Cardiovascular Risk and Quality of Life in Autosomal Dominant Polycystic Kidney Disease Patients on Therapy With Tolvaptan: A Pilot Study

Abstract

Introduction: ardiovascular (CV) complications are the most frequent cause of morbidity and mortality in autosomal dominant polycystic kidney disease (ADPKD) patients. In 2017, the Italian Medicines Agency authorised tolvaptan, a vasopressin V2 receptor antagonist, for the treatment of ADPKD, based on the Tolvaptan Phase 3 Efficacy and Safety Study in ADPKD (TEMPO 3: 4), TEMPO 4: 4 and Replicating Evidence of Preserved Renal Function: An Investigation of Tolvaptan Safety and Efficacy (REPRISE) studies. Aim of the study: To assess the impact of tolvaptan on CV risk and quality of life, evaluated by nutritional, inflammatory, metabolic, instrumental parameters and psychocognitive tests in ADPKD patients. Methods and Materials: We evaluated 36 patients with ADPKD; 10 patients (7 males, mean age 42.5±7.0 years) treated with tolvaptan and 26 controls (11 males, mean age 36.7±9.1 years). They underwent, at T0, monthly, and at T1 (1 year) clinical, laboratory and instrumental evaluation, in addition to psychocognitive tests. Results: In ADPKD patients treated with tolvaptan we found at T1 a decrease in carotid intima media thickness (p=0.048), epicardial adipose tissue thickness (p=0.002), C-reactive protein (p=0.026), sympathovagal balance during the night (p=0.045) and increases flow mediated dilation (p=0.023) with a reduction in depression (Hamilton and Beck tests, p=0.008 and p=0.002, respectively) compared with controls. Conclusions: These preliminary results suggest that treatment with tolvaptan could improve early atherosclerosis and endothelial dysfunction markers and improve the mood in ADPKD patients (probably by the acting on endothelial cell and adipocyte V2 receptors).

Efficacy and safety of tolvaptan versus placebo in the treatment of patients with autosomal dominant polycystic kidney disease: a meta-analysis

“…The estimated growth rates of TKV for patients with Mayo classifications C, D and E were > 3–4.5%, > 4.5–6% and > 6%, respectively, indicating rapid disease progression. However, in our meta-analysis, the subjects were specifically identified as rapidly progressive ADPKD in only two included studies completed in 2020 [ 13 , 21 ]. Second, two included trials did not describe specific doses of tolvaptan.…”

Heart rate variability at rest and in response to stress: Comparative study between hemodialysis and peritoneal dialysis patients

“…); non-traditional factors, including but not limited to inflammation, arterial stiffness, endothelial dysfunction, and autonomic nervous system (ANS) dysregulation, are significant contributors toward this increased burden of cardiovascular disease, 3 with ANS dysfunction playing a major role in the arrhythmogenic background of these patients. 4,5 Heart rate variability (HRV) analysis is a valuable tool for assessing cardiac autonomic regulation in both short-term (minutes) and long-term (24 h) intervals and is traditionally quantified in time-domain and frequency-domain analyses. 6,7 More modern indices, such as non-linear measures of HRV (Poincaré Plot, Entropy, and Detrended Fluctuation Analysis [DFA]), have recently drawn widespread attention, 8 providing additional prognostic information for cardiovascular risk and enabling recording HRV alterations both at rest and during physiological maneuvers.…”

Dietary Aspects and Drug-Related Side Effects in Autosomal Dominant Polycystic Kidney Disease Progression

“…In contrast, and probably due to the limitations of the study (i.e., small sample size), the dietary intervention was not associated with an improvement in quality of life [ 60 ]. Finally, psychocognitive tests were performed by Lai et al on 36 patients with ADPKD (10 treated with tolvaptan and 26 controls), revealing lower rates of depression in the tolvaptan group [ 61 ]. Interestingly, this study also evaluated cardiovascular outcomes such as carotid intima-media thickness, epicardial adipose tissue thickness, and inflammatory parameters.…”

“…Interestingly, this study also evaluated cardiovascular outcomes such as carotid intima-media thickness, epicardial adipose tissue thickness, and inflammatory parameters. Tolvaptan reduced atherosclerosis markers and inflammation, suggesting that its protective role can be partially explained by the improvement in renal function but also by the absence of overhydration due to the aquaretic effects in addition to a direct effect on extrarenal V2 receptors [ 61 ]. In terms of quality of life, a recent meta-analysis has suggested a positive effect of tolvaptan in reducing renal pain and urinary tract infections [ 62 ].…”