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)

Chronic renal allograft dysfunction is often associated with hypertension, but it is unknown to what extent this affects graft structure and function. We investigated the effect of antihypertensive drug treatments on the course and histopathology of chronic renal allograft rejection in a rat model. Recipient animals were treated with a combination of reserpine, hydralazine and hydrochlorothiazide, the angiotensin converting enzyme inhibitor cilazapril, or the angiotensin II receptor blocker L158,809. Systemic blood pressures and tubular stop-flow pressures were measured on day 50 after transplantation; the histopathology was assessed semiquantitatively in kidneys not used for micropuncture studies. Grafts removed from untreated recipients showed inflammation and structural vascular and glomerular lesions consistent with chronic rejection. All treatment regimens decreased the systemic and glomerular capillary pressures and were associated with improved graft survival, decreased proteinuria and a tendency to improved graft function; the histopathology showed a significant amelioration of glomerular mesangiolysis and glomerulosclerosis but no effect was found on the tubulointerstitial lesions; the angiotensin receptor blocker also inhibited graft atherosclerosis. We conclude that hemodynamic and angiotensin II-mediated processes may play a pivotal role in the expression of immune-mediated glomerular lesions of chronic allograft dysfunction.
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PMID:Post-transplant hypertension and chronic renal allograft failure. 858 80

Chronic rejection is the leading cause of late allograft failure, but its pathogenesis is poorly understood. The prominence of the vascular lesions and certain similarities with the pathological features of atherosclerosis suggest that lipids may be involved in the pathogenesis of chronic rejection. Studies have reported an association between different lipid abnormalities and several indicators of chronic renal allograft damage. However, other potential risk factors for the development of chronic rejection were present in most cases, and an independent association between lipids and chronic rejection has not been convincingly demonstrated. In our series of 706 consecutive renal transplants with long-term follow-up, increased post-transplant serum triglycerides, but not total cholesterol, were strong predictors of graft loss to chronic rejection. This effect was independent of other risk factors for chronic rejection such as age, acute rejections, proteinuria and hypoalbuminemia. These results add to existing evidence suggesting that lipid abnormalities may be involved in the pathogenesis of chronic renal allograft rejection.
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PMID:Clinical correlation between renal allograft failure and hyperlipidemia. 858 85

Lipoprotein(a) [Lp(a)] is a plasma lipoprotein whose structure and composition closely resemble that of low-density lipoproteins, but contains an additional protein called apolipoprotein(a) [apo(a)]. Factors which modulate plasma Lp(a) concentrations are poorly understood. The influence of nephrotic syndrome on Lp(a) levels was investigated in 103 patients with nephrotic syndrome: 72 with primary kidney disease and 31 with diabetic nephropathy. Nephrotic patients had significantly higher Lp(a) levels (mean 63 +/- 7 mg/dl; median 42 mg/dl) compared with controls (mean 22 +/- 2 mg/dl; median 8 mg/dl). Fifty-seven percent of the patients and 22% of the controls had values greater than 30 mg/dl. Within all apo(a) isoform classes, higher concentrations of Lp(a) were seen in the nephrotic patients compared with controls. In 17 patients with primary kidney disease remission of the nephrotic syndrome was induced by immunosuppressive treatment and Lp(a) concentration dropped in parallel with the reduction of proteinuria (pretreatment mean, 98 +/- 9 mg/dl vs. remission mean, 25 +/- 5 mg/dl). In 9 patients where multiple measurements were done, multiple regression analysis showed a strong relation of Lp(a) with the amount of proteinuria (p < 0.01). We conclude that most patients with the nephrotic syndrome have Lp(a) concentrations which are substantially elevated compared with control subjects of the same apo(a) isoform. Because Lp(a) concentrations are substantially reduced when remission of the nephrotic syndrome is induced by immunosuppressive drugs, it is likely that nephrotic syndrome directly results in elevation of Lp(a). The high levels of Lp(a) in nephrotic syndrome could potentially cause glomerular injury as well as increase the risk of atherosclerosis and thrombotic events associated with this disorder.
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PMID:Lipoprotein(a) in patients with the nephrotic syndrome: influence of immunosuppression and proteinuria. 867 20

