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)

To examine the hypothesis that sulindac does not inhibit renal prostaglandin (PG) synthesis, we investigated the effects of sulindac and other nonsteroidal anti-inflammatory drugs on PG synthesis in human and in cultured rat renal and vascular smooth muscle (VSM) cells. In 7 patients with chronic glomerular disease, creatinine clearance and proteinuria were not changed by sulindac but were significantly reduced by diclofenac sodium. However, urinary excretion of PGE2 was decreased by both drugs. In cultured glomerular mesangial (GM), renal papillary collecting tubule (RPCT) and VSM cells from mesenteric artery, indomethacin, tiaprofenic acid, aspirin and ibuprofen inhibited both basal and arachidonic acid (AA)-stimulated PG synthesis dose-dependently. Although sulindac sulfoxide, at the same concentrations, inhibited both basal and AA-stimulated PGE2 synthesis in RPCT cells, it was less potent to inhibit PGI2 synthesis in VSM cells or PGE2 synthesis in GM cells. Active form sulindac sulfide inhibited PG synthesis in all types of cells but its inactive form sulfone did not. We conclude that sulindac inhibits renal PG synthesis but has little effect on renal function. This may be explained by its relatively weak potency on glomerular or vascular PG synthesis inhibition possibly due to the different biotransformation of the sulfoxide to the active sulfide in these cells.
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PMID:Effect of sulindac on prostaglandin synthesis in human and in cultured rat renal and vascular smooth muscle cells. 141 44

Vasoactive eicosanoids may be involved in glomerular hyperfiltration following a high protein intake or removal of renal mass. We sequentially measured glomerular filtration rate (GFR), proteinuria (UpV), and urinary eicosanoid excretion in sham-operated (2K) and uninephrectomized (NX) rats on two diets. Compared with 12% protein (LP), 36% protein (HP) initially resulted in a higher GFR and UpV in both 2K and NX rats. Urinary excretion of 6kPGF1 alpha and TxB2 was higher on the HP diet. Ten weeks after NX, PGE2 excretion was slightly reduced, while that of TxB2 and 6kPgF1 alpha was the same as in 2K rats, indicating that the excretion per kidney had increased. From week 40, the GFR of NX rats on the HP decreased, preceded by a progressive increase in UpV. Excretion of PgE2, TxB2, and 6kPgF1 alpha was highest in the phase of proteinuric chronic renal failure. Thus, vasoactive eicosanoids are involved to maintain hyperfiltration induced by high protein intake or NX.
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PMID:Effect of protein intake and unilateral nephrectomy on renal function and eicosanoid excretion in rats. 146 43

We examined whether the renal protective effect of the angiotensin I converting enzyme inhibitor enalapril in stroke-prone spontaneously hypertensive rats (SHRSP) is dose-related and associated with alterations in the urinary excretion of prostaglandin (PG) E2 and 6-keto-PGF1 alpha, a stable breakdown product of prostacyclin. Enalapril maleate at 1.5, 5 and 15 mg/kg/day or vehicle was chronically administered to saline-drinking SHRSP (six per group) starting at 8.1 weeks of age. Vehicle-treated SHRSP developed severe hypertension, proteinuria and strokes (age at death, 14 +/- 1 weeks; mean +/- S.E.). Enalapril prolonged survival dose-dependently and reduced proteinuria; all SHRSP given 15 mg/kg/day lived beyond 23 weeks of age without evidence of stroke or proteinuria. There was no effect of enalapril at any dose on systolic arterial blood pressure in spite of variable levels of urinary protein excretion and onset of stroke in the different groups. Likewise, urinary 6-keto-PGF1 alpha and PGE2 excretion did not differ among the groups except for an increase in 6-keto-PGF1 alpha in the 15 mg/kg/day group at one week after initiation of enalapril therapy. These results are consistent with a dose-related renal protective action of enalapril in saline-drinking SHRSP that is not closely associated with sustained alterations in urinary excretion of renal vasodilatory PGs.
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PMID:The antiproteinuric action of enalapril in stroke-prone spontaneously hypertensive rats is unrelated to alterations in urinary prostaglandins. 154 1

