# The Role of Kidney Immune Cells in Acceleration of Cyst Growth

> **NIH NIH R03** · UNIVERSITY OF ALABAMA AT BIRMINGHAM · 2020 · $111,375

## Abstract

Autosomal dominant polycystic kidney disease (ADPKD) is the most common genetic kidney disease, with the
predominant form resulting from mutations in the gene, PKD1. In ADPKD, cyst expansion/tubular dilation leads
to a loss of nephrons and eventually to kidney failure. There are significant subset of ADPKD patients that
develop severe accelerated cystic disease leading to end stage renal disease earlier in life. Accelerated
cystogenesis may be due, in part, to the effects of “modifying factors” a group of conditions that triggers a
phenotypic switch from slow to rapid cystic growth when superimposed on PKD. We have provided compelling
evidence that hypertrophic signaling is a critical modifier that stimulates rapid cystic disease progression.
Unilateral nephrectomy (UNx) and protein load both stimulates glomerular hyperfiltration and promotes rapid
cystic growth in mouse models of PKD. Interestingly, children with PKD that exhibit glomerular hyperfiltration
were shown to have a higher rate of cyst growth and faster decline in kidney function. Protein load/restriction in
murine models of PKD have been shown to promote/slow cystogenesis. Despite evidence of renal hypertrophy
accelerating cystogenesis, there is a gap in our knowledge of how hypertrophic signaling leads to rapid cyst
growth. Our new data from RNA-seq of kidney tissue comparing UNx to intact kidney from a sham operated
Pkd1 knockout mice, show differentially expressed genes involved in activating/recruiting macrophages and
production of pro-inflammatory cytokines during the hypertrophic signaling. We also show preliminary results
that high protein diet significantly increases kidney weight/cystogenesis in adult Pkd1 mice. This proposal will
determine whether conditions which trigger renal hypertrophy (both UNx and protein load), activate kidney
(resident) macrophages and leads to accelerated cyst growth in adult PKD mice. We will also begin to examine
potential biomarkers linked to rapid cystic progression with a focus of identifying individuals at risk for accelerated
cystogenesis.

## Key facts

- **NIH application ID:** 9938572
- **Project number:** 5R03DK119717-02
- **Recipient organization:** UNIVERSITY OF ALABAMA AT BIRMINGHAM
- **Principal Investigator:** Takamitsu Saigusa
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $111,375
- **Award type:** 5
- **Project period:** 2019-06-01 → 2021-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9938572

## Citation

> US National Institutes of Health, RePORTER application 9938572, The Role of Kidney Immune Cells in Acceleration of Cyst Growth (5R03DK119717-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/9938572. Licensed CC0.

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