Abstract: FR-PO245
CD206+ Resident Macrophages: A Candidate Biomarker for Renal Cystic Disease Activity in Preclinical Models and Patients With Autosomal Dominant Polycystic Kidney Disease
Session Information
- Genetic Diseases of the Kidneys: Cystic - II
November 04, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
Abstract Time: 10:00 AM - 12:00 PM
Category: Genetic Diseases of the Kidneys
- 1101 Genetic Diseases of the Kidneys: Cystic
Authors
- Li, Zhang, The University of Alabama at Birmingham, Birmingham, Alabama, United States
- Zimmerman, Kurt, The University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States
- Cherakara, Sreelakshmi, The University of Alabama at Birmingham, Birmingham, Alabama, United States
- Chumley, Phillip H., The University of Alabama at Birmingham, Birmingham, Alabama, United States
- Haycraft, Courtney J., The University of Alabama at Birmingham, Birmingham, Alabama, United States
- Andersen, Reagan S., The University of Alabama at Birmingham, Birmingham, Alabama, United States
- Croyle, Mandy J., The University of Alabama at Birmingham, Birmingham, Alabama, United States
- Aloria, E.j., The University of Alabama at Birmingham, Birmingham, Alabama, United States
- Thomas, Isis, The University of Alabama at Birmingham, Birmingham, Alabama, United States
- Chweih, Hanan, The University of Alabama at Birmingham, Birmingham, Alabama, United States
- Simanyi, Kristin L., The University of Alabama at Birmingham, Birmingham, Alabama, United States
- George, James F., The University of Alabama at Birmingham, Birmingham, Alabama, United States
- Mrug, Michal, The University of Alabama at Birmingham, Birmingham, Alabama, United States
- Yoder, Bradley K., The University of Alabama at Birmingham, Birmingham, Alabama, United States
Background
Age and renal injury are drivers of renal cystogenesis in PKD mouse models. Since macrophage depletion attenuates injury-induced cystogenesis and macrophage differentiation state is age and injury-dependent, we speculated that a developmental/injury-regulated macrophage subset may influence renal cyst formation.
Methods
We analyzed macrophage populations during renal maturation and their associations with cystogenesis rates in conditional Pkd2 mutant mice. We tested the relevance of these associations by depleting macrophages using the congenital Cx3cr1 null mice. We also assessed parallels between the cystogenic activity-associated macrophage subset and disease activity in patients with ADPKD.
Results
CD206+ macrophages are enriched in juvenile but not adult wild type mouse kidneys. This correlates with the rapid- to slow-onset cystogenesis that occurs in Pkd2 mutant mice with juvenile- vs adult-induction. While CD206+ macrophages are minimal in a normal adult kidney, they accumulate around the cysts in non-injured adult-induced Pkd2 mutants. Using Cx3cr1 null mice, we reduced macrophage number, including CD206+ macrophages, and this resulted in a significant reduction of cyst severity in non-injured adult-induced Pkd2 mutant kidneys. The number of CD206+ resident macrophage-like cells also increased in kidneys from ADPKD patients, and their urinary content correlated with the rate of renal function loss in a small ADPKD patient cohort (Figure).
Conclusion
These data indicate that CD206+ macrophage numbers increase during periods of rapid cyst formation in Pkd2 mutant mice. Depletion of macrophages attenuates cystogenesis in non-injured adult-induced Pkd2 mutants. CD206+ macrophages also accumulate in human ADPKD kidneys, and their urine excretion could serve as a disease activity biomarker.
The number of CD206+ macrophages is increased in ADPKD patient kidneys, and their urinary content correlate with eGFR decline among patients.
Funding
- NIDDK Support