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)

A reduction in prostacyclin (PGI2) production by vascular wall may cause platelet hyperaggregability in diabetics, which is considered to be a possible pathogenesis of diabetic vascular complications. In the present study, the presence of PGI2-stimulatory activity (PSA) in rat and human plasma-derived serum (PDS) was confirmed by cultured bovine aortic endothelial cells. PSA in PDS was significantly decreased in streptozotocin-induced diabetic rats and in patients with non-insulin-dependent diabetes mellitus (NIDDM). PDS from patients with NIDDM showed less PSA prior to the clinical onset of diabetic vascular complications, such as retinopathy and proteinuria. The reduction in PSA was still observed in dialyzed PDS from the patients with NIDDM. The nondialyzable PSA was heat-stable at 56 degrees C for 30 minutes and partially stable at 100 degrees C for five minutes. This activity was not extractable with diethylether and was precipitable with trichloroacetic acid. The study of Sephadex G-50 column chromatography showed that a major part of PSA in dialyzed PDS was found in the area of the molecular weight of 12,000 to 17,000 daltons. In conclusion, the reduction in PSA from diabetics may cause a reduction of PGI2 production by vascular wall, subsequently contributing to the development of diabetic vascular complications.
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PMID:Abnormality in prostacyclin-stimulatory activity in sera from diabetics. 250 15

Fourteen patients with chronic proliferative glomerulonephritis were given for the period of one year 400 mg acetylsalicylic acid and 225 mg dipyridamole per day. During this treatment the thrombocyte aggregation became normal, however, the mean reduction of antiheparin plasma activity was not statistically significant. Normal synthesis of renal prostacyclin declined significantly as a result of treatment, while the renal thromboxane A2 synthesis remained normal even during treatment. Treatment did not influence proteinuria. The mean annual decline of glomerular filtration was greater during the investigation period than the mean annual decline in previous years, the difference was, however, only at the borderline of statistical significance. The authors did not prove a favourable effect of this treatment in patients with chronic proliferative glomerulonephritis.
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PMID:[Treatment of chronic proliferative glomerulonephritis using acetylsalicylic acid and dipyridamole]. 250 56

Preeclampsia, a major cause of fetal and maternal morbidity and mortality, may be difficult to distinguish clinically from other hypertensive disorders of pregnancy. Signs helpful in its diagnosis include presentation during late gestation in a nullipara with edema and proteinuria, and one or more of the following: hemoconcentration, hypoalbuminemia, liver function and/or coagulation abnormalities, and increased urate levels. Measures that may prove useful in differentiating preeclampsia from less dangerous forms of hypertension are decreased antithrombin III levels, increments in serum iron and carboxyhemoglobin, and decreases in urinary calcium. Major pathophysiological features of preeclampsia are decreased cardiac output, pulmonary capillary wedge pressure, and plasma volume; and marked increases in peripheral vascular resistance, as well as exaggerated pressor responses to endogenous angiotensin II and catecholamines. Renal hemodynamics decrease, in part as a result of a characteristic morphological lesion in glomeruli ("endotheliosis"), and there may be increased vascular permeability leading to albumin loss from the intravascular space. When gestation is advanced, termination is the treatment of choice; when temporization is required, several antihypertensive medications whose safety and efficacy have been tested in pregnant women are available. Magnesium sulfate remains the drug of choice for impending convulsions (the eclamptic phase of the disease). Finally, the etiology of preeclampsia remains unknown, but a popular theory suggests that alterations in prostaglandin metabolism may be responsible for the hypertension and coagulopathy in this disorder. In this respect, prophylactic treatment with low doses of aspirin, which decrease platelet thromboxane production but spare endothelial prostacyclin release, may decrease the incidence of preeclampsia in "high-risk" populations.
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PMID:Preeclampsia: pathophysiology, diagnosis, and management. 265 50