Acute renal failure (ARF) induced with large doses of Gentamicin (GM) (an aminoglycoside) was associated with increased urinary TXB (TXA) excretion which provoked a decrease of the ratios of urinary PGE2/TXB2 and 6-keto-PGF1 alpha (PGI2)/TXB2 excretions. Furthermore, as indicated by light microscopy most of the epithelial cells lining the proximal tubules show obvious lesions varying from swelling of their cytoplasm to complete necrosis. Either the inhibitor, OKY-O46, of TXA-synthetase, or volume expansion (VE) with isotonic saline (IS) of the experimental animals diminished urinary TXB excretion which provoked 1) augmentation of the ratios of urinary PGE/TXB and 6-keto-PGF1 alpha/TXB excretions, 2) elevation of creatinine clearance (Ccr) and 3) diminution of proteinuria (PU). This protection against ARF-by OKY-O46 and VE can a can be seen in microscopic sections where necrosis of proximal tubules is almost absent. Only a few proximal tubules show swelling of their epithelial cells and some focal areas of tubule necrosis. We suggest that the metabolites of arachidonic acid (AA), TXA2 a (potent vasoconstrictor agent) and prostaglandins (PGE2 and PGI2), (potent vasodilator factors), play an important role in the development (TXA2) or in the prevention (PGs) of ARF induced by this antibiotic.
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PMID:Does gentamicin induce acute renal failure by increasing renal TXA2 synthesis in rats? 156 Dec 32

This report is on a 35-year-old II-para (status post-Caesarean Section due to breech presentation, at that time normal pregnancy) progress, who was hospitalized with hypertension and proteinuria during the 40th week of pregnancy. Both symptoms occurred initially three days before hospitalization. Blood pressure was within the high normal range (140/90 mmHg) as a result of medication with Dihydralazine (50 mg/die). After induction of labour with prostaglandin (PGE2), the patient delivered normally, and the highest blood pressure measured was 140/90 mmHg, following a subsequent curettage under general anaesthesia, which had to be performed due to incomplete deliver of the placenta. Two hours post delivery, sudden epigastric pain occurred, followed by nausea and vomiting. Blood chemistry showed the development of a severe post-partal HELLP-Syndrome with acute renal failure. The case demonstrates, that the life threatening picture of the HELLP-Syndrome may develop without preexistent severe hypertension or proteinuria. For this reason a post-delivery screening of blood chemistry should be mandatory in cases of severe epigastric or right-upper-quadrant pain.
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PMID:[HELLP syndrome--postpartum]. 174 78

Recently the beneficial effects of captopril (angiotensin-converting-enzyme inhibitor) on diabetic nephropathy, especially proteinuria, have been reported by some investigators. The mechanism whereby proteinuria is reduced, however, have not been clarified yet. The present study was undertaken to evaluate the effects of captopril on urinary albumin excretion in relation to urinary prostaglandins (PGs) excretion in patients with non-insulin-dependent diabetes mellitus (NIDDM). Captopril (37.5 mg/day) was orally administered to 13 diabetic patients for an eight-week period. A single administration of captopril (12.5 mg) was performed in the same patients. The spot urine samples were collected in the early morning and 2 hr after the single administration of captopril. The albumin index (mg/gram-creatinine) was markedly decreased in eight patients (Group A) within four weeks, but no decrease was found in five patients (Group B). Furthermore, in Group A, by the single administration of captopril urinary excretions of 6-keto-PCF1 alpha (a stable metabolite of PGI2) and PGE2 were significantly (p less than 0.05) increased while urinary TXB2 (a stable metabolite of TXA2) excretion did not change significantly. The urinary 6-keto-PGF1 alpha/TXB2 ratio, which is significantly (p less than 0.05) low in diabetic patients was significantly (p less than 0.01) increased up to the normal value in Group A. In Group B, however, there were no significant changes in urinary PGs excretion. These results suggest that captopril enhances the production of intrarenal vasodilatory PGs such as PGI2 and PGE2, which may be deeply involved in the reduction of intraglomerular capillary pressure and urinary protein excretion in diabetic patients.
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PMID:Effects of captopril on urinary excretion of albumin and prostaglandins in patients with diabetic nephropathy. 209 82

