Abstract: FR-PO277
Ion and Metabolite Composition of Cystic Fluid From a Rat Model of Autosomal Recessive Polycystic Kidney Disease (ARPKD)
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
- Klemens, Christine Anne, USF Health Morsani College of Medicine, Tampa, Florida, United States
- Semenikhina, Marharyta, Medical University of South Carolina, Charleston, South Carolina, United States
- Dissanayake, Lashodya Vindana, USF Health Morsani College of Medicine, Tampa, Florida, United States
- Palygin, Oleg, Medical University of South Carolina, Charleston, South Carolina, United States
- Staruschenko, Alexander, USF Health Morsani College of Medicine, Tampa, Florida, United States
Background
Polycystic kidney disease results in fluid-filled cysts in the kidney and is responsible for ~10% of all end-stage renal disease cases. Implementation of ‘omics’ techniques leads to increased understanding of pathogenic changes in many diseases. While several studies have assessed kidney, plasma, and urine metabolites from both human and rodent kidneys, none have explicitly looked at the composition of cyst fluid. This study aimed to reveal ARPKD renal fluid components, which might be critical for understanding cyst formation.
Methods
We used the PCK rat model of ARPKD to simultaneously collect blood from the aorta, urine from the bladder, and cystic fluid directly from renal cysts of male and female rats (12-14 wks). Solute osmolality and electrolyte concentrations were measured. Cyst fluid untargeted metabolomic profiling was performed using LC/MS and analyzed using Metaboanalyst and Ingenuity Pathway Analysis.
Results
The cyst fluid osmolality was significantly lower than urine (430.8 ± 12.0 vs 1215 ± 99 mOsm) but above the typical plasma range (275-290 mOsm). The cyst fluid also had a distinct electrolyte composition relative to plasma and urinary values. The concentrations of Na+ (23.7 ± 1.2 mM) and Cl- (65.5 ± 2.1 mM) in the cystic fluid were significantly lower than plasma or urinary levels. However, K+ (95.2 ± 3.1 mM) was significantly increased compared to blood but not distinct from urinary concentrations. There were no differences observed between male and female cyst electrolytes. Omics analyses indicate that the predominant non-lipid molecule in the cyst fluid were amino acids, while fatty acids and isoprenoids were the most represented lipid chemical classes. KEGG Pathway Analysis determined the top metabolic pathways associated with cyst fluid composition included: Tryptophan, Tyrosine, and Alanine/Aspartate/Glutamate. Significant differences between male and female cyst fluid composition were observed (1,304 compounds upregulated and 1,214 compounds downregulated in males vs females).
Conclusion
Kidney cyst fluid has a distinct electrolyte composition. Additionally, amino acids are the most represented chemical class, and a better understanding of how their presence in cyst fluid influences cyst development may lead to potential intervention strategies.
Funding
- NIDDK Support