Author(s)

My Helbo Malmberg^1,2*, Frank Holden Mose^1,2, Rikke Lund Sønderbæk‎^1,2, June Anita Ejlersen^2,3, Jens Jørgen Jensen³, Erling Bjerregaard Pedersen^1,2, Jesper Nørgaard Bech^1,2

¹University Clinic in Nephrology and Hypertension, Regional Hospital Jutland West, Holstebro, Denmark.
²University of Aarhus, Aarhus, Denmark.
³Department of Nuclear Medicine, Regional Hospital Jutland West, Holstebro, Denmark.

Background: Previous studies have shown that reduced renal plasma flow (RPF) may play a role in progression of renal disease in autosomal dominant polycystic kidney disease (ADPKD). Tolvaptan, a vasopressin 2 antagonist, reduces growth of total kidney volume and slows the decrease in estimated glomerular filtration rate (eGFR) in ADPKD. The purpose of this randomized, cross-over, double-blind, placebo-controlled study was to investigate if acute tolvaptan treatment increases RPF in ADPKD patients. Methods: Eighteen ADPKD patients (chronic kidney disease stages I-III) were investigated twice (min. 10 days apart) after acute treatment with either tolvaptan 60 mg or placebo. Two hours after treatment RPF and GFR were estimated by Technetium-99m diethylenetriamine penta-acetic acid (99-mTc-DTPA) renography. During the examination day, central and brachial blood pressures (BP) were measured using Mobil-O-Graph^® PWA. We also measured plasma concentrations of vasopressin (p-AVP), renin (PRC), angiotensin II (p-AngII) and aldosterone (p-Aldo), urine excretion of aquaporin 2 (u-AQP2), urine output (OU), urine osmolality (u-Osm) and fractional excretion of sodium (FE_Na). Results: 99-mTc-DTPA renography showed a similar RPF (673 ± 262 ml/min after tolvaptan vs. 650 ± 209 ml/min after placebo, p = 0.571) and GFR (78 ± 26 ml/min after tolvaptan vs. 79 ± 21 ml/min after placebo p = 0.774) after tolvaptan and placebo treatment. P-AVP and UO increased and u-Osm decreased after tolvaptan and remained unchanged during placebo. Systolic BP tended to decrease during renography during tolvaptan. Very small or insignificant changes were seen in PRC, p-AngII and p-Aldo. Conclusions: Acute tolvaptan treatment did not change renal hemodynamics in ADPKD.

Autosomal Dominant Polycystic Kidney Disease, Renal Plasma Flow, Glomerular Filtration Rate, Renography, Brachial Blood Pressure, Central Blood Pressure, Vasopressin, Renin, Angiotensin II, Aldosterone

Malmberg, M. , Mose, F. , Sønderbæk‎, R. , Ejlersen, J. , Jensen, J. , Pedersen, E. and Bech, J. (2019) Acute Effects of Tolvaptan on Renal Hemodynamics in Autosomal Dominant Polycystic Kidney Disease
—A Randomized, Cross-Over, Double Blind, Placebo-Controlled Study of Renal Plasma Flow and Glomerular Filtration Rate. Open Journal of Nephrology, 9, 97-114. doi: 10.4236/ojneph.2019.94011.