The present study was designed to determine urinary excretion of kallikrein(KAL)-kinin as well as prostaglandin (PG) E2, TXB2 and 2,3-dinor-TXB2, a major urinary metabolite of TXA2 synthesized in platelets, by specific RIAs in patients with diabetes mellitus (DM). KAL or kinin excretion in 26 type II DM did not differ from control values obtained in 18 age-matched healthy subjects (C), although DM with HbA1 greater than 11% excreted less KAL. Urinary PGE2 excretion (7.6 +/- 2.8 ng/mg creatinine, mean +/- SE) was significantly lower in DM compared to C (17.5 +/- 3.9, p less than 0.05), while DM excreted more TXB2 (0.57 +/- 0.09, p less than 0.01) and 2,3-dinor-TXB2 (0.56 +/- 0.12, N.S.) than C (0.19 +/- 0.02 or 0.33 +/- 0.01). DM with or without mild proteinuria demonstrated lower PGE2, but higher TXB2 and 2,3-dinor-TXB2 excretion. A positive correlation of TXB2/2,3-dinor-TXB2 with proteinuria was observed in this group. However, in DM with massive proteinuria over 500 micrograms/mg creatinine, TXB2 and 2,3-dinor-TXB2 excretion decreased to levels almost identical to C. As a whole, a ratio of TXB2 to PGE2 or 2,3-dinor-TXB2 in DM was significantly higher than in C. The results suggest that a relative preponderance of TXB2 to 2,3-dinor-TXB2 may indicate an augmented renal, in addition to platelet, TXA2 synthesis. An excessive vasoconstrictive and proaggregatory TXA2 renal synthesis, concomitant with a decrease in vasodilatory and antiaggregatory PGE2, may have profound effects on renal functions such as protein excretion in DM.
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PMID:Increased renal TXA2 synthesis in diabetes mellitus: simultaneous determination of urinary TXB2 and 2,3-dinor-TXB2. 233 36

The patients suffering from hypertonic nephritis were examined for renal hemodynamics, the activity of the renin-angiotensin-aldosterone system (RAAS), excretion of PGE2 and PGF2 alpha, and for a number of the parameters of water-electrolyte homeostasis. In A series, the patients suffering from latent and hypertonic nephritis (n = 11 in each group) were compared. In B series, two groups of the patients (n = 13 in each group) suffering from hypertonic nephritis associated with moderate or grave arterial hypertension were compared. The patients under comparison belonging to A and B series did not differ as regards the sex, age, nephritis standing, serum creatinine or proteinuria. As compared with the patients suffering from latent nephritis (A series), the patients with hypertonic nephritis showed a lower effective renal plasma flow, a greater resistance of the renal vessels, lesser PGE2 secretion, and a higher serum sodium concentration. As compared with the patients suffering from moderate hypertension (B series), the patients with associated hypertonic nephritis and grave hypertension demonstrated a higher resistance of the renal vessels, a higher activity of plasma renin, a larger concentration of plasma aldosterone and its excretion with urine, as well as a greater volume of the circulating blood. It is assumed that the development of arterial hypertension associated with hypertonic nephritis may be caused by renal hemodynamics deterioration, by relative activation of the renin-angiotensin system, inhibition of the depressor prostaglandin system and sodium retention. The progression of hypertension may be related to further deterioration of renal hemodynamics attended by RAAS activation and hypervolemia.
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PMID:[Mechanisms of the development of arterial hypertension in hypertonic nephritis]. 279 11

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 membrane attack complex (MAC) of complement (C) has been shown to stimulate prostaglandin (PG) and thromboxane (Tx) synthesis in nucleated cells. Because glomerular epithelial cell injury and altered permeability in rat membranous nephropathy are mediated by the MAC, the authors examined whether MAC-induced proteinuria is linked to glomerular prostanoid synthesis. In kidneys containing non-nephritogenic, non-C-fixing gamma 2 sheep anti-Fx1A (planted antigen) that were perfused in vitro with C-fixing guinea pig anti-sheep IgG and a C source (fresh human plasma, 50% vol/vol in buffered bovine albumin), heavy proteinuria developed, reaching 4.27 +/- 1.20 mg/min/g at 100-120 minutes (n = 8). Cyclooxygenase blockade with 10(-4) M indomethacin (n = 6) inhibited urinary PGE2 excretion (569 +/- 47 to 124 +/- 18 pg/min/g, P less than 0.001) and lowered proteinuria (1.06 +/- 0.42 mg/min/g, P less than 0.001). Reduced protein excretion (0.88 +/- 0.12 mg/min/g, n = 6, P less than 0.001) also occurred with inhibition of Tx synthetase by OKY-046, 10(-4) M, a dose that was shown in separate perfusions to inhibit urinary TxB2 excretion by greater than 85%. Control kidneys, without planted antigen and perfused with anti-sheep IgG and plasma, excreted 0.30 +/- 0.05 mg protein/min/g (n = 6). Because inulin clearance was reduced by indomethacin, renal hemodynamic factors may have contributed to the reduction in proteinuria observed with this drug. However, insulin clearance was not significantly affected by OKY-046, implying that inhibition of Tx synthetase reduced proteinuria independently of changes in renal hemodynamics. Thus, proteinuria in rat membranous nephropathy is due to MAC-dependent glomerular epithelial injury and is mediated, in part, by Tx.
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PMID:A role for thromboxane in complement-mediated glomerular injury. 311 Dec 67


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