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.

Thrombotic microangiopathy due to malignant hypertension complicated with late-onset bleeding after renal biopsy.

A 47-year-old man presented at a local ophthalmological hospital with blurred vision. He had been diagnosed with hypertensive retinopathy and renal failure and was referred to our hospital for treatment. A renal biopsy was done to evaluate pathology of high proteinuria, hematuria, and rapidly progressive glomerulonephritis. Blood pressure remained high despite antihypertensive therapy; anemia and thrombocytopenia gradually progressed. Thrombotic microangiopathy (TMA) was suspected based on red blood cell fragmentation due to hemolytic anemia, thrombocytopenia, and renal failure. However, plasma exchange resolved neither thrombocytopenia nor renal failure, and anemia gradually progressed. Backache suddenly developed 13 days later, and CT findings indicated a retroperitoneal hematoma secondary to bleeding from the kidney. Selective renal artery embolization via angiography stopped the bleeding, but the patient went into hemorrhagic shock. Pathological findings on renal biopsy were identical to those in malignant hypertension, namely an edematous membrane lining, thickened arterioles, and stenosis. We diagnosed thrombotic microangiopathy due to malignant hypertension, without decrease in activities of ADAMTS13 (a disintegrin and metalloprotease with thrombospondin type 1 motif) or its antibodies. Renal failure did not improve, and continuous hemodiafiltration was needed. This procedure stabilized blood pressure and improved the TMA.

Scleroderma renal crisis as an initial presentation of systemic sclerosis: a case report and review of the literature.

Scleroderma renal crisis (SRC) is a life-threatening complication of systemic sclerosis (SSc) that is characterised by new-onset malignant hypertension and progressive acute renal failure, often with associated microangiopathic haemolytic anaemia and thrombocytopenia. SRC was at one time almost uniformly fatal, with death often occurring within a few weeks. With the development of angiotensin-converting-enzyme inhibitors (ACE-I), survival has improved dramatically, but death rates still remain unacceptably high. About 20% of SRC cases occur prior to making a diagnosis of SSc and, in some cases, there is no evidence of skin sclerosis at the time that SRC develops. In this report, we present a case in which a patient developed SRC prior to being diagnosed with scleroderma. Additionally, we review the pathogenesis, presenting signs and symptoms, management and prognosis of SRC.

[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.

[Surgical treatment of a patient with occlusion of the main trunk of the renal artery of the solitary kidney].

Presented herein is a clinical case report of successful stagewise surgical treatment of a patient with atherosclerotic occlusion of the main trunk of the renal artery of the single kidney. Clinically, the patient had signs of ischaemic renal disease in the form of pronounced azotemia being characteristic of the terminal stage of renal insufficiency, as well as malignant arterial hypertension. Besides, the patient had previously endured ischaemic stroke in the vertebrobaslar basin. The patient was subjected to stagewise surgical intervention, i.e., stenting of the upper-pole renal artery followed by open operation--prosthetic repair of the left renal artery with a synthetic prosthesis. Three months thereafter, the patient underwent carotid endarterectomy and operation of transposition of the subclavian artery. The postoperative period turned out uneventful. Currently, no progression of azotemia is observed, neither are there any indications for carrying out restorative therapy of the renal function.

Adult-onset eculizumab-resistant hemolytic uremic syndrome associated with cobalamin C deficiency.

