Nephrosclerosis in young patients with malignant hypertension.

BACKGROUND: Nephrosclerosis is one of the histopathological consequences of severe or malignant hypertension (MH), some of the pathophysiology of which has been extrapolated from essential polygenetic arterial hypertension. Despite our recent description of unsuspected ciliopathies with MH, causes of MH in young patients with severe renal impairment are poorly understood. METHODS: To refine and better describe the MH phenotype, we studied clinical and prognostic factors in young patients receiving a kidney biopsy following their first episode of MH. Patients were identified retrospectively and prospectively from eight centres over a 35-year period (1985-2020). Keywords were used to retrospectively enrol patients irrespective of lesions found on renal biopsy. RESULTS: A total of 114 patients were included, 77 (67%) of whom were men, average age 34 years, 35% Caucasian and 34% African origin. An isolated clinical diagnosis of severe nephrosclerosis was suggested in only 52% of cases, with 24% primary glomerulopathies. Only 7% of patients had normal renal function at diagnosis, 25% required emergency dialysis and 21% were eventually transplanted. Mortality was 1% at the last follow-up. Independent prognostic factors significantly associated with renal prognosis (6-month dialysis) and predictive of end-stage renal disease were serum creatinine on admission {odds ratio [OR] 1.56 [95% confidence interval (CI) 1.34-1.96], P < .001} and renal fibrosis >30% [OR 10.70 (95% CI 1.53-112.03), P = .03]. Astonishingly, the presence of any thrombotic microangiopathy lesion on renal biopsy was an independent, protective factor [OR 0.14 (95% CI 0.02-0.60), P = .01]. The histopathological hallmark of nephrosclerosis was found alone in only 52% of study patients, regardless of ethnicity. CONCLUSIONS: This suggests that kidney biopsy might be beneficial in young patients with MH.

Thrombotic microangiopathy in patients with malignant hypertension.

BACKGROUND: Thrombotic microangiopathy (TMA) is a complication of malignant hypertension (mHTN) attributed to high blood pressure (BP). However, no studies have investigated in patients with mHTN of different aetiologies whether the presence of TMA is associated with specific causes of mHTN. METHODS: We investigated the presence of TMA (microangiopathic haemolytic anaemia and thrombocytopenia) in a large and well-characterized cohort of 199 patients with mHTN of different aetiologies [primary HTN 44%, glomerular diseases 16.6%, primary atypical haemolytic uraemic syndrome (aHUS) 13.1%, renovascular HTN 9.5%, drug-related HTN 7%, systemic diseases 5.5%, endocrine diseases 4.5%]. Outcomes of the study were kidney recovery and kidney failure. RESULTS: Patients with TMA [40 cases (20.1%)] were younger, were more likely female and had lower BP levels and worse kidney function at presentation. Their underlying diseases were primary aHUS (60%), drug-related mHTN (15%), glomerular diseases [all of them immunoglobulin A nephropathy (IgAN); 10%], systemic diseases (10%) and primary HTN (5%). The presence of TMA was 92.3% in primary aHUS, 42.9% in drug-related HTN, 36.4% in systemic diseases, 12.1% in glomerular diseases and 2.3% in primary HTN. No patient with renovascular HTN or mHTN caused by endocrine diseases developed TMA, despite BP levels as high as patients with TMA. A higher proportion of TMA patients developed kidney failure as compared with patients without TMA (56.4% versus 38.9%, respectively). CONCLUSIONS: The presence of TMA in patients with mHTN should guide the diagnosis towards primary aHUS, drug-related mHTN, some systemic diseases and IgAN, while it is exceptional in other causes of mHTN.

Unilateral hypertensive choroidopathy as a sole manifestation in malignant hypertension: optical coherence tomography angiography findings-case report.

BACKGROUND: We present a case of hypertensive choroidopathy due to malignant hypertension with exudative retinal detachment as a sole finding. We use OCT- angiography for initial diagnosis and report findings from extensive follow up. CASE PRESENTATION: A 51-year-old female with no past medical history, presented to our clinic with painless loss of vision in her left eye. Fundus examination revealed only exudative retinal detachment in her left eye that was confirmed with Optical Coherence Tomography. Fluorescein angiography showed hyperfluorescent spots with leakage in late phases. OCTA manifested a focal dark area in the choriocapillaris slab corresponding to flow signal voids, signifying regions of non-perfusion. Her blood pressure was 220/120 mmHG. Complete blood work -up failed to reveal any other possible etiology. During follow-up period of 9 months blood pressure normalized, patient regained visual function and choriocapillaris perfusion was completely restored. DISCUSSIONS AND CONCLUSIONS: Hypertensive choroidopathy with exudative retinal detachment can be the only sign of malignant hypertension and no pre-existing history of a systemic disease is required in order to become apparent. OCTA reveals areas of non-perfusion at choriocapillaris level, proving that it is an essential tool in the diagnosis and follow up of patients with hypertensive choroidopathy. Finally, we propose that early diagnosis prevents permanent damage of the RPE and leads to complete choroidal remodeling and better visual outcomes.

