Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0033687 (proteinuria)
 24,015 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Levels of factor VIII/von Willebrand factor were measured in 105 patients affected by glomerulonephritis either of primary origin or associated with systemic diseases. The median plasma concentration of factor VIII-related antigen was significantly higher in the patients than in healthy controls. Amongst patients with primary glomerulonephritis, higher levels were observed in minimal change nephropathy than in other types. In patients with secondary glomerulonephritis, plasma factor VIII-related antigen was particularly elevated in lupus nephritis and in renal amyloidosis. Altogether, patients with the nephrotic syndrome showed higher levels than patients with lesser degrees of proteinuria. A negative correlation was found between the plasma concentration of factor VIII-related antigen and that of serum albumin but no correlation was observed with the extent of proteinuria. In 48 patients, plasma factor-VIII procoagulant activity was also measured and found to be elevated to the same extent as factor VIII-related antigen in the majority of cases. The urinary excretion of factor VIII-related antigen, evaluated in 72 patients, was found in variable amounts in 31 cases without any correlation with proteinuria. Glomerular deposits of factor VIII-related antigen were an uncommon finding. After 24 months, there was no clear evidence of an unfavourable association between increased plasma levels of factor VIII-related antigen and the course of the disease. Our findings suggest that the measurement of levels of factor VIII/von Willebrand factor in plasma or urine must be interpreted with caution in predicting the clinical course of patients affected by glomerular disease.
 ...
PMID:Factor VIII/von Willebrand factor in glomerular nephropathies. 679 18

1. Diabetic nephropathy is a serious microvascular complication in patients with insulin-dependent diabetes mellitus, resulting in end-stage renal disease in 30-45% of such patients. Despite intensive investigation, the pathophysiology of diabetic renal disease has not been fully elucidated. However, several clinical and experimental studies have suggested that endothelial dysfunction and free-radical activity may be important factors. 2. Forty normotensive patients with insulin-dependent diabetes mellitus of between 10 and 20 years duration with persistent normoalbuminuria (albumin excretion < 30 mg/day) and normal renal function were investigated for markers of endothelial dysfunction (plasma von Willebrand factor, soluble thrombomodulin and angiotensin-converting enzyme activity), free oxygen radical generation (erythrocytic superoxide dismutase and glutathione peroxidase) and oxidant injury (serum malondialdehyde). Glomerular proteinuria (albuminuria, transferrinuria), tubular proteinuria (retinol-binding protein) and tubular enzymuria (N-acetyl glucosaminidase and leucine aminopeptidase) were also measured. 3. Patients were divided into two groups. Group 1 comprised 21 patients with elevated markers of endothelial dysfunction, and group 2 comprised 19 patients with normal levels of plasma von Willebrand factor, soluble thrombomodulin and angiotensin-converting enzyme activity. Thirty-eight healthy subjects matched for age and sex acted as controls. 4. Groups 1 and 2 were similar in age, sex, body weight, duration of diabetes mellitus and recent glycaemic control. Serum cholesterol, serum creatinine and glomerular proteinuria were similar in the three groups. Group 1 patients had significantly increased oxidant injury, tubular enzymuria and proteinuria compared with group 2 patients and control subjects (P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Relationship between markers of endothelial dysfunction, oxidant injury and tubular damage in patients with insulin-dependent diabetes mellitus. 828 43

Proteinuria represents one of the most unfavorable prognostic factors in the progression of nephropathies. Several lines of evidence support a role for proteinuria per se in the development of interstitial fibrosis, albeit the molecular mechanisms are still unknown. We investigated the potential role of integrins expressed on tubular cells in regulating the synthesis and organization of interstitial matrix or as mediators of tubulointerstitial damage in conditions mimicking the nephrotic milieu. Under basal conditions, cultured tubular cells highly expressed alpha 3 beta 1 and, at focal contacts, alpha v beta 3. In contrast, alpha v beta 5 was weakly and diffusely distributed all over the plasma membrane. Cultures on a variety of matrix substrates (fibronectin, laminin, collagen types I and IV, vitronectin, von Willebrand factor, fibrinogen) did not induce any phenotypic change in integrin expression by tubular cells. Conversely, the addition of albumin resulted in a highly increased membrane expression of beta 5, which was organized in typical focal contacts and was related to the dose of albumin added. Immunofluorescence, flow cytometry, immunoprecipitation and RT-PCR experiments argue for a complex mechanism that includes increased post-transcriptionally regulated protein synthesis, accelerated conversion of precursors to mature forms, and increased surface delivery to discrete adhesive structures. Up-regulation of the beta 5 chain in tubular cells was confirmed in 9 out of 11 kidney biopsies from proteinuric glomerulonephritides including membranous and focal sclerosing glomerulonephritis, while it was not expressed in nonproteinuric kidneys including five biopsy specimens. This is the first report indicating that proteinuria up-regulates the surface expression and distribution of a specific integrin chain on tubular cells. These observations suggest the participation of integrins in a hitherto unexplored mechanism of tubulo-interstitial responses to glomerular injury.
 ...
PMID:Tubulointerstitial responses in the progression of glomerular diseases: albuminuria modulates alpha v beta 5 integrin. 888 93

