Kidney Week

Abstract: SA-PO0948

Tissue Is the Issue: Research Biopsy-Driven Reclassification of CKD and AKI in the KPMP

Session Information

• Pathology: Updates and Insights
  November 08, 2025 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Pathology and Lab Medicine

• 1800 Pathology and Lab Medicine

Authors

• Limonte, Christine P., University of Washington, Seattle, Washington, United States

Christine P. Limonte, MD

• Schaub, Jennifer A., University of Michigan, Ann Arbor, Michigan, United States

Jennifer A. Schaub, MD

• Schmidt, Insa Marie, Boston University, Boston, Massachusetts, United States

Insa Marie Schmidt, MD, MPH

• Fallegger, Robin Demian, Universitat Heidelberg, Heidelberg, BW, Germany

Robin Demian Fallegger

• Menon, Rajasree, University of Michigan, Ann Arbor, Michigan, United States

Rajasree Menon, PhD

• Saez-Rodriguez, Julio, Universitat Heidelberg, Heidelberg, BW, Germany

Julio Saez-Rodriguez, PhD

• de Boer, Ian, University of Washington, Seattle, Washington, United States

Ian de Boer, MD, MS

• Parikh, Chirag R., Johns Hopkins Medicine, Baltimore, Maryland, United States

Chirag R. Parikh, MD, PhD, FASN

• Alpers, Charles E., University of Washington, Seattle, Washington, United States

Charles E. Alpers, MD

• Barisoni, Laura, Duke University, Durham, North Carolina, United States

Laura Barisoni, MD

• Hodgin, Jeffrey B., University of Michigan, Ann Arbor, Michigan, United States

Jeffrey B. Hodgin, MD, PhD

• Kretzler, Matthias, University of Michigan, Ann Arbor, Michigan, United States

Matthias Kretzler, MD

• Himmelfarb, Jonathan, Mount Sinai Health System, New York, New York, United States

Jonathan Himmelfarb, MD, FASN

Group or Team Name

• For the Kidney Precision Medicine Project (KPMP).

Background

The Kidney Precision Medicine Project (KPMP) aims to redefine chronic kidney disease (CKD) and acute kidney injury (AKI) by integrating clinical, histopathological, and molecular tissue data. We compared initial clinical categorization to tissue-driven adjudicated diagnoses.

Methods

KPMP enrolls participants for research kidney biopsies with CKD (eGFR <60ml/min/1.73m² or UACR >30mg/g), AKI (creatinine >1.5x baseline), and long-standing diabetes without CKD (“diabetes resilient;” DM-R). At enrollment participants are clinically categorized as CKD due to hypertension (H-CKD) or diabetes (D-CKD), AKI, or DM-R. An integrated adjudicated diagnosis is established by kidney pathologists and nephrologists and mapped to histological descriptors and single-cell transcript profiles.

Results

Adjudication was completed for 229 CKD, 58 AKI, and 15 DM-R participants (Figure). Mean age 58 years; 56% male; eGFR: 53 ml/min/1.73m²; median UACR: 188mg/g. Among those first categorized as D-CKD and H-CKD, 92 (57%) and 38 (57%) had adjudicated diagnoses of diabetic kidney disease (DKD) and hypertensive kidney disease (HKD), respectively. In the AKI group, 28 (48%) had acute tubular injury (ATI) and 13 (22%) had acute interstitial nephritis (AIN). In DM-R, 6 (40%) had DKD. Tubular injury and inflammation in non-fibrotic areas, respectively, were common in DKD (64%;19%) and H-CKD (55%;7%). Biopsy-based reclassification was linked to molecular pathways: epithelial mesenchymal transition and inflammatory response were upregulated while oxidative phosphorylation and fatty acid metabolism were downregulated in DKD vs other CKD types.

Conclusion

Kidney biopsies in CKD and AKI reveal diagnoses and histopathological and molecular heterogeneity not captured by clinical categorization alone.

Funding

• NIDDK Support

Digital Object Identifier (DOI)

• doi: 10.1681/ASN.202566a5sabq