Successful treatment of severe renal failure caused by malignant hypertension using a combination of renin–angiotensin–aldosterone system inhibitors: a case report

Figures

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  Fig. 1. Time course of the patient’s clinical illness. Changes in systolic blood pressure (SBP, blue line), body weight (BW, red line), serum creatinine (Cr, orange line), and the urine protein/creatinine ratio (uPCR, blue bars). PAC, plasma aldosterone concentration; PRA, plasma renin activity

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  Fig. 2. Findings on renal pathological examination. Light microscopic views of small renal arterial occlusive (onion skin-like) lesions (arrows) under periodic acid-Schiff A, periodic acid-methenamine silver B, and Masson’s trichrome C staining. Masson’s trichrome staining also showed atrophic changes in the tubules and fibrosis of the interstitium D. Scale bars: 50 µm

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  Fig. 3. Plasma renin activity in patients with malignant hypertension and those with severe hypertension. Data for plasma renin activity were obtained from previous reports [1, 11, 13–15]. The present case is shown by a closed red triangle

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  Fig. 4. Mineralocorticoid receptor expression in this case. Immunofluorescence revealed that the mineralocorticoid receptor (MR) was localized to the nucleus along the distal nephron in our patient A. Anti-MR antibody was validated in MR−/− mice showing that the nuclear MR signal along the distal nephron was clearly reduced in comparison with control mice, as previously reported [23] B. The anti-MR 6G1 antibody (#MABS496; EMD Millipore Corp, Billerica, MA) was used. Scale bars: 50 µm. PCT, proximal convoluted tubule

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  Fig. 5. A combination of renin–angiotensin–aldosterone system inhibitors could potentially break the vicious cycle in malignant hypertension. Top, the vicious cycle of malignant hypertension (MHT) is caused by overactivation of the renin–angiotensin–aldosterone system (RAAS) [12]. Bottom, both the angiotensin II type 1 receptor (AT1R) and mineralocorticoid receptor (MR) are activated by the RAAS in the acute phase of MHT. Monotherapy with an angiotensin receptor blocker (ARB) or an angiotensin-converting enzyme inhibitor (ACEI) can induce compensatory activation of renin, which may make it difficult to achieve adequate suppression of the AT1R and MR. A direct renin inhibitor (DRI) can effectively suppress the AT1R by inhibiting compensatory activation of renin, while a mineralocorticoid receptor antagonist can decrease blood pressure by inhibiting aldosterone-dependent and independent activation of the MR. Combined therapy can adequately suppress the RAAS and break the vicious cycle of MHT