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)

The interaction of cells within the glomerulus plays an important role in the development and progression of glomerular disease. To investigate the interaction of glomerular mesangial cells (GMC) and epithelial cells (GEC), and mediator(s) of this interaction, we investigated the effect of Adriamycin (doxorubicin hydrochloride)-induced (ADR) rat GMC-conditioned medium (GMC-CM) on the incorporation of 35S, 3H-leucine, and 3H-thymidine in normal rat GEC, as well as 3H-thymidine uptake by normal rat GMC in response to ADR-rat GEC-CM. In addition, changes in the responsiveness to interleukin-6 (IL-6) and the products of IL-6 were assessed in ADR-rat GMC. The results showed that: (1) GMC-CM of ADR-rat with heavy proteinuria stimulated GEC proliferation and the synthesis of sulfated compounds and protein, while the GEC-CM of ADR-rat from the same nephrotic period increased GMC proliferation; (2) the ADR-rat GMC had altered responsiveness to IL-6 and its products. The stimulation index results demonstrated the interaction of GMC and GEC in the ADR-induced rat model, and that this interaction related closely to the degree of proteinuria and was mediated by soluble products of the damaged glomerular cell.
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PMID:The interaction of glomerular mesangial cells and epithelial cells. 963 36

The effect of ticlopidine on rats with adriamycin nephropathy was observed during 26 weeks. In the ticlopidine-treated nephrotic animals (TNG), proteinuria was less than in the untreated nephrotic animals (NG), but this difference was significant only at week 6 (TNG = 47.27 +/- 16.52 versus NG = 100.08 +/- 13.83 mg/24 h, p < 0.01) and week 26 (TNG = 157.00 +/- 28.73 versus NG = 217.00 +/- 21.73 mg/24 h, p < 0.01) after ADR injection. NG presented severe tubulointerstitial abnormalities with a tubulointerstitial lesion index of 3+. No difference in glomerular lesions was observed among the groups (NG median = 6%, TNG median = 4% and TCG median = 2%). The tubulointerstitial lesion index of TNG was less intense (median = 2+) but not different from those of the control groups (CG median = 1+; TCG median = 0+) nor NG (median = 3+). We concluded that the treatment with ticlopidine produced some partially beneficial effects but did not prevent the development of adriamycin-induced nephropathy.
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PMID:Role of ticlopidine on adriamycin-induced nephropathy. 1051 90

In order to assess the effects of mycophenolate mofetil (MMF) on the development of adriamycin-induced nephropathy, the development of this nephropathy in rats treated with MMF was compared to that in non-treated animals (group ADR + V) over 28 weeks. At weeks 8, 16 and 20, 24-h proteinuria of the treated group statistically differed from that of the non-treated group. However, no significant difference in proteinuria was observed thereafter between the groups. At the end of the experiment, there was no significant difference between both groups regarding the frequency of glomerular lesion (Group ADR + V: Md = 35%, P25 = 20%, P75 = 68%; Group ADR + MMF: Md = 27%, P25 = 9.5%, P75 = 54%); tubulointerstitial lesion index (Group ADR + V: Md = 7, P25 = 1.5, P75 = 9; Group ADR + MMF: Md = 8, P25 = 2, P75 = 9); glomerulosclerosis area (group ADR + V = 2779 microm2, P25 = 751.8 microm2, P75 = 3115 microm2; Group ADR + MMF = 1147 microm2, P25 = 3969.7 microm2, P75 = 1560 microm2); and, interstitial fibrosis area (Group ADR + V: Md = 218200 microm2, P25 = 78670 microm2, P75 = 282700 microm2 group ADR + MMF: Md = 136000, P25 = 25010, P75 = 255800 microm2). In conclusion, MMF caused a temporary reduction in proteinuria but did not change the severity of the renal lesion observed after 28 weeks.
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PMID:Effect of mycophenolate mofetil on the progression of adriamycin nephropathy. 1172 7

