Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020473 (hyperlipidemia)
 15,891 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Treatment modalities in severe nephrotic syndrome have to consider (a) the underlying glomerular diseases as well as (b) the extrarenal complications. Occasionally acute renal failure develops on the basis of an unknown nephrotic syndrome; if a primary glomerular disease is diagnosed by biopsy, immunosuppressive therapy is optional. In type I and type II diabetes development of a severe nephrotic syndrome is usually not reversible. To avoid the rapid decline of renal function a consequent antihypertensive therapy is the treatment of choice in this stage of the disease. Treatment of primary glomerular diseases with severe (NS) includes frequently relapsing minimal change nephropathy (MCN) that can be treated with prednisolone 1 mg/kg/day until remission occurs. For prolongation of the remission cyclophosphamide 2 mg/kg/day for eight weeks, or alternatively cyclosporine A 3 to 5 mg/kg/day for six months, can be given. In steroid-resistant focal segmental glomerulosclerosis (FSGS) eight weeks of treatment with cyclophosphamide 2.5 mg/kg/day or six months treatment with cyclosporine A 3 to 5 mg/kg/day can induce a partial or complete remission in up to 20% of the patients. In membranous glomerulopathy with severe NS, one month of therapy with prednisolone followed by chlorambucil for one month (all together 6 months) improves the renal outcome of the patients compared to controls. Alternatively, cyclophosphamide 2 mg/kg/day plus 30 mg prednisolone/day can be given for a couple of months. Extrarenal complications of a severe NS are: (a) edema; (b) thromboembolism; and (c) lipid abnormalities. If nephrotic patients are resistant to orally administered loop diuretics, they should be treated in addition intravenously with hydrochlorothiazide p.o. Nephrotic patients with a serum albumin level < 20 g/liter should be routinely anticoagulated. Extensive hyperlipidemia in severe NS can be treated with HMG-CoA reductase inhibitors.
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PMID:Treatment of severe nephrotic syndrome. 947 89

Examination of 29 patients with decompensated hypothyroidism has detected in them abnormal renal concentration, reduction of the glomerular filtration rate, elevation of the intraglomerular pressure. The detected albuminuria, decreased renal functional reserve and hyperlipidemia suggest initiation of hypothyroidism-related glomerulopathy resultant from physicochemical processes in glomerular endothelium.
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PMID:[Functional renal status in patients with hypothyroidism]. 1063 48

Lipoprotein glomerulopathy (LPG) is a newly recognized renal disease characterized by thrombus-like lipoproteins in the glomerular capillaries and abnormal lipoprotein profiles similar to those in type III hyperlipoproteinemia. Recently, these conditions have been shown to be associated with some apolipoprotein E (apoE) mutations. We found an apoE mutation (designated apoE-Sendai) that substitutes arginine 145 with proline. This mutation occurs most frequently in Japanese patients with LPG. To elucidate the etiological role of this mutation in the apoE gene, we established an experimental model for LPG by transducing apoE-Sendai in apoE knockout mice with the use of an adenovirus vector. Based on the findings in patients with LPG and its animal model, we suggest that the glomerular lesions are not only caused by hyperlipidemia, but also by in situ interaction between lipoprotein-containing mutant apoE with the glomerulus. In this review, we outline the clinical features of LPG and discuss the relationship between apoE mutations and LPG.
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PMID:Etiological significance of apolipoprotein E mutations in lipoprotein glomerulopathy. 1185 53

Lipoprotein glomerulopathy (LPG), characterized by glomerular lipoprotein thrombi, presumably composed of abnormal apolipoprotein E (apoE), leads to a progressive decline in renal function and eventually results in end-stage renal failure. A successful treatment for LPG has not yet been established. The authors treated a 36-year-old woman with LPG and exhibiting a nephrotic syndrome using an intensive lipid-lowering therapy consisting of fenofibrate (300 mg), niceritrol (750 mg), ethyl-icosapentate (1,800 mg), and probucol (500 mg). After the start of treatment, a remarkable decrease in urinary protein excretion and improvement in the hyperlipidemia were obtained; proteinuria was no longer detected 11 months after the initiation of treatment. A second biopsy performed 11 months after the initiation of treatment showed the complete disappearance of the lipoprotein thrombi that had been observed in a diffuse and global manner in the first renal biopsy. These findings suggest that typical LPG could be regressed if the abnormal lipoproteinemia is controlled sufficiently.
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PMID:Resolution of typical lipoprotein glomerulopathy by intensive lipid-lowering therapy. 1250 Feb 44

