Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A single intravenous injection of puromycin aminonucleoside (PAN) results in marked proteinuria and glomerular morphological changes that are similar to minimal change disease in humans. We examined the effect of hydroxyl radical scavengers and an iron chelator on PAN-induced proteinuria. PAN in a dose of 5 mg/100 g body wt significantly increased urinary protein by day 5 (saline: 15 +/- 2, N = 24: PAN: 63 +/- 17, N = 23, P less than 0.001); the proteinuria rapidly increased thereafter, reaching 216 +/- 34, N = 23 by day 7. Concurrent administration of hydroxyl radical scavengers dimethylthiourea, (DMTU 500 mg/kg followed by 125 mg/kg i.p. twice a day) and sodium benzoate (BENZ, 150 mg/kg followed by 125 mg/kg i.p. twice a day) starting the evening before PAN injection markedly reduced proteinuria throughout the course of the study (urinary protein, mg/24 hours on day 7, mean +/- SEM: PAN: 229 +/- 45, N = 15; PAN + DMTU: 30 +/- 5, N = 18; PAN + BENZ: 80 +/- 18, N = 16. Because of the participation of iron in biological systems to generate hydroxyl radical, we also examined the effect of deferoxamine (DFO, 30 mg/day), an iron chelator, on the PAN-induced proteinuria. Concurrent administration of DFO was also protective. In a second series of experiments, DMTU and DFO (administered as described above and then for two additional days after the PAN) provided marked protection even when they were stopped prior to the onset of proteinuria. The protective effects of two hydroxyl radical scavengers and iron chelator implicate an important role for hydroxyl radical in PAN-induced nephrotic syndrome.
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PMID:Evidence suggesting a role for hydroxyl radical in puromycin aminonucleoside-induced proteinuria. 284 72

The acute phase of glomerular injury in a model of antiglomerular basement membrane, antibody-induced glomerulonephritis (antiGBM-GN) in rabbits was shown to be neutrophil-dependent using nitrogen mustard depletion studies. Administration of desferrioxamine (DFX) prevented the development of proteinuria in this model of renal injury [24 hr protein excretion (mean +/- SEM): antiGBM-GN/DFX = 16.2 +/- 2.9 mg compared with antiGBM-GN control = 271.5 +/- 92.2 mg, P less than 0.01]. Antibody binding levels, glomerular filtration rates, circulating complement and neutrophil counts, glomerular C3 deposition, and neutrophil infiltration did not differ between DFX treated and antiGBM-GN groups. In vitro assay systems to assess oxygen radical production [superoxide anion (O2-) and hydroxyl radical (OH.)] by neutrophils activated via the interaction of antiGBM antibody, GBM and complement were established. In these assays, DFX inhibited OH. production by immunologically-stimulated neutrophils (ISN) [nM diphenol/hr/10(6) cells, mean +/- SEM, ISN/DFX = 8 +/- 2 compared with ISN = 191 +/- 22, P less than 0.01] while production of O2- was not affected [nM O2-/hr/10(6) cells, mean +/- SEM, ISN/DFX = 29.1 +/- 4.3 compared with ISN = 32.6 +/- 2.5, P greater than 0.05]. These studies demonstrate that the iron chelator desferrioxamine can prevent neutrophil-dependent immune renal injury by interfering with neutrophil function. Treatment with the hydroxyl radical scavenger dimethylthiourea also significantly attenuated renal injury in antiGBM-GN. Together, the in vivo and in vitro data strongly suggest that neutrophil-dependent immunological renal injury is mediated via hydroxyl radical production by activated neutrophils within glomeruli.
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PMID:Hydroxyl radical mediation of immune renal injury by desferrioxamine. 302 99

