Boosting Tolvaptan Tolerance in ADPKD: Low-Dose Hydrochlorothiazide Improves Patient Well-being Without Compromising...

ADPKD is the most common inherited kidney disorder, marked by numerous renal cysts, increased total kidney volume and progressive renal function decline. Mutations in the PKD1 and PKD2 genes, leading to altered cAMP signaling, drive cyst growth. Elevated antidiuretic hormone (ADH) levels further exacerbate cystogenesis. Tolvaptan, a vasopressin V2 receptor antagonist, is the only approved treatment for slowing ADPKD progression, but its use often results in significant polyuria and thirst, affecting patient quality of life. This case report presents a 31-year-old female with ADPKD, classified as Mayo Class 1D, who showed improved tolerance to tolvaptan after co-administering low-dose hydrochlorothiazide (HCT). The patient experienced a significant reduction in polyuria and thirst while maintaining stable kidney function over four years. The annual decline in eGFR was less than expected for her disease class and improved compared to the first year of tolvaptan therapy. This case suggests that HCT may enhance tolvaptan tolerability without reducing its efficacy. Ongoing studies, such as the HYDRO-PROTECT trial, aim to further explore the benefits of combining HCT with tolvaptan in ADPKD management.