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)

Abnormalities of renal handling of urate occur in a wide variety of physiological and pathological conditions and are mediated by factors including renal blood flow, glomerular filtration rate, urine flow rate, urinary constituents, metabolites, hormones and drugs. The determination of the aetiological factors in each abnormal situation is complex and the problem is discussed in relation to a variety of conditions including renal tubular disorders and mental intoxications, hypertension, toxaemia of pregnancy, glycogen storage disease, fructose administration, hereditary fructose intolerance, as well as obesity, regular alcohol consumption and hyperlipoproteinaemia. Apart from those diseases, usually genetically determined, which are associated with excessive production of urate, the most common causes of hyperuricaemia act at a renal level and result in a reduction in the net renal excretion of urate.
Nephron 1975
PMID:Abnormal renal urate homeostasis in systemic disorders. 105 88

It has been recently suggested that focal glomerulosclerosis (FGS) is analogous to atherosclerosis. Obese Zucker (OZ) rats spontaneously develop hyperlipidemia, proteinuria and FGS. To evaluate the role of the monocyte (MO) and its derivatives in the pathogenesis of the lesion, 30 OZ rats and 15 lean littermates (LZ) were followed for up to 240 days of age. At 75, 120 and 240 days of age, groups of 10 OZ and 5 LZ were assessed with respect to serum total and free cholesterol (TC and FC), triglyceride, lipoprotein electrophoresis, renal histology, histochemistry and immunohistochemistry. All serum lipids were raised at 75 days in OZ rats and increased progressively at 120 and 240 days. The early lesions of FGS were first demonstrated in OZ at 120 days with more advanced lesions at 240 days. FGS was seen in LZ only at 240 days when their serum lipids were raised. Intraglomerular MO infiltration was significantly higher in OZ than in LZ at all time periods (p less than 0.01) and greater in glomeruli with FGS lesions than in those without (p less than 0.01 and 120 days and p less than 0.05 at 240 days). Staining for ED1 and Ia antigens with monoclonal antibodies demonstrated increasing numbers of intraglomerular ED1+ and Ia+ cells with increasing age and extent of FGS. The findings suggest a role for intraglomerular macrophages in the pathogenesis of FGS in OZ.
Nephron 1991
PMID:Monocytes and macrophages in focal glomerulosclerosis in Zucker rats. 194 26

Most hypertensive subjects are overweight, and as a consequence have an increased prevalence of hypercholesterolaemia, impaired glucose tolerance, and left ventricular hypertrophy. Reduction of the blood pressure by antihypertensive drugs without control of the obesity leaves these additional risk factors for cardiovascular disease uncorrected. Weight reduction has a substantial and sustained antihypertensive effect, removes or reduces the need for drug treatment, corrects the associated risk factors, and is clearly the more rational approach to management.
Nephron 1987
PMID:Obesity and hypertension. 369 50

The association between massive obesity and nephrotic syndrome has been rarely reported. We herein describe a patient with massive obesity (209 kg) and nephrotic proteinuria who had a normal renal biopsy. The patient was initially polycythemic and had a supranormal creatinine clearance. After losing 89 kg, his hemoglobin and creatinine clearance returned to normal, and proteinuria decreased to 300 mg/24 h. We postulated that increases in glomerular hydrostatic pressure may result in local alterations of glomerular basement membrane sieving characteristics (biologic membrane thixotropy) with resultant nephrotic proteinuria. Prompt remission of proteinuria with weight loss supports a reversible glomerular hemodynamic alteration as a mechanism for the proteinuria of massive obesity.
Nephron 1985
PMID:Massive obesity and nephrotic proteinuria with a normal renal biopsy. 400 Mar 54

