Kidney Biopsies Challenge Diabetic Nephropathy Diagnoses in CKD, With Christine Limonte, MD

According to data from 39 kidney biopsies, only 54% of patients clinically diagnosed with diabetic kidney disease actually had diabetic nephropathy confirmed on biopsy.1

The data may challenge long-held beliefs about chronic kidney disease (CKD) prognosis, highlighting that before biopsies were performed, only 15% of clinicians expected to find something different, yet 26% reported the results were different than expected.1

These findings come from the Kidney Precision Medicine Project (KPMP), a multicenter prospective cohort study obtaining research protocol biopsies in adults with suspected diabetic kidney disease (DKD) or hypertension-associated chronic kidney disease (HCKD) for comprehensive clinicopathologic characterization.

"Only about half of participants enrolled into the diabetic kidney disease or hypertensive chronic kidney disease cohorts actually had classic diabetic nephropathy or hypertension-associated nephropathy on biopsy, respectively," said study investigator Christine Limonte, MD, assistant professor of medicine at UW Medicine. "A number of participants had unexpected findings, IgA nephropathy, fibrillary glomerulonephritis, as well as nonspecific findings that precluded a definitive diagnosis."

Beyond missed or unexpected diagnoses, biopsies frequently revealed lesions not captured by existing diagnostic frameworks: acute tubular injury, interstitial inflammation extending into nonfibrotic parenchyma, glomerular microaneurysms, and tubular mitochondrial abnormalities. These findings were prevalent even among participants with confirmed diabetic nephropathy, suggesting the histopathologic heterogeneity of common CKD presentations is broader than traditional classifications reflect.

"In our group of 39 participants, we obtained clinician post-biopsy reports and found that over 70% of clinicians reported that biopsy results did affect their prognostic discussions with patients, and in about 38% of cases, impacted clinical management," Limonte noted.

For nephrologists managing patients with presumed DKD or HCKD, these findings underscore the diagnostic limitations of a clinical-only approach.

References

1. Limonte CP, Aw S, Alpers CE, et al. Case Series of Histopathological Findings in Chronic Kidney Disease: Insights From the Kidney Precision Medicine Project. Kidney Medicine. Published online December 2025:101206. doi:https://doi.org/10.1016/j.xkme.2025.101206