Nephrology Xagena

Autosomal-dominant polycystic kidney disease: albuminuria and Tolvaptan

The TEMPO 3:4 Trial results suggested that Tolvaptan ( Samsca ) had no effect compared with placebo on albuminuria in autosomal-dominant polycystic kidney disease ( ADPKD ) patients. However, the use of categorical albuminuria events may have resulted in a loss of sensitivity to detect changes.

The aim of a study was to investigate the effects of Tolvaptan on albuminuria as a continuous variable.

Post hoc analysis of a 3-year prospective, blinded randomized controlled trial, including 1375 ADPKD patients.
Albuminuria was measured in a spot morning urine sample prior to Tolvaptan dosing and expressed as albumin-to-creatinine ratio ( ACR ).

Baseline median ( interquartile range ) ACR was 3.2 ( 1.7-7.1 ) mg/mmol. Of note, 47.9% of ADPKD patients had normal, 48.7% moderately increased and 3.4% severely increased ACR.
Subjects with higher baseline ACR had higher blood pressure and total kidney volume and lower estimated glomerular filtration rate ( eGFR ).

During follow-up, higher baseline ACR was associated with more rapid eGFR loss ( P less than 0.0001 for trend ), but not with rate of growth in total kidney volume.

During the 3-year trial, ACR rose in placebo- and decreased in Tolvaptan-treated patients ( +0.23 versus -0.40 mg/mmol ). The difference ACR increased over time, reaching a maximum of 24% at month 36 ( P less than 0.001 ).

At that time only a minor difference in blood pressure was observed ( mean arterial pressure -1.9 mmHg for Tolvaptan ).

The decrease in ACR was similar in all subgroups investigated, and remained after withdrawal of study drug.

The beneficial effect of Tolvaptan on total kidney volume growth and eGFR loss was stronger in patients with higher baseline ACR.

In conclusion, in autosomal-dominant polycystic kidney disease, higher baseline albuminuria was associated with more eGFR loss.
Tolvaptan decreased albuminuria compared with placebo, independent of blood pressure.
Treatment efficacy of Tolvaptan on changes in total kidney volume and eGFR was more readily detected in patients with higher albuminuria. ( Xagena )

Gansevoort RT et al, Nephrol Dial Transplant 2015; Epub ahead of print