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)

Treatment of membranous nephropathy and the nephrotic syndrome with 2 mg/kg/day of indomethacin resulted in prompt and sustained reduction in urinary protein excretion and the loss of edema fluid, which allowed the withdrawal of diuretic therapy and liberalization of salt intake. The reduction in proteinuria was paralleled by a decrease in urinary prostaglandin E (PGE) and F (PGF) levels. Plasma PGE and PGF levels did not change appreciably. Withdrawal of indomethacin therapy resulted in an increase in urinary protein and urinary PGE excretion. Reinstitution of therapy resulted in reductions in both values. Indomethacin may provide a useful means of reducing proteinuria and controlling edema in some patients with the nephrotic syndrome.
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PMID:Indomethacin and the nephrotic syndrome. 76 92

To elucidate the mechanisms by which indomethacin lowers proteinuria, we studied 20 patients with the nephrotic syndrome. We performed differential macromolecule clearances before and after 3 days of therapy (150 mg/24 h). The fractional clearances of albumin and immunoglobulin G (IgG) decreased by 42 +/- 7 and 44 +/- 10%, respectively (P less than 0.05). Separation of IgG into fractions by preparative electrofocusing in eight selected individuals revealed a proportionate reduction of fractional clearances among anionic (pI = 5.0), neutral (pI = 7.5), and cationic species (pI = 8.5) of IgG. Indomethacin elevated the fractional clearance of uncharged dextrans of radius 28-44 A, while depressing those of dextrans of radius 50-60 A. A heteroporous model that depicts the major portion of the glomerular capillary wall as an isoporous membrane (pore radius = 56 A) and the minor portion as a nondiscriminatory shunt, revealed the former to be unchanged and the latter to be less prominent following indomethacin. A lower fraction of total filtrate volume permeating the shunt, together with a concomitant lowering of overall glomerular filtration rate by 24%, reduced the absolute rate of flux of macromolecule-rich fluid through the shunt pathway from 0.40 to 0.25 ml.min-1.73(-2) (P less than 0.01). We conclude that indomethacin lowered the filtered protein load by restoring barrier size-selectivity while reducing the rate of glomerular ultrafiltration.
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PMID:Mechanism of the antiproteinuric effect of indomethacin in nephrotic humans. 246 70

The present study was undertaken to determine the effects of prostaglandin synthesis inhibition on glomerular hemodynamics in nephrotoxic serum nephritis and to elucidate the mechanisms by which prostaglandin synthesis inhibition reduces proteinuria in nephritic rats. Dextran sieving studies were performed before and after intravenous administration of indomethacin to control rats and to nephritic rats with heavy proteinuria. Indomethacin did not significantly alter mean arterial pressure, glomerular filtration rate or proteinuria in control rats nor were significant changes in dextran sieving observed. By contrast, in nephritic rats indomethacin significantly reduced glomerular filtration rate (2.58 +/- 0.50 vs. 1.39 +/- 0.27 ml/min, P less than 0.001), proteinuria (0.198 +/- 0.079 vs. 0.048 +/- 0.019 mg/min, P less than 0.05) and filtration rate-corrected proteinuria (0.059 +/- 0.033 vs. 0.031 +/- 0.013 mg/ml GFR, P less than 0.05). The fractional clearance of neutral dextrans with molecular radii exceeding 42 A were elevated above control values in nephritic rats (P less than 0.05). After administration of indomethacin, the fractional clearance of neutral dextrans uniformly declined toward control values and remained elevated only for molecular radii exceeding 54 A. Assessment of glomerular hemodynamics in nephritic rats before and after indomethacin showed significant declines in single nephron filtration rate (31.5 +/- 3.0 vs. 21.2 +/- 2.5 nl/min, P less than 0.02), glomerular plasma flow rate (99.5 +/- 6.7 vs. 68.5 +/- 7.8 nl/min, P less than 0.05) and glomerular ultrafiltration coefficient (0.0430 +/- 0.0033 vs. 0.0339 +/- 0.0032 nl.sec-1.mm Hg-1, p less than 0.05). Indomethacin did not significantly change these parameters in control rats.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of indomethacin on glomerular permselectivity and hemodynamics in nephrotoxic serum nephritis. 247 51

