# Accelerated Epithelial Cell Detachment in Progression of Kidney Disease

> **NIH VA I01** · VETERANS HEALTH ADMINISTRATION · 2026 · —

## Abstract

Chronic kidney disease (CKD) is a progressive condition that puts a substantial burden on individuals,
families, and health care systems. CKD is already a leading cause of death world-wide, and the
incidence and prevalence is expected to rise. CKD is about 34% more common in veterans than in the
general population, and U.S. Department of Veterans Affairs cares for over 600,000 veterans with CKD.
The VA spents approximately $18 billion for the care of patients with CKD without including costs for
kidney replacement therapy (KRT). Research has established a multi-modular therapeutic approach
that delays progression of CKD, but the residual risk remains unacceptably high.
TGF beta (TGFβ) pathway is a key-mechanisms for progression of kidney disease, which has multiple
cell-type specific divergent effects. Therefore, focusing on more specific downstream mediators within
the pathway is a promising strategy for intervention.
We identified TGF-beta1 (TGFβ1) signaling as the central upstream mediator of podocyte loss, a
mechanism for progression of kidney disease, in kidney tissue of patients with early-stage kidney
disease. Further analysis identified TGFβ-induced (TGFBI), a TGFβ1 downstream target gene and
secreted protein that functions as anti-adhesive factor, as one of the top genes associated with
podocyte depletion. Furthermore, we found that TGFBI is strongly up regulated in kidney biopsy tissue
from patients with FSGS and diabetic kidney disease (DKD) and in Tgfβ-transgenic mice (Tgfβ-TG), a
model of progressive glomerulosclerosis, in which podocyte loss is a prominent phenotype and
mechanisms of disease progression. In cultured human podocytes, exogenous TGFBI treatment led to
disruption of the cytoskeleton and podocyte detachment. Furthermore, we determined that increased
urinary amounts of TGFBI were highly significant associated with progression in patients with kidney
disease, in particular DKD.
We hypothesize that TGFBI promotes podocyte loss by decreasing at

## Key facts

- **NIH application ID:** 11181981
- **Project number:** 1I01BX007185-01
- **Recipient organization:** VETERANS HEALTH ADMINISTRATION
- **Principal Investigator:** Markus  Bitzer
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2026
- **Award amount:** —
- **Award type:** 1
- **Project period:** 2026-04-01T00:00:00 → 2030-03-31T00:00:00

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11181981

## Citation

> US National Institutes of Health, RePORTER application 11181981, Accelerated Epithelial Cell Detachment in Progression of Kidney Disease (1I01BX007185-01). Retrieved via AI Analytics 2026-05-17 from https://api.ai-analytics.org/grant/nih/11181981. Licensed CC0.

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