Spatial atlas of diabetic kidney disease reveals a B cell-rich subgroup.

Abstract

Diabetic kidney disease (DKD), the leading cause of kidney failure, is marked by clinical and molecular heterogeneity, making therapeutic development exceedingly difficult1. Here we used Xenium and CosMx single-cell spatial transcriptomics, integrated with single-nucleus RNA sequencing, to build a cross-platform kidney atlas that makes tissue architecture computable for prognosis, non-invasive detection and patient selection. Using this atlas, we defined reproducible tissue niches and injury-linked microenvironments and uncovered a profibrotic context that expands with disease and tracks with worse kidney function. Within this architecture, we identified a B cell-predominant, tertiary lymphoid structure-like immune microenvironment that defines a distinct DKD subset with accelerated progression to renal end-points. We developed tissue biomarkers and a matched plasma protein panel that capture this biology, stratify patients in a population biobank and improve risk prediction beyond clinical models-supporting their potential for biomarker-guided selection in future B cell-targeted DKD trials.