Whether the serum levels of endothelin, a vasoconstrictive peptide produced in the endothelial cell, increase in preeclamptic patients is still controversial. We performed immunohistochemical studies to observe the changes in endothelin-1 (ET-1) in preeclamptic kidney tissues. The monoclonal anti-human ET-1 antibody (Yamasa, Japan) and anti-von Willebrand factor (vWF, Dako, Denmark), a marker of endothelial cells, were used for the studies by the strepto-avidin-biotin peroxidase method (ABC-POD Kit, Wako, Japan). Twenty-nine patients and 12 normal controls were divided into four groups. The preeclamptic group included 14 patients diagnosed with preeclampsia by clinical symptoms of hypertension, proteinuria, and edema occurring in late pregnancy and as having preeclamptic nephropathy. They underwent renal biopsy 16.7 +/- 1.0 (mean +/- SEM) days after delivery. The nephrotic group comprised 10 normotensive nonpregnant patients with nephrotic-range proteinuria examined through biopsy before treatment (six cases of minimal change, two of focal segmental glomerulosclerosis, one of membranous nephropathy, and one of IgA nephropathy). The pregnant women with preexisting glomerular disease group included five pregnant women with normal renal function who were normotensive and had no increase in the amount of proteinuria throughout pregnancy. They underwent renal biopsy 10.8 +/- 2.9 days after delivery (two cases of membranous nephropathy, one of focal segmental glomerulosclerosis, one of thin basement membrane disease, and one of non-IgA mesangioproliferative glomerulonephritis). The normal kidney group comprised 12 healthy tissue samples taken from nephrectomized kidneys (five cases of renal cell carcinoma, one case of lipofibrosarcoma, and six cases of kidney transplant donors). In these four groups, ET-1 and vWF showed equally positive staining in small arteries. VWF also showed positive staining in arterioles and peritubular capillaries in all groups. Although the glomeruli showed positive staining with ET-1 along the capillary walls in the normal group and the nonpregnant nephrotic group, they showed very weak or negative results in the preeclamptic group. Moreover, gravida with underlying glomerular disease without superimposed preeclampsia also showed negative findings of ET-1 in the glomeruli. The glomeruli in the four groups showed positive findings, with vWF readings the same as in the controls. These results indicate that the production of ET-1 in the glomerular endothelial cells decreases in cases of both preeclampsia and normal pregnancy, and the condition may be caused by pregnancy itself.
 ...
PMID:Immunohistochemical study of endothelin-1 in preeclamptic nephropathy. 904 Dec 9

The von Willebrand factor (vWF) has been used as a marker of endothelial dysfunction in several diseases. We measured plasma vWF in patients with immunoglobulin A nephropathy (IgAN). In a group of 10 IgAN patients with normal renal function, normal blood pressure, and no proteinuria, vWF plasma levels were significantly higher than in a group of 21 healthy volunteers (134% +/- 38% v 80% +/- 22%; P < 0.01). In another group of 16 IgAN patients with normal renal function and proteinuria ranging between 0.3 and 3.8 g/d, vWF levels were also significantly higher than in the control group (148% +/- 63% v 80% +/- 22%; P < 0.001). Afterward, we studied the effects of enalapril administered for 4 weeks on vWF levels and proteinuria in a group of 11 IgAN patients with normal renal function and proteinuria > or = 1 g/d. After 2 weeks on enalapril treatment, both vWF levels and proteinuria had significantly decreased (vWF: 158% +/- 122% to 117% +/- 72%, P < 0.05; proteinuria: 1.6 +/- 0.7 g/d to 0.9 +/- 0.4 g/ d, P < 0.05). After enalapril withdrawal, both vWF and proteinuria significantly increased. A significant correlation between the variations in vWF levels and proteinuria was observed (r = 0.6; P < 0.05). No correlations between blood pressure and changes in vWF or proteinuria were found. We conclude that endothelial dysfunction is observed in patients with IgAN. This abnormality is already present in some patients with normal blood pressure, normal renal function, and absence of proteinuria. Angiotensin-converting enzyme inhibition induced a significant decrease in both vWF levels and proteinuria.
 ...
PMID:Elevation of von Willebrand factor levels in patients with IgA nephropathy: effect of ACE inhibition. 929 69

