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)

Cyclosporin A (CsA) can reduce proteinuria in various forms of human and experimental glomerulonephritis. This antiproteinuric effect of CsA may be the consequence of diminution of immunological damage, a drug-induced decrease of GFR, or changes in permselectivity of the glomerular basement membrane (GBM). We studied the antiproteinuric effect of CsA in the heterologous phase of a passively induced anti-GBM nephritis in the mouse. This passive model is characterized by acute exudative glomerular lesions and a dose-dependent albuminuria. Rabbit anti-mouse GBM antibodies were administered intravenously in C57B110 mice at day 4, after 3 days of pretreatment with either CsA (75 mg/kg body weight) (n = 15) or olive oil (OO, controls, n = 15) orally. CsA did not influence the severity of the histological lesions. Albuminuria was substantially reduced by CsA (CsA 1.6 +/- 1.8; OO 5.6 +/- 3.2 mg/18 h; P < 0.002). There was a considerable concomitant reduction of the GFR by CsA, as measured with a 51Cr-EDTA single-shot plasma clearance technique before (day-1) and during treatment (day 4): GFR ratio day 4/day-1 for CsA, 0.4 +/- 0.1; for OO controls, 1.1 +/- 0.6; P < 0.01. This drug-induced decrease of GFR was prevented by simultaneous treatment with phenoxybenzamine (PB) twice daily 45 micrograms orally for 4 days (GFR ratio day 4/day-1 for PB and CsA, 0.9 +/- 0.4; controls (PB and OO), 1.0 +/- 0.4; P = NS). Although the CsA-induced GFR reduction was prevented, CsA still reduced albuminuria significantly (PB and CsA, 2.2 +/- 1.8; controls (PB and OO), 5.6 +/- 1.8 mg/18 h; P = 0.003).(ABSTRACT TRUNCATED AT 250 WORDS)
Nephrol Dial Transplant 1995
PMID:Cyclosporin A reduces albuminuria in experimental anti-GBM nephritis independently from changes in GFR. 747 16

The role of immunosuppressive drugs in the treatment of IgA nephropathy (IgAN) remains controversial. The effect of treatment with prednisolone and azathioprine on the clinical course of patients with IgA nephropathy is described in this retrospective study. One hundred and fourteen patients, 66 treated (age 13-77 years) and 48 untreated (age 15-64 years), were evaluated. The two groups of patients differed significantly with respect to heavier proteinuria (median 3.6 g/day, range 0.2-18 g/day), lower serum albumin level (< 40 g/l) and more severe renal histopathological involvement in the treated group (P < 0.01). Oral prednisolone 40 mg/day and azathioprine 2 mg/kg BW/day was commenced initially and after gradual tapering was continued at low dose (5 mg/day) for a median duration of 24 months (range 12-98). The median duration of follow-up was 46 months (range 12-180). The clinical course was defined as progressive or non-progressive on the basis of serial serum creatinine (Scr). Of the patients who presented with renal impairment (Scr > 110 mumol/l), a non-progressive course was observed in 79.5% patients of the treated group (n = 39), while only in 36% of the untreated group (n = 22), the difference was statistically significant (P < 0.001). Slopes of reciprocal of Scr versus time were also calculated by linear regression analysis to represent the trend of renal function for patients who had had 3 or more years follow-up (n = 101). An analysis of variance of these trends in patients with renal impairment at presentation (n = 51) showed significant recovery of renal function in the treated group (n = 33) and a decline of renal function in the untreated group (n = 18, P = 0.004). There was no significant effect of the treatment on proteinuria. The histopathological features that favoured response to the treatment were mesangial proliferation, capsular adhesions and interstitial infiltration on light-microscopy, C3 and fibrin deposits on immunofluorescence (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Nephrol Dial Transplant 1995
PMID:Can immunosuppressive drugs slow the progression of IgA nephropathy? 747 7

An earlier controlled trial showed that over an average of 26 months, enalapril slowed the progression of chronic renal failure. Following completion of the trial, the patients continued to receive antihypertensive treatment according to ordinary clinical criteria. All but four patients in the enalapril group remained on that drug, and two patients in the control group were switched to an angiotensin-converting enzyme (ACE) inhibitor. In the present study the fate of the 70 patients 44 months after termination of the trial was investigated, with a total follow-up of around 7 years. In the original enalapril group, 12 of the 35 patients (34%) were alive without renal replacement therapy versus five of the 35 patients (14%) in the control group. This difference of 20% in favour of having been in the enalapril group in the original trial was significant (P = 0.05; 95% confidence limits 0.5-39.5%). The influence of baseline proteinuria on clinical outcome was analysed. In the original control group, baseline renal clearances of albumin (Calb) and immunoglobulin G (CIgG) were significantly lower in patients surviving without renal replacement therapy at follow-up than in patients who ultimately developed end-stage renal failure (ESRF) (P < 0.05). In the original enalapril group, these baseline clearances were equal in the two renal outcome groups. In all patients, baseline Calb and CIgG were negatively correlated with the rate of change in GFR during the controlled trial (r = -0.37, P < 0.01 and r = -0.28, P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Nephrol Dial Transplant 1995
PMID:Late outcome of a controlled trial of enalapril treatment in progressive chronic renal failure. Hard end-points and influence of proteinuria. 747 21

