Intersecting transcriptomic landscapes of hypertension and kidney function in African American women

Hypertension is a risk factor for chronic kidney disease (CKD) and disproportionately affects African American women, contributing to disparities in kidney health. The biological mechanisms connecting hypertension to reduced kidney function remain poorly understood. This study leverages transcriptomic analyses to uncover shared molecular signatures associated with hypertension and kidney function, focusing on female-specific profiles. The study analyzed whole blood mRNA sequencing data from 344 African American women, divided into discovery (<i>n</i> = 172) and validation (<i>n</i> = 172) datasets, along with 147 African American men. Differential expression (DE) analyses were performed to identify mRNAs associated with hypertension and kidney function [measured as estimated glomerular filtration rate (eGFR)]. Female-specific findings were determined by comparing results between females and males. Pathway enrichment analyses were subsequently conducted to link the identified mRNAs to key biological mechanisms. Comparative analyses revealed unique transcriptomic profiles in females, underscoring the role of sex-specific factors in kidney function. DE analyses identified 95 female-specific genes associated with both hypertension and eGFR. Subsequent pathway enrichment analysis with the 95 genes revealed key pathways related to fibrosis, inflammation, lipid metabolism, and endothelial dysfunction. The list of 95 includes immune system players such as <i>IL32</i> and <i>TNFSF12</i> that amplify inflammation and kidney injury. This study provides novel insights into the transcriptomic mechanisms underlying hypertension and kidney function in African American women. The findings emphasize the importance of addressing sex-specific molecular mechanisms associated with hypertension-related impaired kidney function. Future research should prioritize experimental validation and longitudinal studies to further elucidate these pathways.<b>NEW & NOTEWORTHY</b> African American women experience a disproportionate burden of hypertension and chronic kidney disease, yet their molecular underpinnings remain understudied. This study uniquely integrates transcriptomic data from 344 African American women to uncover 95 female-specific genes jointly associated with hypertension and reduced kidney function. These genes implicate immune activation, cytoskeletal remodeling, and metabolic dysregulation as key contributors to renal decline. By identifying sex-specific molecular pathways, this work advances precision medicine approaches to address kidney health disparities.