Autosomal dominant polycystic kidney disease (ADPKD) is the most frequent monogenic kidney disease. It causes hypertension and progressive renal failure, both strictly linked to oxidative stress (OxSt). Treatment with tolvaptan is a consolidate option which slows renal deterioration rate, although the molecular mechanisms involved are not fully clarified. We evaluated the OxSt state in tolvaptan-treated ADPKD patients, untreated patients and healthy subjects. OxSt was assessed in 9 patients for each group as mononuclear cell protein expression, MYPT-1 phosphorylation state (Western blot) and heme oxygenase (HO-1) (ELISA). p22 phox protein expression was lower in tolvaptan treated ADPKD and controls compared to untreated patients: 0.86 ±0.15 d.u. p=0.015; 0.53 ±0.11, p<0.001; 1.42 ±0.11 respectively. The same was observed for phosphorylated MYPT-1: 0.68 ±0.09, p=0.013 and vs 0.47 ±0.13, p<0.001, 0.96 ±0.28, while HO-1 of untreated patients was significantly lower compared to treated and controls: 5.33 ±3.34 ng/mL, 2.08 ±0.79, p=0.012, 1.97 ±1.22, p=0.012. Tolvaptan-treated ADPKD patients have reduced OxSt, which might contribute to slowing down the loss of renal function.
Keywords: Rho kinase; autosomal dominant polycystic kidney disease; oxidative stress; tolvaptan.
Copyright by Società Italiana di Nefrologia SIN, Rome, Italy.