Nephrotic syndrome and abdominal arterial bruits in a young hypertensive patient: a case report.

We report the case of a 34-year-old black African hypertensive woman who presented with nephrotic proteinuria, mild renal failure and abdominal bruits on physical examination. The renal Doppler ultrasound revealed bilateral artery stenosis. Thoracoabdominal aortic nuclear magnetic resonance showed a restriction of proximal descending aorta with post-stenotic spindle dilation while abdominal aorta and iliac vessels appeared diffusely stenotic with atherosclerotic plaques and infrequent spindle dilations and right ostial renal artery stenosis. Renal angiography failed to reveal renal artery stenosis. Right renal biopsy showed type 1 membrano-proliferative glomerulonephritis in sclerotic evolution and severe arteriolosclerosis. The particularly early onset of the disease suggests that the pathogenesis of the membrano-proliferative glomerulonephritis may be multifactorial and related to vascular hypoplasia and chronic renal hypoperfusion leading to renin angiotensin system activation. Hyperlipidemia secondary to nephrotic syndrome may have accelerated systemic atherosclerosis and progression of renal disease.

Refractory hypertension and rapidly progressive renal failure due to bilateral renal artery stenosis: case report.

INTRODUCTION: We report a case of refractory hypertension and acute renal failure with mild proteinuria due to an unreported bilateral Renal Artery Stenosis, who underwent renal biopsy in the suspicion of rapidly progressive glomerulonephritis. CASE PRESENTATION: A 51-year-old Caucasian male was admitted with refractory hypertension of recent onset and acute renal failure. Duplex Doppler Ultrasonography was performed and provided images highly suggestive for bilateral renal artery stenosis. The patient was referred to the department of interventional radiology, where bilateral selective renal angiography and percutaneous endovascular angioplasty and stenting were performed successfully. CONCLUSION: Duplex Doppler Ultrasonography is thus suggested in patients presenting with refractory hypertension and acute renal failure, especially if atherosclerotic disease and clinical clues of RAS are present. Renal revascularisation with bilateral angioplasty and stenting may play a key role in the treatment of bilateral Renal Artery Stenosis, especially in patients unable to maintain renal function as systemic blood pressure is lowered.

Bilateral native kidney neoplasia detected by ultrasound in functionning renal allograft recipient.

We report the case of bilateral renal clear cell carcinoma in the native kidney, occurring fouryears after renal transplantation. Renal Doppler duplex sonography revealed large solid bilateral neoformation. Total-body computed tomography confirmed the presence of bilateral kidney lesions and also showed the presence of concomitant gross dyscariocinetic lesion of left hemotorax. The patient underwent bilateral native nephrectomy and the histological diagnosis was renal cell carcinoma. Subsequent left upper lobectomy revealed necrotic keratinizing squamous cell carcinoma. Then, the patients was switched tacrolimus to everolimus treatment and mycophenolate mofetil was reduced.

COVID-19-Associated Endothelial Dysfunction and Microvascular Injury: From Pathophysiology to Clinical Manifestations.

Coronavirus-19 disease (COVID-19) affects more people than previous coronavirus infections and has a higher mortality. Higher incidence and mortality can probably be explained by COVID-19 causative agent's greater affinity (about 10-20 times) for angiotensin-converting enzyme 2 (ACE2) receptor compared with other coronaviruses. Here, the authors first summarize clinical manifestations, then present symptoms of COVID-19 and the pathophysiological mechanisms underlying specific organ/system disease. The worse clinical outcome observed in COVID-19 patients with diabetes may be in part related to the increased ADAM17 activity and its unbalanced interplay with ACE2. Therefore, strategies aimed to inhibit ADAM17 activity may be explored to develop new effective therapeutic approaches.

Gut Dysbiosis and Western Diet in the Pathogenesis of Essential Arterial Hypertension: A Narrative Review.

