Polyuria due to vasopressin V2 receptor antagonism is not associated with increased ureter diameter in ADPKD patients

Abstract

Background: Tolvaptan, a vasopressin V2 receptor antagonist, has been shown to reduce the rates of growth in total kidney volume (TKV) and renal function loss in ADPKD patients, but also leads to polyuria because of its aquaretic effect. Prolonged polyuria can result in ureter dilatation with consequently renal function loss. Therefore, we aimed to investigate the effect of tolvaptan-induced polyuria on ureter diameter in ADPKD patients.

Methods: 70 ADPKD patients were included (51 were randomized to tolvaptan and 19 to placebo). At baseline and after 3 years of treatment renal function was measured (mGFR) and MRI was performed to measure TKV and ureter diameter at the levels of renal pelvis and fifth lumbar vertebral body (L5).

Results: In these patients [65.7 % male, age 41 ± 9 years, mGFR 74 ± 27 mL/min/1.73 m² and TKV 1.92 (1.27-2.67) L], no differences were found between tolvaptan and placebo-treated patients in 24-h urine volume at baseline (2.5 vs. 2.5 L, p = 0.8), nor in ureter diameter at renal pelvis and L5 (4.0 vs. 4.2 mm, p = 0.4 and 3.0 vs. 3.1 mm, p = 0.3). After 3 years of treatment 24-h urine volume was higher in tolvaptan-treated patients when compared to placebo (4.7 vs. 2.3 L, p < 0.001), but no differences were found in ureter diameter between both groups (renal pelvis: 4.2 vs. 4.4 mm, p = 0.4 and L5: 3.1 vs. 3.3 mm, p = 0.4).

Conclusions: Tolvaptan-induced polyuria did not lead to an increase in ureter diameter, suggesting that tolvaptan is a safe therapy from a urological point of view.

Keywords: Autosomal dominant polycystic kidney disease; Polyuria; Tolvaptan; Ureter.

Fig. 1

Ureter diameter was measured 3 cm after the pyelo-ureteral junction (upper panel) and on the level of L5 (lower panel), perpendicular from ureter wall to ureter wall, preferably on the coronal T2-half Fourier single-shot turbo spin echo (HASTE) sequence. White lines indicate the place of measurement

Fig. 2

Associations of 24-h volume (upper panels), measured glomerular filtration rate (middle panels) or total kidney volume (log scale, lower panels) with ureter diameter at baseline (left panels) and at year 3 (right panels)

Fig. 3

Associations of ureter diameter at baseline with ureter diameter at year 3 in ADPKD patients at the level of the renal pelvis (upper panel) and lumbar 5 (lower panel) [overall n = 70, tolvaptan use n = 51 (solid line), placebo use n = 19 (dashed line)]