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

About a third of new cases of renal failure in USA are attributed to hypertension despite controversy about the frequency and pathology of so called hypertensive nephrosclerosis. In spite of good documentation that obesity causes renal failure and in spite of the global epidemic of obesity this diagnosis does not feature on most renal failure registries. New documentation that progressive renal failure in hypertension is linked to insulin resistance and analysis of NHANES III data which shows a strong positive significant dose-response relationship between insulin resistance and chronic kidney disease strengthen the view that so called hypertensive nephrosclerosis may be linked more closely to obesity and insulin resistance than to blood pressure. The pathology of the kidney in hypertension has changed. Studies 50 years ago did not show segmental glomerulosclerosis, which has recently been shown to be the key lesion in hypertensive nephrosclerosis. Recent documentation that this is a major mechanism of progression in hypertension together with the fact that similar segmental glomerulosclerosis is the key lesion in obesity and the metabolic syndrome suggests that these factors are more important than hypertension in renal failure attributed to hypertensive nephrosclerosis.
 ...
PMID:Hypothesis: obesity and the insulin resistance syndrome play a major role in end-stage renal failure attributed to hypertension and labelled 'hypertensive nephrosclerosis'. 1594 68

Overweight/obesity represent an underestimated risk factor of renal disease. The incidence of obesity-related glomerulopathy (ORG) tremendously increased within the last decade. The first sign of renal damage in overweight conditions is microalbuminuria or proteinuria, indicating the potential risk of its progression to renal insufficiency and the development of premature cardiovascular events. In the early stage of obesity renal hemodynamics are characterized by a renal hypercirculation and glomerular hyperfiltration, particularly in the presence of hypertension. The hyperfiltration is especially harmful in patients with pre-existing inflammatory and metabolic renal disease, or under the conditions of reduced renal mass. Histopathologically, ORG is characterized by glomerulomegaly with/without signs of focal segmental glomerulosclerosis. Pathogenetically, numerous factors are involved, e.g. enhanced glomerular capillary pressure, adrenergic nerve overactivity, inappropriate activation of the renin-angiotensin-aldosterone system, insulin resistance, hyperinsulinemia and hyperleptinemia, dyslipidemia, enhanced clotting tendency and sodium retention. Diabetic nephropathy is one of the most serious complications of obesity-induced diabetes. In the industrial nations type 2 diabetes is the single most frequent cause of end-stage renal disease. After kidney transplantation, overweight/obesity is associated with a less favourable prognosis for the survival of the graft and the patient. Incidence of renal cell carcinomas is enhanced in overweight/obesity. Obesity-related renal disease may be prevented/postponed by an early weight reduction, by dietary intervention combined with physical exercise. In the advanced stages of renal disease benefits of weight reduction are minimal. Concomitant administration of angiotensin-converting-enzyme inhibitors or angiotensin II receptor 1 blockers exerts antiproteinuric effects and thereby aid in retarding the disease progression. Aimed prevention and treatment of obesity represent a challenge for the healthcare system. The concerted action of physicians, patients and the public health authorities is needed.
 ...
PMID:[Overweight and obesity--risk factors in the development and progression of renal disease]. 1532 63

The obese Zucker rat is a valuable model for studying kidney disease associated with obesity and diabetes. Previous studies have shown that substitution of animal protein with soy ameliorates the progression of renal disease. To explore the participation of nitric oxide (NO) and caveolin-1 in this protective effect, we evaluated proteinuria, creatinine clearance, renal structural lesions, nitrites and nitrates urinary excretion (UNO(2)(-)/NO(3)V), and mRNA and protein levels of neuronal NO synthase (nNOS), endothelial NOS (eNOS), and caveolin-1 in lean and fatty Zucker rats fed with 20% casein or soy protein diet. After 160 days of feeding with casein, fatty Zucker rats developed renal insufficiency, progressive proteinuria, and renal structural lesions; these alterations were associated with an important fall of UNO(2)(-)/NO(3)V, changes in nNOS and eNOS mRNA levels, together with increased amount of eNOS and caveolin-1 present in plasma membrane proteins of the kidney. In fatty Zucker rats fed with soy, we observed that soy diet improved renal function, UNO(2)(-)/NO(3)V, and proteinuria and reduced glomerulosclerosis, tubular dilation, intersticial fibrosis, and extracapilar proliferation. Renal protection was associated with reduction of caveolin-1 and eNOS in renal plasma membrane proteins. In conclusion, our results suggest that renal protective effect of soy protein appears to be mediated by improvement of NO generation and pointed out to caveolin-1 overexpression as a potential pathophysiological mechanism in renal disease.
 ...
PMID:Renal protection by a soy diet in obese Zucker rats is associated with restoration of nitric oxide generation. 1532 66

