UMLS:C0033687 - FACTA Search

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Query: UMLS:C0033687 (proteinuria)
24,015 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This article has three purposes: 1) to summarize recent findings of the Syst-Eur Trial; 2) to provide a short overview of the large trials in hypertension that have compared older with newer drug classes; and 3) to update the results of a meta-regression analysis that addressed the question of: to what extent blood pressure (BP) lowering can explain the findings of recent outcome trials in hypertensive patients or high-risk patients with normotension or hypertension. The Syst-Eur trial showed that in older patients with isolated systolic hypertension, drug treatment starting with a dihydropyridine calcium channel blocker reduced the risk of stroke and of all cardiovascular complications. Furthermore, this treatment regimen improved the prognosis of diabetic patients; reduced the incidence of proteinuria; and prevented dementia, in particular Alzheimer's disease. The pooled evidence from nine recently published actively controlled outcome trials involving 62,605 hypertensive patients proved that calcium channel blockers have the same long-term efficacy and safety as the older drug classes. Compared with diuretics and beta-blockers, calcium channel blockers may offer greater protection against stroke and less protection against myocardial infarction, resulting in similar overall cardiovascular benefit. A meta-regression analysis including 30 trials and 149,407 hypertensive or high-risk patients showed that BP gradients largely accounted for most-if not all-of the differences in outcome. These findings emphasize the desirability of tight BP control. The hypothesis that angiotensin converting enzyme inhibitors or alpha-blockers might influence outcome beyond their BP lowering-effects was not confirmed.
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PMID:Calcium-channel blockade and cardiovascular prognosis: recent evidence from clinical outcome trials. 1212 Oct 11

Hypertension is a nutritional-hygienic disease. Long-term caloric intake in excess of energy expenditures, chronic supraphysiological intake of dietary sodium, excessive alcohol consumption, and psychosocial stressors all contribute to the development of hypertension throughout the world. Elevated BP, particularly systolic BP, has been linked to multiple adverse clinical outcomes including stroke, heart failure, myocardial infarction, renal insufficiency/failure, peripheral vascular disease, retinopathy, dementia, and premature mortality. These undesirable clinical outcomes are typically, although not invariably, preceded by pressure-related target-organ injury such as left ventricular hypertrophy, renal insufficiency and proteinuria. The relation of BP and CKD and, in turn, the prevention of CKD or forestalling its progression by hypertension treatment, will be the focus of this manuscript. In hypertensive persons with reduced kidney function and/or proteinuria, lowering BP with multidrug therapy that is inclusive of pharmacologic modulators of the renin-angiotensin-aldosterone-kinin system is an effective strategy to forestall the progressive loss of kidney function. The totality of data support low therapeutic BP targets for persons with proteinuria >1 g/d. Nevertheless, in persons with CKD, even those with proteinuria below the dipstick positive level (approximately 300 mg/d or urine protein to creatinine ratio of 0.22), aggressive BP control also may be warranted because of the high risk of nonrenal cardiovascular disease. Multiple antihypertensive drugs will be required in the vast majority of patients with diabetes and/or reduced kidney function to attain BP goal. Renin-angiotensin system (RAS) modulator therapy is indicated among persons with diabetes mellitus and CKD. Available data support the use of angiotensin receptor blockers in persons with type 2 diabetes and overt nephropathy for preservation of kidney function. Among persons with type I diabetes with or without overt nephropathy, type 2 diabetes without overt nephropathy and in nondiabetic CKD, the available clinical data support the use of angiotensin-converting enzyme inhibitors as the RAS modulator of choice. Low therapeutic target BP levels <130/80 mmHg in persons with type 2 diabetes mellitus also appear warranted based on available data mostly for reducing the risk of nonrenal cardiovascular disease and overall mortality.
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PMID:Prevention of hypertension and its complications: theoretical basis and guidelines for treatment. 1281 10

Several classes of drugs are used to treat hypertension but how they affect cardiovascular morbidity and mortality in high-risk patients is still under investigation. Recent outcome trials have examined the benefits associated with different levels of blood pressure control or have compared several of the 'newer' classes of antihypertensive drugs, such as angiotensin-converting enzyme (ACE) inhibitors and calcium channel blockers, with 'older' drug classes, such as diuretics and beta-blockers. Other trials have compared antihypertensive drugs with placebo. We performed a meta-regression analysis of 30 clinical trials that included a total of 149,407 patients. We based our analysis on summary statistics reported in the literature, and showed that blood pressure gradients accounted for most, if not all, of the differences in outcome in patients with hypertension or at high cardiovascular risk. We also conducted a study in older patients with isolated systolic hypertension and showed that antihypertensive drug treatment starting with the dihydropyridine calcium channel blocker, nitrendipine, reduced the risk of stroke and all cardiovascular complications. In addition, nitrendipine-based blood pressure-lowering therapy decreased the incidence of dementia. In diabetic patients, nitrendipine reduced the risk of proteinuria, decreased total mortality, and markedly improved cardiovascular prognosis. Taken together, these findings emphasize the desirability of tight blood pressure control.
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PMID:What can be expected from optimal blood pressure control? 1292 1

