Initial eGFR Decline Predicts Tolvaptan Efficacy in ADPKD – Renal and Urology News

Initial declines in estimated glomerular filtration rate (eGFR) after tolvaptan administration predict the drug’s effectiveness in slowing future eGFR decline in patients with autosomal dominant polycystic kidney disease (ADPKD), investigators report.

Toshiki Tanaka, PhD, of Otsuka Pharmaceutical Co., Ltd, in Tokyo, Japan, and colleagues performed a post hoc analysis of the TEMPO 3:4 study involving 961 patients randomized to receive tolvaptan, a vasopressin V2 receptor antagonist, or placebo.

Initial change in eGFR from baseline to week 3 after tolvaptan initiation independently predicted the annual mean rate of change in eGFR. Both the Pearson and Spearman correlation coefficients showed that the larger the initial change in eGFR after drug initiation, the smaller the annual mean rate of change, the investigators reported in Kidney360.

“A greater initial decline in eGFR suggests a more pronounced response to tolvaptan treatment, which subsequently protects the kidney from a further decline in eGFR,” Dr Tanaka’s team explained. “This initial decline in eGFR may be due to reduction of glomerular hyperfiltration by tolvaptan through the suppression of urea recycling in the collecting tubules, and/or reduction of kidney plasma flow by potential volume depletion.”

The investigators noted that similar eGFR declines are observed with initiation of renin-angiotensin-aldosterone-system inhibitors and sodium-glucose cotransporter 2 inhibitors (SGLT2is), indicating drug response and portending kidney protection.

Initial decline in eGFR after starting tolvaptan did not predict the rate of annual growth in total kidney volume, however. This finding suggests that tolvaptan can prevent kidney function decline even if it does not meaningfully slow kidney cyst growth.

Unlike other predictors of tolvaptan’s efficacy, decline in eGFR early after tolvaptan administration can be easily measured in routine clinical practice, Dr Tanaka’s team pointed out.

Most patients had a baseline creatinine clearance of at least 60 mL/min (eGFR of more than 45 mL/min/1.73m2), so these findings may not apply to patients with more advanced kidney disease.

A separate team of investigators followed 55 patients with ADPKD continuously treated with tolvaptan for 6 years to find predictors of response. Higher body mass index (BMI) at baseline was significantly associated with less improvement in annual eGFR rate of change, Shigeo Horie, MD, PhD, of Juntendo University in Tokyo, Japan, and colleagues reported in the International Journal of Molecular Science. Family history was significantly associated with more improvement.

Tolvaptan caused diuresis prompting some patients to consume excessive fluids. Dr Horie’s team suggested that clinicians monitor patients with long-term tolvaptan use for hyponatremia.

Disclosure: The research by Toshiki Tanaka, PhD, and colleagues was supported by Otsuka Pharmaceutical. Please see the original reference for a full list of disclosures.

References:

Mochizuki T, Matsukawa M, Tanaka T, Jiang H. Initial eGFR changes predict response to tolvaptan in ADPKD. Kidney360. Published online February 28, 2024. doi:10.34067/KID.0000000000000404

Yamazaki M, Kawano H, Miyoshi M, et al. Long-term effects of tolvaptan in autosomal dominant polycystic kidney disease: predictors of treatment response and safety over 6 years of continuous therapy. Int J Mol Sci. 2024 Feb 8;25(4):2088. doi:10.3390/ijms25042088