Js-ng-2: long-term efficacy and safety of aliskiren in four cases with malignant hypertension

Objective: Malignant hypertension (MH) is a form of hypertensive emergency defined by a severe increase in blood pressure (BP) with multiple organ injuries. One possible pathophysiology of MH is an acute activation of the renin-angiotensin system (RAS) driven by the intense stimulation of renin secretion in the juxtaglomerulosa cells. Considering this mechanism, aliskiren, a direct renin inhibitor (DRI), can be a treatment option for MH. However, there is little information on the efficacy and safety of DRI in controlling MH. We herein report four cases with MH that have been successfully controlled by DRI for a long term. Case description: All of the four cases (three male and one female; 34 to 57 years of age) developed advanced retinopathy (III or IV grade on Keith-Wagener classification) and severe hypertension (> 200/120 mmHg) at presentation, meeting the criteria for MH according to the 2020 ISH global hypertension practice guideline. Mean systolic/diastolic BP was 215 ± 5/148 ± 8 mmHg. All developed acute kidney injury, with the mean serum creatinine (sCr) of 4.47 ± 1.13 mg/dl on admission. The ranges of plasma renin activity (PRA) and plasma aldosterone concentration (PAC, as measured by RIA) were 11–33 ng/mL/hr and 371–1370 pg/mL, respectively. Followed by initial treatment with an intra-venous calcium channel blocker, these patients were prescribed aliskiren, starting at 150 mg/day once daily, after confirmation of the elevated PRA levels. In general, aliskiren was well tolerated and BP was successfully controlled in all of the four cases (at discharge, mean systolic/diastolic BP was 123/74 mmHg and mean sCr was 3.84 mg/dL). Patients continued to receive aliskiren (at a dose of 150 or 300 mg/day) after the discharge and mean systolic/diastolic BP and sCr were 131 ± 4/84 ± 3 mmHg and 2.02 ± 0.16 mg/dl at two years of follow-up, respectively. The ranges of PRA and PAC of four cases have fallen to 0.2–0.8 ng/mL/hr and 105–203 pg/mL, respectively. Conclusions: In our cases, severe hypertension and target organ damage were fairly controlled with aliskiren on acute and chronic phases of MH. In all of the four cases, PRA declined with anti-hypertensive treatment and was useful in guiding the doses of medications. Although DRI is not a first-line anti-hypertensive drug class, it may be useful in a certain form of MH with high PRA, which merits further study.