Indomethacin has been used to lower proteinuria in human glomerular diseases with controversial results. The mechanism of indomethacin beneficial effects has not been established. A possible explanation is that indomethacin reduces proteinuria by inhibiting the synthesis of renal prostaglandins (PGs); however, appropriate studies to address this issue have never been done. The objectives of the present study were: to investigate whether indomethacin influences protein excretion in an experimental model of immunologically-mediated glomerular disease; to establish if the possible favorable effect of indomethacin on proteinuria is related to a reduction in glomerular filtration rate (GFR); to establish the possible association between the antiproteinuric effect of indomethacin and its inhibitory effect on arachidonic acid (AA) metabolites of renal or extrarenal origin; and to further investigate the relationship between proteinuria and renal thromboxane (Tx) synthesis previously demonstrated in experimental models of nephrotoxic nephritis and adriamycin (ADR) nephrosis. To this purpose we used an experimental immune-complex disease, passive Heymann nephritis (PHN) which was induced in the rat by a single intravenous (i.v.) injection of heterologous serum directed against a brush border component (gp 330 antigen). Indomethacin at a dose of 6 mg/kg intraperitoneally (i.p.) administered for four consecutive days to PHN animals during the period of heavy proteinuria, effectively reduced urinary protein excretion. The reduction in proteinuria does not appear to be a consequence of a reduction in GFR as documented by inulin clearance. Glomerular synthesis and urinary excretion of vasodilatory prostacyclin (PGI2) and PGE2 were decreased or unchanged in PHN animals in respect to control animals.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Indomethacin reduces proteinuria in passive Heymann nephritis in rats. 295 50

The results of a controlled trial to ascertain the usefulness of plasma infusion for the treatment of hemolytic-uremic syndrome (HUS) are reported. Criteria for admission were (1) observation within 8 days from first symptoms, (2) dialysis treatment required, and (3) no special treatments and no more than 25 ml blood/kg previously received. Children were subdivided according to age (less than or more than 3 years) and then randomly assigned to treatment with plasma or symptomatic therapy. Thirty-two children ranging in age from 4 months to 6 years entered this study; 17 received plasma (P+ group) and 15 only symptomatic therapy (P- group). The mean follow-up period was 16 months in both groups. Surgical renal biopsy was performed 29 to 49 days after onset in 11 P+ and 11 P- children, and 33 histologic findings were semiquantitatively evaluated. No death occurred in either group. No differences were found in blood pressure, proteinuria, or hematuria at the end of the follow-up period; in no case were severe arteriolar lesions found. There were no significant differences for the scores of the individual histologic measurements; on electron microscopy, no vascular changes were observed in seven children of the P+ group, whereas in five of seven of the P- group, thickening of the lamina rara interna and arteriolar damage were present. The ability of plasma to stimulate prostacyclin (PGI2) production, measured as its stable derivative 6-keto-PGF1 alpha, was within the normal range for all patients. In our patients with predominant glomerular involvement who were treated in a very early phase of HUS, infusions of plasma did not significantly influence the short- and medium-term clinical outcome and were not effective in severe HUS when given later in the course of the disease. A longer follow-up is needed to ascertain whether the presence of endothelial damage, demonstrated by electron microscopy in children who were not given plasma, is of clinical relevance.
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PMID:Plasma infusion for hemolytic-uremic syndrome in children: results of a multicenter controlled trial. 327 65

