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)

About 10% of all nephroblastomas (Wilms' tumor) present as part of malformation syndromes. The Denys-Drash syndrome (DDS) comprises pseudohermaphroditism, glomerulopathy and, early, often bilateral Wilms' tumors. A nephrectomy was performed in a 4-month-old girl because of a Wilms' tumor. Two months later, low serum albumin levels and proteinuria had developed. A biopsy from the remaining kidney showed a glomerulopathy which could also be seen in the nephrectomy specimen. The morphology was highly characteristic: the innermost layer of the kidney cortex exhibited augmentation of the mesangial matrix only; the intermediate layer showed severe sclerosis of glomeruli with deposition of fibrillary material; and the subcapsular layer revealed very small glomeruli and atrophic tubuli. Fifteen months later, peritoneal dialysis was necessary and due to the high risk of tumor development in the remaining kidney, a nephrectomy was performed. Molecular analysis revealed a point mutation within exon 9 of the WT1 gene (394 ARG-->TRP), which was homozygous in the tumor and heterozygous within renal parenchyma. The DDS is caused by a mutation in the WT1 gene on chromosome 11p13 which occurs during oogenesis or spermiogenesis. The WT1 gene is highly expressed during the development of the genitalia and the kidney; damage in one allele only causes the malformation syndrome. Loss of the second allele of the WT1 gene constitutes the second step of tumorigenesis. The appearance of Wilms' tumors derived from cells homozygous for the mutation reveals the function of the WT1 gene as a tumor suppressor gene.
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PMID:[Glomerulopathy in Denys-Drash syndrome. Case report of a model disease]. 964 50

Normal pregnancy is characterized by a significant reduction in total peripheral vascular resistance and decreased pressor responsiveness to vasodilator agents. This review will consider whether nitric oxide (NO) contributes to these changes, and whether a deficiency of NO produces a preeclampsia like syndrome. The biosynthesis of NO increases in pregnant animals, as assessed by the raised plasma concentration, urinary excretion and metabolic production rate of guanosine 3',5'-cyclic monophosphate (cGMP), the second messenger of NO. In addition, urinary excretion of nitrate, the stable metabolites of NO, increases during pregnancy, paralleling the rise in cGMP. Several studies provide convincing evidence indicating that expression and activity of different NO synthases (NOS) are increased in gravid animals. Acute blockade of NOS causes a dose response increase in blood pressure and reverses the blunted vasopressor response to vasoconstrictor agents. Long-term NOS inhibition produces a pre-eclampsia like syndrome, characterized by maternal hypertension, proteinuria, thrombocytopenia, and renal damage, and lower litter size and fetal weight. Both acute and chronic responses are reduced when L-arginine, the substrate for NOS, is administered in high doses, indicating that these changes are specific to NO inhibition. In conclusion, present data suggest that a disturbance in NO release may contribute to the pathogenesis of pre-eclampsia.
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PMID:Role of nitric oxide in maternal hemodynamics and hormonal changes in pregnant rats. 983 May 12

A French family with hereditary renal amyloidosis (HRA) was studied. The disease presented in 7 of the 8 affected individuals with proteinuria or the nephrotic syndrome. The age of onset was in the fifth decade of life. There is currently no sign of extrarenal involvement in any affected individual. However, the nephropathy in this family is progressive and led to terminal renal failure in 4 patients. Immunohistochemistry studies of glomerular amyloid deposits suggested that the amyloid protein was the fibrinogen A alpha chain. Direct DNA sequencing revealed a G 4993 T transversion and subsequently Arg 554 Leu mutation in the fibrinogen A alpha chain. This is the first description of this fibrinogen A alpha chain mutation in Europe. This family is of French descent and cannot be related to the previously reported Peruvian/Mexican and African-American kindreds.
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PMID:Fibrinogen A alpha chain mutation (Arg554 Leu) associated with hereditary renal amyloidosis in a French family. 1003 86

