Safety of RotigotiNe in Patients With Autosomal Dominant Polycystic Kidney Disease

Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary kidney disease and is caused by mutations in the PKD1 or PKD2 genes, which encode polycystins 1 and 2. Patients develop renal cysts associated with a progressive decline in kidney function, ultimately leading to end-stage renal disease in approximately one third of cases. ADPKD is also characterized by early-onset hypertension and cardiovascular complications, notably intracranial aneurysms. This phenotype is related to abnormal polycystin function in the primary cilia of renal epithelial and vascular endothelial cells, resulting in impaired mechanotransduction of shear stress induced by urinary and blood flow and subsequent alterations in multiple cellular functions. Experimental studies have suggested that stimulation of dopamine receptor type 5 (DR5) may restore endothelial mechanosensitivity. This hypothesis is supported by our preliminary results showing that local administration of dopamine improves endothelial function in patients with ADPKD through restoration of nitric oxide (NO) release in response to increased blood flow. Consistent with these findings, the IMPROVE-PKD study recently demonstrated similar beneficial effects on endothelial function and hemodynamics using rotigotine, a dopamine agonist administered via transdermal patches for two months at a low dose (4 mg/24 h). Dopaminergic stimulation may also prevent renal abnormalities related to polycystin deficiency. We therefo…

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Dominique Guerrot, Pr  ·  02 32 88 54 46  ·  Dominique.Guerrot@chu-rouen.fr

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