Renal disease patients often exhibit alterations in the lipid profile which may become an important risk of accelerated atherosclerosis and contribute to disease progression. Among such alterations, increased levels of lipoprotein(a) [Lp(a)] are common and may be related, in part, to the degree of proteinuria. Omega-3 polyunsaturated fatty acids (omega-3 FA) have been reported to decrease Lp(a) concentrations in nonrenal subjects. In addition, they have recently been shown to reduce proteinuria in patients with chronic glomerular disease. We therefore tested the hypothesis that omega-3 FA treatment in patients with chronic glomerular disease may reduce Lp(a) concentrations. Eight patients (2 with membranous glomerulonephritis, 6 with focal glomerular sclerosis) were submitted to a total of 13 six-week courses of treatment with omega-3 FA, at a dose of 3 g/day with a triglyceride preparation (n = 4) and of 7.7 g/day with an ethyl-ester preparation (n = 9). Both treatments significantly increased the proportions of omega-3 to omega-6 FA in total serum lipids, documenting compliance to treatment. Both treatments were also effective in decreasing serum thromboxane (from mean 490 +/- (SEM) 70 to 325 +/- 49 ng/ml, p < 0.05, in the high-dose group) and prolonging the bleeding time (from 5.8 +/- 0.4 to 7.7 +/- 0.5 min, p < 0.05, in the high-dose group), thus documenting the biological efficacy of treatment. However, despite a significant reduction in serum triglyceride levels (from 137 +/- 20 to 104 +/- 19 mg/dl in the high-dose group), Lp(a) concentrations did not change (292 +/- 120 U/l before, 315 +/- 130 U/l after the high-dose therapy). Treatment-related changes in proteinuria (from 2.9 +/- 0.5 to 2.1 +/- 0.7 g/24 h) were not related at all to changes in Lp(a) levels. We conclude that omega-3 FA do not decrease Lp(a) concentrations in renal patients with chronic glomerular diseases and that Lp(a) levels are unlikely to be related to the degree of proteinuria within the short-term modifications induced by omega-3 FA.
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PMID:Omega-3 fatty acid supplementation and lipoprotein(a) concentrations in patients with chronic glomerular diseases. 885 84

Lipoprotein measurements in a group of 29 patients with massive proteinuria and without hypoalbuminemia, were compared with those observed in matched controls and patients with overt nephrotic syndrome to assess the influence of plasma albumin concentration and proteinuria in modulating blood lipid levels. Plasma apoprotein B and apo B containing lipoproteins were not increased in proteinuric normoalbuminemic patients. There was a good correlation between plasma albumin and oncotic pressure (r = 0.937; P < 0.001). Plasma oncotic pressure was inversely correlated with plasma apoprotein B in nephrotic patients (r = -0.44, P = 0.017) but not in normoalbuminemics (r = 0.17, P = 0.369), suggesting that plasma albumin affects apoprotein B secretion. Other findings, however, indicate that multiple processes are ocurring simultaneously in these patients. There was an accumulation of very low- and intermediate density lipoproteins in normoalbuminemics, suggesting a residual defect in the lipoprotein removal. Also, raised (P < 0.05) lipoprotein(a) levels respect to controls (median, 0.15 g/l) were noted in both, normoalbuminemics (median, 0.72 g/l) and hypoalbuminemics (median, 0.84 g/l) with similar degree of proteinuria (6.4 vs. 6.6 g/24 h), suggesting that other mechanisms may be operative in lipoprotein(a) derangements. Our findings suggest that there is no unique mechanism in the pathogenesis of nephrotic hyperlipidemia but that both hypoalbuminemia and proteinuria can have a distinct contribution, individually or in combination.
Atherosclerosis 1996 Oct 25
PMID:The influence of hypoalbuminemia in the generation of nephrotic hyperlipidemia. 890 50

