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.

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.

Serum Elabela expression is decreased in hypertensive patients and could be associated with the progression of hypertensive renal damage.

BACKGROUND: Elabela, a recently discovered hormonal peptide containing 32 amino acids, is a ligand for the apelin receptor. It can lower blood pressure and attenuate renal fibrosis. However, the clinicopathological relationship between Elabela level and renal damage caused by benign hypertension (BHT) and malignant hypertension (MHT) has not been elucidated. Therefore, we investigated the clinicopathological correlation between serum Elabela level and renal damage caused by BHT and MHT. METHODS: The participants comprised 50 patients and 25 age-matched healthy adults. The 50 patients were separated into two groups: MHT (n = 25) and BHT groups (n = 25). We analyzed their medical histories, demographics, and clinical examinations, including physical and laboratory tests. RESULTS: The results showed that serum Elabela level decreased gradually with a continuous increase in blood pressure from the healthy control group, BHT, to MHT. Moreover, Elabela levels negatively correlated with BMI (R = - 0.27, P = 0.02), SBP (r = - 0.64, P < 0.01), DBP (r = - 0.58, P < 0.01), uric acid (r = - 0.39, P < 0.01), bun (r = - 0.53, P < 0.01), and Scr (r = - 0.53 P < 0.01) but positively correlated with eGFR (r = 0.54, P < 0.01). Stepwise multivariate linear regression analysis showed that SBP was the variable most related to Elabela (t = - 5.592, P < 0.01). CONCLUSIONS: Serum Elabela levels decreased in patients with hypertension, especially malignant hypertension, and has the potential to be a marker of hypertension-related kidney damage.

Clinical Evaluation and Management of Thrombotic Microangiopathy.

Thrombotic microangiopathy (TMA) refers to a diverse group of diseases that share clinical and histopathologic features. TMA is clinically characterized by microangiopathic hemolytic anemia, consumptive thrombocytopenia, and organ injury that stems from endothelial damage and vascular occlusion. There are several disease states with distinct pathophysiological mechanisms that manifest as TMA. These conditions are associated with significant morbidity and mortality and require urgent recognition and treatment. Thrombotic thrombocytopenic purpura and hemolytic uremic syndrome are traditionally considered to be primary forms of TMA, but TMA more commonly occurs in association with a coexisting condition such as infection, pregnancy, autoimmune disease, or malignant hypertension, among others. Determining the cause of TMA is a diagnostic challenge because of limited availability of disease-specific testing. However, identifying the underlying etiology is imperative as treatment strategies differ. Our understanding of the conditions that cause TMA is evolving. Recent advances have led to improved comprehension of the varying pathogenic mechanisms that drive TMA. Development of targeted therapeutics has resulted in significant improvements in patient outcomes. In this article, we review the pathogenesis and clinical features of the different TMA-causing conditions. We outline a practical approach to diagnosis and management and discuss empiric and disease-specific treatment strategies.

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.

Persistently elevated sFlt-1 and recovery of reduced ADAMTS13 activity in malignant hypertension.

BACKGROUND AND OBJECTIVES: Malignant hypertension (MHT) characterized by acute hypertension with retinopathy or multiorgan damage, is a severe form of hypertensive emergency and associated with target organ involvement and poor kidney outcome. However, the underlying mechanisms are unclear. METHODS: Eighty-four patients with acute severe hypertension from the Nephrology Department and Emergency Department in a single center during January 2016 and December 2017 were prospectively enrolled and divided into MHT ( n  = 48) and non-MHT ( n  = 36) subgroups according to target organ evaluation. Forty healthy controls were recruited. Serum soluble Fms-like tyrosine kinase-1 (sFlt-1) levels and plasma ADAMTS13 (a disintegrin and metalloprotease with thrombospondin type 1 motif, member 13) activity were examined at baseline and 12-month follow-up. Renal endpoints were defined as a significant decrease in the estimated glomerular filtration rate (eGFR) of more than 40% or the occurrence of end-stage renal disease. RESULTS: Serum sFlt-1 levels were persistently elevated in MHT. Baseline serum sFLT-1 levels were correlated with plasma ADAMTS13 activity and markers of target organ damage. Plasma ADAMTS13 activity was reduced in both MHT and non-MHT patients and recovered to the normal range at 12-month follow-up. During an average follow-up time of 53 ±â€Š13 months, the restoration of reduced ADAMTS13 activity was correlated with the improvement of kidney function and independently reduced the risk of renal endpoints. CONCLUSIONS: Abnormal angiogenesis and endothelial damage are involved in the pathophysiology of hypertensive emergency. Evaluation of ADAMTS13 and sFlt-1 may help in the diagnosis and assessment of MHT. Recovery of ADAMTS13 predicts better renal outcome in patients with hypertensive emergencies.