Metabolic syndrome is a cluster of the most dangerous cardiovascular (CV) risk factors including visceral obesity, insulin resistance, hyperglycemia, alterations in lipid metabolism and arterial hypertension (AH). In particular, AH plays a key role in the complications associated with metabolic syndrome. High salt intake is a well-known risk factor for AH and CV diseases. Vasoconstriction, impaired vasodilation, extracellular volume expansion, inflammation, and an increased sympathetic nervous system (SNS) activity are the mechanisms involved in the pathogenesis of AH, induced by Western diet. Gut dysbiosis in AH is associated with reduction of short chain fatty acid-producing bacteria: acetate, butyrate and propionate, which activate different pathways, causing vasoconstriction, impaired vasodilation, salt and water retention and a consequent high blood pressure. Moreover, increased trimethylamine N-oxide and lipopolysaccharides trigger chronic inflammation, which contributes to endothelial dysfunction and target organs damage. Additionally, a high salt-intake diet impacts negatively on gut microbiota composition. A bidirectional neuronal pathway determines the "brain-gut" axis, which, in turn, influences blood pressure levels. Then, we discuss the possible adjuvant novel treatments related to gut microbiota modulation for AH control.

Soluble ST2 is a biomarker for cardiovascular mortality related to abnormal glucose metabolism in high-risk subjects.

AIMS: Inflammation plays a role in the development and progression of type 2 diabetes macroangiopathy. Interleukin 33 (IL-33) drives production of Th2-associated cytokines. The soluble form of suppression of tumorigenicity 2 (sST2) acting as a decoy receptor blocks IL-33 and tones down Th2 inflammatory response. We investigated the role of sST2 as a predictor of CV and all-cause mortality in a cohort of patients affected by established atherosclerotic disease. METHODS: 399 patients with atherosclerotic disease from the Tor Vergata Atherosclerosis Registry performed follow-up every year by phone interview. The primary endpoint was cardiovascular death and the secondary endpoint was death for any other disease. RESULTS: sST2 plasma levels were significantly increased from normal glucose-tolerant patients to patients with history of type 2 diabetes (p < 0.00001). Levels of sST2 were significantly correlated with fasting plasma glucose (R = 0.16, p = 0.002), HbA1c (R = 0.17, p = 0.002), and HOMA (R = 0.16, p = 0.004). Dividing patients in tertiles of sST2 levels, those belonging to the highest tertile showed an increased rate of all-cause and cardiovascular mortality, (all-cause mortality p = 0.045 and CVD mortality p = 0.02). A multivariate Cox analysis revealed that sST2 increased the risk in cardiovascular mortality per SD by hazard ratio 1.050 (95% CI 1.006-1.097, p = 0.025) after adjustment for age and hs-CRP while it did not significantly change the risk for all-cause mortality. CONCLUSIONS: High circulating level of sST2 is associated to increased CVD mortality and markers of metabolic dysfunction in subjects with atherosclerotic disease.

Low Molecular Weight Adiponectin Increases the Mortality Risk in Very Old Patients.

Despite its beneficial role on insulin resistance and atherosclerosis, adiponectin has been frequently reported as an independent positive predictor of cardiovascular mortality. Very few information is available regarding adiponectin isoforms and mortality, in particular in advanced aging. Baseline serum levels of Total Adiponectin and its circulating isoforms (HMW-, MMW-, LMW-Adiponectin) were measured in 97 old patients (mean age: 79 years). Patients were followed up for all-cause mortality (study end-point) for an average of 76.4 ± 37.3 months. A positive association was observed for LMW-Ad and all-cause mortality (HR: 1.13, 95% CI: 1.05-1,22, p: 0.002). After multivariate adjustment for age, sex and a previous history of myocardial infarction, higher levels of LMW-Ad were significantly associated with all-cause mortality (HR: 1.11, 95% CI: 1.02-1.21; p: 0.017). Interestingly neither total adiponectin neither the other two circulating isoforms (MMW- and HMW-Ad) showed any significant association with the study end-point. Our data suggest that the association between high serum adiponectin levels and increased mortality rate in elderly is contingent to an unbalanced circulating levels of adiponectin isoforms. The present results support the hypothesis that high levels of Low Molecular Weight adiponectin are a biomarker for mortality risk in very old patients.

Coronary artery calcifications predict long term cardiovascular events in non diabetic Caucasian hemodialysis patients.