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.
 ...
PMID:A male patient with steroid-dependent nephrotic syndrome for 25 years and obesity-associated focal segmental glomerulosclerosis. 1548 Sep 5

We report here the case of a 9-year-old Japanese boy with nephrotic syndrome caused by focal segmental glomerulosclerosis, which was refractory to treatment. Although aggressive immunosuppressive therapy consisting of methylprednisolone pulse therapy combined with cyclosporine A (CsA) and intermittent low density lipoprotein apheresis was effective in overcoming his steroid-resistant state, the child became persistently steroid-dependent, that is, more than 0.75 mg/kg per day of prednisolone combined with CsA was required to maintain a negative test for proteinuria. Since adverse effects of prednisolone, such as short stature, obesity, osteoporosis and cataract, were noted, CsA in his treatment regimen was replaced with tacrolimus at the dose of 0.1 mg/kg per day, with the trough blood level of the drug maintained at around 10 ng/ml. Within 4 months of the inclusion of tacrolimus in the treatment regimen, complete remission was achieved, with no recurrence of the proteinuria, while the prednisolone dose could be tapered to 0.3 mg/kg per day. No adverse effects of tacrolimus were observed. These clinical results suggest that tacrolimus may be the drug of choice in selected patients with refractory nephrotic syndrome, even if pediatric-onset cases, at least those in whom the steroid-sparing effects of CsA is unsatisfactory.
 ...
PMID:Effective therapy of a child case of refractory nephrotic syndrome with tacrolimus. 1550 24

Obesity and metabolic syndrome are associated with glomerulosclerosis and proteinuria, but the mechanisms are not known. The purpose of this study was to determine if there is altered renal lipid metabolism and increased expression of sterol regulatory element-binding proteins (SREBPs) in a model of diet-induced obesity. C57BL/6J mice that were fed a high fat, 60 kcal % saturated (lard) fat diet (HFD) developed obesity, hyperglycemia, and hyperinsulinemia compared with those that were fed a low fat, 10 kcal % fat diet (LFD). In contrast, A/J mice were resistant when fed the same diet. C57BL/6J mice with HFD exhibited significantly higher levels of renal SREBP-1 and SREBP-2 expression than those mice with LFD, whereas in A/J mice there were no changes with the same treatment. The increases in SREBP-1 and SREBP-2 expression in C57BL/6J mice resulted in renal accumulation of triglyceride and cholesterol. There were also significant increases in the renal expression of plasminogen activator inhibitor-1 (PAI-1), vascular endothelial growth factor (VEGF), type IV collagen, and fibronectin, resulting in glomerulosclerosis and proteinuria. To determine a role for SREBPs per se in modulating renal lipid metabolism and glomerulosclerosis we performed studies in SREBP-1c(-/-) mice. In contrast to control mice, in the SREBP-1c(-/-) mice with HFD the accumulation of triglyceride was prevented, as well as the increases in PAI-1, VEGF, type IV collagen, and fibronectin expression. Our results therefore suggest that diet-induced obesity causes increased renal lipid accumulation and glomerulosclerosis in C57BL/6J mice via an SREBP-1c-dependent pathway.
 ...
PMID:Diet-induced obesity in C57BL/6J mice causes increased renal lipid accumulation and glomerulosclerosis via a sterol regulatory element-binding protein-1c-dependent pathway. 1604 11