The long-term results of conversion of cyclosporine to azathioprine and those of continuous CsA therapy were evaluated in a prospective study of 66 renal transplant patients who had been randomly assigned to each treatment group at 3 months following transplantation. The start point of the study was thus at 3 months posttransplant; no differences in the three-year patient and graft survival were found; these consisted of 97% and 94% in the converted group and 100% and 94% in the nonconverted group, respectively. The incidence of one or more antirejection treatments did not differ between the two groups at 3-12 months (16% vs. 17%) or after 12 months (12% vs. 9%). The incidence of hypertension at different intervals ranged from 79% to 100% in the group on continuous CsA therapy versus 50 to 58% in the converted patients. The degree of proteinuria in the 2 groups was not different at at 12 months. At 24 and 36 months the proteinuria (g/24 hr) was higher in the converted group (0.51 +/- 0.18 and 0.53 +/- 0.13; mean +/- SEM) versus the CsA group (0.15 +/- 0.04 and 0.21 +/- 0.09). At 3 years, the mean creatinine clearance for the patients converted to Aza was higher than that found for the continuously CsA-treated patients (67 +/- 8 and 59 +/- 6 ml/min; mean +/- SEM). This study shows that early CsA conversion to Aza gives a slightly better 3-year graft function, although not significantly different, compared with continuous CsA therapy without differences in patient or graft survival.
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PMID:Controlled cyclosporine conversion at three months after renal transplantation. Long-term results. 305 88

The evolution of renal disease was studied in 12 insulin dependent diabetics selected for intermittent clinical proteinuria. After a run in period during which patients were studied three monthly for at least 12 months members of pairs of patients matched for age and duration of diabetes were allocated either to receive continuous subcutaneous insulin infusion or to continue with their usual conventional insulin injection therapy (controls) and studied three monthly for a further year. Mean (SEM) plasma glucose concentration and glycosylated haemoglobin (HbA1) value improved significantly in the insulin infusion group (glucose 10.1 (1.0) v 5.3 (0.3) mmol/l (182 (18) v 95 (5) mg/100 ml); HbA1 9.6 (0.8) v 7.6 (0.5)%; p less than 0.001 and p less than 0.005, run in v experimental periods) but not in the control group. Blood pressure was kept normal throughout. Glomerular filtration rate fell significantly in the insulin infusion and control groups throughout the study, from mean (SEM) baseline values of 114 (16) and 119 (15) ml/min/1.73 m2 to final values of 92 (15) and 95 (13) ml/min/1.73 m2 respectively (p less than 0.05 and p less than 0.01). The mean rate of decline in glomerular filtration rate did not change significantly in either group (run in v experimental periods: insulin infusion group 1.0 v 0.8 ml/min/month; controls 0.8 v 0.9 ml/min/month). Mean (SEM) plasma creatinine concentration rose slightly in the insulin infusion group only (93 (5) to 109 (11) mumol/l (1.1 (0.06) to 1.2 (0.1) mg/100 ml), 0.1 greater than p greater than 0.05; controls 94 (6) to 96 (6) mumol/l (1.1 (0.07) and 1.1 (0.07) mg/100 ml]. The urinary excretion rate of albumin varied widely and unpredictably throughout, while beta 2 microglobulin excretion remained normal and unchanged in both groups. Thus a at the stage of intermittent clinical proteinuria when albumin excretion rate is unpredictably variable (breaking through the "clinically positive" threshold only episodically) renal function, though still in the "normal" range, is already declining progressively; and the study failed to show that sustained improvement in mean glycaemia exerts a significant effect on this early deterioration of renal function.
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PMID:Intermittent clinical proteinuria and renal function in diabetes: evolution and the effect of glycaemic control. 308 Jan 1

The serum lipoprotein concentrations, including high-density lipoprotein (HDL) subfractions and apolipoproteins Al and B were measured in 21 patients (14 male and seven female) with nephrotic range proteinuria (greater than 3g/24hr), well maintained renal function (creatinine clearance greater than 35 mliter/min/1.73m2) and biopsy-proven primary glomerular disease. In these, and in a further five patients (creatinine clearance greater than 15 mliter/min/1.73m2), urinary apolipoprotein Al output was determined. Total HDL cholesterol was similar in patients and controls, but in male patients, HDL2 was low (0.54 +/- 0.10 mmole/liter, mean +/- SEM) compared to controls (0.75 +/- 0.04 mmole/liter, P less than HDL3 was high (0.81 +/- 0.07 in patients and 0.63 +/- 0.02 mmole/liter in controls, P less than 0.01). In women, there was a similar tendency for HDL2 to be lower in patients (0.68 +/- 0.18 mmole/liter) than in controls (0.85 +/- 0.10 mmole/liter). Multiple regression analysis revealed that major determinants of the urinary apolipoprotein Al output were the urinary protein output and selectivity index (multiple r = 0.85). Furthermore, some patients lost apolipoprotein Al into their urine at rates indicating increased production of apolipoprotein Al in the nephrotic syndrome. The serum HDL subfraction concentrations in the nephrotic syndrome could be explained by a combination of increased HDL production and increased urinary loss of low molecular wt HDL.
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PMID:Serum and urinary high density lipoproteins in glomerular disease with proteinuria. 309 2