Changes in glomerular hemodynamics have been observed in animals and humans after a high-protein feeding. It has been postulated that these changes can induce progressive deterioration of renal function favoring loss of glomerular permselectivity properties and subsequent glomerulosclerosis, especially when the renal mass is already reduced surgically or by a disease process. We studied the consequence of long-term protein supplementation on renal function parameters in normal animals and in animals affected by adriamycin nephrosis, a model of renal damage that closely mimics human "minimal change". We also wanted to investigate whether vasodilatory prostaglandins (PGs) generated at the renal level are responsible for the adaptive hemodynamic changes that follow dietary manipulation in normal animals and in animals with experimental nephrosis. The model of glomerular damage we used is characterized by heavy and persistent proteinuria induced in the rat by adriamycin (ADR). Two isocaloric diets were selected containing 20% and 35% protein. High-protein feeding induced a significant increase in glomerular filtration rate in both normal and nephrotic animals. In normal animals the high-protein diet did not modify the urinary excretion of 6-keto-PGF1 alpha, the stable breakdown product of prostacyclin (PGI2), but significantly reduced urinary excretion of prostaglandin E2. In nephrotic rats, the high-protein diet increased urinary excretion of 6-keto-PGF1 alpha, without modifying urinary excretion of prostaglandin E2. Glomerular synthesis of vasodilatory prostaglandins paralleled the urinary excretion pattern. The cyclooxygenase inhibitor indomethacin effectively inhibited urinary excretion of vasodilatory PGs but did not prevent hyperfiltration in normal animals fed the high-protein diet. At variance, when given to nephrotic animals fed the high-protein diet, indomethacin at a dose that reduced 6-keto-PGF1 alpha and prostaglandin E2 urinary excretion by 84% and 93%, respectively, inhibited hyperfiltration. We conclude that the same hemodynamic changes that occur in normal animals given a high-protein diet also take place when glomeruli are uniformly damaged by a disease process as in ADR nephrosis. However, whereas hyperfiltration in normal animals appears to be independent of renal PGs, in nephrotic animals an enhanced renal synthesis of PGI2 appears to play a crucial role in the adaptive changes responsible for hyperfiltration.
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PMID:Role of renal prostaglandins in normal and nephrotic rats with diet-induced hyperfiltration. 346 81

Preeclampsia is a disorder of pregnancy characterized clinically by hypertension, proteinuria, and edema and characterized pathologically in its late stages by widespread microvascular thrombi. There is evidence from a number of studies that production of prostacyclin (prostaglandin I2, PGI2), a potent vasodilator and inhibitor of platelet aggregation, is deficient in preeclamptic compared to normal pregnancy. Traditional therapy utilizes infusions of large amounts of MgSO4, but the physiologic basis for this is not clear. We studied the effect of MgSO4 on PGI2 release by cultured human umbilical vein endothelial cells (HUVEC) by several methods. By platelet aggregometry, the known antiaggregatory effect of intact HUVEC was enhanced by MgSO4. By radioimmunoassay for 6-keto-PGF1 alpha, the stable metabolite of PGI2, it was shown that MgSO4 amplifies release of PGI2 by HUVEC in a dose-dependent manner, with a peak occurring between 2 and 3 mM. In separate experiments, MgSO4 overcame the enhanced adherence of platelets to HUVEC exhausted by repeated exposure to thrombin. Finally, PGI2 production was 2- to 5-fold greater by HUVEC incubated with plasma obtained from preeclamptic patients undergoing MgSO4 therapy than by HUVEC incubated with pretherapy plasma. We conclude that MgSO4 mediates enhanced production of PGI2 by vascular endothelium, thereby potentially enhancing its thromboresistant properties.
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PMID:Magnesium sulfate: rationale for its use in preeclampsia. 351 61

