Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0033687 (proteinuria)
 24,015 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We performed a cross-sectional study in a wide sample of patients with chronic renal failure undergoing conservative therapy (CTh) (n = 79), peritoneal dialysis (PD) (n = 75), and hemodialysis (HD) (n = 51), with the aim of analyzing the impact of the different modes of therapy on serum leptin levels. We used a multivariate approach, taking into consideration the potential effects of other epidemiological, dialysis-related, nutritional, and hormonal factors on serum leptin. Leptin levels were higher in patients treated with PD (median, 36 ng/mL) than in those undergoing CTh (10.8 ng/mL) or HD (5.4 ng/mL) (P < 0.0005). This difference persisted after controlling for gender, body mass index, and fasting insulin levels, suggesting that imbalances in these factors may only partially explain the differences found between the three modes of therapy. Leptin levels showed a significant negative correlation with peritoneal protein losses in PD patients but were poorly associated with factors such as proteinuria, daily peritoneal glucose absorption (PD), renal function, or adequacy of dialysis. Leptin and insulin-like growth factor-I (IGF-I) were significantly correlated in PD patients, but the study design did not allow for establishing a meaning for this correlation. In conclusion, serum leptin levels are increased in PD patients when compared with CTh or HD patients. Differences in gender distribution, fat mass, and insulin levels may partially explain these findings, but other undefined factors also may have a role in producing these results.
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PMID:Hyperleptinemia in uremic patients undergoing conservative management, peritoneal dialysis, and hemodialysis: A comparative analysis. 1056 Nov 55

Hyperleptinemia may be part of the insulin resistance syndrome. We studied serum leptin in preeclampsia, which is an insulin-resistant state, and sought associations between leptin and insulin or insulin sensitivity during and after pregnancy. Twenty-two proteinuric preeclamptic women and 16 normotensive controls were studied during the third trimester. Leptin was higher in preeclampsia (mean +/- SE, 34.6 +/- 3.9 v 20.0 +/- 3.3 microg/L, P = .002) and correlated directly with the level of proteinuria (r = .47, P = .03) and normal pregnancy (r = .52, P = .04), whereas insulin sensitivity as assessed by an intravenous glucose tolerance test showed no relationship to leptin. Leptin was 19.0 +/- 3.6 microg/L in 14 preeclamptic women and 10.1 +/- 2.0 microg/L (P = .11) in 11 controls 3 months after delivery. Leptin correlated directly with insulin both in preeclamptic puerperal women (r = .63, P = .02) and in controls (r = .81, P = .003). Leptin and insulin sensitivity correlated only in preeclamptic puerperal women (r = -.59, P = .02). In conclusion, (1) serum leptin is elevated in preeclampsia, (2) insulin is an important determinant of serum leptin in preeclamptic and normotensive women both during pregnancy and in the puerperium, and (3) hyperleptinemia may be part of the insulin resistance syndrome also in women with prior preeclampsia.
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PMID:Leptin during and after preeclamptic or normal pregnancy: its relation to serum insulin and insulin sensitivity. 1069 Sep 55

