Case presentation: a severe case of cobalamin c deficiency presenting with nephrotic syndrome, malignant hypertension and hemolytic anemia.

BACKGROUND: The etiology of nephrotic syndrome can vary, with underlying metabolic diseases being a potential factor. Cobalamin C (cblC) defect is an autosomal recessive inborn error of metabolism caused by mutations in the MMACHC gene, resulting in impaired vitamin B12 processing. While cblC defect typically manifests with hematological and neurological symptoms, renal involvement is increasingly recognized but remains rare. CASE PRESENTATION: We describe a 7-month-old male patient presenting with fatigue and edema. His first laboratory findings showed anemia, thrombocytopenia, hypoalbuminemia and proteinuria and further examinations reveals hemolysis in peripheric blood smear. During his follow up respiratory distress due to pleural effusion in the right hemithorax was noticed. And fluid leakage to the third spaces supported nephrotic syndrome diagnosis. The patient's condition deteriorated, leading to intensive care admission due to, hypertensive crisis, and respiratory distress. High total plasma homocysteine and low methionine levels raised suspicion of cobalamin metabolism disorders. Genetic testing confirmed biallelic MMACHC gene mutations, establishing the diagnosis of cblC defect. Treatment with hydroxycobalamin, folic acid, and betaine led to remarkable clinical improvement. DISCUSSION/CONCLUSION: This case underscores the significance of recognizing metabolic disorders like cblC defect in atypical presentations of nephrotic syndrome. Early diagnosis and comprehensive management are vital to prevent irreversible renal damage. While cblC defects are more commonly associated with atypical hemolytic uremic syndrome, this case highlights the importance of considering cobalamin defects in the differential diagnosis of nephrotic syndrome, especially when associated with accompanying findings such as hemolysis. Our case, which has one of the highest homocysteine levels reported in the literature, emphasizes this situation again.

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.

Atypical presentation of malignant hypertension.

A woman in her 30s presented with complaints of sudden onset of defective vision in the right eye for 2 days, with history of headache for a month. On examination, best corrected visual acuity was 20/40 in the right eye and 20/20 in the left eye. Anterior segment examination was normal. Fundus examination of both the eyes showed generalised arteriolar attenuation with diffuse, hyperaemic disc oedema and serous retinal detachment at macula in the right eye. Her blood pressure (BP) was 230/140 mm Hg. Other systemic evaluation was unremarkable. In the review visit, patient's BP reduced to 140/100 mm Hg, and visual acuity in the right eye improved to 20/20. Fundus in the right eye showed resolving disc oedema with macular star formation, and the left eye had developed soft exudates. This seemed to confirm the diagnosis of the disc oedema being caused by hypertension and a highly asymmetrical presentation of hypertensive retinopathy.

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.

Malignant Hypertension and Bilateral Primary Aldosteronism.

Malignant hypertension triggers incremental renin activity, whereas primary aldosteronism suppresses such activity. We encountered a patient with malignant hypertension refractory to multiple anti-hypertensive agents. Repeated neurohormonal assessments, instead of a single one, eventually uncovered trends in an incremental aldosterone concentration, ranging from 221 up to 468 pg/mL, with a decline in the renin activity from 2.3 to <0.2 ng/mL/h. Adrenal venous sampling confirmed bilateral aldosterone secretion. Following the diagnosis of bilateral primary aldosteronism, we initiated a mineralocorticoid receptor antagonist, which improved his blood pressure. Repeated neurohormonal assessments are encouraged to correctly diagnose underlying primary aldosteronism with malignant hypertension.

Management of hypertensive crisis: British and Irish Hypertension Society Position document.

Patients with hypertensive emergencies, malignant hypertension and acute severe hypertension are managed heterogeneously in clinical practice. Initiating anti-hypertensive therapy and setting BP goal in acute settings requires important considerations which differ slightly across various diagnoses and clinical contexts. This position paper by British and Irish Hypertension Society, aims to provide clinicians a framework for diagnosing, evaluating, and managing patients with hypertensive crisis, based on the critical appraisal of available evidence and expert opinion.

Malignant arterial hypertension in a 2-month-old girl: Etiological diagnosis and treatment.

A 2-month-old girl presented with malignant arterial hypertension revealing bilateral renal artery stenosis secondary to neurofibromatosis type 1 (NF1). Life-supporting care was initiated immediately. High-dose peripheral vasodilator therapy induced life-threatening toxicity; vascular surgery was therefore performed. Technical difficulties due to the young age and low body weight of the patient resulted in fatal bleeding. Renovascular disease is an important cause of pediatric hypertension. NF1-associated renovascular hypertension in young pediatric patients is rare, and its highly specialized management is best delivered via a multidisciplinary approach. The long-term prognosis remains poor.

Malignant Hypertension: Current Perspectives and Challenges.

Malignant hypertension is a hypertensive emergency, with rapid disease progression and poor prognosis. Although recognized as a separate entity more than a century ago, significant knowledge gaps remain about its pathogenesis and treatment. This narrative review summarizes current viewpoints, research gaps, and challenges with a view to pooling future efforts at improving treatment and prognosis.

A importância do diagnóstico precoce da hipertensão maligna: Relato de caso / The importance of early diagnosis of malignant hypertension - Case report

A hipertensão maligna é uma síndrome constituída por hipertensão arterial grave, retinopatia com papiledema (com ou sem insuficiência renal) e necrose fibrinóide de arteríolas renais, a qual pode apresentar evolução clínica rapidamente progressiva e fatal.Nela ocorrem lesões vasculares que consistem predominantemente de proliferação miointimal e necrose fibrinóide arteriolar, as quais podem se desenvolver agudamente e comprometer o lúmen dos pequenos vasos. O prognóstico da hipertensão maligna é quase sempre fatal se não for reconhecida ou não for tratada adequadamente, apresentando uma mortalidade de cerca de 80% em dois anos, principalmente em decorrência da evolução para síndrome de insuficiência cardíaca e insuficiência renal terminal. (AU).

