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)

The adipocyte hormone, leptin, is secreted in proportion to adipose mass and is implicated in the regulation of energy balance via its central actions on food intake and sympathetic nervous system activity. The placenta was also shown recently to be a possible source of leptin in pregnant women, raising the possibility that the normal relationship between leptin and adiposity may be altered in pre-eclampsia. We therefore sought to assess the extent to which maternal second trimester serum leptin concentrations differed for women who would subsequently develop pre-eclampsia and those who would remain normotensive. This nested case-control study population comprised 38 women with pregnancy-induced hypertension and proteinuria (pre-eclampsia) and 192 normotensive women. Multiple least-squares regression procedures were used to assess the independent relationship between leptin concentrations and risk of pre-eclampsia. Serum leptin concentrations, measured by radioimmunoassay, were highly correlated with maternal pre-pregnancy and second trimester body mass index (r = 0.71 and r = 0.74 respectively; P < 0.001 for both) among normotensive women, and to a lesser extent among women who developed pre-eclampsia (r = 0.29 and r = 0.42; P = 0.09 and 0.02 respectively). Among women with a pre-pregnancy body mass index of < or = 25 kg/m2, pre-eclampsia cases compared with controls had higher mean second trimester leptin concentrations after adjustment for confounding factors. In contrast, pre-eclampsia cases had lower mean leptin concentrations than controls for those women with a pre-pregnancy body mass index above 25 kg/m2. Other factors in addition to the level of adiposity may therefore influence serum leptin concentrations in pre-eclamptic pregnant women. Our results suggest the possibility that leptin, like several other placentally derived substances (e.g. steroid hormones, eicosanoids and cytokines), may be involved in the pathogenesis of pre-eclampsia. Further work is needed to confirm our findings and to assess the metabolic importance and determinants of leptin concentrations in uncomplicated and pre-eclamptic pregnancies.
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PMID:Pre-eclampsia disrupts the normal relationship between serum leptin concentrations and adiposity in pregnant women. 1021 9

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

Acylation-stimulating protein (ASP) is an adipocyte-derived protein that has recently been suggested to play an important role in the regulation of lipoprotein metabolism and triglyceride (TG) storage. ASP also appears to have a role in the regulation of energy balance. In addition to its role as a hormonal regulator of body weight and energy expenditure, leptin is now implicated as a regulatory molecule in lipid metabolism. However, little is known about the alterations in fasting plasma ASP and leptin concentrations in the nephrotic syndrome. As hyperlipidemia is one of the most striking manifestations of the nephrotic syndrome, we have investigated fasting plasma ASP and leptin levels and their relation to lipid levels in this syndrome. Twenty-five patients with untreated nephrotic syndrome and 25 age-, sex-, and body mass index-matched healthy controls were included in the study. Fasting plasma lipoproteins, TG, total cholesterol, lipoprotein(a), apolipoprotein AI (apoAI), apoB, urinary protein, plasma albumin, third component of complement (C3), ASP, and leptin levels were measured in both groups. Total cholesterol, TG, low and very low density lipoproteins, lipoprotein(a), apoB, and urinary protein levels were increased in the patient group, whereas plasma albumin, high density lipoprotein cholesterol, and apoAI levels were decreased compared with those in the control group (P < 0.001). Plasma ASP levels were significantly higher in the patient group compared with the control subjects (133.72 +/- 65.14 vs. 29.93 +/- 12.68 nmol/liter; P < 0.001), whereas leptin (2.69 +/- 2.06 vs. 3.99 +/- 2.99 ng/ml; P = 0.118) and C3 (1.01 +/- 0.25 vs. 1.06 +/- 0.23 g/liter; P = 0.662) levels were not significantly different between the two groups. Plasma leptin levels were correlated with body mass index in both nephrotic patients (r(s) = 0.86; P < 0.001) and controls (r(s) = 0.98; P < 0.001), but were not correlated with the other parameters. Fasting ASP concentrations showed no correlation with body mass index, proteinuria, plasma albumin, leptin, or any lipid parameter in either group, but C3 levels (in patient group: r(s) = 0.92; P < 0.001; in control group: r(s) = 0.68; P < 0.001). Our findings showed that plasma ASP levels were significantly elevated, whereas leptin levels were normal in the nephrotic syndrome. Increased ASP levels in the setting of dyslipidemia in the nephrotic syndrome raise the possibility of an ASP receptor defect in adipocytes, which also suggests the existence of so-called ASP resistance. Moreover, it is possible that ASP activity is maximal, but cannot keep up with increased rates of lipid production by the liver. Thus, further studies are needed to elucidate the mechanism or source (adipocytes, the liver, or both) of elevated ASP concentrations in the nephrotic syndrome.
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PMID:Increased fasting plasma acylation-stimulating protein concentrations in nephrotic syndrome. 1183 32