Leptin is a small peptide hormone that is mainly, but not exclusively, produced in adipose tissue. The circulating leptin concentration therefore directly reflects the amount of body fat. Leptin was identified through positional cloning of the obese (ob) gene, which is mutated in the massively obese ob/ob mouse, and it has a pivotal role in regulating food intake and energy expenditure. It binds to the so-called long receptor (Ob-Rb) in the hypothalamus and regulates food intake through the release of other neurotransmitters. Moreover, leptin exerts several other important metabolic effects on peripheral tissue, including modification of insulin action, induction of angiogenesis, and modulation of the immune system. As a small peptide, leptin is cleared principally by the kidney. Not surprisingly, serum leptin concentrations are increased in patients with chronic renal failure and those undergoing maintenance dialysis. Whether the hyperleptinemia of chronic renal failure contributes to some uremic manifestations, such as anorexia and weight loss, requires additional investigation. The kidney expresses abundant concentrations of the truncated isoform of the leptin receptor Ob-Ra, but only a small amount of the full-length receptor Ob-Rb. We recently discovered that leptin has direct effects on renal pathophysiological characteristics. Both cultured glomerular endothelial cells and mesangial cells obtained from the diabetic db/db mouse possess the Ob-Ra receptor, but whether biological effects of leptin are transduced through this receptor remains unknown. In glomerular endothelial cells, leptin stimulates cellular proliferation, transforming growth factor-beta1 (TGF-beta1) synthesis, and type IV collagen production. Conversely, in mesangial cells, leptin upregulates synthesis of the TGF-beta type II receptor, but not TGF-beta1, and stimulates glucose transport and type I collagen production through signal transduction pathways involving phosphatidylinositol-3-kinase. These data suggest that leptin triggers a paracrine interaction in which glomerular endothelial cells secrete TGF-beta, to which sensitized mesangial cells may respond. Both cell types increase their expression of extracellular matrix in response to leptin. Infusion of leptin into normal rats for 3 weeks fosters the development of focal glomerulosclerosis and proteinuria. Additional previously described direct and indirect effects of leptin on the kidney include natriuresis, increased sympathetic nervous activity, and stimulation of reactive oxygen species. These findings collectively suggest that the kidney is not only a site of leptin metabolism, but also a target organ for leptin action in pathophysiological states.
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PMID:Leptin and renal disease. 1177 95

Pre-eclampsia, or pregnancy-induced hypertension, is a major cause of maternal and fetal morbidity and mortality complicating 7-10% of pregnancies. Although mechanisms underlying pre-eclampsia are not well understood, endothelial dysfunction is considered to underscore many of the pre-eclamptic manifestations including hypertension, proteinuria and edema. Leptin, the obese gene product from adipocytes, is produced by the placenta during pregnancy. Serum leptin levels are elevated under normal pregnancy especially during the second trimester, which rapidly decreases and returns to normal after delivery, indicating the role of leptin as a gestational hormone for energy balance. Recent studies have revealed that the placental production of leptin may be pathologically augmented under pre-eclampsia although conflicting data also have been reported. Nevertheless, hyperleptinemia and possible further augmentation under pre-eclampsia may predispose to the development of maternal leptin resistance, which may be a component of insulin resistance predisposing the onset of endothelial dysfunction. This review summarizes recent findings regarding the putative changes of serum leptin levels during pre-eclampsia and the potential consequences on the vascular system.
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PMID:Leptin, leptin resistance and endothelial dysfunction in pre-eclampsia. 1264 50

Leptin may contribute to renal pathology in some situations by stimulating transforming growth factor-beta1 (TGF-beta1) synthesis. The soluble leptin receptor (sOb-R) is a transport protein contributing to binding and activation of circulating leptin. We investigated the interaction between serum and urinary leptin, TGF-beta1, and serum sOb-R levels in 38 patients with minimal change nephrotic syndrome (MCNS) aged between 6 and 12 years and 10 age- and sex-matched healthy controls (group III). Patients were divided into two groups: group I, proteinuria exceeding >40 mg/m(2) per hour and group II, patients in remission. Serum leptin levels in group I were significantly lower than those in group II and group III ( P=0.011, P=0.007, respectively). There was a negative correlation between serum leptin levels and proteinuria ( r=-0.52, P=0.02) as well as between serum leptin and sOb-R levels ( r=-0.82, P=0.000) in group I. Urine leptin and sOb-R levels in group I were significantly higher than in group II ( P=0.0021, P=0.001, respectively) and group III ( P=0.07, P=0.009, respectively). Serum TGF-beta1 levels in healthy controls (406+/-424 pg/ml) were significantly lower than those in groups I and II ( P=0.004, P=0.000, respectively). However, no significant correlation was found between the serum TGF-beta1 and leptin levels in MCNS patients. In conclusion, low serum leptin, high serum TGF-beta1 and sOb-R levels, and elevated urine leptin concentrations were observed at the onset of MCNS. Since long-term proteinuria and leptinuria might be associated with the progression of renal damage, future in vivo and in vitro studies are needed to explain the interaction between these parameters in different types of nephrotic syndrome.
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PMID:Leptin, soluble leptin receptor, and transforming growth factor-beta1 levels in minimal change nephrotic syndrome. 1289 74

