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)

An association between renal microvascular complications and hemorheological alterations has been suggested in diabetes mellitus. Therefore, a hemorheologic approach in the treatment of diabetic microproteinuria has been proposed. Eighty-two type I and type II diabetic patients with microproteinuria were randomized and assigned to two different protocols: protocol A, patients treated with pentoxifylline (Trental 400); protocol B, patients without hemorheologic treatment, in whom hypoglycemic therapy was just more strictly enforced. A significant improvement of the hemorheologic pattern and a significant marked reduction of albumin excretion rate and proteinuria was found in diabetic patients treated with pentoxifylline, independently of the degree of metabolic control. These results were readily achieved and were confirmed throughout the study. Moreover, these results were comparable to those obtained in diabetic patients of protocol B. Pentoxifylline might therefore be considered as the first useful therapeutic agent in the treatment of diabetic microproteinuria.
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PMID:Pentoxifylline, albumin excretion rate and proteinuria in type I and type II diabetic patients with microproteinuria. Results of a short-term randomized study. 375 50

Pentoxifylline is a drug with hemorheological actions used in the management of microcirculatory abnormalities, such as those usually seen in diabetic patients. The drug has been successfully used in improving peripheral and central circulation, as well as proteinuria of long-term diabetes. With the hypothesis that pentoxifylline reduces proteinuria in patients with IDDM and NIDDM, with a wide range of urinary protein excretion, 86 diabetic patients were studied. Forty-one patients with IDDM were stratified in 2 subgroups: one of 18 patients with microalbuminuria, and the other of 23 patients with overt proteinuria. In the same way, 45 patients with NIDDM were divided in 2 subgroups: one of 23 patients with microalbuminuria, and the other of 22 patients with proteinuria. Patients in each subgroup were randomized to receive either placebo or pentoxifylline 1,200 mg/d, during 4 months, using a double blind design. At the beginning of the study and after treatment, 24-hour urinary albumin excretion was measured by nephelometry in each patient.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Pentoxifylline reduces proteinuria in insulin-dependent and non insulin-dependent diabetic patients. 773 73

MRL-lpr/lpr mice develop an autoimmune disease similar to human systemic lupus erythematosus (SLE). The main characteristics of this disease are increasing autoantibody formation, elevated plasma levels of immune complexes, a massive lymphoproliferation, a rising proteinuria, and arthritic symptoms. Finally, the mice die at an age of about 6 months due to a fatal immune complex glomerulonephritis. Macrophages are involved in the development of SLE due to their functions as antigen-presenting as well as cytokine-producing cells. T and B cells are involved in the disease by secreting cytokines and producing antibodies. Pentoxifylline (PTX), a xanthine derivative, is known to exert different effects on functions of leukocytes and erythrocytes and has been used in clinical studies, e.g., in septic shock syndrome. In our studies we first investigated the in vitro effect of PTX on macrophages and lymphocytes derived from MRL-lpr mice. Our investigations concerning production of superoxide anion and TNF-alpha by LPS and/or IFN-gamma activated bone marrow and peritoneal macrophages, MHC class II expression on these cells, and the proliferative capacity and Il-2 production of mitogen activated lymphocytes, revealed that PTX reduces the activation and the inflammatory response of these cells. Based on these results, we further investigated the effect of in vivo treatment with PTX. MRL-lpr mice treated with PTX showed diminished proteinuria, reduced titer of dsDNA-autoantibodies in the plasma and an increased survival rate. Our data clearly demonstrate that PTX is able to diminish the severity of the disease and to prolong the life of MRL-lpr/lpr mice.
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PMID:In vitro and in vivo effects of pentoxifylline on macrophages and lymphocytes derived from autoimmune MRL-lpr/lpr mice. 785 38

