Molecular Signatures of Glomerular Neovascularization in a Patient with Diabetic Kidney Disease

Abstract

The Kidney Precision Medicine Project (KPMP) aims to create a kidney tissue atlas, define disease subgroups, and identify critical cells, pathways, and targets for novel therapies through molecular investigation of human kidney biopsies obtained from participants with AKI or CKD. We present the case of a 66-year-old woman with diabetic kidney disease who underwent a protocol KPMP kidney biopsy. Her clinical history included diabetes mellitus complicated by neuropathy and eye disease, increased insulin resistance, hypertension, albuminuria, and relatively preserved glomerular filtration rate (early CKD stage 3a). The patient's histopathology was consistent with diabetic nephropathy and arterial and arteriolar sclerosis. Three-dimensional, immunofluorescence imaging of the kidney biopsy specimen revealed extensive periglomerular neovascularization that was underestimated by standard histopathologic approaches. Spatial transcriptomics was performed to obtain gene expression signatures at discrete areas of the kidney biopsy. Gene expression in the areas of glomerular neovascularization revealed increased expression of genes involved in angiogenic signaling, proliferation, and survival of endothelial cells, as well as new vessel maturation and stability. This molecular correlation provides additional insights into the development of kidney disease in patients with diabetes and spotlights how novel molecular techniques used by the KPMP can supplement and enrich the histopathologic diagnosis obtained from a kidney biopsy.