# Pathobiology of autoimmune-mediated diffuse podocytopathy

> **NIH NIH R01** · BRIGHAM AND WOMEN'S HOSPITAL · 2024 · $796,293

## Abstract

Project Summary/Abstract
Minimal change disease and primary focal and segmental glomerulosclerosis are morphologic
expressions of a diffuse podocytopathy of to date unknown cause, and all present with acute
onset Nephrotic Syndrome. Although the majority of patients achieve clinical remission, relapse
and treatment failure is common, and when progressing to end stage kidney disease, the disease
frequently and vigorously recurs in the allograft. We recently published a groundbreaking study
that identified circulating autoantibodies against the extracellular domain of nephrin in a subset of
adults and children with non-genetic Minimal Change Disease and in a single patient with
recurrent disease in the allograft, which correlate with disease activity. Our findings underpin the
paradigm-shifting hypothesis that at least a subset of these diseases are mediated by an organ-
specific, antibody-mediated autoimmune disease of B cell origin which causes an acquired diffuse
podocytopathy by means of direct action of the autoantibodies on the podocyte, an essential
component of the kidney filter. The current proposal now aims at proving this concept by 1)
establishing pathogenic autoimmunity in anti-nephrin mediated podocytopathy by means of
analyzing immunophenotypes and immunological signatures, and by 2) identifying direct
downstream pathomechanistic effects by nephrin autoantibodies that cause changes in podocyte
structure and function. Altogether, results from these studies will serve as critical basis for the
development of novel, personalized and targeted treatment strategies for our patients with
minimal change disease, primary focal and segmental glomerulosclerosis as well as those
patients with recurrent disease in the transplant.

## Key facts

- **NIH application ID:** 10882264
- **Project number:** 1R01DK135667-01A1
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** Astrid Weins
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $796,293
- **Award type:** 1
- **Project period:** 2024-09-05 → 2029-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10882264

## Citation

> US National Institutes of Health, RePORTER application 10882264, Pathobiology of autoimmune-mediated diffuse podocytopathy (1R01DK135667-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10882264. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*