Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Focal and segmental glomerulosclerosis (FSGS) is a common, non-specific renal lesion. Although it is often secondary to other disorders, including HIV infection, obesity, hypertension and diabetes, FSGS also appears as an isolated, idiopathic condition. FSGS is characterized by increased urinary protein excretion and decreasing kidney function. Often, renal insufficiency in affected patients progresses to end-stage renal failure, a highly morbid state requiring either dialysis therapy or kidney transplantation. Here we present evidence implicating mutations in the gene encoding alpha-actinin-4 (ACTN4; ref. 2), an actin-filament crosslinking protein, as the cause of disease in three families with an autosomal dominant form of FSGS. In vitro, mutant alpha-actinin-4 binds filamentous actin (F-actin) more strongly than does wild-type alpha-actinin-4. Regulation of the actin cytoskeleton of glomerular podocytes may be altered in this group of patients. Our results have implications for understanding the role of the cytoskeleton in the pathophysiology of kidney disease and may lead to a better understanding of the genetic basis of susceptibility to kidney damage.
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PMID:Mutations in ACTN4, encoding alpha-actinin-4, cause familial focal segmental glomerulosclerosis. 1070 Jan 77

Focal segmental glomerulosclerosis represents a finding in several renal disorders, characterized by proteinuria and sometimes by arterial hypertension and progressive decline in renal function. There are primary (idiopathic and familial) and secundary forms. In the last 20 years several familial cases has been reported, with a great genetic heterogeneity (dominant and recessive forms) and with multiple associations with particular MHC class-I and class-II gene loci, being Al, DR3 o DR7 the most frequently reported. We described three members of same family with focal segmental hyalinosis that shared the HLA haplotype A31 B61 DR13. This association has not been described previously. We highlight that genetic and acquired factors (obesity, hypertension...) could have importance in the development of progressive renal failure in these patients.
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PMID:[Familial focal and segmentary hyalinosis]. 1277 84

Adrenal myelolipomas are rare benign tumors, usually discovered by chance in patients with hypertension, obesity or various endocrine disorders. Focal segmental glomerulosclerosis (FSGS) can occur as a primary disease or in a variety of secondary settings. So far, no association between the two conditions has been described. We report a case of a woman admitted for nephrotic syndrome, in which a coexistence of FSGS and bilateral large adrenal myelolipomas was revealed.
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PMID:Focal segmental glomerulosclerosis in a patient with large bilateral asymptomatic adrenal myelolipomas. 1466 65

An obese male patient with steroid-dependent nephrotic syndrome since age 6 years had a thirty-third relapse at the age of 29 years. Renal biopsy showed focal segmental glomerulosclerosis. Proteinuria disappeared after treatment with prednisolone. He went into complete remission and renal function remained normal at the age of 31 years. Focal segmental glomerulosclerosis associated with obesity was suspected. Long-term follow-up with renal biopsy is necessary in obese children with steroid-dependent nephrotic syndrome.
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PMID:A male patient with steroid-dependent nephrotic syndrome for 25 years and obesity-associated focal segmental glomerulosclerosis. 1548 Sep 5

We studied the glomerular architecture in renal biopsies of 95 patients undergoing bariatric surgery for extreme obesity but whose renal function was normal. The comparison group was 40 control patients having protocol biopsies. These latter patients had normal weight and renal function, were non-diabetic, non-hypertensive, and were undergoing nephrectomy or donating a kidney. Logistic regression models determined associations between the clinical and biochemical variables and glomerular lesions. Arterial hypertension, sleep apnea syndrome (SAS), and microalbuminuria were prevalent in the obese patients, as was hyperglycemia to a lesser extent. Focal and segmental glomerulosclerosis was present in only five extremely obese (EO) patients but absent in controls. Increased mesangial matrix, podocyte hypertrophy, mesangial cell proliferation, and glomerulomegaly were more frequent in the obese cohort than in the control group. Body mass index was a significant independent risk factor associated with glomerular lesions in all 135 patients and in the 95 EO patients, whereas SAS was associated with glomerulomegaly only in the EO. Our study shows that EO patients who lack overt clinical renal symptoms have a variety of glomerular abnormalities that correlate with body mass.
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PMID:Renal injury in the extremely obese patients with normal renal function. 1885 52