Targeting of anti-tumor drugs to the urinary bladder for the treatment of bladder carcinoma may be useful, since these agents generally have a low degree of urinary excretion and are highly toxic elsewhere in the body. The anti-tumor drug doxorubicin was coupled to the low-molecular weight protein lysozyme via the acid-sensitive cis-aconityl linker. All free amino groups of the lysozyme were used for drug attachment to achieve intact excretion of the doxorubicin-aconityl-lysozyme conjugate into the bladder. In the bladder, the cytotoxic drug should be regenerated through acidification of the urine. First, the doxorubicin-aconityl-lysozyme conjugate was tested in rats for its target specificity and general toxicity. Wistar rats were injected intravenously with 2 mg/kg free doxorubicin or 10 mg/kg lysozyme-conjugated doxorubicin. Total urinary excretion of doxorubicin was about 10 times higher if the drug was coupled to lysozyme (39 +/- 3% versus 4.4 +/- 0.4%). Free doxorubicin had no detectable toxic effects on heart, liver and lung but caused severe renal damage (proteinuria, N-acetylglucosaminidase excretion and glomerulosclerosis). None of the rats injected with doxorubicin-lysozyme conjugate showed such renal toxicity. Second, we tested whether doxorubicin could be released from the conjugate in the bladder through acidification of the urine and if the released doxorubicin could still exert a cytotoxic effect. Doxorubicin-aconityl-lysozyme (2 mg/kg conjugated doxorubicin, i.v.) was administered in rats with acidified urine (pH 6.1 +/- 0.1) and in rats with a high urinary pH (8.2 +/- 0.4). Ten times more doxorubicin was released from the conjugate in the group with acidified urine (15 +/- 7% versus 1.7 +/- 0.1%). In agreement with this, cytotoxicity was also higher in the low pH group (IC50 of 255 +/- 47 nM versus 684 +/- 84 nM doxorubicin). In conclusion, a specific delivery of doxorubicin to the urinary bladder combined with a reduced toxicity of doxorubicin in the kidneys can be achieved by coupling this anti-tumor drug to the low-molecular weight protein lysozyme via an acid-labile linker. A release of cytotoxic doxorubicin in the urinary bladder can be achieved by acidification of the urine. This technology, after further optimization, may provide an interesting tool for the treatment of bladder carcinoma.
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PMID:Targeting of doxorubicin to the urinary bladder of the rat shows increased cytotoxicity in the bladder urine combined with an absence of renal toxicity. 1199 90

The effects of cyclosporine A (CSA) administration, started as early as renal lesion is induced, on the development of Adriamycin-induced nephropathy were assessed by comparing the time course of this nephropathy in rats receiving CSA with that in non-treated animals (group ADR) over 16 weeks. Throughout the experiment, no significant difference in proteinuria was observed between the groups. At the end of the experiment, there was no significant difference between the groups regarding the frequency of glomerular lesion (Group AADR: Md = 23%, P25 = 15%, P75 = 75%; Group ADR-CSA: Md = 48%, P25 = 11%, P75 = 70%); tubulointerstitial lesion index (Group ADR: Md = 1.5, P25 = 1.0, P75 = 2.5); glomerulosclerosis area (Group ADR = 18.2 +/- 4.2%; Group ADR-CSA = 13.2 +/- 1.4%); and, interstitial fibrosis area (Group ADR+V: 1.75 +/- 0.10%; group ADR-CSA: 1.34 +/- 0.09%). In conclusion, CSA, when administered since nephropathy induction does not change the course of the disease.
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PMID:Effect of cyclosporine on adriamycin induced nephritis. 1238 Sep 2