A 20-year-old man was hospitalized for malignant hypertension, mechanical hemolysis, and kidney failure. Kidney biopsy confirmed glomerular and arteriolar thrombotic microangiopathy. Etiologic analyses, which included ADAMTS13 activity, stool culture, complement factor proteins (C3, C4, factor H, factor I, and MCP [membrane cofactor protein]), anti-factor H antibodies, HIV (human immunodeficiency virus) serology, and antinuclear and antiphospholipid antibodies, returned normal results. Malignant hypertension was diagnosed. Ten months later, we observed a relapse of acute kidney injury and mechanical hemolysis. Considering a diagnosis of complement dysregulation-related atypical hemolytic uremic syndrome (HUS), we began treatment with eculizumab. Despite the efficient complement blockade, the patient's kidney function continued to decline. We performed additional analyses and found that the patient's homocysteine levels were dramatically increased, with no vitamin B12 (cobalamin) or folate deficiencies. We observed very low plasma methionine levels associated with methylmalonic aciduria, which suggested cobalamin C disease. We stopped the eculizumab infusions and initiated specific treatment, which resulted in complete cessation of hemolysis. MMACHC (methylmalonic aciduria and homocystinuria type C protein) sequencing revealed compound heterozygosity for 2 causative mutations. To our knowledge, this is the first report of adult-onset cobalamin C-related HUS. Considering the wide availability and low cost of the homocysteine assay, we suggest that it be included in the diagnostic algorithm for adult patients who present with HUS.

Use of a pulsatile perfusion pump for renal autotransplantation in a patient undergoing thoracoabdominal bypass for malignant hypertension secondary to Takayasu arteritis.

Aortorenal bypass is an effective and durable therapy for autoimmune-induced renovascular hypertension. However, when technical and patient factors preclude this option, renal autotransplantation can be a viable alternative. We present a 32-year-old woman who underwent aortobi-iliac bypass with left renal autotransplantation for malignant hypertension secondary to Takayasu arteritis. This is the first description of using machine preservation with a continuous pulsatile perfusion pump to maintain renal preservation before reimplantation. Our method proved safe to the patient and allowed for protection of the organ from prolonged warm ischemia and intraoperative hypoperfusion during a complex reconstruction.

[Treatment of hypertensive emergencies and malignant hypertension: the possibility of using urapidil].

The review considers the possibility of using parenteral urapidil for treatment of hypertensive crises. The drug having a dual mechanism of action and properties of combining α-blocker and a centrally acting drug, has a high efficiency, comparable to that of the other groups of drugs, and a good tolerability. In a review of the features of the mechanism of action of the drug, its pharmacokinetics and pharmacodynamics. The data key studies demonstrating the features of the antihypertensive action of parenteral urapidil. Detailed proof of the effectiveness of urapidil in complicated and uncomplicated hypertensive crisis, the treatment of perioperative hypertension, treatment of hypertension in patients with pheochromocytoma and in pregnant women with preeclampsia.

Mesangial cells are responsible for orchestrating the renal podocytes injury in the context of malignant hypertension.

AIM: Two populations of renal cells fully possess functional contractile cell apparatus: mesangial cells and podocytes. Previous studies demonstrated that in the context of malignant hypertension overproduction of Angiotensin-II by the contracting mesangial cells aggravated hypercellularity and apoptosis of adjacent cell populations. The role of podocytes in pathogenesis of malignant hypertension is unclear. We investigated responsiveness of normal vs. hyperglycaemic podocytes to pressure in a model of malignant hypertension. METHODS: Rat renal podocytes and mesangial cells were subjected to high hydrostatic pressure, using an in vitro model of malignant hypertension. Part of them was pre-exposed to hyperglycaemic medium. Alternatively, the cells were cultured in conditioned medium collected from mesangial cells pre-exposed to pressure. RESULTS: Angiotensin-II was significantly increased in normoglycaemic mesangial cells subjected to pressure, triggering enhanced proliferation and apoptosis. No augmented Angiotensin-II, proliferation or apoptosis were evident in pressure-exposed normoglycaemic podocytes. In hyperglycaemic mesangial cells, but not podocytes, basal Angiotensin-II and apoptosis were augmented, along with abrogated proliferation. Challenge with exogenous Angiotensin-II or Angiotensin-II-containing conditioned medium, induced apoptosis both in podocytes and mesangial cells. CONCLUSIONS: 1. Unlike mesangial cells, podocytes do not respond to high pressure or hyperglycaemia per se. Resultantly, neither high pressure nor hyperglycaemia, trigger apoptosis of podocytes in vitro. However, surplus of Angiotensin-II, amply produced in vivo by the adjacent mesangial cells, would seem to be sufficient for initiating apoptosis of both mesangial cells and podocytes. 2. Hyperglycaemia abrogates cell replication. Resultantly, in diabetic patients regeneration of renal tissue damaged by the incidence of malignant hypertension may become compromised or completely lost.

