Tolvaptan resistance is related with a short-term poor prognosis in patients with lung cancer and syndrome of inappropriate anti-diuresis

Posted on Scarica PDF

Antonio Lacquaniti1, Susanna Campo1, Alessandro Russo2, Vincenzo Adamo2, Paolo Monardo1

1 Nephrology and Dialysis Unit, Papardo Hospital of Messina, Italy
2 Medical Oncology Unit A.O. Papardo & Department of Human Pathology, University of Messina, Messina, Italy

Corresponding author:
Dr. Paolo Monardo
Nephrology and Dialysis Unit, Papardo Hospital, Messina, Italy
Phone: 00390903993597
Fax: 00390903992337
Mail: pmonardo66@gmail.com

 

Abstract

Purpose: Tolvaptan (TVP), a vasopressin receptor antagonist, represents a therapeutic option in the syndrome of inappropriate anti-diuresis (SIAD). The aim of this study was to evaluate the effect of TVP to treat and solve hyponatremia in oncologic patients.
Methods: 15 oncologic patients who developed SIAD have been enrolled. Patients receiving TVP belonged to group A, whereas group B was characterized by hyponatremic patients treated with hypertonic saline solutions and fluid restriction.
Results: In group A, the correction of serum sodium was achieved after 3.7±2.8 days. In group B, the target levels were obtained more slowly, after 5.2±3.1 days (p: 0.01) than in group A. The hospital stay and incidence of re-hospitalization were higher in group B than in group A. In this latter, 37% of patients had hyponatremic relapses, notwithstanding the progressive increase of doses from 7.5 to 60 mg per day of TVP, revealing a complete lack of response to TVP. In these patients, a growth of tumor mass or new metastatic lesions has been revealed.
Conclusion: TVP improved hyponatremia more efficiently and stably than hypertonic solutions and fluid restrictions. Positive consequences have been obtained about the rate of chemotherapeutical cycles concluded, hospital stay, rate of relapse of hyponatremia, and re-hospitalization.
Our study also suggested potential prognostic information that could be deduced from TVP patients, in whom sudden and progressive hyponatremia occurred, despite TVP dosage increase. A re-staging of these patients to rule out tumor mass growth or new metastatic lesions is suggested.

Keywords: hyponatremia, paraneoplastic syndrome, syndrome of inappropriate anti-diuresis, tolvaptan, vasopressin

Introduction

The prognosis of oncologic patients is often related to the onset of electrolytic disorders, particularly if hyponatremia occurs [1]. The syndrome of inappropriate anti-diuresis (SIAD) represents the main cause of hyponatremia, even though differential diagnosis with concomitant comorbidities (heart failure, nephrotic syndrome, extracellular volume depletion, pulmonary disorders) and drugs (tricyclic antidepressants, selective serotonin reuptake inhibitors, opioids, chemotherapeutic agents and immunotherapy) needs to be carried out [2, 3].

In particular, SIAD is directly associated with malignancy as expression of a paraneoplastic endocrine effect mediated by an ectopic production of vasopressin (AVP) by cancer cells. Moreover, medications, particularly chemotherapic agents, such as vinca alkaloids, alkylating agents, and platinum compounds, which increase the AVP synthesis/release, could induce SIAD. Other drugs, such as cyclophosphamide, could enhance the water permeability of the distal tubule, in the absence of high AVP levels [1].

 

La visualizzazione dell’intero documento è riservata a Soci attivi, devi essere registrato e aver eseguito la Login con utente e password.

The pathway of vasopressin as a pharmacological target in nephrology: a narrative review

Posted on Scarica PDF

Michi Recupero

Recupero Michi, Fulignati Pierluigi, Naticchia Alessandro, D'Alonzo Silvia, D'Ascenzo Francesca, Costanzi Stefano

Autore corrispondente:
Dott. Recupero Michi
Scuola di Specializzazione in Nefrologia,
U.O.C.  Nefrologia, Università cattolica del sacro cuore
Fondazione  Policlinico Universitario A. Gemelli IRCCS, Roma, Italia
tel: 3299314372.
e-mail: m.recupero@hotmail.it

 

Abstract

ADH is a hormone secreted by neurohypophysis that plays different roles based on the target organ. At the renal level, this peptide is capable of causing electrolyte-free water absorption, thus playing a key role in the hydro-electrolytic balance. There are pathologies and disorders that jeopardize this balance and, in this field, ADH receptor inhibitors such as Vaptans could play a key role. By inhibiting the activation pathway of vasopressin, they are potentially useful in euvolemic and hypervolemic hypotonic hyponatremia. However, clinical trials in heart failure have not given favourable results on clinical outcomes. Even in SIADH, despite their wide use, there is no agreement by experts on their use.

Since vaptans inhibit the cAMP pathway in tubular cells, their use has been proposed to inhibit cystogenesis. A clinical trial has shown favourable effects on ADPKD progression.

Because vaptans have been shown to be effective in models of renal cysts disorders other than ADPKD, their use has been proposed in diseases such as nephronophthisis and recessive autosomal polycystic disease. Other possible uses of vaptans could be in kidney transplantation and cardiorenal syndrome.

Due to the activity of ADH in coagulation and haemostasis, ADH’s activation pathway by Desmopressin Acetate could be a useful strategy to reduce the risk of bleeding in biopsies in patients with haemorrhagic risk.

 

Keyword: vasopressin, vaptans, hyponatremia, ADPKD, biopsy

Sorry, this entry is only available in Italian.

Introduzione

La vasopressina, nota anche come adiuretina o arginin-vasopressina (AVP) o ormone antidiuretico (ADH), è un ormone neuropeptidico prodotto a livello dei nuclei sopraottico e paraventricolare che viene secreto dall’ipofisi posteriore in risposta ad un aumento della tonicità plasmatica o alla diminuzione del volume plasmatico (1).

 

La visualizzazione dell’intero documento è riservata a Soci attivi, devi essere registrato e aver eseguito la Login con utente e password.