Pheochromocytoma manifesting as cortical blindness secondary to PRES with associated TMA: a case report and literature review.

BACKGROUND: Pheochromocytomas are neoplasms originating from neuroectodermal chromaffin cells leading to excess catecholamine production. They are notorious for causing a triad of headaches, palpitations, and sweats. Though the Menard triad is one to be vigilant of, symptomatic presentation can vary immensely, hence the tumor earning the label "the great masquerader." CASE PRESENTATION: We report a case of pheochromocytoma initially presenting with cortical blindness secondary to posterior reversible encephalopathy syndrome and thrombotic microangiopathy from malignant hypertension. Our patient was seen in our facility less than a week prior to this manifestation and discharged after an unremarkable coronary ischemia work-up. In the outpatient setting, she had been prescribed multiple anti-hypertensives with remarkably elevated blood pressure throughout her hospitalization history. CONCLUSION: Pheochromocytoma presenting with malignant hypertension and hypertensive encephalopathy should be expected if left untreated; nonetheless, the precipitation of cortical blindness is rare in the literature. This case contributes an additional vignette to the growing literature revolving adrenal tumors and their symptomatic presentation along with complex management. It also serves to promote increased diagnostic suspicion among clinicians upon evaluating patients with refractory hypertension.

Intrarenal alterations of the angiotensin-converting enzyme type 2/angiotensin 1-7 complex of the renin-angiotensin system do not alter the course of malignant hypertension in Cyp1a1-Ren-2 transgenic rats.

The role of the intrarenal renin-angiotensin system (RAS) in the pathophysiology of malignant hypertension is not fully understood. Accumulating evidence indicates that the recently discovered vasodilator axis of the RAS, angiotensin-converting enzyme (ACE) type 2 (ACE2)/angiotensin 1-7 (ANG 1-7), constitutes an endogenous system counterbalancing the hypertensiogenic axis, ACE/angiotensin II (ANG II)/AT1 receptor. This study aimed to evaluate the role of the intrarenal vasodilator RAS axis in the pathophysiology of ANG II-dependent malignant hypertension in Cyp1a1-Ren-2 transgenic rats. ANG II-dependent malignant hypertension was induced by 13 days' dietary administration of indole-3-carbinol (I3C), a natural xenobiotic that activates the mouse renin gene in Cyp1a1-Ren-2 transgenic rats. It was hypothesized that pharmacologically-induced inhibition of the ACE2/ANG 1-7 complex should aggravate, and activation of this axis should attenuate, the course of ANG II-dependent malignant hypertension. Blood pressure (BP) was monitored by radiotelemetry. ACE2 inhibitor (DX 600, 0.2 µg/day) and ACE2 activator (DIZE, 1 mg/day) were administrated via osmotic minipumps. Even though ACE2 inhibitor significantly decreased and ACE2 activator increased intrarenal ANG 1-7 concentrations, the course of BP, as well as of albuminuria, cardiac hypertrophy and renal glomerular damage, were not altered. It was shown that intrarenal alterations in the ACE2/ANG 1-7 complex did not significantly modify the course of malignant hypertension in I3C-induced Cyp1a1-Ren-2 transgenic rats. Thus, in our experimental setting alterations of this intrarenal vasodilator complex of the RAS do not significantly modify the form of malignant hypertension that clearly depends on the inappropriately increased activity of the ACE/ANG II/AT1 receptor axis.

A case report of malignant hypertension in a young woman.

