Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Focal and segmental glomerulosclerosis (FGS) is an important cause of the nephrotic syndrome and renal failure in children and adults. This review will present a detailed description of the pathological and clinical features of FGS and discuss in depth the modern concepts of its pathogenesis, which recent studies indicate is multifactorial and analogous to that of atherosclerosis.
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PMID:Ideas in pathology. Focal and segmental glomerulosclerosis. 206 66

Focal glomerulosclerosis (FGS) is commonly seen in human and in experimental models of chronic renal disease. Although considerable experimental data suggest that hypertension is important in progressive nephron damage, recent studies also have indicated that abnormal lipid metabolism may be an independent risk factor in the pathogenesis of FGS. Indeed, the synergistic impact of hypertension and hyperlipidemia in the pathogenesis of FGS may be analogous to the role of these factors in the pathogenesis of atherosclerosis. This review focuses on some of the recent and pertinent data that support a role of lipid-mediated glomerular injury in the pathogenesis of progressive renal disease.
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PMID:Hyperlipidemia and the progression of renal disease. 327 33

To better characterize the heavy proteinuria occasionally described in cholesterol atheroembolic renal disease (CAE), we reviewed the clinical features and histological findings of 24 patients found at renal biopsy to have CAE. Twelve (50%) had a typical clinical presentation soon after an invasive vascular procedure. Eight (33%) underwent biopsies to evaluate proteinuria and four (17%) with insidiously developing renal failure to exclude rapidly progressive glomerulonephritis. All had usual and similar risk factors for CAE; 71% were male, 96% had peripheral vascular disease, 79% had recently undergone an invasive vascular procedure, 74% were hypercholesterolemic, and all were hypertensive. Proteinuria was higher and serum creatinine lower in the proteinuria group. In the nine (38%) nephrotic patients, serum creatinine measurements were lower (2.7 +/- 1.2 v 5.6 +/- 2.4 mg/dL), duration of renal disease to biopsy longer, and time from biopsy to dialysis greater (23.5 +/- 14.8 v 0.03 +/- 0.098 mo, P < 0.05 for all). Focal segmental glomerulosclerosis (FSGS) was observed in 15 (63%) of the biopsy specimens. Although FSGS itself did not occur more commonly in nephrotic patients, these patients did have a higher fraction of segmentally sclerosed glomeruli (0.158 +/- 0.097 v 0.026 +/- 0.050, P < 0.01). A variant of FSGS, the cellular lesion with epithelial cell prominence and capillary loop collapse, was observed in 7 of 9 (78%) patients with nephrotic-range proteinuria, but in only 3 of 12 (25%) patients with lesser degrees of protein excretion (P < 0.05). The cellular lesion was accompanied by higher mean proteinuria, 7.6 +/- 4.3 versus 2.1 +/- 2.4 g/24 hr (P < 0.01). In a larger group of patients with a similar age range as the CAE group who were identified by search of a computerized biopsy database, membranous nephropathy was the only other form of idiopathic glomerulonephritis that occurred with CAE. One of 82 (1.2%) patients with membranous nephropathy also had CAE, compared with 20 of 102 (19.6%) with FSGS (P < 0.0002, chi2). Thus, the finding of FSGS with CAE was not coincidence. Mean follow-up was 20 +/- 26 months (range, 0 to 103 months). Six patients (25%) were followed-up at least 3 years after renal biopsy. These findings indicate that extended survival in CAE is not rare and that heavy proteinuria occurs as part of a chronic disorder with distinctive histological features. Cholesterol atheroembolism with FSGS should be considered in the differential diagnosis of nephrotic syndrome in elderly patients with advanced atherosclerosis.
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PMID:Focal segmental glomerulosclerosis associated with nephrotic syndrome in cholesterol atheroembolism: clinicopathological correlations. 904 Dec 8

Focal segmental glomerulosclerosis (FSGS) is an important cause of end-stage renal failure (ESRF) in children. Our previous studies have shown that Arab children in Israel have a worse prognosis compared with Jewish patients despite similar clinical presentation and management. Progression of proteinuric glomerular diseases has been associated with alterations in lipid metabolism, and similarities have been drawn between the mechanisms underlying atherosclerosis and glomerulosclerosis. Paraoxonase (PON) is a high-density lipoprotein (HDL)-associated enzyme involved in preventing the oxidation of low-density lipoprotein (LDL), and an association has been shown between two genetic polymorphisms in PON1 and the risk of coronary artery disease. The aim of this study was to determine the frequency of these genetic polymorphisms in PON1 in Arab and Jewish children with FSGS and to determine any association with severity of outcome. Forty-seven children (21 Arab and 26 Jewish) with biopsy-proven FSGS and 274 healthy controls of matching ethnic origin were studied. The glutamine (A)-192-arginine (B) and the methionine (M)-55-leucine (L) polymorphisms were analyzed. The frequency of the A allele was similar in patients and controls (0.68 versus 0.71), as was that of the L allele (0.63 versus 0.6). When subgroups were analyzed, the prevalence of the LL genotype in Arab patients was significantly greater than in Jewish patients (57.1% versus 26.9%, P: < 0.05) and Arab controls (57.1% versus 28.9%, P: < 0.03). A trend in association was found between homozygosity for the L allele and progression of renal disease in Arab children. Homozygosity for the L allele is a risk factor for developing FSGS in Arab children and may be associated with a worse prognosis.
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PMID:Genetic polymorphism in paraoxonase is a risk factor for childhood focal segmental glomerulosclerosis. 1109 50

For a century, nephrosclerosis was ascribed to nonmalignant hypertension and aging. However, it was intuitively perceived that hypertension may follow rather than explain this nephrovasculopathy. Hypertensive nephrosclerosis was long considered a major cause of end-stage renal failure (ESRD). This is especially true in blacks of African descent but not in other ethnic populations. The term 'nephrosclerosis' is still an easy way out to classify a patient with renal insufficiency. This leads to neglect the possibility of an overlooked nephropathy complicated by hypertension and to believe that drastic blood pressure control may retard the progression to ESRD. Several clinical and experimental lines of evidence lead to the understanding that nephrosclerosis, especially in blacks, is a genetic renovasculopathy that precedes the rise in blood pressure. The identification of coding region variants in APOL1 encoding apolipoprotein L-1 in black but also white and Asians opens new lines of research on the genetics of nephroangiosclerosis and of FSGS. Metabolic derangements, such as obesity, oxidative stress, dyslipidemia and atherosclerosis may be considered confounding factors with regard to nephrosclerosis. Histomorphometric studies led to sorting out the lesions due to aging from those stemming from hypertension. They shed new light not only on glomerular lesions that comprise ischemic obsolescence but also on glomerulomegaly and focal-segmental sclerosis, the latter due to a loss of renal autoregulation. It appears that the control of hypertension is not credited with the expected benefit for slowing the decline of renal function. 'Nephrosclerosis' can be considered an umbrella term of poor significance that should be replaced by its pathologic description, that is, arterionephrosclerosis and incite to elucidate the various genetic and metabolic factors that lead to a lesion in quest of a specific disease.
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PMID:Nephrosclerosis: a term in quest of a disease. 2587 43