To determine whether perturbations of haemostatic function and lipoprotein metabolism prevail long after preeclampsia and increase the risk of future coronary heart disease (CHD), we conducted a follow-up study in women with (cases, n = 25) or without (controls, n = 24) a history of preeclampsia. Blood samples were taken in the follicular and in the luteal phases of a menstrual cycle. Levels of blood pressure (BP) and proteinuria measured during the index pregnancy were included in the evaluation. Compared to control women who had undergone a normal pregnancy, the formerly preeclamptic patients had higher systolic (p <0.01) and diastolic (p <0.05) BPs and increased plasma levels of von Willebrand factor (vWF), fibrinogen, cholesterol, triglycerides and very low density lipoprotein (VLDL) (all p <0.05). The lipid, vWF, and fibrinogen levels were positively related to the degree of BP elevation but not to the degree of proteinuria during the index pregnancy. Except for the increase in vWF level, all biochemical perturbations were only present in the luteal but not in the follicular phase samples. In conclusion, persistent endothelial dysfunction with ensuing dysregulation of blood pressure, haemostatic perturbation and dyslipoproteinemia after preeclampsia may indicate a proneness to future CHD.
 ...
PMID:Haemostatic, endothelial and lipoprotein parameters and blood pressure levels in women with a history of preeclampsia. 1023 35

In diabetic nephropathy, heparan sulfate glycosaminoglycan side chains are reduced in glomerular basement membranes proportionally to the degree of proteinuria. Recently, it was demonstrated that additional therapy with danaparoid sodium, a mixture of sulfated glycosaminoglycans with mainly heparan sulfate, lowered proteinuria in type 1 diabetes patients with diabetic nephropathy. A randomized placebo-controlled parallel study was performed with 750 anti-Xa units of danaparoid sodium once daily in type 2 diabetes patients with severe proteinuria. The aim of the study was to evaluate the possible effects of danaparoid sodium on proteinuria, endothelial dysfunction, and hard exudates in the retina and to determine the safety/tolerability of this drug. Twenty-two patients completed the study, and one patient had to stop prematurely after 6 wk of danaparoid sodium treatment because of urticaria at the injection sites. Apart from a small decrease of hemoglobin and minor skin hematomas at the injection site in five patients in the danaparoid sodium group, no other safety parameters showed any clinically or statistically significant difference between and within groups. The relative change in time of both the urinary albumin and protein excretion rate corrected for creatinine did not differ between both treatment arms (P = 0.2 and 0.49, respectively). No retinal complications or changes of hard exudates occurred. von Willebrand factor was elevated in both groups, but was not influenced by either treatment modality. Contrary to the beneficial effects that occurred in type 1 diabetes patients with diabetic nephropathy, treatment for 8 wk with 750 anti-Xa units of danaparoid sodium gave no reduction of proteinuria, hard exudates, and von Willebrand factor.
 ...
PMID:Effect of danaparoid sodium on proteinuria, von Willebrand factor, and hard exudates in patients with diabetes mellitus type 2. 1036 73

Glycoprotein IIIa/IIb is a membrane receptor for fibrinogen and von Willebrand factor that plays an important role in platelet aggregation. The beta integrin chain of this receptor, GPIIIa, is polymorphic, and the allele known as PlA2 has been associated with coronary thrombosis. The GPIIIa genotype of a cohort of 119 consecutive renal allograft recipients (46.3 +/- 13 yr; 85 M/34 F; 24.4% diabetic patients) was determined by PCR-restriction fragment length polymorphism, and those patients were followed for at least 12 mo. From 119 patients with at least 1 yr of follow-up, those who suffered an acute rejection (n = 52) showed a lower proportion of HLA-DR beta1 identity with the donor (7.7% versus 23.9%; P = 0.03), a higher proportion of cytomegalovirus-positive (CMV+) donors/CMV- recipients (21% versus 7.5%; P = 0.05), and the PlA2 allele was more frequent (48.1% versus 26.9%; P = 0.02) compared with patients free of acute rejection (n = 67). No other variable was associated with acute rejection in the univariate analysis. The impact of the three above-mentioned significant variables on acute rejection was analyzed by stepwise logistic regression. The presence of the PlA2 allele yielded an odds ratio of 2.75 (95% confidence interval, 1.01 to 7.93) and an HLA-DR beta1 identity of 0.2 (95% confidence interval, 0.06 to 0.99) for suffering an acute rejection episode. In addition, the serum creatinine at discharge was higher in PlA2-positive versus PlA2-negative patients (2.2 +/- 1.6 versus 1.5 +/- 0.6 mg/dl, respectively; P = 0.01), and the prevalence of proteinuria >1.5 g/d 1 yr after transplantation was significantly higher among patients showing the PlA2 allele (16% versus 3%; P = 0.02). Finally, in the entire cohort of patients, the 2-yr graft survival was significantly lower in PlA2-positive (n = 43) compared with PlA2-negative (n = 76) patients (85.7% versus 97.2%; P = 0.015). No differences were found in patient survival (95.2% versus 98.7%, respectively). Proportional hazards regression analysis (Cox regression model) confirmed that serum creatinine level at discharge is the best predictor of allograft survival, followed by CMV status, delayed graft function, and the glycoprotein IIIa/IIb genotype. The PlA2 polymorphism is an independent risk factor for acute renal graft rejection, affecting short-term graft survival. Future studies aimed at preventing the hemostatic imbalance favoring platelet aggregation associated with this polymorphism may be important in preventing acute rejection and its impact on chronic rejection.
 ...
PMID:The PlA2 polymorphism of the platelet glycoprotein IIIA gene as a risk factor for acute renal allograft rejection. 1058