We present a 5-years old boy with acquired Fanconi-de Toni-Debre syndrome being a effect of therapy for Ewing's sarcoma. At the age of 3 years, this boy was diagnosed as suffering from Ewing sarcoma of his right femur. The boy received a course of 8-month pre-surgery (6 VIDE--Vincristine, Ifosfamide, Doxorubicin, Etoposide cycles and 2 VAI--Vincristine, Actinomycin, Ifosfamide cycles) and 6-month post-surgery (6 VAI--Vincristine, Actinomycin, Ifosfamide cycles) cytostatic therapies according to EWING, EURO 99 protocol. In forth month of post-surgery cytostatic therapy, progressive malaise, polyuria, polydypsia, and recurrent vomiting occurred. The association between those symptoms and malignancy was excluded. Laboratory studies revealed hypokaliemia, hypophosphatemia, proximal tubular acidosis, proteinuria, glucosuria, aminoaciduria, hyperkaliuria and hyperphosphaturia. Acquired Fanconi-de Toni-Debre syndrome due to toxic effect of cytostatic therapy on renal proximal tubules was diagnosed. At present, two years after the time the diagnosis was made, despite constant substitution of potassium, phosphates and bicarbonates, deficit of body mass and height, and bone mineral density abnormalities are observed.
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PMID:[Acquired Fanconi-de Toni-Debre syndrome due to therapy for Ewing's sarcoma in 5-years old boy]. 1689 36

Mesangiolytic glomerulopathy is an uncommon complication of irradiation and chemotherapy of THP-COP [pirarubicin, cyclophosphamide (CPA), vincristin (VCR), predonisolone (PSL)] and CHOP (CPA, Doxorubicin, VCR, PSL). We report a case of 63-year-old man 7 months status post radiation, and 10 months post chemotherapy for gastric lymphoma. The patient showed proteinuria and mild renal insufficiency. Renal biopsy revealed marked mesangiolysis in the glomeruli without any immune depositions. After the administration of angiotensin II receptor blocker, the patient's renal function remained stable for over two years. Mesangiolysis was thought to be a characteristic glomerular lesion in this patient treated with both chemoagents and radiation.
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PMID:Mesangiolytic glomerulopathy after radiotherapy and chemotherapy of gastric lymphoma. 1802 69

The objective of this study was to evaluate the efficacy of Chinese herbs on Doxorubicin-induced focal and segmental glomerulosclerosis (FSGS) in rats. Twenty age-matched male Wistar rats were divided into two groups: group A (n = 10) given only water ad libitum served as the control group and group B (n = 10) was given Chinese herbs (40 ml/kg with drug concentration 1.75 g/ml) beginning at day zero. All rats were administered doxorubicin (7 mg/kg) intravenously. All the rats were placed in metabolic cages at day 0, 7, 14, 21, and 28, and daily proteinuria was measured. At day 28, the animals were killed by cervical dislocation, followed by immediate organ collection for histologic analysis of kidneys; blood was collected by tail vein and cardiac puncture (at day 28) for the measurement of serum albumin. Body weight (BW) and food intake were recorded. The rats in groups A and B demonstrated severe susceptibility to doxorubicin injection with the onset of proteinuria (80-100 mg/24h) at day 7. The rats in group B were partly resistant to doxorubicin nephropathy with decreasing proteinuria and increasing serum albumin compared with group A (p < 0.05). All 10 rats in group A developed at least 5% glomerulosclerosis with tubular casts at day 28. In contrast, the rats in group B developed less severe histologic renal disease. The difference in histologic scores between the two groups were significant at day 28 (12 in group B vs. 20 in group A, p = 0.002). Food intake of Group B animals progressively increased to reach 67-73% of those observed before the doxorubicin administration with 28-43% in Group A. After the 4-wk experimental period, BW in Group A decreased more significantly than that in Group B (-20 +/- 3 and -16 +/- 1%, respectively, p = 0.035, paired T test). Chinese herbs seem to reduce proteinuria and attenuate renal histologic severity in rats with doxorubicin-induced FSGS and may offer an alternative to the treatment of FSGS.
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PMID:Protection by Chinese herbs against Doxorubicin-induced focal and segmental glomerulosclerosis in rats. 1860 70

