Dietary Taurine Increases Cystic Burden in Rat Model of Autosomal Recessive Polycystic Kidney Disease

Polycystic Kidney Disease (PKD) is the fourth leading cause of end-stage renal disease, characterized by the presence of fluid-filled cysts in the kidneys and hepatic tissue. Despite its clinical significance, there is limited information on the detailed composition and functional role of cystic fluid. Using the PCK (Pkhd1) rat model of autosomal recessive polycystic kidney disease (ARPKD), we extracted cystic fluid and analyzed the distribution of amino acids. Our findings revealed that taurine was the most abundant amino acid in the cyst fluid, with levels nearly five times higher than the second most abundant amino acid, glutamate. Taurine, a critical osmolyte involved in cellular volume regulation, particularly in the kidneys, was found in significantly elevated concentrations in cystic fluid and plasma of PCK rats. We hypothesize that dysregulated taurine transport in PKD leads to its accumulation within kidney and liver cysts, contributing to cyst growth and disease progression. 6 four-week-old male PCK rats were given either water supplemented with 3% taurine (ad libitum) or regular water for eight weeks (N=3 in each group). Body weight, food and water consumption, and urine samples were collected weekly. The animals were then euthanized to obtain tissue, urine, cystic fluid, and plasma for biochemical and histological analyses. Kidney and liver sections were stained with Masson’s-Trichrome or labeled with Ki-67 antibody (IHC) to quantify cystic index and nuclear proliferation of the cystic. Unpaired student t-tests or 2-way ANOVA with Sidak correction for multiple comparisons were used to determine significance p<0.05 and data is mean ± SEM. The taurine group had a significantly higher liver cystic index compared to control (6.6±0.3 vs. 5.4±0.5, p≤0.05). Additionally, there was a trend toward an increased cystic index in kidney samples from the taurine group (6.4±4.7) compared to the control group (2.1±0.4), and increased 2 kidney to total body weight ratios (10.5±0.7 vs 9.0±0.2). Urine volumes were consistently elevated in the taurine group throughout the study, reaching 27.7±6.0 mL compared to 14.3±1.0 mL in the control group at week 8 (P-interaction <0.001, P-time <0.001, P-treatment - 0.06). Correspondingly, urine osmolality was reduced in the taurine group with 1298±189 vs. 1881±82 mOsm at week 8 (2-way ANOVA, P-interaction - 0.454, P-treatment - 0.049, P-time - 0.117). No significant changes were observed in body or organ weights between the taurine and control groups. Additionally, the percentage of Ki67-positive nuclei in the cystic epithelium was comparable between the two groups. Our data suggest a potential role for taurine accumulation within PKD cysts as a driver of cystic growth and altered osmolality concentrating ability. To further investigate this hypothesis, additional experiments are being conducted in female subjects and with a larger sample size.

R25DK134324, R00HL153686 (to CAK), NIDDK R01DK126720, U24DK126110 subaward (to OP)

This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.