By Sally Robertson, medwireNews Reporter
A vasopressin V2-receptor blocker slows the increase in total kidney volume and decline in kidney function in patients with autosomal dominant polycystic kidney disease (ADPKD), report US researchers.
In a large, phase III trial, tolvaptan was associated with slowed kidney growth and decreased functional decline and with a reduced frequency of ADPKD-related complications when administered over 3years.
"In most patients with the disease, relentless cyst growth within the kidneys destroys the tissue, causes hypertension and painful complications, and negatively impacts the quality of life," described lead author Vicente Torres, from the Mayo Clinic in Rochester, Minnesota, in a press statement.
Preclinical studies have indicated that vasopressin V2-receptor antagonists inhibit cyst growth and slow the decline of kidney function, but these have included a small number of patients, noncontemporary controls, and unmatched ethnic groups.
In the current trial, which included 1445 patients from 129 sites worldwide who had a total kidney volume of 750 mL or more and a creatinine clearance of 60 mL per minute or more, individuals were randomly allocated to receive a mean dose of 95 mg tolvaptan or 110 mg placebo every day for 36 months.
Over the treatment period, total kidney volume increased by 2.8% per year with tolvaptan, compared with 5.5% per year with placebo. And the decline in kidney function, as assessed by creatinine level, was slower in the tolvaptan group compared with placebo at -2.61 mg/mL each year versus -3.81 mg/mL each year.
For each 100 person-years of follow up, there were fewer ADPKD-related events in the tolvaptan group than in the placebo group, at 44 versus 50 events, with lower rates of worsening kidney function, at 2 versus 5 events, and kidney pain, at 5 versus 7 events.
The effect of tolvaptan was most pronounced during the first year of treatment, probably due to an acute decrease in the secretion of cyst fluid, say the researchers. By contrast, the effect on glomerular filtration rate became apparent only after the first year of treatment.
However, a substantial number of patients discontinued tolvaptan due to adverse events related to aquaresis (thirst, polyuri, nocturia, and polydypsia) as a result of the excretion of electrolyte-free water. The treatment was also associated with increased levels of liver enzymes and uric acid, hypernatremia, and gout.
In an accompanying editorial, Rudolf Wuthrich (University Hospital, Zurich, Switzerland) and Changlin Mei (Changzheng Hospital, Shanghai, China) say "the side effects of an aquaretic drug… will affect the quality of life in a substantial number of patients - an issue that must be weighed against the possible benefits of delayed dialysis and transplantation, decreased kidney pain, and fewer urinary tract infections."
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