The single dose administration of the aminonucleoside of puromycin (PAN) induces a nephrotic syndrome in rats characterized by massive proteinuria and progressive histologic changes. This model of acute parenchymal nephritis is thought to be mediated by the renal recruitment of monocytes and macrophages. To investigate the role of leukocytes in the experimental nephrotic syndrome model, the effects of two methylxanthines, pentoxifylline (45 mg/kg i.p. twice daily) and torbafylline (5 mg/kg i.p. twice daily) were compared with controls over a 2-week period. Pentoxifylline treatment was associated with 3- and 6-fold reductions in urinary protein excretion at 7 and 14 days, respectively, compared with PAN-treated control animals (p < .01). Similarly, 14-day dosing of torbafylline resulted in a 3-fold decrease in urinary protein excretion. Glomerular filtration and electrolyte excretion rates were similar between all treatment groups. There were significant reductions in glomerular neutrophil and macro-phage counts, but not T-cells (OX19+) or suppressor/cytotoxic T-cells (0X8+), in kidneys of rats given either treatment compared with PAN con-trol rats. In summary, both pentoxifylline and torbafylline attenuated the proteinuria and glomerular macrophage and neutrophil infiltration associated with PAN administration. These data support the role of macrophages and neutrophils in the pathogenesis of acute parenchymal injury and the potential role of pentoxifylline or related analogues in the attenuation of the ensuing renal deficit associated with minimal lesion disease.
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PMID:Role of neutrophils and macrophages in experimental nephrosis of the rat. 950 60

Urinary TNF-alpha excretion correlates with proteinuria in patients with membranous nephropathy (MGN). Pentoxifylline suppresses or reduces the production of TNF-alpha. Between April, 1999 and August, 2000, we did a single-centre, prospective, pilot study to assess the effects of pentoxifylline (1200 mg/day) on proteinuria in patients with idiopathic MGN. Ten patients were included and treated for 6 months. Pentoxifylline significantly decreased proteinuria from 11 g/day [range 4.6-27] to 1.8 (0-10.9); p=0.001). Pentoxifylline may be a safe and effective adjunct to steroids and immunosuppressants in patients with MGN.
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PMID:Use of pentoxifylline in membranous nephropathy. 1142 74

Previous studies have reported that pentoxifylline, a phosphodiesterase inhibitor, attenuates experimental mesangial proliferative glomerulonephritis. This study hypothesized that pentoxifylline could also attenuate the renal disease progression in rats with remnant kidney. After 5/6 subtotal nephrectomy, rats developed progressively elevated proteinuria and plasma creatinine, glomerulosclerosis, interstitial inflammation, and fibrosis, all of which were attenuated by 40 to 60% by pentoxifylline. However, the elevated BP was not changed by pentoxifylline. Pentoxifylline reduced the upregulation of monocyte chemoattractant protein-1 gene by 60% in the cortex of remnant kidney, as well as in a dose-dependent manner in the albumin- or angiotensin II-stimulated proximal tubular cells. It also reduced the upregulation of mitogenic and profibrogenic genes by 50%, including platelet-derived growth factor, fibroblast growth factor-2, transforming growth factor-beta(1), connective tissue growth factor, and types I and III collagen in the cortex of remnant kidney. Furthermore, pentoxifylline was found to decrease the numbers of interstitial myofibroblasts by 60% in the cortex of remnant kidney and suppress the proliferation of cultured interstitial fibroblasts. It also reduced the angiotensin II-induced or transforming growth factor-beta(1)-induced expression of connective tissue growth factor gene in cultured fibroblasts and mesangial cells. Combining pentoxifylline with an angiotensin-converting enzyme inhibitor, cilazapril, almost completely attenuated the renal disease progression in rats with remnant kidney. In conclusion, pentoxifylline alone can attenuate the chronic renal disease progression. Its combination with cilazapril has the potential to prevent the renal disease progression almost completely.
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PMID:Pentoxifylline attenuated the renal disease progression in rats with remnant kidney. 1244 23

Current interventions with proven efficacy, such as glycemic and blood pressure control, dietary protein restriction, and angiotensin II blockade, slow the progression of chronic kidney disease (CKD); however, whether long-term cessation of CKD progression is possible remains unclear. Because of the pathogenetic complexity of this condition, multidrug interventions with the least adverse effects should be investigated as the next step in attempts to stop CKD progression. Pentoxifylline, a non-selective phosphodiesterase inhibitor with indiscernible toxicity, exerts potent inhibitory effects against cell proliferation, inflammation, and extracellular matrix accumulation, all of which play important roles in CKD progression. Pentoxifylline monotherapy markedly reduces proteinuria in patients with membranous nephropathy. Moreover, limited human studies have proven pentoxifylline efficacy in reducing proteinuria in patients with diabetes receiving angiotensin-converting enzyme inhibitors, and in patients with nephrotic syndrome secondary to lupus nephritis despite immunosuppressive therapy. Further clinical trials are necessary to examine whether pentoxifylline can improve renal outcomes in patients receiving interventions of proven efficacy.
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PMID:The renoprotective potential of pentoxifylline in chronic kidney disease. 1581 41