Dyslipoproteinemia in non-insulin-dependent diabetes mellitus (NIDDM) is an important risk factor in the development of atherosclerosis and glomerulosclerosis. The lipid profile of NIDDM patients is characterized by elevated serum triglycerides and VLDL levels and reduced HDL cholesterol levels. Serum LDL levels may be elevated as well in some patients with NIDDM, but several alterations in the biochemical and physical properties of LDL particles are more characteristic resulting in reduced receptor specific uptake of these lipoproteins. Non-enzymatic glycosylation of LDL and augmented oxidation is common in diabetic patients making lipoproteins susceptible for uptake by the macrophage scavenger receptors and thus leading to foam cell formation and further glomerular damage. A reduction in the progression of diabetic nephropathy by lowering proteinuria and thereby serum cholesterol during treatment with ACE-inhibitors demonstrates the importance of such a therapy. The multiple factors involved in the pathogenesis of diabetic nephropathy are difficult to evaluate in regard to their individual contribution. Nevertheless antiproteinuric and lipid lowering therapy can be expected to reduce vascular damage and the progression of diabetic nephropathy.
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PMID:Potential role of lipids in the progression of diabetic nephropathy. 890 13

To gain insight into the contribution of immunologic and hemodynamic factors in the progressive demise of structure and function in chronic renal allograft dysfunction, we studied the histological changes, the immunostainable glomerular anionic sites, and glomerular capillary hydrostatic pressures of rat renal allografts with chronic rejection. Recipient animals were left untreated, received 8 weeks of treatment with the immunosuppressive drug cyclosporine, or received antihypertensive drugs consisting of the combination of reserpine, hydralazine and hydrochlorothiazide, the angiotensin-converting enzyme inhibitor cilazapril, or the angiotensin II receptor blocker L-158,809. Grafts in untreated recipients developed chronic interstitial inflammation, as well as vascular and glomerular lesions consistent with chronic rejection. These lesions were associated with immunohistochemical loss of the negatively charged heparan sulfate proteoglycan side chain. All treatment regimens decreased the systemic and glomerular capillary pressures and were associated with no loss of function, decreased proteinuria, and a tendency to improved graft function. Cyclosporine prevented all histological manifestations of rejection, and antihypertensive drugs decreased the extent of glomerular mesangiolysis and glomerulosclerosis; L-158,809 and cilazapril also inhibited graft atherosclerosis and tubular atrophy. We conclude that chronic rejection is primarily an immune-mediated process, but hemodynamic and angiotensin II-mediated effects may play a pivotal role in the expression of immune-mediated lesions.
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PMID:Antihypertensive drug treatment in chronic renal allograft rejection in the rat. Effect on structure and function. 897 Jun 20

Disturbances in serum lipids, hemostasis and platelet functions are frequent features in some kidney diseases and may contribute to the progression of atherosclerosis with its complications. Recently, an attention has been paid on beneficial effects of fish oil on serum lipids and hemostasis, and proteinuria. The purpose of this work was to assess platelet functions, some hemostatic parameters and serum lipids in patients with chronic glomerulonephritis treated with Trienyl. The study was performed on 7 patients with glomerulonephritis, before, 3 and 6 months following fish oil treatment. A small and nonsignificant rise in cholesterol, HDL and LDL was found, whereas triglycerides level fell significantly following 3 and 6 months of therapy Fibrinogen concentration was lowered significantly 6 months following fish oil administration. Platelet aggregation in platelet-rich plasma remained unaltered during therapy, whereas platelet responses to ADP and arachidonic acid in the whole blood were inhibited after 6 months of the therapy. Unsaturated omega 3 fatty acids in Trienyl alter lipid metabolism, platelet/vessel wall interactions and proteinuria and therefore might be beneficial in therapy of glomerulonephritis, particularly in combination treatment.
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PMID:[Effect of treating glomerulonephritis with omega 3 fatty acids for selected parameters of hemostasis, blood platelet function and lipid metabolism]. 899 60