Seven patients with steroid-resistant nephrotic syndrome were treated with FK 506 monotherapy. Four patients were children with focal sclerosing glomerulonephritis (FSGS). Three of these had evidence for chronic progressive renal disease consisting of interstitial fibrosis and tubular atrophy on pretreatment renal biopsies. Two patients had also failed cyclosporin A (CsA), two cyclophosphamide, and one chlorambucil prior to treatment with FK 506. Three patients were adults with mesangial proliferative, membranoproliferative, and membranous glomerulonephritis. Three patterns of response were noted: (1) a reduction in proteinuria to normal levels; (2) partial response (50% reduction) or; (3) no improvement. All patients except one experienced at least a 50% reduction in protein excretion at some time during FK 506 therapy. Two of the children and one adult reduced protein excretion to essentially normal values. One patient had no sustained reduction in protein excretion and is considered to be a treatment failure, although her protein excretion was approximately 50% of pretreatment values intermittently. The drug was generally well tolerated. The most common side-effect was nephrotoxicity, which was reversible. These encouraging results suggest that FK 506 monotherapy may be effective in controlling the proteinuria of some patients with steroid-resistant nephrotic syndrome. The use of this drug may extend our understanding of the role of T lymphocytes and cytokines in the pathogenesis of glomerulonephritis. Further study of this agent in a larger population of patients is warranted.
Nephrol Dial Transplant 1993
PMID:Pilot trial of FK 506 in the management of steroid-resistant nephrotic syndrome. 750 98

In order to examine the mechanism by which the oral carbonaceous adsorbent, AST-120 delays the appearance of glomerular sclerosis, experiments were carried out in 120 male Sprague-Dawley rats weighing 285-320 g. The rats were first subjected to 2/3, 3/4, and 4/5 nephrectomy (n = 40). The experiments were begun at 2 weeks after the surgery, and were performed over an 8-week period. Half of each group (n = 20) was administered 1 g/day of liquid AST-120, and the other half received liquid vehicle solution with pair feeding in each group. In the 2/3 nephrectomized group the administration of AST-120 delayed the occurrence of glomerular hypertrophy and prevented the appearance of glomerular sclerosis without any significant differences in renal function, systemic blood pressure (SBP), and urinary protein excretion (U-P). In the 3/4 nephrectomized group the administration of AST-120 delayed the appearance of glomerular hypertrophy and sclerosis with significant decreases in SBP and U-P. In the 4/5 nephrectomized group the administration of AST-120 delayed the appearance of glomerular sclerosis and prevented a decrease in renal function. It is concluded that administration of the oral adsorbent AST-120 delays the occurrence of glomerular sclerosis by delaying the appearance of glomerular hypertrophy, systemic hypertension, and the increase in proteinuria. It can be therefore mentioned that the accumulating substances in the digestive tract worsen the abnormal milieu of chronic renal failure.
Nephrol Dial Transplant 1995
PMID:Correction by oral adsorbent of abnormal digestive tract milieu in rats with chronic renal failure. 756 81

Monoclonal autoantibodies were obtained from Lewis rats with active Heymann nephritis. Two cloned rat/mouse hybridomas, 3D9B and 5B8C, that secreted rat IgG2a autoantibodies were selected for their ability to react with gp330 in ELISA and propagated further. Their specificity was confirmed by immunoprecipitation of crude antigens from a yolk sac carcinoma cell line expressing gp330. The size of the precipitated molecule was identical to that immunoprecipitated by previously described anti-gp330 antibodies. Indirect immuno-electron microscopy showed that 3D9B exclusively stained the intermicrovillous areas of the tubular brush border membrane, while 5B8C stained the full tubular microvillous membrane and the glomerular epithelial coated pits. Passive transfer of 3D9B did not induce Ig deposits or functional renal damage within 7 days. However, injection of 5B8C caused granular glomerular deposits within 1 h, subepithelial immune aggregates within 6 days and antibody deposition on the brush border within 7 days. Only ascites production of clone 5B8C in rats, but not in mice, caused subepithelial immune deposits and abnormal proteinuria. This study shows that a single monoclonal autoantibody to gp330 is able to induce a mild form of Heymann nephritis.
Nephrol Dial Transplant 1995
PMID:Glomerulopathy induced by a single monoclonal autoantibody against GP330. 762 90

