Rethinking Diabetic and Hypertensive CKD Through the Lens of Precision Medicine

Kidney biopsies in patients with common forms of chronic kidney disease (CKD) reveal unexpected diagnoses, unsuspected disease processes, and findings that standard frameworks often miss, challenging long-held assumptions about what diabetic and hypertensive kidney disease actually looks like.

Investigators from the Kidney Precision Medicine Project (KPMP), a multi-center consortium pursuing comprehensive clinical, histopathological, and molecular characterization of kidney disease, highlighted the clinical utility of research biopsies in a broader CKD population, beyond the high-risk or severe presentations where biopsies have traditionally been performed.

In a pilot cohort of 39 adults with CKD due to diabetes or hypertension, over a quarter of treating clinicians were surprised by biopsy results, and in 77% of cases, findings directly shaped prognostic discussions. Unsuspected diagnoses, acute processes, and nonspecific findings were common, suggesting that the true histopathologic landscape of diabetic and hypertensive kidney disease is far broader than clinical labels imply. For a field that has long relied on those labels to guide care, these findings raise an important question: how much are we missing?

"In addition to these completely unexpected diagnoses such as IGA nephropathy and fibrillary glomerulonephritis, which would prompt a change in management, we frequently observed acute tubular injury and inflammatory infiltrates, which are not traditionally incorporated into our classic frameworks for diabetic nephropathy and hypertension associated kidney disease," said study investigator Christine Limonte, MD, assistant professor of medicine at UW Medicine.

These findings point to a fundamental gap in how diabetic and hypertensive kidney disease has traditionally been understood, one built largely around glomerular pathology and severe clinical presentations, leaving tubular, interstitial, and vascular injury undercharacterized. KPMP's ability to pair detailed biopsy review with molecular data offers a path toward filling that gap, and potentially toward classifying patients by the specific biology driving their disease rather than by diagnosis alone.

"I think there's a lot of potential here, especially within the Kidney Precision Medicine Project, to dive further into those specific lesions and use the molecular data that's being obtained to better understand the underlying biology of those lesions and potentially get to a point where we can subtype someone's diabetic nephropathy or diabetes related chronic kidney disease based on their specific patterns of biopsy findings," Limonte added.

Editor’s Note: Limonte reports no relevant disclosures.