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)

Anticoagulation has been reported to ameliorate antiglomerular basement membrane glomerulonephritis (anti-GBM-GN) while its effect on chronic immune complex glomerulonephritis (IC-GN) as studied in the NZB mouse is unclear. Chronic serum sickness IC-GN was induced in rabbits by injecting bovine serum albumin (BSA) daily. Anti-GBM-GN was induced by i.v. injection of a known amount of heterologous anti-GBM antibody. Heparin was administered beginning at two to six weeks after the first BSA injections or before the administration of anti-GBM antibody, on various schedules from 5000 U every 12 hr to 8000 U every 8 hr. With this dosage the partial thromboplastin time remained greater than 1-1/2 to 2-1/2 times the control at the time of the subsequent heparin injection. Heparinized and nonheparinized groups were matched according to duration of disease, maximum anti-BSA concentrations or anti-GBM antibody dosage--and no significant differences were found in proteinuria; severity of the glomerular histologic lesions; or immunofluorescence patterns of immunoglobulin G (IgG), third component of complement (C3), BSA or fibrinogen-related antigen(s) (FRA). Crescent formation was not prevented. This study shows that heparin in the maximum permissible dosage is ineffective in preventing glomerular FRA deposition or altering the progression of experimental IC-GN or anti-GBM-GN in rabbits.
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PMID:Failure of heparin to affect two types of experimental glomerulonephritis in rabbits. 12 30

The present studies were designed to characterize the extent and pathogenesis of the glomerular lesions which occur in the viable portion of the kidney following partial renal infarction in rats. Control rats with two normal kidneys had a mean blood pressure of 112 mm Hg, minimal proteinuria and no glomerular pathology on light (LM), electron (EM) or immunofluorescence microscopy (IFM). Rats with two-thirds infarction of one kidney (stage II) became hypertensive, although less than 4% of the glomeruli from either kidney were abnormal. Rats with two-thirds infarction of one kidney and contralateral nephrectomy (stage III) developed proteinuria and hypertension whether fed a normal, low or high Na+ diet. By light microscopy 37% of glomeruli were abnormal 28 days after partial infarction and contralateral nephrectomy and thereafter the percent of abnormal glomeruli increased. Detectable amounts of immunoglobulin and complement (C3) were present in kidneys of stage II or III rats but were always accompanied by more extensive albumin and fibrin deposits. Basement membrane deposits characteristic of immune complexes were not seen on EM. Administration of antihypertensive medication to stage III rats significantly lowered blood pressure and reduced the number of abnormal glomeruli on LM; however, IFM abnormalities remained prominent. Platelet thrombi seen by EM and abundant glomerular fibrin deposits seen on IFM suggested that coagulation mechanisms may be prominent in the pathogenesis of the renal lesion. Heparin-treated stage III rats had significantly lower blood urea nitrogen concentrations, blood pressures and proportion of abnormal glomeruli although glomerular deposition of serum proteins was still present on IFM. These observations suggest that this glomerulopathy is initiated by an unknown agent(s) which increased capillary permeability. This lesion progresses via thrombotic mechanisms which are prevented by heparin administration.
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PMID:Pathogenesis of the glomerulopathy associated with renal infarction in rats. 94 Feb 76

14 cases of idiopathic rapidly progressive glomerulonephritis (I. R. P. G. N.) treated by heparin between 1968 and 1974 were collected by the authors. Extra-capillary crescents (E. C. C.) occurred in 75 to 100% of glomeruli in ten patients and in 50 to 75% in four. Gross proteinuria, hematuria and renal failure were always present. 9 patients were admitted with primary oligo-anuric renal failure. 11 patients were treated by repeated hemodialysis before and during anticoagulant treatment. Heparin was given by intra-venous injection every 3 hours for one to two months with Howell times range from 150 to 200% of control. Heparin was the only treatment in 6 cases, and was given with dipyridamole in 4, with prednisone in 3 and with azathioprine in one case. 5 severe or fatal hemorragic complications were observed. The clinical course was usually unfavorable with 5 early deaths, 3 provisional steady-states with 2 late deaths. Six patients were treated by periodic hemodialysis. Repeat kidney biopsies were obtained in 8 patients. The findings suggest that heparin affects mainly the E. C. C. and fibrinoid deposits but not glomerular sclerosis. The inefficiency of all current treatments of primary oligo-anuric IRPGN is stressed. In patients with better initial renal function choice between anticoagulant and/or immuno-depressive drugs must be scrutinized in individual cases bearing in mind potential iatrogenic complications. In equivocal cases, patients should be referred to the chronic hemodialysis and/or transplantation program.
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PMID:The use of heparin in the treatment of idiopathic rapidly progressive glomerulonephritis. 124 88