Literature data point to the relationship between leptin concentration and certain markers of the metabolic syndrome, including cholesterol, triglycerides and apolipoproteins. A substantial lipid metabolism disturbance occurs in children with idiopathic nephrotic syndrome (NS). The aim of the study was to find out whether in NS children, serum and urine leptin levels change proportionally to lipid metabolism disturbances. The study was performed on two groups: (I) 30 children with NS (A) before, (B) during, prednisone therapy after proteinuria regression; (II) 25 healthy children. Serum and urine leptin levels were determined by the immunoenzymatic ELISA method. Serum leptin level in NS children before and after treatment was similar to that in the control group (p>0.05). Leptin urinary excretion in group A was approximately 60 times and in group B 24 times higher than in the controls (p<0.01). Before treatment, children with NS had increased concentrations of TC, TG, LDL, beta-lipoprotein, apolipoprotein B (apo B) (p<0.01) and reduced HDL and apolipoprotein A (apo A) (p<0.01). The conclusions were that: (1) in NS children leptin urinary excretion increases but its level is unchanged in serum; (2) serum leptin level is correlated with lipid parameters.
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PMID:Serum and urine leptin concentration in children with nephrotic syndrome. 1578 10

The objective of this study was to evaluate the change in maternal serum leptin levels in preeclampsia and to study the relationship between maternal serum leptin and thyroid-stimulating hormone (TSH), body mass index (BMI), newborn weight, and proteinuria. Eighty-five pregnant women were included in this prospective study, of whom 50 were preeclamptic and 35 were normotensive. Maternal serum leptin levels were measured by the radioimmunoassay technique and TSH levels were measured by the electrochemiluminescence immunoassay method. The maternal serum leptin levels of preeclamptic and normotensive pregnant women were compared. In each group, the relationship between maternal serum leptin levels and TSH levels, BMI, newborn weight, and proteinuria was evaluated. The maternal serum leptin level was significantly higher in the preeclamptics than in the normotensive pregnant women. In the preeclamptic group, there was a strong positive correlation between maternal serum leptin levels and BMI (r =- 0.80; p < 0.001), a very weak positive correlation between maternal serum leptin levels and proteinuria (r = 0.305; p < 0.05), and a very weak inverse correlation between maternal serum leptin levels and birth weight (r = -0.377; p < 0.01). In the same group, there was no correlation between maternal serum leptin and serum TSH levels (r = 0.22; p > 0.05; Pearson correlation test). Leptin may be involved in the pathology of preeclampsia, and elevated maternal serum leptin levels may be a marker for the early stages of preeclampsia in pregnant women.
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PMID:Serum leptin levels in preeclamptic pregnant women: relationship to thyroid-stimulating hormone, body mass index, and proteinuria. 1583 51

