Molecular Signatures of Diabetic Kidney Disease Hiding in a Patient with Hypertension-Related Kidney Disease

Abstract

The Kidney Precision Medicine Project (KPMP) seeks to establish a molecular atlas of the kidney in health and disease and improve our understanding of the molecular drivers of chronic kidney disease and acute kidney injury. Herein, we describe the case of a 66-year-old woman with chronic kidney disease who underwent a protocol KPMP kidney biopsy. Her clinical history included well-controlled diabetes mellitus, hypertension, and proteinuria. The patient's histopathology was consistent with modest hypertension-related kidney injury, without overt diabetic kidney disease (DKD). Transcriptomic signatures of the glomerulus, interstitium, and tubular subsegments were obtained from laser microdissected tissue. The molecular signatures uncovered revealed evidence of early DKD adaptation and ongoing active tubular injury with enriched pathways related to mesangial cell hypertrophy, glycosaminoglycan biosynthesis, and apoptosis. Molecular evidence of DKD was found across the nephron. Novel molecular assays can supplement and enrich the histopathologic diagnosis obtained from a kidney biopsy.