Thirty-one patients with chronic mesangial-proliferative glomerulonephritis, histologically and clinically active, confirmed on biopsy, were included in a randomized therapeutic experiment. Of the total, 15 were treated by a combined prednisone, azathioprine, cyclophosphamide, Heparoid Spofa forte ling., Heparin retard Spofa and dipyridamole therapy. The control group comprised 16 untreated patients. One year later, a similar progression of glomerulonephritis was seen in both groups. Both treated and control patients exhibited a slight, but significant, decrease in proteinuria and a slow fall in the glomerular filtration rate. Despite a short period of follow-up, we succeeded to demonstrate, convincingly enough, that combined cyclophosphamide, azathioprine, prednisone, Heparoid ling., Heparin retard Spofa and dipyridamole therapy should not be indicated in chronic mesangial-proliferative glomerulonephritis.
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PMID:Effect of combined immunosuppressive anticoagulant and antiplatelet therapy of the course of chronic mesangial-proliferative glomerulonephritis. 393 33

From the clinical point of view proteinuric hypertension or preeclampsia is the most important form of hypertension in pregnancy and carries the greatest risks for mother and foetus. The syndrome 'preeclampsia' differs from other types of hypertension and its effects on mother and foetus are not clearly benefited by lowering the blood pressure with drugs. The characteristic morphological changes and altered vascular reactivity which develop in preeclampsia commence at about 14 weeks gestation, long before hypertension or proteinuria appear. Many abnormalities in coagulation mechanisms appear in preeclampsia and some may play an important part in pathogenesis. Increased plasminogen activator inhibitor may play a key role. Antihypertensive drugs used during pregnancy may reduce foetal mortality and the incidence of preeclampsia. Calcium supplementation and aspirin may reduce the incidence of preeclampsia in high risk subjects. Heparin and dipyridamole may reduce the risk of preeclampsia in high risk patients with renal disease.
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PMID:Hypertension in pregnancy. 819 15

A highly cationic staphylococal protein (designated p70, MW 70 kD, pI > 10) belongs to the groups of bacterial proteins that can bind immunoglobulin without specific antigen-antibody recognition; heparin inhibition tests indicated a charge interaction. This study evaluated the nephritogenicity of p70, which has affinity for the glomerular basement membrane (GBM), and the influence of various mediator systems on the induction of glomerulonephritis by p70. The left kidneys of intact rats, rats given cobra venom factor (complement-depleted), or rats given anti-adhesion molecules (ICAM-1 and LFA-1a) were perfused with p70. Proteinuria started within 24 h and persisted at day 5. Intraglomerular infiltration of cells was seen as early as 15 min, peaking at day 1. Deposits of rat IgG and C3 were seen in a subendothelial location 15 min after p70 perfusion in the left kidney and were found in a predominantly subepithelial location from 1 day onwards. Complement depletion and blockade of adhesion molecules suppressed proteinuria from day 2 onwards; these manipulations also prevented the recruitment of infiltrating cells and partially hindered the transfer of IgG across the GBM and the accumulation of IgG in the subepithelial region. In the non-perfused right kidneys, deposits of IgG and C3 were comparable to those in the left kidneys, suggesting that p70-IgG complexes formed in the circulation may also contribute to the deposits in the GBM. Heparin inhibition tests indicated an electrostatic interaction between p70 and immunoglobulin. Complement and inflammatory mediator systems (granulocytes, monocytes/macrophages, and/or lymphocytes) were required to provoke glomerular injury. p70 might play a role in acute glomerulonephritis following Staphylococcus aureus infection.
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PMID:Glomerular injury induced by cationic 70-kD staphylococcal protein; specific immune response is not involved in early phase in rats. 966 12