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.

Management of hypertensive crisis in a patient with underlying kidney disease: A case report.

RATIONALE: This case report elucidates the management of a hypertensive crisis in a patient with underlying kidney disease, shedding light on the intricate interplay between these conditions. This unique case contributes valuable insights to the scientific literature. PATIENT CONCERNS: The patient exhibited severe headache, visual disturbances, and chest pain. Clinical evaluation revealed elevated blood pressure and impaired kidney function, emphasizing the importance of monitoring hypertension and renal health in such cases. DIAGNOSES AND INTERVENTIONS: The primary diagnoses included malignant hypertension and underlying kidney disease. Immediate interventions comprised intravenous antihypertensive agents and rigorous hemodynamic monitoring, yielding favorable outcomes. Blood pressure gradually returned to acceptable levels, and renal function improved during treatment. CONCLUSIONS: This case underscores the critical need for timely recognition and management of hypertensive crises in patients with preexisting kidney dysfunction. Simultaneously addressing both conditions is vital for successful outcomes. Healthcare practitioners must remain vigilant in assessing the intricate relationship between hypertension and kidney disease, employing tailored interventions for optimal results. LESSON LEARNED: The primary lesson from this case is the necessity of a comprehensive approach to managing hypertensive crises in individuals with underlying kidney disease. Early intervention and a multidisciplinary strategy are essential to achieve positive clinical outcomes and prevent potential complications.

National Trends in Mortality and Urgent Dialysis after Acute Hypertension in Japan From 2010 Through 2019.

BACKGROUND: Despite increasing incidences of hypertension, recent trends in mortality and urgent dialysis following acute hypertension (AHT) remain undetermined. METHODS: This retrospective observational cohort study evaluated 50 316 hospitalized AHT patients from 2010 to 2019, using an administrative claims database in Japan. We examined trends in incidence, urgent dialysis, mortality, and its risk factors using Poisson regression models. Using International Classification of Disease and Related Health Problems, 10th Revision codes, AHT was categorized into 5 spectrums: malignant hypertension (n=1792), hypertensive emergency (n=17 907), hypertensive urgency (n=1562), hypertensive encephalopathy (n=6593), and hypertensive heart failure (HHF; n=22 462). RESULTS: The median age of the patients was 76 years, and 54.9% were women. The total AHT incidence was 70 cases per 100 000 admission year. The absolute death rate increased from 1.83% (95% CI, 1.40-2.40) to 2.88% ([95% CI, 2.42-3.41]; Cochran-Armitage trend test, P<0.0001). Upward trends were observed in patients aged ≥80, with lean body mass index ≤18.4, and with HHF. Urgent dialysis rates increased from 1.52% (95% CI, 1.12-2.06) to 2.60% (2.17-3.1; Cochran-Armitage trend test; P=0.0071) in 48 235 patients, excluding maintenance dialysis patients. Older age, men, lean body mass, malignant hypertension, HHF, and underlying chronic kidney disease correlated with higher mortality risk; greater hospital volume correlated with lower mortality risk; and malignant hypertension, HHF, diabetes, chronic kidney disease, and scleroderma correlated with a higher risk of urgent dialysis. CONCLUSIONS: Mortality and urgent dialysis rates following AHT have increased. Aging, complex comorbidities, and HHF-type AHT contributed to the rising trend of mortality.

Cortisol-Producing Adrenocortical Carcinoma Presenting with Hypertensive Emergency.