Preterm birth is associated with decreased nephron mass and obesity that may impact on kidney disease progression in later life. Our objectives were to examine the relative risks of obesity and preterm birth on the progression of kidney disease in children. In a retrospective cohort study, 80 (44 obese and 36 non-obese) patients with proteinuric kidney disease were studied for disease progression and glomerular histomorphometry. Of the obese, 22 had been born at term (Obese-T) and 22 had been preterm (Obese-PT). Seventeen non-obese children with focal glomerular sclerosis, born at term (NO-FSGS), and 19 non-obese preterm (NO-PT) children, served as controls. Insulin resistance as measured by the homeostatic model assessment (HOMA-IR) was elevated in all obese children. Obese-PT patients had increased risk of renal demise during childhood when compared with Obese-T children [hazard ratio 2.4; 95% Confidence interval (95% CI) 1.1 to 7.1; P = 0.04]. In obese children, although proteinuria often exceeded nephrotic range, average levels of serum albumin remained normal. Preterm patients were more likely to have reduced renal mass (odds ratio 4.7; P = 0.006), but obesity was not a factor. Renal histomorphometry showed glomerulomegaly in obese patients, regardless of birth weight. Obesity and preterm birth appear to impose additive risks for progression of kidney disease in childhood.
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PMID:Obesity and preterm birth: additive risks in the progression of kidney disease in children. 1921 91

Focal segmental glomerulosclerosis (FSGS) is one of the most common forms of acquired glomerular disease leading to end-stage kidney disease. Its incidence is rising around the world. There is no proven therapy for those patients who do not respond to corticosteroids and it can recur in 20% to 25% of patients who receive a kidney transplant. The disease can be primary, or it can be secondary to various conditions including vesicoureteral reflux, obesity, medications, and infections. Recent advances have demonstrated the important role of genetic mutations in podocyte proteins as a cause of FSGS. There is an urgent need for randomized clinical trials to develop safe and effective therapy for FSGS that occurs in the native or transplanted kidney.
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PMID:Focal segmental glomerulosclerosis and chronic kidney disease in pediatric patients. 2189 74

FSGS is a lesion, not a disease. The separation into primary FSGS (a result of immunologic-mediated injury) versus secondary FSGS (related to a variety of causes) is often difficult. Even when this particular issue is carefully evaluated, the therapeutic implications are not always apparent. Newer literature on both biomarker discovery and on the genetic basis of FSGS is reviewed in this context. In addition, the thorny implications of obesity as it relates to the FSGS lesion are discussed. An overall practical algorithmic approach to the management and treatment of the FSGS lesion that integrates these controversial overlap areas is suggested.
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PMID:Glomerular diseases: FSGS. 2399 Jan 65

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

Focal segmental glomerulosclerosis (FSGS) is a histological pattern of glomerular injury, rather than a single disease, that is caused by diverse clinicopathological entities with different mechanisms of injury with the podocyte as the principal target of lesion, leading to the characteristic sclerotic lesions in parts (i.e., focal) of some (i.e., segmental) glomeruli. The lesion of FSGS has shown an increasing prevalence over the past few decades and is considered the most common glomerular cause leading to ESKD. Primary FSGS, which usually presents with nephrotic syndrome, is thought to be caused by circulating permeability factors that have a main role in podocyte foot process effacement. Secondary forms of FSGS include maladaptive FSGS secondary to glomerular hyperfiltration such as in obesity or in cases of loss in nephron mass, virus-associated FSGS, and drug-associated FSGS that can result in direct podocyte injury. Genetic FSGS is increasingly been recognized and a careful evaluation of patients with atypical primary or secondary FSGS should be performed to exclude genetic causes. Unlike primary FSGS, secondary and genetic forms of FSGS do not respond to immunosuppression and tend not to recur after kidney transplantation. Distinguishing primary FSGS from secondary and genetic causes has a prognostic significance and is crucial for an appropriate management. In this review, we examine the pathogenesis, clinical approach to distinguish between the different causes, and current recommendations in the management of FSGS.
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PMID:Focal Segmental Glomerulosclerosis: State-of-the-Art and Clinical Perspective. 3272 52


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