Previous studies showed a renoprotective effect of l-arginine in experimental uremia. Whether this was caused by an increased nitric oxide (NO) release or depended on l-arginine per se is not clear. Here, we evaluated whether chronic administration of an NO donor, molsidomine, controlled systemic blood pressure and renal disease progression and prolonged survival in rats with renal mass reduction (RMR). Rats with RMR received the following daily in the drinking water: group 1 (n = 21), no specific therapy (vehicle); group 2 (n = 12), molsidomine, 120 mg/L; group 3 (n = 9), lisinopril, 25 mg/L; and group 4 (n = 12), reserpine, 5 mg/L, hydralazine, 80 mg/L, and hydrochlorothiazide, 25 mg/L, from day 21 after surgery, when rats had hypertension and proteinuria, until the death of the vehicle-treated rats. Molsidomine normalized systemic hypertension, only partially reduced proteinuria and serum creatinine levels, but significantly prolonged animal survival, particularly in the early stage of the disease. Lisinopril at a similar systemic blood pressure was even better than molsidomine in limiting proteinuria, preserving renal function, and prolonging survival, but triple therapy, despite being effective on blood pressure, offered no renoprotection or prolonged survival. Endothelin-1 (ET-1) levels, formed in excessive amounts by the kidneys of these animals, were reduced by molsidomine and lisinopril, but not by triple therapy. The prolongation of survival by NO donor could be attributed to its effect of reducing ET levels, which in turn may limit the smooth muscle cell proliferation and matrix accumulation responsible for organ and, especially, myocardial fibrosis in uremia.
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PMID:Renoprotection by nitric oxide donor and lisinopril in the remnant kidney model. 1019 19

The administration of L-arginine to normal animals leads to an increase in renal plasma flow and glomerular filtration rate (GFR). Administration on a chronic basis of N-nitro-L-arginine methylester (L-NAME), an antagonist of L-arginine, increases blood pressure and reduces the ultrafiltration coefficient. In rats with ureteral obstruction, the administration of L-arginine increases GFR and renal blood flow in the postobstructive kidney. Administration of L-arginine decreased the macrophage infiltration of the renal parenchyma that occurs in this model. L-arginine administration also blunted the increases in interstitial volume, collagen deposition, and expression of alpha-smooth muscle actin in the obstructed kidney. L-arginine administration to rats with subtotal nephrectomy reduced proteinuria and the number of abnormal glomeruli. Some of these effects may be mediated by nitric oxide (NO). In rats with diabetes, administration of L-arginine decreased hyperfiltration and proteinuria. The role of arginine and NO in glomerular diseases is controversial. In general most of the evidence indicates a beneficial change in the renal pathology and function in animals with glomerulonephritis receiving L-arginine. Most of the evidence indicates that the L-arginine-NO pathway has an important role in ameliorating hypertension, renal disease, inflammation and atherosclerosis.
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PMID:Can L-arginine manipulation reduce renal disease? 1022 37

Nephrotic-range proteinuria is associated with a several-fold increase risk of cardiovascular infarction. This increased risk is accompanied by endothelial dysfunction, which is not related to increased blood pressure and is not correctable by acute administration of L-arginine. The latter is in direct contrast to what has been found in patients with primary hypercholesterolemia, suggesting that either hypoalbuminemia itself or other aspects of the dyslipidemia characteristic of the nephrotic syndrome impair endothelial function. Lysophosphatidylcholine (lyso-PC) is formed during oxidative modification of cholesterol, and lyso-PC in oxidized low-density lipoprotein (LDL) is responsible for reduced endothelial function in vitro. However, in the circulation, lyso-PC is tightly bound to albumin. Indeed, the addition of albumin can restore endothelial function, which was previously disturbed by lyso-PC. Hypoalbuminemia induces a shift in lyso-PC to lipoproteins, notably LDL, and to erythrocytes. The latter directly induces a reduction in deformability that can also be corrected by the addition of albumin. Hypoalbuminemia may disturb endothelial function, either by directly affecting Gi-protein-dependent signal transduction or indirectly by changing the configuration of the cell membrane. Such a change in cell membrane configuration will disturb binding of ligands to receptors and of endothelial nitric oxide (NO) synthase to caveolin. However, other pathways have been suggested, such as stimulation by lyso-PC of vasoconstriction mediated by protein kinase C. It remains to be shown whether lipid-lowering and antiproteinuric strategies have independent positive effects on endothelial function in nephrotic subjects.
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PMID:Endothelial function in proteinuric renal disease. 1041 39