BACKGROUND Hypertensive crisis is a relatively common condition often due to uncontrolled essential hypertension, but also potentially driven by one of many possible secondary etiologies. In this report, we detail a case of new-onset resistant hypertension leading to hypertensive emergency complicated by myocardial infarction and congestive heart failure secondary to underlying cortisol-producing metastatic adrenocortical carcinoma. CASE REPORT A 57-year-old woman with no past medical history presented with generalized weakness and weight gain. Her blood pressure was 239/141 with a pulse of 117. Other vital signs were normal. A physical exam was notable for obesity and lower-extremity edema. Initial serum investigations were notable for leukocytosis, hypokalemia, metabolic alkalosis, and elevated troponin and BNP. An ECG showed anterolateral ST depression and left ventricular hypertrophy. A coronary angiogram revealed no coronary artery disease. Her ejection fraction was 25% by echocardiogram. Further investigation revealed severely elevated serum cortisol levels. CT scans were notable for left adrenal mass with evidence of hepatic, lung, and bone metastasis. A liver biopsy confirmed metastatic adrenocortical carcinoma. The patient was started on antihypertensives and a steroidogenesis inhibitor, with improvement in her blood pressure. She received palliative chemotherapy but later elected to pursue hospice care. CONCLUSIONS This report highlights the potential for underlying cortisol excess and adrenocortical carcinoma as a potential secondary etiology of resistant hypertension and hypertensive crisis. Due to the aggressive nature of this tumor, as demonstrated in this patient, a high index of suspicion and prompt attention are required for patients presenting with these clinical manifestations.

Desarrollo inicial de un fitofármaco derivado del jugo de citrus limón (limón) para el tratamiento de crisis hipertensivas / Development of a phyto-drug derived from citrus lemon juice to treat acute blood pressure elevations

Objetivo: Obtener un fitofármaco a base de extracto seco de limón con estándares de calidad, procesamiento amigable con el medio ambiente y con antecedentes de efectividad y seguridad, evaluando sus efectos en pacientes hipertensos con frecuentes crisis hipertensivas. Métodos y resultados: Se seleccionó la población de limónes de las Regiones Metropolitana y Coquimbo con las concentraciones más altas de ácido ascórbico y flavonoides totales, respectivamente. Se utilizó liofilización para obtener jugo de limón en polvo. Sólo durante el período de estudio, se informó un caso de aumento/ crisis hipertensiva. La formulación con la concentración más alta de ácido ascórbico disminuyó la presión arterial sistólica y diastólica en 16 mmHg desde 10 minutos hasta 60 minutos. Por otro lado, la formulación con mayor concentración de flavonoides disminuyó la presión arterial en 12 a 30 mmHg desde 5 a 60 minutos. Conclusión: Se obtuvo un producto innovador como complemento al manejo de los aumentos de presión arterial. Los principios activos con mayor contribución al mecanismo antihipertensivo del jugo de limón corresponden a compuestos fenólicos, específicamente, flavonoides.

Aim: To obtain a product based on a dry extract of standardized phytodrug lemon with high quality standards, using an environmentally friendly process; to evaluate its effects in hypertensive patients suffering frequent episodes of hypertensive crisis. Methods and Results: Lemons with high concentration of ascorbic acid (Coquimbo Region) or total flavonoids (Metropolitan Region) were selected. Lyophilization was used to obtain juice powder. During the study period only one case of hypertensive crisis was reported. The formula with the highest concentration of ascorbic acid decreased systolic and diastolic blood pressure by 16 mmHg from 10 minutes up to 60 minutes. On the other hand, the formula with the highest concentration of flavonoids decreased blood pressure from 12 to 30 mmHg between 5 and 60 minutes. Conclusion: An novel product to help decrease acutely elevated blood pressure was obtained that can be used as a complement to the management of acute blood pressure rises. The active principles with greater contribution to the antihypertensive mechanism of lemon juice corresponded to phenolic compounds, specifically flavonoids.

Eight-and-a-half syndrome in a patient with hypertensive emergencies.

An 88-year-old white female was admitted with a hypertensive emergency and a sudden onset of abnormal extraocular movements and facial (cranial nerve VII) palsy. This article presents a case of the eight-and-a-half syndrome and discusses its underlying clinicopathology, including a review of the neuroanatomy related to the lesion causing the eight-and-a-half syndrome in this patient.

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.