A progressive chain of pathophysiological events links cardiovascular risk factors to clinical manifestations of disease and life-threatening cardiovascular events. This chain--the cardiovascular continuum--underlies cardiovascular disease and holds the key to its prevention and treatment. Progressive tissue damage can result in morbidity from congestive heart failure, end-stage heart disease, nephrotic proteinuria and dementia and, eventually, death from cardio- or cerebrovascular causes. The renin-angiotensin-aldosterone system (RAAS) is involved at all stages of the cardiovascular continuum, because the effector molecules of the RAAS, angiotensin II in particular, have direct pathobiological effects on a variety of tissues, including the endothelium, vascular smooth muscle and the renal mesangium. Clinical trials of angiotensin II receptor blockers (ARBs) and angiotensin-converting enzyme (ACE) inhibitors have demonstrated the essential validity of this hypothesis. Interruption of the RAAS has been shown to reduce cardiovascular morbidity and mortality in patients with left ventricular hypertrophy, heart failure and post-myocardial infarction, as well as renal disease in patients with type 2 diabetes. Key questions remain, however. What are the clinical effects of combination ARB and ACE inhibitor treatment? How will combinations of RAAS blockade with other agents, such as statins, affect the cardiovascular continuum? Answers to these questions will require well-planned, adequately powered clinical trials, such as the Programme of Research tO evaluate Telmisartan End-organ proteCTION (PROTECTION) and the ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial (ONTARGET) programmes. However, it is already clear that RAAS blockade is an essential part of blocking progression along the cardiovascular continuum.
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PMID:The cardiovascular continuum and renin-angiotensin-aldosterone system blockade. 1582 52

Hypertension is a well known risk factor for cardiovascular and cerebrovascular events such as heart attacks and strokes. In addition, it is associated with earlier changes in organ systems in the body, such as left ventricular hypertrophy (LVH), proteinuria and renal failure, retinopathy and vascular dementia which are grouped under the term "target organ damage" (TOD). There are many processes involved in the pathogenesis of TOD and these include endothelial activation, platelet activation, increased thrombogenesis, changes in the renin aldosterone angiotensin system (RAAS), and collagen turnover. All these changes work hand in hand and lead to the production of hypertensive TOD. In this review, we aim to provide an overview of the recent advances in pathophysiology of hypertensive TOD, and examine how these changes lead to the production of TOD. A better understanding of these pathogenic processes would help us better devise treatment strategies in preventing the dreaded complications associated with hypertension.
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PMID:Target organ damage in hypertension: pathophysiology and implications for drug therapy. 1672 71

Dentatorubral-pallidoluysian atrophy (DRPLA) is an autosomal dominant neurodegenerative disorder characterized by various combinations of myoclonus epilepsy, ataxia, choreoathetosis and dementia. No specific therapy has been established and renal complication is rare. We report two cases of DRPLA with renal complications. Hematuria and proteinuria had gradually progressed for 2 and 13 years in these patients. Renal biopsy findings revealed focal glomerulosclerosis in one case and end-stage kidney disease in the other case. Angiotensin-converting enzyme inhibitor and angiotensin receptor II antagonist were administered to both patients, resulting in improved proteinuria and preserved renal function in one patient, while renal function continued to deteriorate in the other patient. Although renal complication is rare in patients with DRPLA, the presence of renal disease has to be suspected in patients with persistent proteinuria.
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PMID:Renal complications in two patients with dentatorubral-pallidoluysian atrophy. 1726 99