To study the effectiveness and nephrotoxic side-effects of cyclosporin A (CsA) in renal transplant recipients, a prospective randomised trial was designed to compare CsA with azathioprine (Aza). Each treatment group consisted of 40 patients; in the CsA group, 18 were randomly selected for conversion to Aza after 3 months. The 1-year graft survival for CsA-treated patients was 87% compared with 66% for the Aza group (P = 0.033). Anti-rejection therapy was administrated to 78% of the patients in the Aza group and 47% of those in the CsA group (P less than 0.01). There was no difference in the incidence of primary non-functioning kidneys, cytomegalovirus infections, hypertension, or degree of proteinuria between the two treatment groups. At 3 months the mean creatinine clearance was 42 +/- 2 ml/min (mean +/- SEM) for the CsA group compared with 56 +/- 4 ml/min for the Aza group (P less than 0.01), whereas the mean creatinine clearances at 6 months for both the converted and the non-converted CsA-treated patients did not differ from that found in the Aza-treated group. At 1 year, the mean creatinine clearance for CsA-treated patients who were converted to Aza was higher than that found for Aza-treated patients (62 +/- 7 vs 50 +/- 6 ml/min; P less than 0.05). Furthermore, the increment in creatinine clearance observed after conversion from CsA to Aza at 3 months showed a linear relationship (r = 0.9061) with the CsA trough levels before discontinuation of the drug. This indicates that CsA treatment induces a dose-dependent, nephrotoxic side-effect which is probably reversible.
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PMID:A prospective randomised comparative study on the influence of cyclosporin and azathioprine on renal allograft survival and function. 311 Jun 62

As in previous studies an improved single radial immunodiffusion technique was used for albumin, calculating the albumin/creatinine ratio in spot urine (mg/g/1.73 m2). This ratio was 4.7 +/- 0.0174 (geometric mean +/- SEM as logarithm) in 130 healthy controls, the highest value being 10.8. The 182 non-selected ambulatory diabetic patients presented three subgroups, each showing a non-gaussian frequency distribution: 47% with normal values (5.0 +/- 0.0224); 42% with ratio values from 11.0 to 88.8 (22.7 +/- 0.0269, significantly differing from the controls); 11% with clinical proteinuria (subsequently excluded from the study). Type I (9.6 +/- 0.0452; n = 76) and type II diabetic patients (10.7 +/- 0.0430; n = 86) significantly differed (p less than 0.001) from the controls but not from one another. Irrespective of the diabetes type, ratio values were significantly correlated with the duration of diabetes, age of patients, age of diagnosis (for instance 16.2 +/- 0.0974 in 15 patients aged greater than 65 years versus 9.1 +/- 0.0792 in 23 patients aged less than 20 years), glycemia level and chronic complications (especially retinopathy). Therefore, more than half the diabetic patients, non-selected, presented an increased albumin excretion as compared to the controls. On the other hand, microalbuminuria appears to be linked to age, duration of the disease and quality of the metabolic control rather than to the diabetes type.
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PMID:Is microalbuminuria a different problem for type I and type II diabetes mellitus? 312 5