When the chimney is blocked: malignant renovascular hypertension after endovascular repair of abdominal aortic aneurysm.

BACKGROUND: The Chimney graft (CG) procedure is one of the novel modification techniques of the endovascular aneurysm repair (EVAR) surgery to treat suprarenal and juxtarenal abdominal aortic aneurysms. Other indications for the use of CG placement include thoracic and thoracoabdominal aneurysms with supraortic branches orifice involvement and cases of common iliac artery aneurysms with or without internal iliac artery involvement. The technique is used in patients who due to aortic-neck morphology and lack of adequate fixation and/or sealing zones are not eligible for standard EVAR. In this procedure, a parallel stent-graft is placed adjacent to the main body of the aortic endograft to maintain blood supply to renovisceral or supraortic branches, once the body of the aortic stent-graft is deployed. Symptomatic occlusions of the CG with novel renovascular hypertension were not described until now. CASE PRESENTATION: A-64-year-old male patient, presented with new-onset malignant hypertension, 13 months after an EVAR operation with CG placement to the left renal artery. The patient was on preventive clopidrogel therapy, which was withheld temporarily for several days, one month before presentation. Imaging studies revealed a novel form of iatrogenic renovascular hypertension, caused by occlusion of the CG. Any attempt to recanalize the covered stent or revascularize the left kidney was rejected and conservative treatment was chosen. Seven months after presentation, blood pressure was within normal ranges with little need for antihypertensive therapy. CONCLUSIONS: Physicians should be aware that the novel emerging techniques of EVAR to overcome the limitations of the aortic-neck anatomy may still adversely influence the renal outcome with potential development of new-onset hypertension.

[Hypertensive crisis: pathogenesis, clinic, treatment].

Contemporary data on mechanisms of development, types, and clinical picture of hypertensive crisis (HC) are presented. Algorithms of rational therapy of uncomplicated and complicated HC are considered. Appropriateness of the use in HC of antihypertensive drugs with multifactorial action is stressed. These drugs include urapidil - an antihypertensive agent with complex mechanism of action. Blocking mainly the postsynaptic 1-adrenoreceptors urapidil attenuates vasoconstrictor effect of catecholamines and decreases total peripheral resistance. Stimulation of 5HT1-receptors of medullary vasculomotor center promotes lowering of elevated vascular tone and prevents development of reflex tachycardia.

[Management of resistant hypertension]. / Prise en charge d'une hypertension artérielle résistante.

High blood pressure is one of the leading factors influencing the cardiovascular risk. Despite current knowledge on the management of hypertension and the numerous antihypertensive drugs available, hypertension remains insufficiently controlled and part of these "uncontrolled" patients meet the definition of resistant hypertension. Resistant hypertension is defined by the failure of lowering blood pressure values to blood pressure target (office blood pressure < 140/90 or 130/80 mmHg in patients with diabetes or chronic kidney disease) despite appropriate treatment with optimal doses of three antihypertensive drugs from three different classes, one of which is a diuretic. Pseudoresistance should be excluded by using 24h ambulatory blood pressure or home blood pressure. The management of resistant hypertension includes the screening of secondary forms of hypertension and the identification of life style factors such as obesity, excessive alcohol and dietary sodium intake, volume overload, drug-induced hypertension. The treatment associates lifestyle changes, discontinuation of interfering substances, association of antihypertensive drugs on top of the initial triple therapy (including diuretic, blockers of the renin-angiotensin system and calcium channel blockers) ie aldosterone antagonists as fourth line treatment. New device-based approaches aiming to decrease the sympathetic tone including renal denervation and baroreceptor stimulation are under development.

Systemic sclerosis with thrombotic thrombocytopenia purpura and malignant hypertension.