Vascular calcifications are frequent in chronic renal disease and are associated to significant cardiovascular morbidity and mortality. The long term predictive value of coronary artery calcifications detected by multi­layer spiral computed tomography for major cardiovascular events was evaluated in non­diabetic Caucasian patients on maintenance hemodialysis free of clinical cardiovascular disease. Two­hundred and five patients on maintenance hemodialysis were enrolled into this observational, prospective cohort study. Patients underwent a single cardiac multi­layer spiral computed tomography. Calcium load was quantified and patients grouped according to the Agatston score: group 1 (Agatston score: 0), group 2 (Agatston score 1­400), group 3 (Agatston score 401­1000) and group 4 (Agatston score >1000). Follow­up was longer than seven years. Primary endpoint was death from a major cardiovascular event. Actuarial survival was calculated separately in the four groups with Kaplan­Meier method. Patients who died from causes other than cardiovascular disease and transplanted patients were censored. The "log rank" test was employed to compare survival curves. One­hundred two patients (49.7%) died for a major cardiovascular event during the follow­up period. Seven­year actuarial survival was more than 90% for groups 1 and 2, but failed to about 50% for group 3 and to <10% for group 4. Hence, Agatston score >400 predicts a significantly higher cardiovascular mortality compared with Agatston score <400 (p<0.0001); furthermore, serum Parathyroid hormone levels > 300 pg/l were associated to a lower survival (p < 0.05). Extended coronary artery calcifications detected by cardiac multi­layer spiral computed tomography, strongly predicted long term cardiovascular mortality in nondiabetic Caucasian patients on maintenance hemodialysis. Moreover, it was not related to conventional indices of atherosclerosis, but to other non­traditional risk factors, as serum Parathyroid hormone levels. A full cost­benefit analysis is however necessary to justify a widespread use of cardiac multi­layer spiral computed tomography in clinical practice.

Obesity-related metabolic syndrome: mechanisms of sympathetic overactivity.

The prevalence of the metabolic syndrome has increased worldwide over the past few years. Sympathetic nervous system overactivity is a key mechanism leading to hypertension in patients with the metabolic syndrome. Sympathetic activation can be triggered by reflex mechanisms as arterial baroreceptor impairment, by metabolic factors as insulin resistance, and by dysregulated adipokine production and secretion from visceral fat with a mainly permissive role of leptin and antagonist role of adiponectin. Chronic sympathetic nervous system overactivity contributes to a further decline of insulin sensitivity and creates a vicious circle that may contribute to the development of hypertension and of the metabolic syndrome and favor cardiovascular and kidney disease. Selective renal denervation is an emerging area of interest in the clinical management of obesity-related hypertension. This review focuses on current understanding of some mechanisms through which sympathetic overactivity may be interlaced to the metabolic syndrome, with particular regard to the role of insulin resistance and of some adipokines.

Preoperative embolization reduces the risk of cathecolamines release at the time of surgical excision of large pelvic extra-adrenal sympathetic paraganglioma.

A 30-year-old woman with severe hypertension was admitted to the hospital with a history of headache, palpitations, and diaphoresis following sexual intercourse. Twenty-four hour urinary excretion of free catecholamines and metabolites was markedly increased as was serum chromogranin A. Computed tomography scan revealed a large mass in the left adnex site and magnetic resonance imaging confirmed the computer tomography finding, suggesting the presence of extra-adrenal sympathetic paraganglioma. I-metaiodobenzyl guanidine scintigram revealed an increased uptake in the same area. Transcatheter arterial embolization of the mass resulted in marked decreases in blood pressure and urinary excretion of free catecholamines and metabolites. Surgical excision of the mass was then accomplished without complication. Preoperative embolization is a useful and safe procedure which may reduce the risk of catecholamines release at the time of surgical excision in large pelvic extra-adrenal sympathetic paraganglioma.

Metabolic syndrome, chronic kidney, and cardiovascular diseases: role of adipokines.

Obesity is a chronic disease, whose incidence is alarmingly growing. It is associated with metabolic abnormalities and cardiovascular complications. These complications are clustered in the metabolic syndrome (MetS) leading to high cardiovascular morbidity and mortality. Obesity predisposes to diabetic nephropathy, hypertensive nephrosclerosis, and focal and segmental glomerular sclerosis and represents an independent risk factor for the development and progression of chronic kidney disease (CKD). Albuminuria is a major risk factor for cardiovascular diseases (CVDs). Microalbuminuria has been described as early manifestation of MetS-associated kidney damage and diabetic nephropathy. Obesity and MetS affect renal physiology and metabolism through mechanisms which include altered levels of adipokines such as leptin and adiponectin, oxidative stress, and inflammation. Secretory products of adipose tissue also deeply and negatively influence endothelial function. A better understanding of these interactions will help in designing more effective treatments aimed to protect both renal and cardiovascular systems.