Polycystic kidney disease (PKD) is the fourth leading cause of renal failure and characterized by the progressive formation of fluid-filled cysts that ultimately lead to end-stage kidney disease. The main cause of renal damage is due to the buildup and enlargement of fluid filled cysts, thus understanding cyst fluid composition and solute transport is essential. In prior analyses of cyst fluid from PCK rats (well-established model of autosomal recessive PKD), we found that ~60% of the cyst fluid consisted of amino acids and peptide fragments, with taurine present at high concentrations (~6 mM). We also observed elevated urinary taurine levels in PCK rats compared to healthy Sprague Dawley controls. Based on these findings, we hypothesized that dietary taurine supplementation would enhance its accumulation and exacerbate cyst growth whereas β-alanine supplementation lowers systemic and cystic taurine levels which would reduce cystic burden in PCK rats. PCK rats were randomly assigned to one of the three treatment groups: Vehicle (water), 3% Taurine, and 3% β-alanine (n ≥ 6, M or F/group). The protocol began immediately after weaning (4 weeks old), when baseline measurements were recorded. Total body weight, food intake, urine output, and water intake were measured biweekly, and the study concluded after 10 weeks on the protocol (14-15 weeks age). All quantitative measurements are presented as mean ± SEM and reported in the order of Vehicle, 3% taurine, and 3% β-alanine. Taurine supplementation significantly increased urine output in males (6.5 ± 1.0, 15.6 ± 3.1, 4.9 ± 0.8 mL/24 hr) and water intake (30.3 ± 3.2, 42.9 ± 6.2, 25.2 ± 2.7 mL/24 hr), with similar trends observed in females. Liver protein expression of the key taurine metabolic enzymes CDO1 and CSAD were significantly decreased in the taurine and increased in the β-alanine supplemented groups (n ≥ 4, M/group) compared with vehicle (CDO1: 1.0 ± 0.1, 0.7 ± 0.1, 1.1 ± 0.1, p< 0.0001; CSAD: 1.0 ± 0.1, 0.5 ± 0.1, 1.2 ± 0.1, p< 0.0001). Circulating taurine concentrations were elevated in the taurine group and reduced in the β-alanine group relative to vehicle (178 ± 16, 833 ± 176, 71 ± 15 µM, n ≥ 6, M or F/group but only male values are shown, p=0.0022). Urinary taurine excretion (normalized to creatinine) was also increased in the taurine group, with an upward trend in the β-alanine group (1.0 ± 0.1, 42 ± 6, 1.9 ± 0.1, n = 3, M/group, p=0.0001). Taurine supplementation increased its accumulation in cyst fluid, while β-alanine did not reduce cyst fluid taurine levels relative to vehicle (4.5 ± 0.6, 125 ± 12, 4.9 ± 0.5 mM, n ≥ 6 M or F/group but only male values shown, p< 0.0001). Kidney cystic index did not differ significantly among groups (n = 4, M/group). Liver cystic index was higher in the taurine, but not β-alanine, group compared with vehicle (3.2 ± 0.4, 4.6 ± 0.3, 4.0 ± 0.3 % cystic index, n = 4, M/group, p=0.0374), likely due to a greater number of cysts (0.9 ± 0.0, 1.3 ± 0.0, 1.2 ± 0.0 cysts/mm 2 , p=0.0202). Taurine supplemented females exhibited significantly higher liver-to-body weight ratios relative to vehicle, whereas no statistical differences were observed in males (female: 45 ± 1, 57 ± 1, 49 ± 1, p< 0.0001; male: 42 ± 1, 43 ± 1, 41 ± 0, n ≥ 8, M or F/group). While the overall impact of taurine supplementation is still unresolved, the results point to taurine metabolism as a modifiable pathway and raise the possibility that targeted dietary interventions could complement future therapeutic strategies for PKD. Funding information: R00 HL153686 (to CAK), and R01 DK126720 (to OP) This abstract was presented at the American Physiology Summit 2026 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.
Garimella et al. (Fri,) studied this question.