BACKGROUND: Malignant hypertension is a condition characterized by severe hypertension and multi-organ ischemic complications. Albeit mortality and renal survival have improved with antihypertensive therapy, progression to end-stage renal disease remains a significant cause of morbidity and mortality. The underlying cause of malignant hypertension, which can be primary or secondary hypertension, is often difficult to identify and this can substantially affect the treatment outcomes, as we report here. CASE PRESENTATION: A 33-year-old woman presented with severe hypertension and acute renal failure. Initial evaluation demonstrated hyperreninemia with hyperaldosteronism and a possible renal artery stenosis at the contrast-enhanced CT scan. Although this data suggested the presence of a secondary form of hypertension, further exams excluded our first diagnosis of renal artery stenosis. Consequently, the patient did not undergo renal angiography (and the contrast media infusion associated with it), but she continued to be medically treated to achieve a tight blood pressure control. Our conservative approach was successful to induce renal function recovery over 2 years of follow-up. CONCLUSION: This case highlights the difficulty in differentiating between primary and secondary forms of malignant hypertension, particularly when the patient presents with acute renal failure. Clinicians should consider renal artery ultrasound as a first level diagnostic technique, given that the presentation of primary malignant hypertension can often mimic a renal artery stenosis. Secondly, adequate control of blood pressure is essential for kidney function recovery, although this may require a long time.

Catastrophic APS in the context of other thrombotic microangiopathies.

The catastrophic antiphospholipid syndrome (CAPS) is a rare disease that affects 1 % of cases with antiphospholipid syndrome (APS). CAPS can mimic or overlap with different thrombotic diseases; many patients present with a microthrombotic storm or thrombotic microangiopathic hemolytic anemia (TMHA). Thus, the differential diagnosis of CAPS includes thrombotic thrombocytopenic purpura (TTP), typical and atypical hemolytic uremic syndrome (HUS), systemic infections, malignancies, pregnancy-related disorders, malignant hypertension, heparin-induced thrombocytopenia, and drug-induced thrombotic microangiopathies. Antiphospholipid antibody (aPL) positivity has been proposed as the clue in this differential diagnosis; however, aPL can also occur in healthy people and in those with infections or malignancies. Thus, the differential diagnosis of an aPL-positive patient presenting with a microthrombotic storm is broad; the workup should include a special attention to signs of infection and disseminated malignant disease, assessing the funduscopic signs of malignant hypertension, testing ADAMTS13 activity and anti-heparin-platelet factor 4 (HPF4) antibodies, and searching previous exposure to certain drugs. This article aims to review the main diseases included in the differential diagnosis of CAPS in the context of other thrombotic microangiopathies.

Facial nerve palsy in a 3-year-old child with severe hypertension.

We report an interesting case of a child with new-onset malignant hypertension (HTN) associated with facial paralysis. A review of the medical literature on this association and discussion of diagnostic and management aspects are included.

Severe visual loss caused by unrecognized malignant hypertension in a 15-year-old girl.

A 15-year-old girl presented with acute bilateral loss of central visual acuity due to hypertensive retinopathy level IV. She was found to have unrecognized malignant arterial hypertension associated with end-stage renal failure. At the time of diagnosis she also had severe left ventricular hypertrophy (LVH). Hypertension was successfully treated with combined anti-hypertensive therapy, but renal function did not recover. The patient underwent successful kidney transplant 4 months later and over a period of 20 months hypertensive retinopathy and LVH gradually resolved. This report emphasizes the importance of routine measurement of blood pressure and describes the possible consequences of unrecognized arterial hypertension in children. Early diagnosis and appropriate treatment are necessary to avoid development and progression of target organ damage and promote better long-term cardiovascular prognosis.

[Hypertensive urgency and emergency]. / Hypertensive Krise.

European and North-American guidelines for the diagnosis and therapy of arterial hypertension refer to hypertensive crisis as an acute and critical increase of blood pressure>180/120 mmHg. Presence of acute hypertensive target organ damage, such as stroke, myocardial infarction or heart failure, in this situation defines a "hypertensive emergency". In these patients, immediate lowering of blood pressure (about 25% within one to two hours) in an intensive care setting is mandatory to prevent further progression of target organ damage. In contrast to hypertensive emergencies, hypertensive urgencies are characterized by an acute and critical increase in blood pressure without signs or symptoms of acute hypertensive target organ damage. In these patients, blood pressure should be lowered within 24 to 48 hours in order to avoid hypertensive target organ damage. In general, hospitalization is not required, and oral antihypertensive therapy usually is sufficient. However, further and continuing outpatient care has to be ensured.

Posterior reversible encephalopathy syndrome: a neurologic phenomenon in cancer patients.

