Patients with autosomal dominant polycystic kidney disease (ADPKD) and lower levels of kidney function may benefit from long-term treatment with tolvaptan, researchers concluded.

In a clinical trial, Wendy E. Boertien, MD, PhD, of University Medical Center Groningen in Groningen, The Netherlands, and colleagues enrolled 29 ADPKD patients who were stratified into 3 groups based on estimated glomerular filtration rate (eGFR) at inclusion: less than 30, 30–60, and greater than 60 mL/min/1.73 m2. For all study analyses, the researchers used measured GFR (mGFR) as determined by 125I-iothalamate clearance. They evaluated changes in total kidney volume (TKV) using magnetic resonance imaging (MRI). Investigators evaluated subjects at baseline and after 3 weeks of treatment with tolvaptan given in increasing dosages, if tolerated (doses of 60, 90, and 120 mg/day in weeks 1, 2, and 3, respectively). Of the 29 patients, 27 completed the study. Subjects had a mean age of 46 years. Their mGFR at baseline ranged from 18 to 148 mL/min/1.73 m2.

Tolvaptan treatment led to a significant increase in urine volume and free-water clearance and a significant decrease in urine osmolality and total kidney volume (TKV), the investigators reported in the American Journal of Kidney Diseases (2015;65:833-841). From baseline to final treatment, mean urine volume rose from 2,584 to 5,930 mL per 24 hours. Mean free-water clearance increased from -0.5 to 3.0 L per 24 hours. Mean urine osmolality decreased from 359 to 139 mOsm/kg, and mean TKV decreased from 2,147 to 2,052 mL. The researchers also observed significant decreases in kidney injury marker excretion.

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Changes in urine volume, free-water clearance, urine osmolality, and TKV were less pronounced in patients with lower baseline mGFRs, the investigators noted. In subjects with lower mGFRs, however, the increase in fractional free-water clearance was greater than in patients with higher GFRs. “This latter finding suggests that tolvaptan also is effective in patients with decreased kidney function,” the authors noted.

Among the study strengths was the inclusion of ADPKD patients with a wide range of GFRs, use of measured GFR at 3 time points with a gold standard method instead of using eGFR, and the use of MRI to measure kidney volume at those same time points. The researchers acknowledged limitations of the study, including the relatively small number of participants and the absence of a control group.

In an accompanying editorial, Bharathi Reddy, MD, and Arlene B. Chapman, MD, of the University of Chicago, called the new findings “informative, hypothesis generating, and exciting and should give impetus for developing predictive models for benefit of tolvaptan therapy and the potential efficacy of tolvaptan use in patients with ADPKD and advanced kidney disease.”