneous and systemic RAAS in black PN patients may explain the increased incidence and severity of renal disease. (c) 2022 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.