Posterior reversible encephalopathy syndrome is a well-recognized entity associated with a variety of benign and malignant conditions. This syndrome typically manifests itself with headache, visual loss, and seizures. Radiographic abnormalities consist of white matter edema involving the posterior parietal and occipital lobes, manifested as increased T2 and fluid-attenuated inversion recovery signal intensity on magnetic resonance imaging. In the last decade, there has been a reported increase in the incidence of posterior reversible encephalopathy syndrome in cancer patients. The diagnosis can be challenging in this patient population. Early recognition and initiation of appropriate therapy with removal of the causative agent is essential in order to prevent permanent neurologic sequelae.

Renal fibromuscular dysplasia with malignant hypertension cured by balloon angioplasty with stenting.

We presented a 31-year-old female patient with a history of hypertension and severe pulsing headache for about 3 months. The patient had pulsing headaches over the past 3 months with increased very high blood pressure (BP = 220/130 mmHg), sometimes with blurred vision, nausea and vomiting, with no known pathological conditions in her medical history or family background. A digital subtraction angiography confirmed tight stenosis (90%) in the middle segment of the right renal artery. Balloon angioplasty with a stent was the treatment of choice. Blood pressure dropped to normal after treatment.

Malignant Hypertension:A Systemic Cardiovascular Disease: JACC Review Topic of the Week.

Malignant hypertension (MHT) is a hypertensive emergency with excessive blood pressure (BP) elevation and accelerated disease progression. MHT is characterized by acute microvascular damage and autoregulation failure affecting the retina, brain, heart, kidney, and vascular tree. BP must be lowered within hours to mitigate patient risk. Both absolute BP levels and the pace of BP rise determine risk of target-organ damage. Nonadherence to the antihypertensive regimen remains the most common cause for MHT, although antiangiogenic and immunosuppressant therapy can also trigger hypertensive emergencies. Depending on the clinical presentation, parenteral or oral therapy can be used to initiate BP lowering. Evidence-based outcome data are spotty or lacking in MHT. With effective treatment, the prognosis for MHT has improved; however, patients remain at high risk of adverse cardiovascular and kidney outcomes. In this review, we summarize current viewpoints on the epidemiology, pathogenesis, and management of MHT; highlight research gaps; and propose strategies to improve outcomes.

Pulmonary renal syndrome secondary to malignant hypertension.

A man in his early 30s presented with sudden-onset respiratory distress, haemoptysis and reduced urine output. He was in volume overload with a blood pressure recording of 240/180 mm Hg. Pulmonary renal syndrome was suspected and he was initiated on plasmapheresis, followed by steroid pulse therapy. Chest radiography and the presence of fragmented red cells on the peripheral smear were unexplained. These were later explained by hypertensive nephropathy and thrombotic microangiopathy changes on renal biopsy. His respiratory and haematological parameters improved with blood pressure control. Malignant hypertension closely resembles pulmonary renal syndrome, which must be remembered in order to avoid plasmapheresis and high-dose immunosuppressive therapy.

A multi-centre case series of patients with coexistent intracranial hypertension and malignant arterial hypertension.

OBJECTIVE: To describe the clinical characteristics, outcomes, and management of a large cohort of patients with concomitant malignant arterial hypertension and intracranial hypertension. METHODS: Design: Retrospective case series. SUBJECTS: Patients aged ≥ 18 years with bilateral optic disc oedema (ODE), malignant arterial hypertension and intracranial hypertension at five academic institutions. Patient demographics, clinical characteristics, diagnostic studies, and management were collected. RESULTS: Nineteen patients (58% female, 63% Black) were included. Median age was 35 years; body mass index (BMI) was 30 kg/m2. Fourteen (74%) patients had pre-existing hypertension. The most common presenting symptom was blurred vision (89%). Median blood pressure (BP) was 220 mmHg systolic (IQR 199-231.5 mmHg) and 130 mmHg diastolic (IQR 116-136 mmHg) mmHg), and median lumbar puncture opening pressure was 36.5 cmH2O. All patients received treatment for arterial hypertension. Seventeen (89%) patients received medical treatment for raised intracranial pressure, while six (30%) patients underwent a surgical intervention. There was significant improvement in ODE, peripapillary retinal nerve fibre layer thickness, and visual field in the worst eye (p < 0.05). Considering the worst eye, 9 (47%) presented with acuity ≥ 20/25, while 5 (26%) presented with ≤ 20/200. Overall, 7 patients maintained ≥ 20/25 acuity or better, 6 demonstrated improvement, and 5 demonstrated worsening. CONCLUSIONS: Papilloedema and malignant arterial hypertension can occur simultaneously with potentially greater risk for severe visual loss. Clinicians should consider a workup for papilloedema among patients with significantly elevated blood pressure and bilateral optic disc oedema.