Patients with diabetes mellitus have a variety of platelet and coagulation system dysfunctions. At least theoretically, these can contribute to microvascular complications. Intensive glycemic control has been demonstrated to decrease microvascular complications in type 1 diabetics. We studied 16 patients with type 1 diabetes mellitus (11 men and five women; mean age, 39 years) with albuminuria greater than 0.1 g/d and/or proteinuria greater than 0.3 g/d and a creatinine clearance rate higher than 30 mL/min. They received a regimen including three to four injections of insulin per day with or without a weekly infusion of intravenous insulin, and were evaluated for 6 months. We compared the plasma level of von Willebrand factor, platelet aggregation responses to adenosine diphosphate (ADP), epinephrine, and collagen, and platelet adhesion at the beginning of the study and at follow-up intervals. Glycemic control improved significantly. There were no significant differences in the platelet aggregation responses to ADP (1.59 +/- 0.34 v 1.88 +/- 0.23 mmol/L, P = .3; normal, 4.6 +/- 0.2), epinephrine (0.50 +/- 0.20 v 1.11 +/- 0.31 mmol/L, P = .06; normal, 7.6 +/- 1.5), or collagen (92.4 +/- 6.61 v 82.60 +/- 3.78 seconds, P = .6; normal, 79.1 +/- 3.1) or in platelet adhesion (126.31 +/- 16.95 v 195.08 +/- 30.2 platelets, P = .34; normal, 68.6 +/- 1.4). Baseline von Willebrand factor increased, but not significantly (166.38% +/- 10.6% v 142.72% +/- 14.73%, P = .21; normal, 102.0% +/- 6.0%). In type 1 diabetic patients with established microvascular complications of nephropathy, a statistically significant improvement in glycemic control did not improve the in vitro platelet function abnormalities. Improved glycemic control delays the progression of microvascular disease through mechanisms not measured by tests of platelet function.
 ...
PMID:Improved glycemic control and platelet function abnormalities in diabetic patients with microvascular disease. 1064 69

We reported 2 children with suspected primary vasculitis of mesenteric vessels. Both children were admitted to our hospital with the complaints of abdominal pain, bloody stool or diarrhea. Laboratory examination simultaneously revealed leukocytosis with dominant neutrophils, positive CRP, and hypoalbuminemia. Although prothrombin time and activated partial thromboplastin time were within normal limits, the increased levels of FDP-E, D-dimer, and von Willebrand factor activity were observed, which suggested the endothelial cell activation and the coagulation/fibrinolysis system activation. Abdominal echography and CT scanning demonstrated the edematous thickening of intestinal or colon walls probably due to the vasculitic permeability changes of mesenteric artery. During the disease courses, skin rash, bleeding tendency, arthritis and proteinuria were not observed, and no autoantibodies including anti-nuclear antibody, anti-DNA antibody, and myeloperoxidase-antineutrophil cytoplasmic antibody, were detected. Taken together, we suspected these children as restricted vasculitis of mesenteric vessels. Intravenous prednisolone was administrated, and the clinical and laboratory abnormalities recovered completely within 2 weeks. Thus, we suggested that the leukocyte counts, CRP, and the determination of von Willebrand factor and coagulation/fibrinolysis study accompanied with X-ray, echography, and CT scanning will be useful for the early diagnosis of vasculitis before the pathologic and irreversible vascular damage are demonstrated.
 ...
PMID:[Two children with suspected primary vasculitis of mesenteric vessels--a case report]. 1086 31


<< Previous 1 2 3 Next >>