Endothelin 1 (ET-1) is a potent vasoconstrictor implicated in the control of blood pressure and renal function. Its effects can be modulated by nitric oxide (NO), which inhibits ET-1 production and action. Recently, we reported that ET-1 production can also be modulated by angiotensin II (AngII) in vivo. To investigate the interactions between NO, ET-1, and AngII in hypertension and renal dysfunction, we assessed immunoreactive ET-1 (ir-ET-1) concentration in plasma and urine as well as in vascular and renal tissues of rats with chronic inhibition of NO synthesis, in the presence and the absence of the AngII type 1 receptor antagonist losartan. Normal (protocols A and B) and uninephrectomized rats (protocol C) received the L-arginine analog N(G)-nitro-L-arginine methyl ester (L-NAME), an inhibitor of NO synthesis, 0.05% (protocol A) or 0.1% (protocols B and C), with or without losartan (20 mg x kg(-1) x day(-1)). After 6 weeks, systolic blood pressure was significantly increased in L-NAME rats compared with the controls (p < 0.01), while serum creatinine and urea, creatinine clearance, and proteinuria were similar to control values. However, ir-ET-1 concentration in plasma and in the thoracic aorta was augmented in animals receiving 0.1% L-NAME (1 < 0.01), while it was unchanged in the mesenteric arterial bed, preglomerular arteries, and glomeruli. In contrast, ir-ET-1 concentration was decreased in the renal papilla (p < 0.05) as well as in the urine of L-NAME rats (p < 0.01). Treatment with losartan significantly attenuated the rise in systolic blood pressure induced by L-NAME (p < 0.01). Losartan also normalized the increased ir-ET-1 concentration in plasma and in the thoracic aorta, but had no effect on tissues with normal or reduced ir-ET-1 levels. These results indicate that chronic inhibition of NO synthase with L-NAME induces hypertension without renal dysfunction. Increased ET-1 production in some blood vessels and elevated circulating ET-1 concentration may contribute to the maintenance of high blood pressure. The reduction of systolic blood pressure by losartan supports a role for AngII in the pathogenesis of this form of hypertension, which may be due, at least in part, to the modulation of ET-1 production.
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PMID:Renal and vascular effects of chronic nitric oxide synthase inhibition: involvement of endothelin 1 and angiotensin II. 1053 60

1. The purpose of the present study was to examine the effect of nitric oxide (NO) inhibition on mean arterial pressure (MAP), endothelin (ET) and the renin-aldosterone system in pregnancy in the non-human primate (baboon). 2. Twenty pregnant baboons (Papio hamadryas) were examined prospectively after the administration of an oral NO inhibitor in different phases of pregnancy. Haemodynamic responses to NO inhibition, evidence of pre-eclampsia and the renin-aldosterone system were examined under anaesthesia. 3. Oral NL-nitro-L-arginine (NOLA; 5 or 10 mg/kg) was given for 1 week in early (6-8 weeks gestation), middle (14-16 weeks gestation) and late (22-24 weeks gestation) pregnancy and while non-pregnant. Mean arterial pressure, heart rate, haematology, biochemistry, ET, plasma renin activity (PRA) and aldosterone were measured. Foetal effects of NOLA were also examined by ultrasound and neonatal measurements. 4. Nitric oxide inhibition led to an increase in MAP in non-pregnant animals (9 mmHg) and in middle and later pregnancy (6 and 7 mmHg, respectively). Mean arterial pressure in early pregnancy was not affected. A reduction in PRA occurred after NO inhibition in all stages of pregnancy. Significant proteinuria occurred only in late pregnancy. 5. Nitric oxide is involved in the maintenance of lower blood pressure in late pregnancy and inhibition leads to an increase in blood pressure and proteinuria in the baboon. Nitric oxide insufficiency may contribute to the clinical manifestations of human pre-eclampsia. Nitric oxide was not involved in the normal vasodilation of early primate pregnancy.
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PMID:Low-dose nitro-L-arginine administration in baboon (Papio hamadryas) pregnancy. 1056 3

