Decreased salivary flow rate as a dipsogenic factor in hemodialysis patients: Evidence from an observational study and a pilocarpine clinical trial

Decreased salivary flow rate causes xerostomia (symptoms of oral dryness) in patients who undergo hemodialysis (HD); however, whether it thus contributes to thirst and excess interdialytic weight gain (IDWG) remains undetermined. In the observational study, 3 mo of data of 90 stable HD patients were collected, and sensations of thirst and xerostomia were assessed by 100-mm visual analog scales (VAS). Multivariate analyses revealed that the VAS oral dryness score was an independent determinant for thirst, daily IDWG, and IDWG%. Unstimulated whole salivary flow rate (UWS) was measured in 45 participants and was negatively correlated with VAS oral dryness score (r = -0.690, P ≤ 0.001), daily IDWG (r = -0.361, P = 0.016), and daily IDWG% (r = -0.302, P = 0.045). In the interventional trial, the test drug was 5 mg of oral pilocarpine solution or placebo. Sixty hyperdipsic HD patients (IDWG% > 2%/d) were randomly assigned to either the sequence pilocarpine (2 wk)-washout (3 wk)-placebo (2 wk)-washout (2 mo)-placebo (3 mo) or placebo (2 wk)-washout (3 wk)-pilocarpine (2 wk)-washout (2 mo)-pilocarpine (3 mo) with 35 participants completing the trial. During the 2-wk crossover period (the first to seventh weeks), pilocarpine increased UWS and decreased xerostomia and thirst. The IDWG_2d decreased (by approximately 0.2 kg; P = 0.013) but not IDWG_3d. During the 3-mo interventional period, pilocarpine increased UWS but decreased both IDWG_2d (by 0.76 kg; P = 0.021) and IDWG_3d (by 1.07 kg; P = 0.007). It also modestly increased serum albumin and decreased mean BP. Pilocarpine-related adverse effects were generally mild. In conclusion, decreased salivary flow is a dipsogenic factor in HD patients, and pilocarpine can alleviate it.