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)

Obesity-related glomerulopathy (ORG) is a secondary form of focal and segmental glomerulosclerosis (FSGS) occurring in severely obese patients. A significant percentage of individuals with ORG will develop renal insufficiency or end stage renal disease. We report here a 17-year-old girl with morbid obesity (body mass index 56.8 kg/m(2)) and ORG presenting with nephrotic range proteinuria, who failed to improve following treatment with diet, exercise and angiotensin-converting enzyme inhibitor (ACEi)/angiotensin receptor blocker (ARB) therapy. Laparoscopic gastric bypass surgery was performed, and within 2 weeks following the surgery, the patient had lost 5.7 kg body weight and showed a remarkable decrease in protein excretion to one tenth of pre-surgery levels. More than 1 year after surgery, the patient's urine protein and kidney function have remained normal while off renin-angiotensin system inhibition therapy. This is the first report of successful use of gastric bypass surgery for obesity-related glomerulopathy in an adolescent. We propose that gastric bypass surgery be considered for patients with ORG.
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PMID:Obesity-related focal and segmental glomerulosclerosis: normalization of proteinuria in an adolescent after bariatric surgery. 1894 98

The incidence of obesity-related nephropathy (ORG) is increasing with the growing incidence of obesity. ORG is associated with morbid obesity, proteinuria and renal biopsy findings of focal global and segmental glomerulosclerosis (FSGS), which can be associated with significant renal impairment. Weight reduction is associated with improvement of ORG, however, conservative measures aiming at long-term weight reduction are difficult to achieve. Bariatric surgery is the most effective way of achieving long-term weight reduction. We present a case of ORG with nephrotic-range proteinuria and FSGS on renal biopsy. Following bariatric surgery, patient achieved successful weight reduction with significant decrease in proteinuria and stabilization of renal function.
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PMID:Resolution of nephrotic syndrome after successful bariatric surgery in patient with biopsy-proven FSGS. 1920 53

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

A proportion of patients with refractory nephrotic syndrome (NS) due to focal segmental glomerulosclerosis (FSGS) often require long-term hospitalization, which results in the loss of quality of life (QOL) of the patients. An-11-year-old girl was brought to a regional hospital with an 8-day history of generalized edema. Laboratory studies revealed massive proteinuria without hematuria and marked hypoalbuminemia associated with hyperlipidemia. A percutaneous renal biopsy revealed lesions characteristic of FSGS. Although methylprednisolone pulse therapy was administered followed by oral prednisolone combined with cyclosporine A, heavy proteinuria persisted for the next 4 months. The patient was referred subsequenthy to our hospital for further examinations. High-dose intermittent mizoribine pulse therapy, LDL-apheresis, cyclosporine A, tacrolimus and intravenous cyclophosphamide pulse therapy proved to be partially effective. As a result, long-term hospitalization and intravenous administration of albumin, diuretics and immunoglobulin was required for this patient. Also, she developed severe steroid toxicity such as obesity, cataract and osteoporosis. A third renal biopsy revealed an advanced stage of FSGS lesions, suggesting subsequent development of end-stage renal disease (ESRD). Since the patient suffered from long-term hospitalization over 3 years and significant loss of QOL, we therefore proposed early initiation of peritoneal dialysis (PD), as in cases of congenital NS, in order to preserve the patient's general condition without intravenous drug administrations and for the preparation of a future renal transplantation. After obtaining informed consent from the patient and her family, the initiation of PD was performed at the age of 15 years before the ESRD state(serum creatinine level 2.0 mg/dL). The patient was successfully free from intravenous drug administrations and hospitalization, and the QOL was significantly improved thereafter. We, therefore, suggest that early initiation of PD might be a treatment of choice for elected patients with severe refractory nephrotic syndrome such as this presented case.
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PMID:[Early initiation of peritoneal dialysis for the treatment of a patient with refractory nephrotic syndrome]. 1923 11

