Effect of Vasopressin on the Hypothalamic-Pituitary-Adrenal Axis in ADPKD Patients during V2 Receptor Antagonism

Abstract

<b><i>Background:</i></b> Patients with autosomal dominant polycystic kidney disease (ADPKD) are treated with a vasopressin V2 receptor antagonist (V2RA) to slow disease progression. This drug increases vasopressin considerably in these patients with already elevated baseline levels. Vasopressin is known to stimulate the hypothalamic-pituitary-adrenal (HPA) axis through V1 and V3 receptor activation. It is unknown whether this increase in vasopressin during V2RA treatment affects glucocorticoid production. <b><i>Methods:</i></b> Twenty-seven ADPKD patients were studied on and off treatment with a V2RA and compared to age- and sex-matched healthy controls and IgA nephropathy patients, the latter also matched for kidney function. Vasopressin was measured by its surrogate copeptin. Twenty-four-hour urinary excretions of cortisol, cortisone, tetrahydrocortisone, tetrahydrocortisol, allotetrahydrocortisol, and the total glucocorticoid pool were measured. <b><i>Results:</i></b> At baseline, ADPKD patients demonstrated a higher copeptin concentration in comparison with healthy controls, while urinary excretion of cortisol and cortisone was lower (medians of 0.23 vs. 0.34 μmol/24 h, <i>p</i> = 0.007, and 0.29 vs. 0.53 μmol/24 h, <i>p</i> < 0.001, respectively). There were no differences in cortisol and cortisone excretion compared to IgA nephropathy patients. Cortisol, cortisone, and total glucocorticoid excretions correlated with kidney function (<i>R</i> = 0.37, 0.58, and 0.19, respectively; all <i>p</i> < 0.05). Despite that V2RA treatment resulted in a 3-fold increase in copeptin, only cortisone excretion increased (median of 0.44 vs. baseline 0.29 μmol/24 h, <i>p</i> < 0.001), whereas no changes in cortisol or total glucocorticoid excretion were observed. <b><i>Conclusions:</i></b> Increased concentration of vasopressin in ADPKD patients at baseline and during V2RA treatment does not result in activation of the HPA axis. The impaired glucocorticoid production in these patients is related to their degree of kidney function impairment.

Vaptans or voluntary increased hydration to protect the kidney: how do they compare?

“…Similarly, increased concentration of vasopressin in ADPKD patients at baseline and during tolvaptan treatment did not result in activation of the hypothalamic-pituitary-adrenal axis. The impaired glucocorticoid production in these patients was found to be related to their degree of kidney function impairment [56].…”

Efficacy of combination triple therapy with vasopressin, steroid, and epinephrine in cardiac arrest: a systematic review and meta-analysis of randomized-controlled trials

“…At lower doses, VP activates the intravascular P2 purinergic and oxytocin receptors (OTR), through which, lower doses of VP mediate endothelial vasodilation, attenuate coronary vasoconstriction caused by V1 vascular receptors (V1Rs),and exert a positive inotropic effect [ 14 , 15 ]. Moreover, VP stimulates secretion of cortisol directly through V1R and V3R on adrenal cortex [ 16 ]. However, the result of a previous systematic review of the randomized clinical trials (RCTs) could not display a benefit for VP, in combination with EP or only VP over EP, in improving survival of out-of-hospital cardiac arrest (OHCA) [ 17 ].…”