In glomerulonephritis, there is intraglomerular activation of inducible nitric oxide synthase (iNOS) leading to high output production of nitric oxide (NO). This can result in supraphysiologic amounts of NO and cause oxidative injury. It is unknown whether mechanisms of cellular defense against NO-mediated injury exist. Induction of the heme catabolizing enzyme heme oxygenase-1 (HO-1), which generates biliverdin, carbon monoxide (CO), and iron (Fe), may provide such a mechanism, as CO and Fe are two negative modulators of iNOS activity and expression. This study assessed whether upregulation of HO-1 by a specific inducer, hemin, negatively modulates iNOS expression and activity in anti-glomerular basement membrane antibody-mediated glomerulonephritis. Glomerular HO-1 expression in nephritic animals was upregulated by treatment with hemin (30 micromol/kg body wt). iNOS and HO-1 mRNA expression were assessed by reverse transcription-PCR of glomerular total RNA from nephritic animals or nephritic animals pretreated with hemin. iNOS activity in glomeruli was measured by assessing conversion of [14C] L-arginine to [14C] L-citrulline. HO-1 protein levels in glomeruli were assessed by Western blot analysis. The effect of hemin treatment on monocyte/macrophage infiltration was assessed by enumeration of ED-1-positive cells in nephritic glomeruli. iNOS and HO-1 were coinduced in nephritic glomeruli. Hemin treatment of nephritic animals resulted in upregulation of glomerular HO-1 levels and a two- to threefold reduction in glomerular iNOS mRNA levels. iNOS activity in glomeruli was significantly reduced in hemin-treated nephritic animals in which proteinuria was also attenuated without a change in monocyte/macrophage infiltration. Hemin (100 to 200 microM) also reduced iNOS protein levels and enzyme activity in cultured mesangial cells stimulated with cytokines. These studies demonstrate that in glomerular immune injury, hemin treatment upregulates glomerular HO-1 with an attendant downregulation of iNOS expression, and thus points to regulatory interaction between the two systems. The beneficial effect of hemin treatment on proteinuria could be linked to downregulation of iNOS.
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PMID:Heme oxygenase-1 induction attenuates inducible nitric oxide synthase expression and proteinuria in glomerulonephritis. 1058 93

Burn injuries trigger a pronounced inflammatory response in the burned skin, resulting in oedema formation and impaired circulation. This response involves activation of the nitric oxide (NO) synthetic pathway, which could play a key role in the complex hemodynamic and hemostatic changes occurring as a result of a burn trauma. The results presented in full-thickness skin burns of rats show that the NO-precursor, L-arginine (n = 10), inhibit burn-induced plasma extravasation as compared to saline-treated burned controls (n = 10) (p<0.001) to a level not significantly different from nonburned animals. Administration of the NO-synthase inhibitor. NG-nitro-L-arginine (L-NNA) (n = 10), did not significantly influence burn extravasation compared to burned controls. Accumulated urine volume 90 min post-burn increased ten-fold in burned animals treated with L-arginine compared to saline-treated burned controls (p<0.001) and nonburned animals (p<0.001), while L-NNA had no significant effect on diuresis. A significantly increased proteinuria occurred in L-arginine treated burned animals as compared to burned controls and nonburned controls (p<0.001), whereas L-NNA did not significantly influence the leakage of protein in the urine. Activation of NO synthesis significantly suppresses burn edema and strongly increases diuresis along with increased proteinuria.
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PMID:Importance of nitric oxide in the regulation of burn oedema, proteinuria and urine output. 1063 Mar 14


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