Thrombotic thrombocytopenia purpura (TTP) is a rare clinical syndrome characterized by microangiopathic hemolytic anemia (MAHA), thrombocytopenia, neurologic symptoms, acute renal impairment, and fever. It has been seldom reported in systemic sclerosis (SSc). Systemic renal crisis is an infrequent complication of SSc, and is characterized by new onset malignant hypertension, rapidly progressive oliguric renal failure, and MAHA. In this study, we present a case of SSc of 1 month duration, with TTP accompanied by new onset malignant hypertension. The patient responded to plasmapheresis but still died of septic shock.

Malignant hypertension due to a large reninoma: a case report.

A thirty-year-old-man was admitted due to visual loss from malignant hypertension. Hypokalemia and urinary potassium loss were found. Plasma renin activity (PRA) and aldosterone were investigated and found to be elevated compatible with secondary hyperaldosteronism. A computed tomography of the abdomen showed a 11.7 x 11.3 x 12 cm ill-defined, nonhomogeneous mass at the middle part of right kidney. The preoperative diagnosis was renal cell carcinoma and the patient underwent right radical nephrectomy. Following nephrectomy, plasma PRA and plasma aldosterone levels declined and serum potassium level returned to normal. A reninoma is a rare benign renal neoplasm arising from juxtaglomerular apparatus. The tumor produces an excessive amount of renin resulting in secondary hyperaldosteronism, thereby causing hypertension with hypokalemia. The authors describe a case of reninoma in a young man, who presented with malignant hypertension and the largest reninoma ever reported.

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 secondary to renovascular disease during infancy--an unusual cause of failure to thrive.

An 11-month-old girl presented with a history of failure to thrive, vomiting, polydipsia, polyuria and visual inattention. She was found to have malignant hypertension due to unilateral renal artery stenosis. This was successfully treated with percutaneous transluminal balloon angioplasty. Nearly 10 years following this initial presentation, she remains normotensive on no anti-hypertensive medications.

IgA nephropathy associated with a novel N-terminal mutation in factor H.

Most patients with IgA nephropathy exhibit complement deposition in the glomerular mesangium. Certain cases of IgA nephropathy have been associated with reduced levels of complement factor H. A recent study could not demonstrate mutations at the C-terminal of factor H. We describe a novel heterozygous mutation in factor H, position A48S (nucleotide position 142 G > T, alanine > serine), detected in exon 2 of a 14-year-old girl with IgA nephropathy. The patient exhibited reduced levels of C3 and factor H, the latter suggesting that the mutation affected factor H secretion. The patient developed initial signs and symptoms of glomerulonephritis at the age of 9 years but presented again at the age of 14 years with weight gain, renal failure, nephrotic-range proteinuria and malignant hypertension. Blood tests suggested the development of microangiopathic hemolytic anemia (MAHA) but the renal biopsy was mostly indicative of chronic changes associated with IgA nephropathy as well as vascular changes associated with malignant hypertension. Immunofluorescence exhibited deposits of IgA, C3, and IgM. Screening of the factor H gene revealed, in addition to the mutation, three heterozygous hemolytic uremic syndrome -associated risk polymorphisms (-257 c/t, 2089 a/g, and 2881 g/t) which may have increased the patient's susceptibility to the occurrence of MAHA triggered by malignant hypertension. The combined clinical picture of IgA nephropathy and MAHA may have been partly related to the alterations in factor H.

Multidisciplinary management of giant functional petrous bone paraganglioma.

Giant and functional paragangliomas of the skull base are rare. Their endocrinological and surgical management is challenging. We report the case of an aggressive giant noradrenalin-secreting paraganglioma of the right temporal bone. Three procedures of embolisation were performed. The second one was complicated by a hypertensive crisis due to catecholamine release. The tumour was resected via a widened transcochlear approach. Tumour residue was treated by gamma knife radiosurgery, without additional growth at the last follow-up. This case illustrates the interest of multidisciplinary management of giant skull base paragangliomas.