Enlarged glomerular size is a feature of focal segmental glomerulosclerosis, obesity-related glomerulopathy, diabetic nephropathy, and hypertension. The distribution of glomerular volumes within different cortical zones and glomerular volume alterations with age and obesity may contribute to understanding the evolution of these diseases. We analyzed the distributions of volumes of individual glomeruli in the superficial, middle, and juxtamedullary cortex of normal human kidneys using the disector/Cavalieri method. Volumes (V(glom)) of 720 nonsclerotic glomeruli (30 per kidney, 10 per zone) were estimated in autopsy kidneys of 24 American men, 12 aged 20 to 30 yr and 12 aged 51 to 69 yr. Black and white individuals were represented equally. The range of individual V(glom) within subjects varied from two- to eight-fold. There were no significant zonal differences in V(glom) in the young or those with body surface area (BSA) < or = 2.11 m(2). In contrast, superficial glomeruli in the older age group, in those with BSA > 2.11 m(2), and in white subjects were significantly larger than juxtamedullary glomeruli. Black subjects tended toward larger V(glom) than white subjects, and this difference was significant and most marked in the juxtamedullary zone and independent of age, BSA, and glomerular number. There is a wide range in individual V(glom) in adults. BSA, race, and age independently influence V(glom) in different zones of the renal cortex. These findings might reflect processes of aging and susceptibility factors to renal disease.
 ...
PMID:Determinants of glomerular volume in different cortical zones of the human kidney. 1610 83

Diabetic nephropathy characterized by proteinuria and sclerosis is the leading cause of renal failure, but its mechanisms are not well understood. Zucker Obese (ZO) rat model of obesity, insulin resistance, and hypertension has been used to study nephropathy. We hypothesize that chronically elevated intrarenal angiotensin II (ANG II) down-regulates nephrin, a key slit-pore protein and up-regulates fibrogenic molecule transforming growth factor (TGFbeta1) and thus result in progression of nephropathy in type 2 diabetes. Untreated or angiotensin converting enzyme (ACE) inhibitor, captopril, treated ZO and control Lean (ZL) rats were used to measure intrarenal levels of ANG II, glomerular nephrin, TGFbeta1, collagen and fibronectin with age using radioimmunoassay, RT-PCR and immunoblot techniques. Progression of nephropathy was established by measuring proteinuria and sclerosis. ZO rats developed obesity, hyperglycemia, hyperinsulinimia, increase in intrarenal ANG II and proteinuria. Expression of glomerular nephrin decreased while expression of TGFbeta1 and matrix components increased in ZO rats. Captopril treatment prevented increase in intrarenal ANG II, and reversed expression of nephrin, TGFbeta1, collagen and fibronectin. We conclude that in this model of type 2 diabetic nephropathy, chronically elevated intrarenal ANG II causes proteinuria via decrease in nephrin and glomerulosclerosis via TGFbeta1 mediated increase in matrix component.
 ...
PMID:Chronically increased intrarenal angiotensin II causes nephropathy in an animal model of type 2 diabetes. 1614 87

We report a unusual case of idiopathic nodular glomerulosclerosis mimicking changes that develop in diabetic nephropathy. A 66-year-old non-diabetic female developed nephrotic range proteinuria and the work up was unremarkable. Light and electron microscopy showed mesangial expansion with Kimmelsteil-Wilson nodules and diffuse glomerular basement membrane thickening without any electron dense deposits. Diabetes mellitus was excluded by repeated clinical and laboratory investigations. Forty two similar cases have been reported. Exact etiology for the development of non-diabetic glomerulosclerosis is unclear. But, hypertension, smoking, obesity, intermittent hyperglycemia predating the diagnosis of diabetes possibly explain the development of nodular glomerulosclerosis in these patients. Long-term follow-up to screen for the delayed onset of diabetes or its complications may be worthwhile.
 ...
PMID:Nodular glomerulosclerosis in a non-diabetic patient: case report and review of literature. 1629 90

The increasing prevalence of obesity is a major public health concern, affecting more than one third of the Swiss population. The renal effects of obesity per se, independent of hypertenison or diabetes, though, are less known. Obesity is positively correlated with proteinuria and the development of glomerulomegaly and focal segmental glomerulosclerosis. The pathophysiology of the obesity-associated kidney disease is complex, including hemodynamic and physical factors and increased synthesis of vasoactive and fibrogenic substances by adipose tissue. The most important therapeutic approach is weight reduction. Angiotension converting enzyme (ACE) inhibition is effective in reducing proteinuria, but longer follow-up is required to determine the long term benfits of ACE inhibition.
 ...
PMID:[Obesity: what impact on renal function?]. 1656


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>