Wharton's jelly is abundant in extracellular matrix, which is known as a storage site to concentrate and stabilise growth factors in the vicinity of cells. It was previously found that Wharton's jelly contains significant amounts of insulin-like growth factor (IGF)-1 and IGF-binding proteins (BPs). IGF-1 is a stimulator of biosynthetics of collagen and sulphated glycosaminoglycans. Preeclampsia (edema, proteinuria, hypertension (EPH)-gestosis) is accompanied by an accumulation of sulphated glycosaminoglycans in Wharton's jelly. IGF-1 and BPs may play an important role in such a remodelling of this tissue. It was decided to evaluate the alterations in amounts of IGF-1 and BPs in Wharton's jelly of newborns delivered by mothers with preeclampsia. Studies were performed on Wharton's jelly of 10 controls and 10 newborns delivered by mothers with preeclampsia (edema, proteinuria > 500 mg/l, arterial pressure: systolic > 140 mm Hg, diastolic > 90 mmHg). Radioimmunological techniques were employed to determine IGF-1 and IGF-BPs (BP-1 and BP-3). It was found that preeclampsia is associated with a decrease in IGF-1 and IGF-BP-1 in Wharton's jelly. A slight increase in IGF-BP-3 was found. Ligand blotting demonstrated that BP-3 (not BP-1) is a main component of Wharton's jelly, which binds IGF-1. Heparin drastically inhibited the binding of IGF-1 by BP-3. It is known from our previous studies that preeclampsia is associated with an increase in the amount of sulphated glycosaminoglycans (heparin, heparan sulphate, dermatan sulphate) in Wharton's jelly. This may be a factor, which prevents the binding of IGF-1 by BPs and facilitates the binding of IGF-1 to cells, stimulating them to produce sulphated glycosaminoglycans in Wharton's jelly.
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PMID:Preeclampsia is associated with alterations in insulin-like growth factor (IGF)-1 and IGF-binding proteins in Wharton's jelly of the umbilical cord. 1102 64

Heparin may have a beneficial effect in proteinuric renal diseases, where negative charges of the glomerular capillary membrane are compromised. We evaluated the role of low molecular weight heparin (LMWH - 3000 Da) in puromycin aminonucleoside (PAN)-induced focal and segmental glomerulosclerosis in male Wistar rats: Controls (C) n=7, LMWH-treated group, n=9, subcutaneously (SC), 6 mg/kg every day. The PAN group (n=7) received 7 doses on weeks 0, 1, 2, 4, 6, 8, 10 (SC - 2mg/100g), and a group PAN+LMWH (n=6). After 12 weeks, cholesterol and triglycerides were higher in nephrotic groups, as well as proteinuria and urinary IgG. Kidney weight, glomerular volume, and glomerular sclerosis index were higher in the PAN-treated groups. Glomerular capillary length density (L(Vcap)) and glomerular capillary surface density (S(Vcap)) were lower in the PAN group, and mesangial fractional volume was higher. Fibronectin immunostaining was more intense in the PAN group, and collagens I and III were absent in the studied glomeruli. Thus, LMWH prevented mesangial expansion and capillaries changes, showing antiproliferative properties, despite worsening glomerular permeability changes in the PAN model. In conclusion, LMWH interferes in the complications of PAN model, but not through inhibition of the proteinuria.
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PMID:Low molecular weight heparin in the treatment of puromycin-induced nephrosis. 1649 22

