Tolvaptan in the treatment of autosomal dominant polycystic kidney disease: patient selection and special considerations

Abstract

Standard of care therapies for autosomal dominant polycystic kidney disease (ADPKD) may limit morbidity and mortality due to disease-related complications, but they do not delay disease progression. Tolvaptan, a selective vasopressin V2 receptor antagonist, delays the increase in kidney volume (a surrogate marker for disease progression), slows the decline in renal function, and reduces pain in ADPKD patients with relatively preserved renal function. The most common adverse events of tolvaptan are linked to its aquaretic effect, and rare cases of idiosyncratic hepatitis were observed. Additional ongoing studies will determine whether the benefits are sustained over time, whether they can be observed in patients with advanced kidney disease, and whether they can be translated in terms of quality of life and cost/effectiveness parameters. Tolvaptan is currently approved in Europe and several countries throughout the world. In real-life conditions, selection of patients that would be good theoretical candidates to tolvaptan is a key but complex question. Eligibility criteria slightly differ from one country to another, and several models (based on conventional data, genetics, renal volume) were recently proposed to identify patients with evidence or risk of rapid disease progression. Eligible patients will ultimately make the decision to start tolvaptan, after complete information, consideration, and balancing of benefits, adverse events, and risks.

Long-acting somatostatin analogue treatments in autosomal dominant polycystic kidney disease and polycystic liver disease: a systematic review and meta-analysis

“…Both the major tolvaptan ADPKD trials (TEMPO38 and REPRISE39) demonstrated a significant risk of developing hepatotoxicity in 16 patients in the tolvaptan treatment group compared with 1 in the placebo group. The EMA have estimated a rare risk of severe hepatitis which may affect approximately 1 in 4000 ADPKD patients treated with tolvaptan 40…”

Management of portal hypertension and ascites in polycystic liver disease

“…As liver function is preserved in PLD patients, we hypothesize that the risks of vaptans is lower in this group and its use for PLD‐related portal hypertension needs further investigation. However, the high cost of tolvaptan, which ranges between € 15 000 and € 30 000 per year, is a major barrier for widespread use …”

“…However, the high cost of tolvaptan, which ranges between € 15 000 and € 30 000 per year, is a major barrier for widespread use. [64][65][66] Lastly, large volume paracentesis (with or without albumin replacement) under radiological guidance should be used to achieve symptomatic relief, reduce fluid burden and alleviate abdominal distension. 15,45 The presence of spontaneous bacterial peritonitis, although infrequent, should be considered.…”

Rationale and study protocol of ACQUIRE, a prospective, observational study measuring quality of life, treatment preference and treatment satisfaction of autosomal dominant polycystic kidney disease (ADPKD) patients in Europe

“…Treatment with tolvaptan during early-stage chronic kidney disease (CKD) has been shown to slow total kidney volume growth and glomerular filtration rate (GFR) decline [ 10 ]. Based on clinical trial data, long-term treatment models indicate tolvaptan may delay ESRD by up to 6.5 years [ 12 ]. However, tolvaptan treatment can lead to hepatotoxicity and higher doses are not well tolerated due to a range of side effects, including aquaresis and polydipsia.…”