To better characterize the heavy proteinuria occasionally described in cholesterol atheroembolic renal disease (CAE), we reviewed the clinical features and histological findings of 24 patients found at renal biopsy to have CAE. Twelve (50%) had a typical clinical presentation soon after an invasive vascular procedure. Eight (33%) underwent biopsies to evaluate proteinuria and four (17%) with insidiously developing renal failure to exclude rapidly progressive glomerulonephritis. All had usual and similar risk factors for CAE; 71% were male, 96% had peripheral vascular disease, 79% had recently undergone an invasive vascular procedure, 74% were hypercholesterolemic, and all were hypertensive. Proteinuria was higher and serum creatinine lower in the proteinuria group. In the nine (38%) nephrotic patients, serum creatinine measurements were lower (2.7 +/- 1.2 v 5.6 +/- 2.4 mg/dL), duration of renal disease to biopsy longer, and time from biopsy to dialysis greater (23.5 +/- 14.8 v 0.03 +/- 0.098 mo, P < 0.05 for all). Focal segmental glomerulosclerosis (FSGS) was observed in 15 (63%) of the biopsy specimens. Although FSGS itself did not occur more commonly in nephrotic patients, these patients did have a higher fraction of segmentally sclerosed glomeruli (0.158 +/- 0.097 v 0.026 +/- 0.050, P < 0.01). A variant of FSGS, the cellular lesion with epithelial cell prominence and capillary loop collapse, was observed in 7 of 9 (78%) patients with nephrotic-range proteinuria, but in only 3 of 12 (25%) patients with lesser degrees of protein excretion (P < 0.05). The cellular lesion was accompanied by higher mean proteinuria, 7.6 +/- 4.3 versus 2.1 +/- 2.4 g/24 hr (P < 0.01). In a larger group of patients with a similar age range as the CAE group who were identified by search of a computerized biopsy database, membranous nephropathy was the only other form of idiopathic glomerulonephritis that occurred with CAE. One of 82 (1.2%) patients with membranous nephropathy also had CAE, compared with 20 of 102 (19.6%) with FSGS (P < 0.0002, chi2). Thus, the finding of FSGS with CAE was not coincidence. Mean follow-up was 20 +/- 26 months (range, 0 to 103 months). Six patients (25%) were followed-up at least 3 years after renal biopsy. These findings indicate that extended survival in CAE is not rare and that heavy proteinuria occurs as part of a chronic disorder with distinctive histological features. Cholesterol atheroembolism with FSGS should be considered in the differential diagnosis of nephrotic syndrome in elderly patients with advanced atherosclerosis.
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PMID:Focal segmental glomerulosclerosis associated with nephrotic syndrome in cholesterol atheroembolism: clinicopathological correlations. 904 Dec 8

Until the mid eighties most conceptual knowledge of peripheral transcapillary plasma protein transport has been based on experiments with the lymph collection methods, picturing macromolecular exchange as a slow, mainly unidirectional flux from plasma to lymph. All sieving or restriction is assumed to occur at the capillary membrane level reducing interstitial as well as lymphatic plasma protein concentrations. However, in newer experiments using rapidly resolving tracer techniques, transcapillary albumin fluxes are found 10 to 20 times higher than the lymphatic return. This may imply serial barriers to plasma-lymph transport, i.e. a relatively permeable porous endothelial barrier, and a tight interstitial barrier. The possible outline of this hypothesis and its major implications are discussed. The interstitial barrier is assumed to be formed by the contents of the interstitial space itself, preferentably by the anionic glycosaminoglycanes (GAGs) of the interstitial gel matrix. In the interface between the barriers immediately below the endothelial lining, interstitial plasma protein concentrations may reach close to plasma levels. Thus diseases or conditions that alter plasma protein concentrations, plasma protein fluxes or matrix composition are likely to promote coagulation or precipitation in this interzone. In diabetic microangiopathy loss of fixed anionic charge in the glomerular basal membrane is an important initial step leading to proteinuria. However, the loss of anionic charge seems to be general, afflicting the GAG components of the glomerular membrane, the interstitial matrix, and in the walls of large arteries. By raising the interstitial protein flux as well as by decreasing the antiprecipitating and anticoagulative properties of the matrix, this may lead to increased precipitation. It may therefore be the single pathogenetic factor most likely to explain the perivascular hyalinosis and accelerated atherosclerosis of the disease. Very similar mechanisms may enhance atherosclerosis in nondiabetic patients precipitated by factors like elevated plasma levels of lipoproteins and fibrinogen, aging, and hypertension.
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PMID:Whole body capillary exchange of albumin. Alterations in diabetic microangiopathy. 906 63


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