The increasing prevalence of obesity in the industrialized world is causing an alarming epidemic. Almost 70% of American adults are overweight or obese. The link between increasing body weight and hypertension is well established. Obesity hypertension through metabolic, endocrinic, and systemic hemodynamic alteration causes structural vascular and cardiac adaptations that trigger concentric, eccentric left ventricular hypertrophy and electrophysiological changes, which may increase the risk for congestive heart failure and sudden cardiac death as a result of arrhythmias. The increased renal blood flow in conjunction with a decreased renal vascular resistance causes renal hyperperfusion and hyperfiltration. Such changes lead to glomerulomegaly, focal segmental glomerulosclerosis, tubulointerstitial inflammation, and fibrosis that characterize the renal damage in obese hypertensive subjects. We propose that weight reduction, with the addition of other nonpharmacological approaches that included exercise and reduction in alcohol intake, should be the first choice to treat obesity hypertension. Salt restriction may be helpful only in salt-sensitive patients. The benefits of diet in obese patients include improvement of insulin sensitivity, reduction in sympathetic nervous and renin angiotensin system activities, and restoration of leptin sensitivity. As a consequence of these and other metabolic changes, the previously described systemic and renal hemodynamic alterations improved and the cardiovascular and renal morphological changes induced by obesity were lessened. After reviewing the medications available, we believe that owing to the cardiovascular and renal morbidity and mortality that characterized obesity hypertension, the ACEI or ARBs offer the best cardio-renal protection and should be the pharmacologic treatment of choice. If these alone do not control BP adequately, then a low-dose diuretic should be added as a second approach. Although we strongly believe in our proposal, more multicenter long-term clinical pharmacological trials are needed to evaluate the efficacy and safety of the antihypertensive approaches in the treatment of obesity hypertension.
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PMID:Obesity and hypertension: mechanisms, cardio-renal consequences, and therapeutic approaches. 1942 2

Obesity hypertension and metabolic syndrome have become major public health concerns. Nowadays, aldosterone is recognized as an important mediator of cardiovascular and renal damage. In the kidney, aldosterone injures glomerular visceral epithelial cells (podocytes), the final filtration barrier to plasma macromolecules, leading to proteinuria and glomerulosclerosis. Mineralocorticoid receptor (MR) antagonists effectively ameliorate proteinuria in patients or in animal models of hypertension, diabetes mellitus and chronic kidney disease (CKD), as well as in patients who experience 'aldosterone breakthrough.' Recently, clinical and experimental studies have shown that plasma aldosterone concentration is associated with obesity hypertension and metabolic syndrome. We showed that spontaneously hypertensive rats (SHR)/cp, an experimental model of obesity hypertension and metabolic syndrome, are prone to glomerular podocyte injury, proteinuria and left ventricular diastolic dysfunction, especially when the animals are fed a high-salt diet. Inappropriate activation of the aldosterone/MR system underlies the renal and cardiac injuries. Adipocyte-derived aldosterone-releasing factors (ARFs), although still unidentified, may account for aldosterone excess and the resultant target organ complication in SHR/cp. On the other hand, recent studies have shown that MR activation triggers target organ disease even in normal or low aldosterone states. We identified a small GTP (guanosine triphosphate)-binding protein, Rac1, as a novel activator of MR, and showed that this ligand-independent MR activation by Rac1 contributes to the nephropathy of several CKD models. We expect that ARFs and Rac1 can be novel therapeutic targets for metabolic syndrome and CKD. Future large-scale clinical trials are awaited to prove the efficacy of MR blockade in patients with obesity hypertension and metabolic syndrome.
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PMID:Mineralocorticoid receptor activation in obesity hypertension. 1952 18

Changes in the maternal diet either throughout pregnancy, or at defined stages therein, can have pronounced effects on organogenesis in conjunction with endocrine sensitivity. These processes can be brought about by either maternal consumption of an imbalanced diet and/or a global reduction in macro or micro-nutrient intake. The magnitude of adaptation in the fetus or offspring is dependent on which organ is most rapidly growing and developing at that particular stage of the life cycle. For a majority of organs, the period of developmental plasticity extends beyond the fetal period, continuing through lactation and into the juvenile period. During lactation, enhanced growth of the offspring appears to be a primary determinant of the magnitude of adverse cardiovascular outcome. Consequently, a change in organ development during pregnancy may not necessarily equate with compromised function in later life. In the kidney, for example, adaptations in its endocrine sensitivity to maternal nutrient restriction through fetal development can be protective against the adverse consequences of later obesity. Such adaptations do not simply represent epigenetic modifications but a plethora of responses that, taken together, can prevent, or delay, at least in the kidney, the onset of apoptosis and later glomerulosclerosis.
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PMID:Tissue specific adaptations to nutrient supply: more than just epigenetics? 1953 69