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a hereditary systemic arteriopathy presenting with migraines, mood disorders, focal neurologic deficits, recurrent ischemic attacks and dementia in young adults. The genesis of this disease relates to missense mutation of the Notch3 gene. We report here a newly identified CADASIL patient and discuss unique vascular lesions observed in the kidney. A 64-year-old female was admitted to our hospital for the investigation of proteinuria, hematuria and progressive neurological abnormalities. Her mother and brother died of cerebral infarction at a relatively young age despite a lack of apparent risk factors for arteriosclerosis. Over the past 4 months before admission, she had suffered from frequent transient ischemic attacks despite appropriate antiplatelet therapy. Blood examination revealed mild renal insufficiency and urinalysis revealed moderate protein excretion and dysmorphic hematuria. Magnetic resonance imaging of the brain revealed multiple infarcts and leukoencephalopathy. Histopathological analysis of the kidney revealed focal segmental mesangial proliferation, the loss and degeneration of arterial medial smooth muscle cells and arterial intimal thickening. Immunofluorescence analysis of glomeruli revealed IgA deposition in the mesangial area. Electron microscope analysis revealed electron-dense deposition also in the mesangial area. In addition, granular osmophilic material (GOM) was observed in the extraglomerular mesangial area and around the vascular smooth muscle cells. Genetic analysis of Notch3 revealed an R141C missense mutation and she was diagnosed with CADASIL complicated with IgA nephropathy. In immunohistological analysis, Notch3 stains were positive in vascular smooth muscle cells of the interlobular arteries and both afferent and efferent arterioles, and weak in the glomerular mesangial area. Antihypertensive treatment using angiotensin II receptor blocker and a low protein diet were initiated, and her urinary protein excretion decreased to 0.2 g/day. However, due to the progression of her neurological abnormalities, she became socially withdrawn. In CADASIL, GOM, abnormal accumulation of Notch3 ectodomain, is thought to induce the degeneration and loss of vascular smooth muscle cells and subsequent intimal thickening. Analysis of our cases provided that these morphological abnormalities were also observed in the CADASIL patient kidney.
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PMID:Renal involvement in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). 1739 Jul 43

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a systemic arterial disease characterized by impairment of vascular smooth muscle cell structure and function related to NOTCH3 mutations. Pathological findings include pathognomonic granular osmiophilic material (GOM) deposition with nonspecific hyalinization within the artery wall in a variety of tissues. The main clinical presentation is iterative strokes in young adults despite the lack of cardiovascular risk factors, leading to early dementia. Although arteriosclerosis and GOM have been found in kidneys from patients with CADASIL, kidney disease has been described only once up to now, in association with immunoglobulin A nephropathy. We report the case of a 61-year-old patient with a medical history of CADASIL and recent mild hypertension. His mother also showed neuropsychiatric symptoms and end-stage renal disease of unknown cause. The patient had a chronic kidney disease defined by means of estimated glomerular filtration rate using the 4-variable Modification of Diet in Renal Disease Study equation of 58 mL/min/1.73 m(2) associated with mild proteinuria and intermittent microscopic hematuria. Renal histological analysis showed severe arteriosclerosis and mild interstitial fibrosis. Glomeruli did not show mesangial immunoglobulin A deposition or focal segmental proliferation. Electron microscopic analysis showed typical GOM deposition in the vicinity of altered vascular smooth muscle cells in interlobular and juxtaglomerular arteries. The nephroangiosclerosis-like lesions were unusually severe in contrast to the recent mild hypertension. The presence of GOM strongly suggests that renal lesions were related to the NOTCH3 mutation. Here, we describe the first case of familial occurrence of kidney disease with decreased kidney function in the absence of coexisting nephropathy in patients with CADASIL. We discuss the role of NOTCH3 mutation in the pathogenesis of nephroangiosclerosis through functional impairment of renal microcirculation or primary Notch3-related vascular disease.
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PMID:Nephroangiosclerosis in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy: is NOTCH3 mutation the common culprit? 1857 91

A 71-year-old man presented with quadriplegia, seizures, dysarthria, motor aphasia and urinary incontinence lasting for several years. The development of proteinuria and increased susceptibility to infections brought the physician's attention to possible underlying autoimmune diseases. Laboratory investigations revealed evidence for systemic lupus erythematosus (SLE) and antiphospholipid syndrome. Imaging studies showed obstructive hydrocephalus. Several courses of methylprednisolone therapies followed by maintenance therapy with low-dose steroid, ventriculoperitoneal shunt, and antihypertensives improved the proteinuria and dysarthria but not the urinary incontinence or dementia. A thromboembolic event in the central nervous system secondary to phospholipid antibodies or lupus activity may represent a pathogenetic basis for hydrocephalus. When encountering a patient with hydrocephalus but without apparent predisposing factors, it is always important to include SLE as a differential diagnosis.
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PMID:Hydrocephalus in an elderly man with systemic lupus erythematosus. 1951 33

We report a 51-year-old woman who presented with dementia, livedo racemosa, polyarthralgia, mild renal insufficiency, proteinuria, and thrombocytopenia. Cutaneous and renal biopsy specimens both showed an identical specific occlusive arteriolopathy consistent with Sneddon syndrome and antiphospholipid syndrome. However, no antiphospholipid antibodies were detected and we, therefore, diagnosed seronegative antiphospholipid-like syndrome. We discuss the nosology of this entity and its association with non-antiphospholipid antibody-related Sneddon syndrome. The common denominator of Sneddon syndrome and antiphospholipid syndrome with or without antiphospholipid antibodies seems to be the endothelial damage and occlusive arteriolopathy. Skin biopsy is useful to confirm the diagnosis of seronegative antiphospholipid-like syndrome.
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PMID:Livedo, dementia, thrombocytopenia, and endotheliitis without antiphospholipid antibodies: seronegative antiphospholipid-like syndrome. 1964 81

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