Genes may predict which patients with polycystic kidney disease benefit from tolvaptan
Patients with autosomal dominant polycystic kidney disease who had mutations in two specific genes were more likely to respond favorably to treatment with tolvaptan than those who showed no mutations.
This finding led Akinari Sekine, MD, of Toranomon Hospital in Tokyo, and colleagues to suggest that examining patients’ genetic makeup may help predict which are more likely to benefit from the drug.
According to the researchers, autosomal dominant polycystic kidney disease (ADPKD) has been linked to mutations in the polycystic kidney disease 1 (PKD1) gene and the polycystic kidney disease 2 (PKD2) gene, with mutations occurring in 78% and 15% of patients with the disease, respectively. They added that approximately 7% of patients with ADPKD do not appear to have the mutations.
“The only therapeutic drug for patients with ADPKD is tolvaptan, a vasopressin V2-receptor antagonist that slows the rate of decline of the estimated glomerular filtration rate (eGFR),” they wrote.
To evaluate the relationship between these genetic characteristics and the treatment effects of tolvaptan, Sekine and colleagues included 18 patients with ADPKD who had been treated at Toranomon Hospital and undergone genetic testing between April 2016 and February 2020. Patients were categorized into one of the following four groups: PKD1 truncating, PKD1 non-truncating, PKD2, or no mutation in PKD1 or PKD2.
The median degrees of improvement in annual eGFR were 2.5 (45%) mL/min/1.73 m2 for patients in the PKD1 truncating group, 0.4 (10%) mL/min/1.73 m2 for those in the PKD1 non-truncating group, 0.6 (28%) mL/min/1.73 m2 for those in the PKD2 group and 0.7 (37%) mL/min/1.73 m2 for those with no mutation in either PKD1 or PKD2.
In addition, researchers found that, compared with the group of patients with a PKD1 or PKD2 mutation, the group with no mutation had significantly less improvement in both annual eGFR (0.6 mL/min/1.73 m2 vs. 0.7 mL/min/1.73 m2) and annual rate of increase in total kidney volume (6.7 vs. 1.1%).
Sekine and colleagues acknowledged the relatively small size of the study population and suggested that a large, prospective, multicenter study be conducted to confirm the findings.
“Despite these limitations, the study still led to the interesting finding that the efficacy of tolvaptan seems to differ between patients with ADPKD with no PKD1/PKD2 mutation and typical ADPKD patients with a PKD1/PKD2 mutation,” they concluded.
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