The therapeutic approach to childhood nephrotic syndrome is based on a series of studies that began with an international collaborative effort sponsored by the International Study of Kidney Disease in Children in 1967. The characteristics of children presenting with nephrotic syndrome have changed over recent decades with greater frequency of the challenging condition focal segmental glomerulosclerosis and a greater prevalence of obesity and diabetes mellitus, which may be resistant to glucocorticoids in the former and exacerbated by long-term glucocorticoid therapy in the latter 2 conditions. The Children's Nephrotic Syndrome Consensus Conference was formed to systematically review the published literature and generate a children's primary nephrotic syndrome guideline for use in educational, therapeutic, and research venues.
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PMID:Management of childhood onset nephrotic syndrome. 1965 90

Heterocyclic indazole derivatives are claimed in patent WO2008138448 as inhibitors of the serum- and glucocorticoid-inducible-kinase 1 (SGK1) and drugs for the pharmacological treatment of SGK1-related diseases, such as diabetes, obesity, metabolic syndrome, systemic and pulmonary hypertension, cardiac fibrosis, hypertrophy and insufficiency, arteriosclerosis, glomerulosclerosis, nephrosclerosis, nephritis, nephropathy, deranged electrolyte excretion, fibrosing and inflammatory disease (e.g., liver cirrhosis, lung fibrosis, rheumatism, arthrosis, Crohn s disease, chronic bronchitis, radiation fibrosis, sclerodermia, cystic fibrosis, scar formation and Alzheimer' disease), tumor growth, peptic ulcers and some disorders hitherto not conclusively shown to involve SGK1. Most of the claims are supported by the literature. SGK1 is ubiquitously expressed and its expression is stimulated by hyperglycemia, cell shrinkage, ischemia, glucocorticoids, mineralocorticoids and several inflammatory mediators including TGF-ss. SGK1 is activated by insulin and growth factors via the phosphatidylinositol-3-kinase pathway. SGK1 regulates ion channels (including ENaC, KCNE1/KCNQ1), carriers (including NCC, NHE3, SGLT1), Na(+)/K(+)-ATPase, enzymes (including glycogen-synthase-kinase-3) and transcription factors (including FOXO3a, ss-catenin, NF-kappaB). A gain-of-function SGK1 gene variant, carried by approximately 3 - 5% of Caucasians and approximately 10% of Africans, is associated with increased blood pressure, obesity and type 2 diabetes. In vitro and in vivo experiments suggested a critical role of SGK1 in renal fluid retention and hypertension, glucose-induced obesity, coagulation and increased matrix protein formation.
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PMID:Heterocyclic indazole derivatives as SGK1 inhibitors, WO2008138448. 2002 Dec 89

There is now solid knowledge for associating overweight and obesity with CKD. The risk for ESRD is progressively higher at increasing body mass index (BMI) levels and in extremely obese individuals such risk is 5 times higher than that in persons with normal body mass. Visceral fat, insulin resistance and inflammation are nicely inter-correlated in cross sectional studies in CKD patients but it is still untested whether the association between waist circumference or waist-hip ratio and CKD underlies a causal connection. Notwithstanding knowledge on the quantitative relationship between risk factors implicated in kidney damage is still limited, evidence derived from clinical series in patients with various renal diseases (IgA nephropathy, renal agenesia or post-nephrectomy) supports the hypothesis that obesity is an important factor in the progression and perhaps even in the initiation of CKD. Hyperfiltration is commonly found in obese persons. Due to high sympathetic activity, high levels of angiotensin II and hyperinsulinemia, obese persons display enhanced sodium reabsorption in the proximal tubule and are unable to rapidly increase sodium excretion. Enhanced proximal salt reabsorption determines a reduced delivery of sodium to the macula densa and therefore promotes afferent vasodilatation and enhanced renin synthesis. As a result of high local angiotensin II levels, the efferent arteriole is constricted in the obese. Glomerulomegaly and focal glomerulosclerosis represent the anatomical counterparts of glomerular hyperfiltration-hypertension. Hyperfiltration apart, evidence is emerging that inflammatory cytokines produced by fat cells trigger inflammation in the kidney and that this mechanism contributes to reduce renal function in the obese.
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PMID:Overweight, obesity and metabolic alterations in chronic kidney disease. 2008 47


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