Malignant hypertension is a syndrome consisting of severe arterial hypertension, retinopathy with papilledema (with or without renal failure) and fibrinoid necrosis of renal arterioles, which may present a rapidly progressive and fatal clinical course. In this pathology may occur vascular lesions that consist mainly of myointimal proliferation and arteriolar fibrinoid necrosis, which can develop acutely and compromise the light from the small blood vessels. The prognosis of malignant hypertension is almost always fatal if it is not recognized or not adequately treated, with a mortality rate of about 80% in 2 years, mainly as a result of progression into heart failure syndrome and end-stage renal failure syndrome (AU).

[A study on malignant arterial hypertension: about 168 cases at the unit of nephrology-internal medecine of the University Hospital Center, Treichville, Abidjan]. / Hypertension artérielle maligne en milieu néphrologique à Abidjan: à propos de 168 cas colligés au Service de Néphrologie-Médecine Interne du Centre Hospitalier Universitaire de Treichville.

INTRODUCTION: malignant arterial hypertension (MAH) is a nosologic disorder which has not been described in Nephrology. The purpose of this study was to describe the profile of patients with MAH in the Division of Nephrology and to identify prognostic factors. METHODS: we conducted a retrospective, descriptive and analytical study from January 2013 to December 2018 in the Unit of Nephrology of the University Hospital Center in Treichville. The diagnosis of MAH was retained in patients with diastolic blood pressure (DBP) ≥ 130 mmHg, Keith Wegener grade III/IV hypertensive retinopathy, one or multiple visceral, cardiac and/or brain and/or renal diseases. RESULTS: we collected data from 168 patients. The average age of patients was 41.10 ± 14.86 years, with male predominance (sex ratio 1.54). Cardiovascular risk factors were AH (79.20%), alcohol (32.10%), tobacco (19.60%), chronic kidney disease (15.30%) and diabetes (11.30%). They were admitted with dyspnea (39.29%), hypertensive crisis (26.16%), consciousness disorders (10.12%). Clinical examination showed anemia (82.10%), lower limb edema (63.10%), acute pulmonary edema (37.50%). Arterial hypertension resulted in renal failure (95,9%), left ventricular hypertrophy (92.81%), stroke (16,67%), and cardiac and renal involvement (85%). Renal failure was chronic in 78% of cases. The causes of MAH were essential AH (56,8%), chronic glomerulonephritis (29.8%), and diabetes (6%). Outcome was favorable in 66,7% of cases and overall mortality rate was 25.6%. In multivariate analysis uremia ≥ 2g/l [OR=5,07; 95%CI = 2,39-10.75; p = 0.0001], hperkalaemia [OR = 3.50; 95% CI = 1.70 - 7.19; p = 0.001], hyponatremia [OR = 2.90; 95% CI= 1.40 - 6.03; p = 0.004], haemoglobin level < 12g/dl [OR=5,91; 95% CI=1,34-26,00; p=0,019] and end-stage renal disease [OR = 6.06; 95% CI = 2.04 - 18.18; p = 0.001] were factors associated with the occurrence of death. CONCLUSION: MAH is a consequence of poorly treated or untreated AH. It mainly affects young adults with multivisceral complications. In our Hospital, these were dominated by end-stage chronic renal disease. Hence the importance of early diagnosis and adequate management in patients with AH.

Retinal Arteriolar Occlusions and Exudative Retinal Detachments in Malignant Hypertension: More Than Meets the Eye.

BACKGROUND: Malignant hypertension is macrovascular and microvascular endothelial injury responsible for multiple organ damage. Considering the anatomical and functional homologies between the posterior pole of the eye and the kidney, ophthalmological explorations may inform clinicians on the mechanisms underpinning concurrent kidney injury in this condition. More specifically, we investigated whether the wall-to-lumen ratio (WLR) of retinal arterioles measured by adaptive optics ophthalmoscopy could be correlated to WLR of kidney arterioles as determined by pathology. We sought to estimate the incidence of retinal arteriole occlusion a supposedly uncommon complication of malignant hypertension. METHODS: All patients hospitalized in our renal Intensive Care Unit for malignant hypertension between 2016 and 2019 were referred to ophthalmological examinations. RESULTS: Twenty-seven patients were included. Median retinal WLR was 0.39 [0.31-0.47] and was correlated with initial systolic (r = 0.56, P = 0.003) and mean blood pressure (r = 0.46, P = 0.02) upon admission. The retinal WLR was not correlated to renal pathological findings, as assessed by juxtaglomerular WLR (r = 0.38, P = 0.2), ratio of glomerulosclerosis (r = -0.39, P = 0.2), or tubulointerstitial fibrosis (r = -0.45, P = 0.08). Retinal WLR was not associated with neurological or cardiovascular end-organ damage. Branch retinal artery occlusion was detected in 18.5% of patients and exudative retinal detachment (ERD) in 29.6% of patients, without any significant correlation with canonical signs of retinal hypertension including optic disc swelling. CONCLUSIONS: In the setting of malignant hypertension, we failed to demonstrate a significant relationship between WLR and other meaningful end-organ injuries. However, branch retinal artery occlusion and ERD may have been hitherto underestimated.