Kidney Week

Abstract: TH-PO0237

Transcriptomic Profiling of Human Kidney Biopsies Reveals Distinct Mechanisms in Diabetic Nephropathy with and Without HIV Infection Compared with HIV-Associated Nephropathy (HIVAN)

Session Information

• CKD: Mechanisms of Injury and Fibrosis - 1
  October 22, 2026 | Location: Exhibit Hall A, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: CKD (Non-Dialysis)

• 2203 CKD (Non-Dialysis): Mechanisms

Authors

• Niu, Yangyang, Icahn School of Medicine at Mount Sinai Department of Medicine, New York, New York, United States

Yangyang Niu, MD, PhD

• D'Agati, Vivette D., New York-Presbyterian/Columbia University Irving Medical Center, New York, New York, United States

Vivette D. D'Agati, MD

• Wei, Chengguo, Albert Einstein College of Medicine, New York, New York, United States

Chengguo Wei, PhD

• Zhang, Weijia, Albert Einstein College of Medicine, New York, New York, United States

Weijia Zhang, PhD

• Yi, Zhengzi, Albert Einstein College of Medicine, New York, New York, United States

Zhengzi Yi

• Lee, Kyung, Icahn School of Medicine at Mount Sinai Department of Medicine, New York, New York, United States

Kyung Lee, PhD, FASN

• He, John Cijiang, Icahn School of Medicine at Mount Sinai Department of Medicine, New York, New York, United States

John Cijiang He, MD, PhD, FASN

Background

The burden of chronic kidney disease is rising in people living with HIV (PLWH), driven in part by increasing rates of diabetes. While HIV-associated nephropathy remains prevalent, particularly in Africa, the molecular interplay between HIV infection and diabetic nephropathy (DN) in PLWH is poorly understood.

Methods

We performed transcriptomic profiling of FFPE kidney biopsy samples from 11 controls, 26 DN, 24 DN in PLWH (HIV-DN), and 11 HIVAN cases using RNA CaptureSeq. Analyses included differential gene expression, pathway and transcription factor enrichment, kinase enrichment, immune and cell-type deconvolution, and drug prediction (LINCS L1000). Two candidate pathways and drug predictions were functionally validated in HIVAN Tg26 mice.

Results

Compared to DN, HIVAN exhibited marked activation of innate immune pathways and cell cycle dysrequlation, whereas HIV-DN showed prominent cell cycle alterations without significant immune activation. Deconvolution analysis demonstrated progressive loss of proximal tubular cells and podocytes from DN to HIV-DN to HIVAN, accompanied by increased immune cell infiltration predominantly in HIVAN. Kinase enrichment identified innate immune regulators (JAKs, IRAKs) across all groups, with stronger enrichment in HIVAN. Notably, cell cycle-associated kinases were uniquely enriched in HIV-related kidney disease (HIV-DN and HIVAN). Drug prediction using LINCS L1000 identified HSP90 inhibitors as top therapeutic candidates. In vivo, inhibition of IRAK1/4 and HSP90 pathways ameliorated kidney injury and reversed disease-associated transcriptional signatures in Tg26 mice.

Conclusion

HIV-associated kidney disease is characterized by distinct transcriptional programs, with enhanced cell cycle dysregulation and innate immune activation compared to DN alone. Targeting IRAK1/4 and HSP90 pathways represents a promising therapeutic strategy for HIV-related kidney disease.

Funding

• NIDDK Support