The immunosuppressive effectiveness and nephrotoxic side-effects of either high-dose cyclosporin (CsA) (16 mg/kg per day) or low-dose (9 mg/kg per day) in combination with azathioprine (Aza) (1 mg/kg per day) were studied in 80 renal transplant patients who also received low-dose corticosteroids. At 3 months, patients who received high-dose CsA were randomly assigned to either continuation of CsA or conversion to Aza, whereas in the triple-therapy group either CsA or Aza was discontinued. No differences in patient (97.5%) or graft survival (90%-92.5%) were found at 1 year. There were no differences in the incidence of primary non-functioning kidneys. The incidence of acute rejection episodes was 45% in the high-dose CsA group and 55% in the group treated with low CsA doses together with Aza (not significant). At 3 months the mean creatinine clearance was 60 +/- 4 ml/min (mean +/- SEM) in the high-dose group (mean cumulative CsA dose 0.96 g/kg) compared with 55 +/- 3 ml/min in the low-dose group (mean cumulative CsA dose 0.60 g/kg). At 1 year no differences in the degree of proteinuria or the incidence of hypertension was found between the different groups. The best mean creatinine clearance at 1 year (77 +/- 5 ml/min) was found in patients who received high doses of CsA for 3 months followed by conversion.
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PMID:High- and low-dose regimens of cyclosporin in renal transplantation: immunosuppressive efficacy and side-effects. 314 26

Proteinuria is a major manifestation of glomerular disease (glomerulonephritis, GN). We examined the effect of trans-epoxysuccinyl-L-leucylamido-(4-guanidino)butane (E-64), a specific and irreversible cysteine proteinase inhibitor, on urinary protein excretion in a complement- and neutrophil-independent model of antiglomerular basement membrane (GBM) antibody disease. A single injection of rabbit antirat-GBM IgG produced a marked increase in urinary protein excretion 24hr after injection. In two separate studies using different pools of antiGBM IgG, administration of E-64 (5mg every 6h starting 2hr prior to induction of GN) reduced proteinuria (-45 +/- 7%, and -41 +/- 14%, Mean +/- SEM, n = 6; P less than 0.001) in the 24 hour period following induction of the disease. This reduction in urinary protein excretion was accompanied by a marked decrease in the specific activity of the cysteine proteinases cathepsins B and L in glomeruli (B: -97%; L: -84%) and renal cortex (B: -87%; L: -75%) isolated from the same E-64-treated rats compared to same saline-treated controls. These data, combined with the specificity of E-64 for cysteine proteinases, suggest a potential role for cysteine proteinases in the increased GBM permeability and proteinuria in this experimental model of glomerular disease.
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PMID:The cysteine proteinase inhibitor, E-64, reduces proteinuria in an experimental model of glomerulonephritis. 317 11

Administration of puromycin aminonucleoside (PAN) to Wistar rats induces proteinuria and enhanced mesangial deposition of circulating macromolecules. After proteinuria of longer duration focal and segmental glomerular hyalinosis and sclerosis (FSGHS) develops. The present report analyzes these aspects of PAN nephrosis in PVG/c rats, a strain previously shown to be remarkably resistant to proteinuria and FSGHS with aging or after uninephrectomy. In Wistar rats multiple injections of PAN during five months resulted in sustained severe proteinuria and FSGHS lesions in 8.1 +/- 1.0% (mean +/- 1 SEM) of their glomeruli (N = 6). In PVG/c rats a 1.3-fold higher dose of PAN was needed to induce chronic proteinuria similar to the Wistar rats. After five months 3.3 +/- 0.9% of their glomeruli showed FSGHS (N = 6, P less than 0.01) and the glomerular lesions were considerably less advanced. In acute PAN nephrosis induced by a single intravenous injection of PAN the mesangium of Wistar rats contained large amounts of lipid in contrast to a few small mesangial lipid droplets in nephrotic PVG/c rats. After injection of colloidal carbon in nephrotic PVG/c rats no enhanced carbon accumulation was found in the mesangium when compared to nonproteinuric controls. This result clearly differs from the increased mesangial sequestration of circulating material in nephrotic Wistar, and most other rat strains. The unchanged mesangial traficking of macromolecules in nephrotic PVG/c rats and the low incidence of FSGHS lesions in the presence of sustained glomerular proteinuria may reflect a relative resistance to PAN-induced glomerular damage in this particular rat strain.
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PMID:Differences in puromycin aminonucleoside nephrosis in two rat strains. 336 53


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