We have identified 17 obese patients (body mass index, BMI, 37.9 +/- 4.1) with proteinuria > 1 g/day (1.3-6.4 g/24 h, mean 3.1 +/- 1.7). Their age was 34-70 years (48.3 +/- 10); 11 were females and 6 males. Six patients had only one functioning kidney and a sleep apnea syndrome had been diagnosed in 5. Renal biopsies, obtained in 5 cases, showed focal glomerulosclerosis in 2 cases, minimal changes in 2 and mesangial proliferation in 1. Nine patients (group 1) were treated with hypocaloric diets; body weight significantly decreased (BMI 37.1 +/- 3, 34 +/- 3.5 and 32.6 +/- 3.2 at 0, 6 and 12 months, respectively) as well as proteinuria (2.9 +/- 1.7, 1.2 +/- 1 and 0.4 +/- 0.6 g/24 h). There was a significant correlation between body weight loss and decrease in proteinuria (r = 0.69, p < 0.05). Eight patients (group 2) were treated with captopril, without dietary changes. BMI remained stable but proteinuria showed a dramatic decrease, similar to that in group 1 (3.4 +/- 1.7, 1.2 +/- 0.9 and 0.7 +/- 1 g/24 h, respectively). Renal function remained stable in both groups. In summary, both body weight loss and captopril treatment can induce a sharp decrease in obesity-related proteinuria.
Nephron 1995
PMID:Effects of body-weight loss and captopril treatment on proteinuria associated with obesity. 761 15

Coronary heart disease (CHD) is more common in patients with chronic renal failure and is a major cause of death after renal transplantation. Elevated serum levels of lipoprotein(a) (Lp(a)) are a known risk factor for CHD in the general population and levels have been reported to be increased in renal transplant recipients. It has been suggested that cyclosporin may elevate Lp(a) levels. We therefore measured the serum concentration of Lp(a) in 50 renal transplant recipients who were receiving cyclosporin alone as immunosuppressive therapy and 50 who were treated with azathioprine and prednisolone, but not cyclosporin. The patients attended two renal transplant centres, one where cyclosporin alone was used as immunosuppressive treatment when possible and another where many patients commenced on azathioprine and prednisolone remain on this medication rather than cyclosporin. Patients in each group were matched for age and sex, but the time since transplantation was greater in those not receiving cyclosporin. Transplant function, obesity and the underlying cause of renal disease were similar in both groups of patients. Median Lp(a) concentration in the cyclosporin monotherapy group was 32.0 (range <0.8-140.3) mg/dl and was significantly (p < 0.05) greater than that of the azathioprine and prednisolone group which was 18.3 (range <0.8-167.7) mg/dl. The serum high-density lipoprotein (HDL) cholesterol concentration, which was 1.24 +/- 0.39 mmol/l (mean +/- SD) in patients receiving cyclosporin, was significantly (p < 0.05) less than that of those treated with azathioprine and prednisolone in whom it was 1.41 +/- 0.40 mmol/l. The lower level in those on cyclosporin was due to a decrease in the HDL2 subfraction. Serum lipid and lipoprotein concentrations were otherwise similar in the two groups of patients. The serum level of Lp(a) after renal transplantation may be influenced by the choice of immunosuppressive therapy.
Nephron 1997
PMID:Influence of immunosuppressive therapy on lipoprotein(a) and other lipoproteins following renal transplantation. 906 48

Haemodialyzed (HD) patients have been found to have an increased bile cholesterol level and an increased saturation index in bile. These changes were markedly enhanced in the presence of a low-protein diet. To evaluate whether such changes influence the prevalence of cholelithiasis in patients with end-stage renal failure, real-time sonography was performed to detect the presence of gallstones (GS) in 54 HD (28 males, 26 females, mean age 52.4 +/- 15.4 years) and 39 continuous ambulatory peritoneal dialysis (CAPD; 22 males, 17 females, mean age 59.1 +/- 14.9 years) patients. No patient had diabetes. The patients' charts were reviewed for the following data: age, sex, primary renal disease, obesity (20% above ideal weight), history suggestive of gallbladder disease or previous cholecystectomy, duration of dialysis, and serum cholesterol levels. Overall, cholelithiasis was documented in 12 of 93 (12.9%) patients, 7 HD and 5 CAPD. When comparing the factors outlined above, no significant difference was found between HD and CAPD patient groups, either with or without cholelithiasis. Gallbladder disease was asymptomatic in all except 1 patient who required cholecystectomy. Using a healthy control group consisting of local age- and sex-matched inhabitants, GS were found in 8 of 134 (6%) of them (p > 0.05). We conclude that the prevalence rate of GS in our dialysis population (HD and CAPD) is similar to that of a local general population following a western-style diet, irrespective of dialysis mode.
Nephron 1998
PMID:Prevalence of cholelithiasis in non-diabetic haemodialysis and continuous ambulatory peritoneal dialysis patients. 945 3