Thromboxane (TX) A2 is a potent vasoconstrictor as well as a proaggregator of platelets. Augmented TXB2 platelet synthesis and attenuated vascular prostacyclin formation have been demonstrated in diabetes mellitus. We undertook to establish a simple method of extracting urinary TXB2 (UTXB2) and to elucidate the pathophysiologic role of renal TXA2 in diabetes mellitus. One-step extraction of UTXB2 with an octadecylsilyl-silica column was sufficient as pretreatment for TXB2 radioimmunoassay because recovery of UTXB2 was good, the eluate was parallel with the dose-response curve, and the value coincided with that obtained by the conventional method. When platelet TXA2 synthesis was completely suppressed by administration of 100 mg aspirin, urinary TXB2 excretion (UTXB2V) declined to 41% of the initial levels, suggesting that renal TXA2 formation contributes significantly to UTXB2V. UTXB2V was 94.5 +/- 14.0 ng/day or 108.8 +/- 17.3 ng/gm creatinine in controls. Approximately half of the patients with diabetes demonstrated a UTXB2 level higher than the mean + 2 SD level of controls. Although UTXB2V did not show a significant correlation with protein excretion, UTXB2V in patients with diabetes with proteinuria greater than 100 mg/day was augmented (224.4 +/- 30.5 ng/day) compared with that in patients with diabetes without proteinuria greater than 100 mg/day. Furthermore, UTXB2V correlated negatively with the p-aminohippuric acid clearance rate, but not with the creatinine clearance rate. The results suggest that renal TXA2 synthesis may be augmented in diabetic nephropathy and may play a pathophysiologic role in renal hemodynamics as well as in protein excretion.
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PMID:Increased thromboxane B2 excretion in diabetes mellitus. 358 44

Hypertension in pregnancy has implications for both maternal and fetal welfare. Extrapolation from concepts of mechanisms operating in hypertension in general to pregnancy-related hypertension is not justified. In the latter, the major features are a hyper-adrenergic state, plasma volume reduction and an increased systemic resistance. A reduction in uteroplacental perfusion may result from or may activate the mechanisms that elevate blood pressure. Humoral factors (e.g. hormonal attenuation of vascular reactivity) and prostacyclin deficiency may be central to the disordered physiology. Treatment of hypertension in pregnancy should aim at avoiding the vascular damage due to blood pressure elevation but not cause a reduction in uteroplacental perfusion. Unlike earlier antihypertensive regimens using centrally acting sympatholytics, adrenergic neuron blockers or diuretics, regimens using beta-blockers or combinations of beta-blockers with alpha-blockers or vasodilating agents such as hydralazine permit effective blood pressure control, even in severe hypertension, and pregnancy can often proceed until term or until fetal maturity is secured. Adverse effects on the fetus (growth retardation, cardiorespiratory depression, hypoglycaemia, hyperbilirubinaemia) formerly attributed to beta-blockers are more likely related to poorly controlled hypertension. Specific benefits of maternal beta-adrenoceptor blockade are suggested by evidence for prevention of proteinuric deterioration and a decrease in the incidence and severity of respiratory distress in premature infants. Hypertension in pregnancy still presents a formidable therapeutic challenge and requires comprehensive management with close monitoring of fetal welfare. The presence or development of proteinuria in a hypertensive pregnant woman implies a major increase in risk to the fetus and warrants immediate admission to hospital for specialist management.
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PMID:Hypertension in pregnancy. Pathophysiology and management. 614 40

Thrombotic thrombocytopenic purpura (TTP) is usually accompanied by renal disfunction presumable due to diffuse thrombotic occlusions in the microcirculation. Two patients with TTP and slight renal failure with proteinuria and microscopic hematuria, were treated by repeated plasma exchanges with fresh frozen plasma, associated with prednisone and cyclophosphamide in one case, and prednisone alone in the other one. Platelet count, hematocrit and lactic dehydrogenase reverted to normal values within the fourth exchange; circulating immune complexes were never detected. Plasma factor stimulating prostacyclin activity lacked in only one patient and returned to normal levels after plasma exchange without being affected during a hematologic relapse. Renal function and urinary abnormalities reverted to normal by the end of plasma exchange and nine and six months renal and hematologic follow-up is still negative. Renal abnormalities in TTP seem to take advantage of early treatment by plasma exchange, which further to replacement of missing plasma factors, can account for the removal of toxic substances to be further investigated on.
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PMID:Renal abnormalities reverted by plasma exchange in thrombotic thrombocytopenic purpura. 668 92


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