Short-Term Tolvaptan Increases Water Intake and Effectively Decreases Urinary Calcium Oxalate, Calcium Phosphate and Uric Acid Supersaturations

Abstract

Purpose Many patients cannot effectively increase water intake and urine volume to prevent urinary stones. Tolvaptan, a V2 receptor antagonist, blocks water reabsorption in the collecting duct and should reduce urinary supersaturation (SS) of stone forming solutes, but this has never been proven. Materials and Methods We conducted a double blind, randomized, placebo-controlled, crossover study in 21 adult calcium urinary stone formers stratified as majority calcium oxalate(CaOx, n=10) or calcium phosphate(CaP, n=11). Patients received tolvaptan 45 mg/day or placebo for 1 week, followed by a washout week and crossover to tolvaptan or placebo for week 3. A 24h urines was collected at the end of weeks 1 and 3. Results Tolvaptan vs. placebo decreased urinary osmolality (204±96 vs 529±213 mOsm/kg, P<0.001) and increased urinary volume (4.8±2.9 vs 1.8±0.9 L, P<0.001). The majority of urinary solute excretion rates including sodium and calcium did not significantly change, although oxalate secretion slightly increased (23±8 to 15±8 mg/24h, P = 0.009). Urinary CaOx SS (−0.01±1.14 vs 0.95±0.87 DG, P<0.001), CaP SS (−1.66±1.17 vs −0.13±1.02 DG, P<0.001) and Uric Acid SS (−2.05±4.05 vs −5.24±3.12 DG, P=0.04) all dramatically decreased. Effects did not differ between CaOx and CaP groups (P>0.05 for all interactions). Conclusions Tolvaptan increases urine volume and decreases urinary SS in calcium stone formers. Further study is needed to determine if long term use of V2 receptor antagonists results in fewer stone events.

Coexistence of autosomal dominant polycystic kidney disease type 1 and hereditary renal hypouricemia type 2: A model of early‐onset and fast cyst progression

“…Future studies of ADPKD patients with kidney disease discordance by NGS targeting a panel of potential cystic or CKD modifier genes have the potential to unreveal genetic contributors to kidney disease progression in ADPKD. Moreover, our results illustrate that tolvaptan treatment by decreasing urinary osmolality dramatically decreased urine uric acid supersaturation (Table ) and decreased the risk of urine uric acid crystallization‐precipitation, and presumably, by activating the Nrf2/HO‐1 antioxidant pathway, as it has been proposed, was an effective approach in this patient.…”

“…Thus, tolvaptan may activate the Nrf2/HO‐1 antioxidant pathway through phosphorylation of protein kinase RNA‐like endoplasmic reticulum kinase (PERK) . On the other hand, tolvaptan blocks water reabsorption in the collecting duct and should decrease urinary supersaturation of stone forming solutes, thus uric acid supersaturation dramatically decreased, as we can observe in our proband after a period of treatment with tolvaptan (a decrease of the urinary uric acid concentration) (Table ). Interestingly, in our proband serum, uric acid levels also seem to increase slightly on tolvaptan action (Table ), as it was demonstrated by Irazabal et al Although it is possible that urinary uric acid reabsorption and/or secretion was also affected by tolvaptan, tolvaptan should act exclusively in the collecting duct, and it is not believed that any significant uric acid transport occurs beyond the proximal tubule.…”

Fecal transplant modifies urine chemistry risk factors for urinary stone disease

“…; Cheungpasitporn et al. ). The observed significant decrease in urinary calcium and oxalate seen at 4 weeks post‐transplant suggests that the GMB can influence CaOx balance.…”

Incidence and characteristics of kidney stones in patients with horseshoe kidney: A systematic review and meta-analysis

“…Kidney stone disease, also known as nephrolithiasis, is a common problem worldwide,[ 1 2 3 4 5 6 7 8 ] with a prevalence of 7% in the adults, and ≥30% recurrence rate within 10 years. [ 1 3 9 ] The incidence of kidney stones is globally increasing with an estimated prevalence ranging up to 15%.…”