Preeclampsia affects 3-5% of pregnancies and can have a significant impact on health for both mother and fetus. Risk factors include maternal co-morbidities such as obesity and chronic hypertension, paternal factors, and genetic factors. New hypertension and proteinuria during the second half of pregnancy are key diagnostic criteria, but the clinical features and associated prognostic implications are somewhat heterogeneous and may reflect different mechanisms of disease. Renal dysfunction and proteinuria correspond to the pathologic finding of glomerular endotheliosis, and generally resolve after cure of preeclampsia through fetal and placenta delivery. The molecular mechanisms behind this disease are being discovered and refined. The initial etiologic agents are currently unknown. Pathologic studies show abnormal development of an ischemic placenta with a high-resistance vasculature, which cannot deliver an adequate blood supply to the fetoplacental unit. Endothelial dysfunction plays a central role in the pathogenesis of the maternal syndrome. Dysfunctional endothelial cells produce altered quantities of vasoactive mediators, which lead to a tip in the balance towards vasoconstriction. An imbalance in circulating angiogenic factors is emerging as a prominent mechanism that mediates the endothelial dysfunction and the clinical signs and symptoms of preeclampsia. Soluble fms-like tyrosine kinase 1 (sFlt1), an endogenous anti-angiogenic factor that is a potent vascular endothelial growth factor (VEGF) antagonist, is highly elevated in preeclampsia. VEGF is not only important in angiogenesis, but also in maintaining endothelial health including the formation of endothelial fenestrae (a hallmark of the glomerular vascular endothelium). sFlt1 overexpression in animals induces glomerular endotheliosis with the loss of endothelial fenestrae that resembles the renal histological lesions of preeclampsia. More severe forms of preeclampsia, including the HELLP syndrome, may be explained by a concomitant elevation in both sFlt1 and soluble endoglin, another anti-angiogenic factor. Unraveling of the molecular mechanisms behind preeclampsia may help to expand our armamentarium to treat patients in a more directed fashion, as current management consists of supportive care and expedited delivery. Finally, long-term outcomes of women with preeclampsia include a significantly increased risk for hypertension and cardiovascular disease, including mortality, which may warrant more aggressive screening and treatment in this population.
Nephron Clin Pract 2007
PMID:Pre-eclampsia: clinical manifestations and molecular mechanisms. 1757 Sep 33

Although first described as early as 1898 and long considered a vestigial organelle of little functional importance, the primary cilium has become one of the hottest research topics in modern cell biology and physiology. Primary cilia are nonmotile sensory organelles present in a single copy on the surface of most growth-arrested or differentiated mammalian cells, and defects in their assembly or function are tightly coupled to many developmental defects, diseases and disorders. In normal tissues, the primary cilium coordinates a series of signal transduction pathways, including Hedgehog, Wnt, PDGFRalpha and integrin signaling. In the kidney, the primary cilium may function as a mechano-, chemo- and osmosensing unit that probes the extracellular environment and transmits signals to the cell via, e.g., polycystins, which depend on ciliary localization for appropriate function. Indeed, hypomorphic mutations in the mouse ift88 (previously called Tg737) gene, which encodes a ciliogenic intraflagellar transport protein, result in malformation of primary cilia, and in the collecting ducts of kidney tubules this is accompanied by development of autosomal recessive polycystic kidney disease (PKD). While PKD was one of the first diseases to be linked to dysfunctional primary cilia, defects in this organelle have subsequently been associated with many other phenotypes, including cancer, obesity, diabetes as well as a number of developmental defects. Collectively, these disorders of the cilium are now referred to as the ciliopathies. In this review, we provide a brief overview of the structure and function of primary cilia and some of their roles in coordinating signal transduction pathways in mammalian development, health and disease.
Nephron Physiol 2009
PMID:Primary cilia and signaling pathways in mammalian development, health and disease. 1927 29

The sharp rise in the prevalence of chronic kidney disease (CKD) that parallels an increase in the prevalence of obesity in the recent years is a cause for great concern. CKD increases the rate of cardiovascular disease (CVD), development of end-stage renal disease, and leads to premature death. Although no direct causality link between obesity and CKD can yet be established, this appears highly likely. CKD should be regarded as a major complication of overweight and obesity, regardless of whether the association was independent or through the influence of diabetes, hypertension, CVD, metabolic syndrome and high fructose intake. We review the literature on the complex but positive association between obesity and CKD, the pathological effect of excess adiposity in kidney injury and the potential role of weight reduction therapy in reducing the burden of CKD.
Nephron Clin Pract 2009
PMID:Overweight, obesity and chronic kidney disease. 1939 Feb 12


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