In rat membranous nephropathy, formation of the C5b-9 membrane attack complex (MAC) leads to proteinuria in association with glomerular visceral epithelial cell (GEC) injury. These alterations in GEC function and morphology might result from changes in intracellular free Ca2+ concentration [( Ca2+]i) and activation of phospholipases. We demonstrate that in cultured rat GEC, antibody-directed formation of noncytolytic amounts of the MAC induced a rapid and sustained increase in [Ca2+]i that was partly inhibited by ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA). The MAC elevated levels of inositol bis- (IP2) and trisphosphate (IP3), as well as 1,2-diacylglycerol (DAG) and phosphatidic acid (PA). In permeabilized GEC, IP3 released Ca2+ from intracellular stores. Cellular 45Ca2+ uptake was also increased by the MAC. Thus, in GEC, the MAC induced Ca2+ mobilization from intracellular stores secondary to activation of phospholipase C and production of IP3, as well as enhanced Ca2+ influx. In addition, C5b-9 stimulated release of arachidonic acid (AA), prostaglandin F2 alpha, and thromboxane A2. Indomethacin partially inhibited the increase in DAG levels observed with the MAC, whereas the prostaglandin H2/thromboxane A2 analogue U46619 elevated DAG, suggesting that an eicosanoid product of MAC-induced AA release may enhance the activation of phospholipase C. Activation of phospholipases by the MAC may lead to altered GEC function and thereby contribute to the pathophysiological changes that characterize complement-dependent rat membranous nephropathy.
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PMID:Complement C5b-9 complex activates phospholipases in glomerular epithelial cells. 251 64

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

Immediate and longer-term (five-day) effects of indomethacin on proteinuria and renal function were examined in a group of nephrotic subjects with glomerular filtration rates (GFR) that ranged from near normal to moderately impaired. The modifying role of the patients' sodium/volume (S/V) status on renal prostaglandin inhibition was systematically evaluated by renal clearance and balance studies. After patients were S/V-depleted for five days, indomethacin (75 mg/d) decreased protein excretion by 45%. The decrement in proteinuria was greater than 2 times greater than the fall in creatinine clearance and was unrelated to baseline clearance. In acute clearance studies, 75 mg indomethacin administered orally immediately reduced protein excretion, effective renal plasma flow (CPAH), GFR (C inulin), Na, K, and free water excretion. Indomethacin responsiveness (reduced proteinuria) correlated with the change in PGE2 excretion. The effect of indomethacin on protein excretion and renal hemodynamics was apparent, but blunted, when dietary Na intake was increased to 200 mEq/d. Mean BP increased during indomethacin therapy only when patients were S/V-expanded.
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PMID:Reduction of proteinuria by indomethacin in patients with nephrotic syndrome. 346 3

Seven salt depleted patients with the idiopathic nephrotic syndrome were treated with various non-steroidal anti-inflammatory drugs. Indomethacin, diclofenac-sodium and flurbiprofen decreased proteinuria, glomerular filtration rate, plasma renin activity and renal prostaglandin E2 excretion by 59%, 19%, 55% and 68% respectively. Sulindac induced no major changes in proteinuria, glomerular filtration rate, plasma renin activity and renal prostaglandin E2 excretion. The relative change in proteinuria and glomerular filtration rate during non-steroidal anti-inflammatory drug treatment correlated strongly with that of the renal prostaglandin E2 excretion (r = 0.89 and r = 0.70, respectively p less than 0.05). It is likely that the anti-proteinuric effect of non-steroidal anti-inflammatory drugs is dependent on their potency to inhibit renal prostaglandin synthesis and it is suggested that this effect is mediated by lowering transcapillary glomerular hydraulic pressure.
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PMID:Reduction of urinary protein and prostaglandin E2 excretion in the nephrotic syndrome by non-steroidal anti-inflammatory drugs. 351 75