Leptin is a peptide hormone that is mainly, but not exclusively, produced in adipose tissue and plays a pivotal role in regulating food intake and energy expenditure. Besides its effects on regulation of body weight, appetite and energy expenditure, leptin exhibits influence on the immune system and may contribute to the deterioration of renal function. These direct and indirect renal effects of leptin could partly explain obesity-associated kidney disease and may be also relevant for diabetic nephropathy in type 2 diabetes. Leptin is primarily metabolized in the kidney, presumably by binding to megalin, a multiligand receptor in the proximal tubule, tubular uptake and endocytosis. The kidney expresses abundant concentrations of the small isoform of the leptin receptor (Ob-Ra). In cultured renal rat endothelial cells and mesangial cells obtained from db/db mice, leptin can signal through the Ob-Ra receptor isoform. The peptide stimulates proliferation of glomerular endothelial cells, increases TGF-beta1 synthesis, and collagen type IV production. In contrast, leptin did not influence TGF-beta1 production in mesangial cells, but the peptide stimulates glucose transport in these cells, increased collagen type I synthesis, and lead to an upregulation of surface TGF-beta type II receptors through signal transduction pathways involving phosphatidylinositol-3-kinase. Leptin also stimulates hypertrophy, but not proliferation in cultured rat mesangial cells. Infusion of leptin for 3 weeks into normal rats fosters development of glomerulosclerosis and proteinuria. In addition, transgenic mice with leptin overexpression demonstrated a increase in collagen type IV and fibronectin mRNA in the kidney. Additional previously described direct and indirect effects of leptin on the kidney include natriuretic effects, an increase in sympathetic nervous activity, and stimulation of reactive oxygen species. These findings collectively suggest that the kidney is a target organ for leptin and that this hormone might play an important role in renal pathophysiology.
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PMID:Leptin and renal fibrosis. 1692 41

Leptin, one of adipocytokines, plays a wide range of important roles in reproductive biology. We have previously reported that low hypo-adiponectinemia might be involved in the pathophysiology of overweight preeclampsia (PE) patients. Moreover, recent reports have underscored the importance of circulating angiogenic factors in the pathophysiology of PE. Here, we examined whether leptin in conjunction with adiponectin and/or angiogenic factors plays some role in the pathophysiology of PE. We performed a cross-sectional study in 34 PE patients and normal pregnancies matched for gestational age and body mass index as controls. We measured serum concentrations of leptin, adiponectin, the angiogenic factors vascular endothelial growth factor (VEGF), placental growth factor, and the soluble VEGF receptors sFlt-1 and sFlk-1. We observed that leptin levels in PE patients were significantly higher compared with those in controls, but did not observe significant differences between normal- and overweight patients in both groups. We also showed a significant negative correlation between leptin and adiponectin in controls, but not in PE patients. There was a significant correlation between leptin and sFlt-1 in PE patients, while there were significant differences of body mass index, mean blood pressure and proteinuria between high and low leptin/sFlt-1 ratio group in PE patients. Moreover, there was a significant difference of leptin level between IUGR and normal growth group in PE patients. These results suggest that the circulating increased leptin might be derived mainly from the placenta and regulated by the placental hypoxic condition, whereas adiponectin might be derived mainly from adipose tissue; and that leptin might play some role through insulin resistance, autonomic activation, or direct effect on endothelium with other angiogenic factors in pathophysiology of PE compared with the exaggerated release of adiponectin from adipose tissue.
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PMID:Circulating leptin and angiogenic factors in preeclampsia patients. 1849 Aug 35

The reversibility of diabetic nephropathy remains controversial. Here, we tested whether replacing leptin could reverse the advanced diabetic nephropathy modeled by the leptin-deficient BTBR ob/ob mouse. Leptin replacement, but not inhibition of the renin-angiotensin-aldosterone system (RAAS), resulted in near-complete reversal of both structural (mesangial matrix expansion, mesangiolysis, basement membrane thickening, podocyte loss) and functional (proteinuria, accumulation of reactive oxygen species) measures of advanced diabetic nephropathy. Immunohistochemical labeling with the podocyte markers Wilms tumor 1 and p57 identified parietal epithelial cells as a possible source of regenerating podocytes. Thus, the leptin-deficient BTBR ob/ob mouse provides a model of advanced but reversible diabetic nephropathy for further study. These results also suggest that restoration of lost podocytes is possible but is not induced by RAAS inhibition, possibly explaining the limited efficacy of RAAS inhibitors in promoting repair of diabetic nephropathy.
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PMID:Reversibility of structural and functional damage in a model of advanced diabetic nephropathy. 2364 Oct 56


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