We previously reported that a combined therapy with heparin/warfarin and renin-angiotensin system (RAS) inhibitors dramatically reduces proteinuria for prolonged periods in advanced IgA nephropathy (IgAN). In the present study, we prospectively analyzed whether the combined therapy can inhibit the progressive decline in renal function of patients with progressive IgAN. Patients who had a marked linearity of decline in loss of glomerular filtration rate (GFR), assessed by reciprocal serum creatinine plots vs. time for more than one year, were recruited in this study if they were histologically diagnosed as IgAN at this point of declining renal function. Twelve patients were eligible for trial entry; reciprocal serum creatinine plot suggested end-stage renal failure within 5 years. All patients were treated with continuous intravenous infusion of heparin for 8 weeks, followed by oral administration of warfarin, ACE inhibitors and/or angiotensin II receptor blockers and dypiridamole. Eight patients were further given corticosteroid for 2 years because of the presence of acute glomerular lesions such as cellular crescent or angionecrosis. All patients were followed-up for at least 12 months, and the mean follow-up period was 34 +/- 20 (range 12-79) months. After the combined therapy, urinary protein excretion was significantly reduced from 2.4 +/- 1.5 g/day at baseline to 0.7 +/- 0.5 g/day at final observation, while the mean serum creatinine was not significantly different. Of note, the mean slope of 1/serum creatinine significantly increased from -0.009 to +0.0002 dl/mg/week (p < 0.05). Moreover, histological analysis of a repeat kidney biopsy which was performed in 5 patients at 2 years after the institution of the combined therapy revealed that the percentage of cellular/fibrocellular crescent and the degree of mesangial matrix expansion were significantly attenuated (19-->0.1% and 1.6-->0.6 score, respectively) while the percentage of global sclerosis and tubulointerstitial lesion did not increase. These results indicate that our combined therapy with heparin/warfarin and RAS inhibitors can inhibit the progressive decline in renal function Combined Heparin/Warfarin and RAS Inhibitors in Progressive IgAN 115 of patients with progressive IgAN through its marked antiproteinuric and anti-inflammatory effects.
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PMID:Prospective trial of combined therapy with heparin/warfarin and renin-angiotensin system inhibitors in progressive IgA nephropathy. 1749 47

Angiotensin-converting enzyme inhibitors and angiotensin II (AngII) type 1 receptor blockers lower proteinuria and preserve renal function in diabetic nephropathy (DN). The antiproteinuric effects are greater than their blood pressure reduction, involving the sieving properties of the glomerular filter. In DN, glomerular staining for heparan sulfate proteoglycans is decreased. AngII inhibits heparan sulfate synthesis. Also, heparins modulate AngII signaling in glomerular cells, inhibiting aldosterone synthesis and lowering proteinuria in DN. Is the antiproteinuric effect of heparins due to its interference with the renin-angiotensin-aldosterone system? Ten volunteers each with DN and glomerulonephritis and control subjects were examined before and after low-dosage enoxaparin. Renal hemodynamics were determined with (99m)Tc-DTPA and (131)I-hippurate clearance. Glomerular filtration rate (GFR), effective renal plasma flow, mean arterial pressure, and heart rate were measured at baseline and during AngII infusion before and after enoxaparin while on normal salt and salt restriction. Enoxaparin did not lower aldosterone levels. GFR remained stable in all groups. AngII caused a significant decrease in effective renal plasma flow, whereas mean arterial pressure and heart rate increased significantly. Enoxaparin did not influence the AngII-induced changes of renal hemodynamics during normal salt intake or salt restriction. All groups showed identical responses to AngII before and after enoxaparin. In patients with diabetes, enoxaparin caused a significant decrease in proteinuria. It is concluded that the antiproteinuric effect of heparins in DN cannot be explained via interaction with the renin-angiotensin-aldosterone system. The absence of hemodynamic changes combined with reduced proteinuria point to intrinsic alterations in the glomerular filter. The effects were seen only in DN, not in glomerulonephritis.
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PMID:Proteinuria-lowering effect of heparin therapy in diabetic nephropathy without affecting the renin-angiotensin-aldosterone system. 1769 88


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