Patients with bioptically ascertained glomerulonephritis of the years 1969-1981 were examined. At the time of the kidney biopsy etiology, onset of the disease and data of the findings were evaluated. Moreover, in 160 out of 300 patients after-examinations were performed. Especially also the examination of patients with erythrocyturia was carried out with the help of the phase contrast microscopy. In a second part of the examinations which we report on 2 therapy studies were performed. In the first therapy study the effectiveness of the therapy with prednisolone (n = 33), prednisolone + cytostatic drug (n = 43) as well as the indomethacin treatment (n = 52) in patients with and without nephrotic syndrome was examined. We found that an initial prednisolone dose of more than 50 mg/die for at least over 1 month is more successful than a low prednisolone dose. Indomethacin has no clinically provable therapeutic effect in the nephrotic syndrome. In normal renal function the duration of the disease has no ascertained influence on the results of the therapy. In the second therapy study the effectiveness of the CAA- (n = 27) and the CAAP-therapy, respectively, (n = 98) (cytostatic drugs, anticoagulant drugs, thrombocyte aggregation inhibitors and prednisolone) was investigated. The results of the therapy depending upon the clinical course and the morphological findings revealed that there is an indication to the CAA-CAAP-therapy in nephrotic syndromes in glomerulonephritis with and without sclerosation as well as in glomerulonephritis with relapsing exacerbations with and without sclerosations. No indication for this therapy is given in chronic courses of glomerulonephritis with slight proteinuria and in nephrotic syndromes with hypertension.
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PMID:[Diagnosis and therapy of chronic glomerulonephritis in long-term follow-up]. 370 78

We investigated the effect of captopril, an orally active angiotensin converting enzyme inhibitor, on urinary protein excretion in puromycin aminonucleoside nephrotic rats. The administration of captopril (10 mg/100 g body weight) decreased proteinuria on days 10-14 following the administration of puromycin aminonucleoside (73.0 versus 125.0 mg, p less than 0.01), without affecting glomerular filtration rate. The beneficial effect of captopril was not abolished by the continuous intravenous infusion of angiotensin II (10 micrograms/kg/h for 9 days) or subcutaneous injections of aprotinin (50,000 KIU/day for 3 days). Indomethacin, in moderate (5 mg/kg/day for 3 days) or high (10 mg/kg/day) doses, abolished the captopril attenuation in urinary protein excretion. The salutory effect of captopril was characterized by a reduction in the fractional excretion of protein without compromising the glomerular filtration rate. No difference in renal ultrastructure was noted in captopril-treated versus control animals. Captopril was ineffective in reducing urinary protein excretion in rats with adriamycin-induced glomerulopathy. We conclude that captopril acts to reduce proteinuria in renal disease states arising from depletion of the glomerular basement membrane polyanion. The mechanism of action is postulated to be an alteration in renal hemodynamics, namely increased blood flow and a decrease in the ultrafiltration coefficient, that are the consequence of increased intrarenal prostaglandin production.
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PMID:The effect of captopril on urinary protein excretion in puromycin aminonucleoside nephrosis in rats. 389 1

1 The effects of aspirin, prednisolone, and indomethacin on nephrotoxic serum nephritis in rats was studied. The nephritis was induced by a single intravenous injection of nephrotoxic serum (NTS, rabbit anti-serum against the water-soluble renal antigen of the rat). The injection of NTS induced the heterologous phase of proteinuria (within a day after NTS injection) and then the autologous phase (5 to 7 days after NTS injection). The effect of drugs given before the NTS (i.e. prophylactically) or after the NTS (i.e. therapeutically) was investigated. 2 Aspirin, which was given orally at doses of 150 and 250 mg/kg daily from the day before NTS injection, suppressed the development of proteinuria in both the heterologous and the autologous phase, and lowered the serum cholesterol level towards the normal level. Aspirin (250 mg/kg daily, orally) had no significant effect against the established proteinuria in the autologous phase. 3 Prednisolone, which was given orally at doses of 3 and 5 mg/kg daily from the day before NTS injection, elevated the proteinuria in the heterologous phase, while inhibiting the development of proteinuria in the autologous phase. Prednisolone (5 mg/kg daily, orally) was ineffective against established proteinuria in the autologous phase. 5 Indomethacin (3 mg/kg daily, orally) did not exert any significant effect on proteinuria in either the heterologous or the autologous phase.
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PMID:Effects of aspirin, prednisolone and indomethacin on nephrotoxic serum nephritis in the rat. 707 88


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