Proteinuria (albuminuria) reflects dysfunction of the glomerular permeability barrier in which inflammatory cytokines play a key role. Pentoxifylline (PTX) is a phosphodiesterase inhibitor that possesses potent anti-inflammatory and immunomudulatory effects. This study evaluated the effectiveness of PTX to reduce proteinuria and inflammatory mediators in patients with proteinuric primary glomerular diseases. Seventeen patients with primary glomerular diseases, a persistent spot proteinuria exceeding 1.5 g/g creatinine (Cr) and a glomerular filtration rate between 24 and 115 ml/min/1.73 m(2) were treated with PTX 400 mg twice daily for 6 months. Before and after the treatment, serum Cr, plasma renin activity and aldosterone concentrations, plasma and urinary tumor necrosis factor (TNF)-alpha, interleukin-1beta and monocyte chemoattractant protein (MCP)-1, as well as urinary protein and Cr were measured. PTX significantly reduced urinary protein excretion, along with an increase of serum albumin. A significant correlation existed between the basal urinary protein/Cr and the basal urinary MCP-1/Cr ratios. PTX lowered the urinary MCP-1/Cr ratio, and the percent reduction of urinary protein/Cr ratio correlated directly with the precent decrease of urinary MCP-1/Cr ratio after PTX treatment. There was no significant change in blood pressure, renal function, biochemical parameters, plasma renin activity and aldosterone concentrations, or plasma TNF-alpha and MCP-1 levels during the study. In conclusion, administration of PTX 800 mg per day is safe and effective for reducing proteinuria in patients with proteinuric primary glomerular diseases. This beneficial effect occurs in close association with a reduction of urinary MCP-1 excretion.
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PMID:Pentoxifylline ameliorates proteinuria through suppression of renal monocyte chemoattractant protein-1 in patients with proteinuric primary glomerular diseases. 1654 Oct 21

The prevalence of diabetes and its complications is increasing worldwide. Among the microvascular complications, diabetic nephropathy is the most frequent cause of end-stage renal disease. Although angiotensin-converting-enzyme inhibitors have been cited as the first line of therapy for the management of microalbuminuria, the rate of remission from microalbuminuria to normoalbuminuria has been lower than the expected. Furthermore, due to the elevated frequency of side effects of the rennin-angiotensin blockers new approaches for the treatment of microalbuminuria are needed. Pentoxifylline, a xanthine derivate drug with hemorheologic properties and primarily indicated for the therapy of disturbances of blood fluidity, is also an antagonist of adenosine 2 receptors and have anti-inflammatory and immunomodulatory effects, properties that promote beneficial changes in the blood flow conditions and kidney function. Current evidence shows that the short-term use of pentoxifylline has low side-effects, reduces both proteinuria and microalbuminuria in subjects with diabetes, and is as effective as captopril in the reduction of microalbuminuria in non-hypertensive type 2 diabetic patients. Although this data suggests that pentoxifylline could be useful for preventing the development of end-stage renal disease is necessary to conduct long-term studies to evaluate the role of pentoxifylline in the treatment of diabetic nephropathy and the prevention of chronic renal failure. In this article, we review the clinical evidence that show the efficacy of pentoxifylline in the management of microalbuminuria in diabetic patients.
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PMID:Efficacy of pentoxifylline in the management of microalbuminuria in patients with diabetes. 1822 Jun 96

Chronic kidney disease (CKD) as a considerable health problem may have proteinuria as the main complication and strong risk factor to reach end-stage renal disease (ESRD). Decreasing proteinuria is the mainstay of therapy in order to delay the progression of CKD. Current therapeutic regimens provide only partial renoprotection, and a substantial number of patients who have proteinuria progress to ESRD. Pentoxifylline (PTF) is known for its potent inhibitory effects against cell proliferation and inflammation which play important roles in CKD progression. Data derived from both human studies and animal models demonstrated that PTF has broad-spectrum renoprotective effects and therefore, provide a scientific basis for the use of PTF as an anti-proteinuric agent. Conclusion of this review is that short-term use of PTF may produce a significant reduction of proteinuria in subjects with diabetic and also non-diabetic kidney diseases but the reports of long-term use of PTF also show that urinary protein excretion exhibits a progressive and sustained reduction in patients treated with PTF. Whether the long-term use of PTF could be a pharmacological alternative for delaying or preventing the development of end stage renal disease, is among the questions that remained to be appropriately answered in large-scale clinical trials.
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PMID:A review of the potential benefits of pentoxifylline in diabetic and non-diabetic proteinuria. 2150 59


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