Doxorubicin-induced nephropathy leads to epithelial sodium channel (ENaC)-dependent volume retention and renal fibrosis. The aldosterone-sensitive serum- and glucocorticoid-inducible kinase SGK1 has been shown to participate in the stimulation of ENaC and to mediate renal fibrosis following mineralocorticoid and salt excess. The present study was performed to elucidate the role of SGK1 in the volume retention and fibrosis during nephrotic syndrome. To this end, doxorubicin (15 mug/g body wt) was injected intravenously into gene-targeted mice lacking SGK1 (sgk1(-/-)) and their wild-type littermates (sgk1(+/+)). Doxorubicin treatment resulted in heavy proteinuria (>100 mg protein/mg crea) in 15/44 of sgk1(+/+) and 15/44 of sgk1(-/-) mice leading to severe nephrotic syndrome with ascites, lipidemia, and hypoalbuminemia in both genotypes. Plasma aldosterone levels increased in nephrotic mice of both genotypes and was followed by increased SGK1 protein expression in sgk1(+/+) mice. Urinary sodium excretion reached signficantly lower values in sgk1(+/+) mice (15 +/- 5 mumol/mg crea) than in sgk1(-/-) mice (35 +/- 5 mumol/mg crea) and was associated with a significantly higher body weight gain in sgk1(+/+) compared with sgk1(-/-) mice (+6.6 +/- 0.7 vs. +4.1 +/- 0.8 g). During the course of nephrotic syndrome, serum urea concentrations increased significantly faster in sgk1(-/-) mice than in sgk1(+/+) mice leading to uremia and a reduced median survival in sgk1(-/-) mice (29 vs. 40 days in sgk1(+/+) mice). In conclusion, gene-targeted mice lacking SGK1 showed blunted volume retention, yet were not protected against renal fibrosis during experimental nephrotic syndrome.
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PMID:Serum- and glucocorticoid-inducible kinase 1 in doxorubicin-induced nephrotic syndrome. 1876 91

Recent studies indicated pulse pressure as a risk factor for left ventricular hypertrophy, myocardial infarction, congestive heart failure and stroke as well as chronic renal failure progression. The present study examined the effects of carvedilol and its combination with captopril on blood pressure, left ventricular hypertrophy, kidney vascular changes and kidney function in spontaneously hypertensive rats with adriamycin nephropathy. Four groups of 20 SHR each were involved: (1) control group: SHR; (2) ADR group: SHR treated with ADR (2mg/kg i.v. twice in 20 days); (3) ADR-C group: SHR treated with ADR and carvedilol (30 mg/kg/day) and (4) ADR-CC group: SHR treated with ADR and carvedilol (30 mg/kg/day) and captopril (60 mg/kg/day). Systolic-, diastolic- and mean-pressures and pulse pressure were determined at weeks 6 and 12 after the second ADR injection; and body weight, creatinine clearance and proteinuria at weeks -3, 6 and 12. The rats were sacrificed at week 6 or 12, the weights of the left and right ventricles and kidneys measured and the kidney vascular index was calculated as described by Bader and Mayer. Both carvedilol alone and combined with captopril significantly reduced systemic blood pressure but the effect of the latter was more pronounced and registered from week 4 till the end of the study. Carvedilol and its combination with captopril significantly decreased SBP, DBP and MAP. They also decreased PP, prevented the development of LVH, and renal vascular changes and slowed the progression of chronic renal failure and these effects were stronger in the ADR-CC group than in the ADR-C group. The antihypertensive drugs failed to prevent proteinuria in ADR SHR. Significant positive correlations were found between PP (but not SBP, DBP and MAP) and both proteinuria and Ccr in all groups of rats. In conclusion, carvedilol alone, but more strongly in combination with captopril, significantly reduced blood pressure, PP, LVH, renal blood vessel changes and chronic renal failure progression.
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PMID:Effect of carvedilol on pulse pressure and left ventricular hypertrophy in spontaneously hypertensive rats with adriamycin nephropathy. 1901 53


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