Obesity, which has reached epidemic proportions in the United States and other western countries, may be complicated by hypertension, an increased incidence of renal cancer or proteinuria. Patients with obesity-associated proteinuria show focal glomerulosclerosis and glomerulomegaly on biopsy, usually have minimal clinical edema and relatively normal levels of serum albumin, cholesterol and blood pressure, and can progress to end-stage renal disease. Severe obesity may also be an additive risk factor in patients with preexisting nephropathy or reduced renal mass. The pathophysiology of obesity-associated proteinuria is unclear but may include hyperfiltration, increased renal venous pressure, glomerular hypertrophy, hyperlipidemia and increased synthesis of vasoactive and fibrogenic substances, including angiotensin II, insulin, leptin and transforming growth factor-beta1. These substances may individually or interactively affect glomerular hyperfiltration, mesangial cell hypertrophy and matrix production, and the production of collagen, fibronectin, transforming growth factor-beta and other fibrogenic mediators of change. Although angiotensin-converting enzyme inhibition has proven to have an impact, perhaps temporarily, on obesity-associated proteinuria in humans, weight reduction early in the course of the disease would appear the most important therapeutic approach.
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PMID:Obesity and renal disease. 1198 Dec 64

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

Obesity and hyperhomocysteinaemia are found very frequently after kidney transplantation (Tx). They may independently represent risk factors for development of atherosclerosis and chronic allograft nephropathy. In a prospective metabolic study, we monitored, over a period of 24 months, a total of 118 obese transplant patients [body mass index (BMI) > or =30 kg/m(2)] with hyperhomocysteinaemia. We compared the findings of a new therapeutic regimen at 1 year (start of the study) and 2 years after renal transplantation. Based on a Subjective Global Assessment Scoring Sheet, we started at the end of the first year with an individualized hypoenergic-hypolipidaemic diet (IHHD). Subsequently, after corticoid withdrawal, IHHD was supplemented regularly with orlistat at a dose of up to 3 x 120 mg/day, statins (pravastatin 10-40 mg), folic acid 5 mg/day and vitamin B6 50 mg/day, and followed-up for up to 2 years. All patients were on a regimen of cyclosporin A and mycophenolate mofetil. During the study period, there was a significant decrease in BMI (P < 0.025) and total homocysteine level (P < 0.001). Long-term therapy was associated with a significant decrease in serum leptin (P < 0.001) and lipid metabolism parameters (P < 0.01). The mean values of serum folate and vitamin B6 also increased significantly (P < 0.01); creatinine clearance, mean blood pressure, proteinuria, lipoprotein(a) and apolipoprotein E isoforms did not differ significantly. Based on our results, we assume that obesity and hyperhomocysteinaemia after renal transplantation can be treated effectively by modified immunosuppression (corticosteroid withdrawal), long-term diet (IHHD), folic acid and vitamin B6 supplementation, and drugs suppressing digestion or absorption to reduce atherosclerotic and chronic allograft nephrop-athy processes.
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PMID:Obesity and hyperhomocysteinaemia after kidney transplantation. 1281 77

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

In patients with nephrotic syndrome, severe proteinuria is related to significant leptinuria; serum leptin levels remain unchanged. The goal of this study was to elucidate the role of the soluble leptin receptor (sOB-R) in maintaining serum leptin levels in nephrotic patients. Patients with proteinuria were compared with patients in remission of nephrotic syndrome. In this group proteinuria did not exceed 100 mg/m(2) of body surface area per day. The period of remission was at least 6 months and was equal in all patients included. The sOB-R level (mean +/- SD) in serum of patients with nephrotic syndrome was significantly higher during proteinuria (61.0 +/- 17.8 ng/ml) than those in remission or in control patients (36.7 +/- 7.0 ng/ml, 36.6 +/- 12.0 ng/ml, respectively, P < 0.0001). The ratio between serum leptin levels and the sOB-R (free leptin index) was significantly lower in the proteinuric group (0.012 +/- 0.005 vs. 0.06 +/- 0.03 and 0.07 +/- 0.03 in remission and control group, respectively) (P < 0.001). Urinary sOB-R excretion was similar in all groups. Our data suggest that the counteracting pathway in case of leptin loss in parallel to severe proteinuria in nephrotic syndrome is the up-regulation of its soluble binding protein in serum, which can keep total serum leptin levels constant.
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PMID:Increased soluble leptin receptor in children with nephrotic syndrome. 1460 96


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