Both ACEi and a low-protein diet (LPD) are reported to reduce urinary protein excretion in patients with stable non-diabetic renal disease. To test whether the combination of both may have an additive antiproteinuric effect, we studied the effects of single treatment with ACEi (10 mg enalapril o.d.), LPD (target, 50% reduction in protein intake), and the combination of both in 14 of such patients with stable proteinuria exceeding 3 g per day. Baseline measurements were performed while patients were on a normal protein diet (NPD). In group A (n = 7), first the effects of a LPD were investigated, whereafter the effects of addition of ACEi to LPD were studied. In group B (n = 7), first the effects of ACEi were investigated, whereafter the effects of addition of a LPD to ACEi were studied. Each treatment period lasted 2 months. LPD decreased proteinuria with 17% in patients without ACEi treatment (group A), and similarly with 19% in patients with ACEi treatment (group B). The antiproteinuric response obtained with the LPD in individual patients ranged from -63% to +1%. This variation is at least partly explained by interindividual differences in diet compliance, since the antiproteinuric effect of the LPD was found to correlate with the achieved reduction in protein intake (r = 0.58, P < 0.05). ACEi lowered proteinuria with 32% during the NPD (group B), and similarly with 43% during the LPD (group A).(ABSTRACT TRUNCATED AT 250 WORDS)
Nephrol Dial Transplant 1995
PMID:Additive antiproteinuric effect of ACE inhibition and a low-protein diet in human renal disease. 762 91

Since 1988, 11 cases of a new entity, 'Lipoprotein glomerulopathy' (LG), were described in Japan. Some of these reports suggested that this glomerular lipid storage is due to excess apo E associated with heterozygous E2/3 apo E isoform. We report the first case of LG in a white European with no such lipid abnormalities. Proteinuria was discovered in 1967 when he was 42. Blood pressure and renal function were normal. Family history was negative. Renal biopsy disclosed lesions which were only understood at the time of the Japanese publications. They were composed of endocapillary glomerular deposits. Staining for lipids disclosed capillary loop obstruction with lipid droplets. Electron microscopy showed confluent droplets of various sizes obstructing capillary loops. Proteinuria progressively increased. In 1974 repeat renal biopsy showed the same lipid deposits, now associated with focal-segmental glomerulosclerosis (FSGS). Several serum lipoprotein and apolipoprotein studies ruled out any specific lipid derangement. This suggested a local glomerular disorder, presumably affecting the glomerular endocapillary disposal of lipids. A third biopsy showed progressive glomerular destruction by FSGS with persistence of the lipid droplets. Renal insufficiency progressed and haemodialysis was started in 1992. This observation suggests that LG is a local glomerular, not a general lipid disorder and indicates that this disease is not restricted to Asian patients.
Nephrol Dial Transplant 1995
PMID:Lipoprotein glomerulopathy: first case in a white European. 762 1

The objective of this trial was to determine the long-term antiproteinuric effect of a low-dose of the angiotensin-converting-enzyme inhibitor (ACEI) captopril in patients with idiopathic membranous nephropathy (IMN), stable renal function, and no indicators of poor long-term prognosis. Fourteen adult IMN outpatients (median age 53 years) with a median duration of disease of 3 years received 12.5 mg of captopril twice a day for 12 months in a prospective trial. The effects of therapy were evaluated on the basis of plasma creatinine, 24-h proteinuria, the proteinuria selectivity index, albuminaemia, and serum IgG levels. Data were compared by means of the non-parametric paired Wilcoxon test. Three patients withdrew from the trial. Renal function remained stable in the 11 who completed the study. A clear decrease in proteinuria was observed after 1 month of therapy, which persisted with time and was associated with a trend towards a further long-term decrease. An increase in serum albumin was only observed after 6 months of therapy, again with a trend towards an increase over time. Serum IgG levels increased during therapy. This study together with data from the literature suggests a potential long-term benefit of angiotensin-converting-enzyme inhibitors in moderately proteinuric IMN. Prospective trials comparing low-dose and high-dose ACEI to no treatment or a placebo in non-severe IMN are now required.
Nephrol Dial Transplant 1995
PMID:Low-dose angiotensin-converting-enzyme inhibitor captopril to reduce proteinuria in adult idiopathic membranous nephropathy: a prospective study of long-term treatment. 864 93

In summary, the decreased concentration of heparan sulphate within the extracellular matrix of patients with insulin-dependent diabetes mellitus is caused by a combination of genetic factors and poor metabolic control. Decreased concentrations of heparan sulphate are seen in patients with diabetes mellitus and proteinuria and this might be the explanation for the proteinuria as well as the expansion of the mesangium and the intimal dysfunction, including increased permeability of the vessel wall to macromolecules, which is present in such patients. Thus, the effective remodelling of extracellular matrix might explain coincidence of proteinuria, decline in renal function and premature atherosclerosis in patients with diabetes mellitus.
Nephrol Dial Transplant 1994
PMID:Nephropathy and coronary death--the fatal twins in diabetes mellitus. 780 Feb 2


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