Fenoldopam Mesylate

Hypertensive crises in children represent critical medical situations characterized by severe hypertension and potential organ damage. Fenoldopam, a dopaminergic medication, offers a viable therapeutic option for managing such clinical scenarios. We aimed to evaluate efficacy and safety of fenoldopam in the management of hypertensive urgencies and emergencies.

This retrospective analysis focused on pediatric patients affected by acute or chronic kidney disease, aged 1 month–18 years, admitted to the Pediatric Nephrology and the Pediatric Intensive Care Unit at University-Hospital of Padua, Italy, who presented with a hypertensive crisis treated with fenoldopam between March 2010 and December 2022.

The study included 74 patients with median age 10 years (interquartile range [IQR] 4–15 years) who received 102 fenoldopam infusions. Seventy-two percent were already receiving antihypertensive treatment before admission. In all cases, fenoldopam was associated with a reduction of blood pressure (BP) after 8 h of treatment, but in 87% of patients reduction of the initial mean arterial pressure (MAP) was higher than 25% of calculated drop pressure. MAP normalized in 26% of cases after 24 h and in 35% after 48 h. Occurrence of hypotension was 7%, while hypokalemia was observed in 13% of cases. Patients who presented a MAP reduction not exceeding 25% of calculated drop pressure received a lower median fenoldopam dose (0.2 mcg/kg/min; IQR 0.1–0.2) compared with patients having a MAP reduction > 25% of calculated drop pressure (0.4 mcg/kg/min; IQR 0.2–0.6; p = 0.002).

Fenoldopam seems effective and safe for the treatment of hypertensive crises in children with kidney disease, at a starting dose of 0.2 mcg/kg/min. Strict BP monitoring is required to identify possible excessive drop pressure in the first hours of infusion.

Altered polycystin-mediated endothelial flow mechanosensitivity contributes to the development of hypertension and cardiovascular complications in patients with autosomal dominant polycystic kidney disease (ADPKD). Stimulation of endothelial type 5 dopamine receptors (DR5) can acutely compensate for the endothelial consequences of polycystin deficiency, but the chronic impact of this approach must be evaluated in ADPKD. Nineteen patients with ADPKD on standard of care therapy were randomized to receive a 2-month treatment with the DR agonist rotigotine using transdermal patches, nine at 2 mg/24hours and ten at 4 mg/24hours or while ten were untreated. Rotigotine at the dose of 4 mg/24hours significantly increased nitric oxide release (nitrite levels from 10±30 to 46±34 nmol/L) and radial artery endothelium-dependent flow-mediated dilatation (from 16.4±6.3 to 22.5±7.3%) in response to hand skin heating. Systemic hemodynamics were not significantly modified but aplanation tonometry showed that rotigotine at 4 mg/24hours reduced aortic augmentation index and pulse pressure without affecting carotid-to femoral pulse wave velocity. Plasma creatinine and urea, urinary cyclic AMP, which contributes to cyst growth in ADPKD and copeptin, a surrogate marker of vasopressin, were not affected by rotigotine. In mice with a specific deletion of polycystin-1 in endothelial cells, chronic infusion of the peripheral DR5 agonist fenoldopam also improved mesenteric artery flow-mediated dilatation and reduced blood pressure. Thus, our study demonstrates that in patients with ADPKD, chronic administration of rotigotine improves conduit artery endothelial function through the restoration of flow-induced nitric oxide release as well as hemodynamics suggesting that endothelial DR5 activation may represent a promising pharmacological approach to prevent cardiovascular complications of ADPKD.