Lipoprotein glomerulopathy (LPG) is a rare disease, characterized by a special histology, including dilated glomerular capillaries filled with pale-stained and meshlike lipoprotein thrombi. It always presents with proteinuria or nephrotic syndrome. Although hyperlipidemia is not always seen, most patients have type III hyperlipoproteinemia with apolipoprotein (apo) E2/3 phenotyping. Although the clinical feature of LPG is rarely described, LPG associated with other glomerulopathy, including IgA nephropathy, membranous nephropathy, and lupus nephritis, has been documented. Until now, there have been no reports of psoriasis vulgaris associated with LPG. The authors present 2 cases of LPG with apo E3/3 genotyping associated with psoriasis vulgaris. The first patient was a 65-year-old woman who presented with nephrotic syndrome with daily urinary protein loss of 9.05 g and itchy erythematous scaly plaques on her trunk and lower limbs for 1 year. The renal biopsy results showed LPG, and the skin biopsy results showed psoriasis. The second patient was a 50-year-old man with history of psoriasis over his trunk and 4 limbs for 30 years. He also presented with nephrotic syndrome with daily urinary protein loss of 7.55 g. The renal biopsy results also showed LPG. The genotype of apo E showed E3/3, and lipoprotein electrophoresis showed a type III hyperlipoproteinemia-like pattern in both cases. The authors suggest that presence of apo E3/3 genotype cannot rule out the diagnosis of type III hyperlipoproteinemia and LPG. Besides, LPG should be included in the differential diagnosis of psoriatic patients with nephrotic syndrome, especially in Asian patients who show poor response to traditional therapy. Renal biopsy should be performed to make the definitive diagnosis.
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PMID:Lipoprotein glomerulopathy associated with psoriasis vulgaris: report of 2 cases with apolipoprotein E3/3. 1295 7

Kidney transplantation is the best treatment for patients with end-stage renal disease, both in terms of survival benefit and quality of life. The major limitation is the continuing shortage of kidneys suitable for transplantation, reinforcing the need to maximise graft survival. After the first year of transplantation, chronic renal allograft dysfunction (CRAD) is the first cause of late graft deterioration and failure. CRAD has been defined as a progressive renal dysfunction, independent of acute rejection, drug toxicity and recurrent or de novo nephropathy, with features on biopsy of chronic allograft nephropathy (CAN) characterised by vascular intimal hyperplasia, tubular atrophy, interstitial fibrosis and chronic transplant glomerulopathy. Protocol biopsy-based studies have demonstrated a high and early prevalence of CAN lesions during the first year in patients with normal and stable renal function. Beyond 1 year, the injuries associated with calcineurin inhibitors (CNIs) appear to be very common. The physiopathology of CRAD is complex and multifactorial. Both alloantigen-dependent factors (acute rejection, HLA matching, donor-specific antibodies, inadequate immunosuppression) and alloantigen-independent factors (donor age, brain death, ischaemia/reperfusion injuries, hypertension, hyperlipidaemia, cytomegalovirus, CNI-related nephrotoxicity) are involved. Consequently, CRAD appears as a dynamic process, evolving with time, and immunosuppressive regimens need to be modulated in order to provide the most suitable treatment at the different phases of its natural history. On the basis of this scheme, the new paradigm would be the use of a CNI-based regimen during the period of maximal risk of (subclinical) acute rejection, followed by a conversion to a CNI-free regimen in order to avoid the long-term consequences of nephrotoxicity. Fortunately, new agents are being introduced in clinical practice providing a large range of combinations and allowing individualisation of immunosuppressive regimens. Large, prospective, multicentre trials are warranted, and the challenge is to define new endpoints of CRAD and to determine the best therapeutic strategy.
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PMID:Combating chronic renal allograft dysfunction : optimal immunosuppressive regimens. 1574 97

Chronic rejection is currently the most prevalent cause of renal transplant failure. Clinically, chronic rejection presents by chronic transplant dysfunction, characterized by a slow loss of function, often in combination with proteinuria and hypertension. The histopathology is not specific in most cases but transplant glomerulopathy and multilayering of the peritubular capillaries are highly characteristic. Several risk factors have been identified such as young recipient age, black race, presensitization, histoincompatability, and acute rejection episodes, especially vascular rejection episodes and rejections that occur late after transplantation. Chronic rejection develops in grafts that undergo intermittent or persistent damage from cellular and humoral responses resulting from indirect recognition of alloantigens. Progression factors such as advanced donor age, renal dysfunction, hypertension, proteinuria, hyperlipidemia, and smoking accelerate deterioration of renal function. At the tissue level, senescence conditioned by ischemia/reperfusion (I/R) may contribute to the development of chronic allograft nephropathy (CAN). The most effective option to prevent renal failure from chronic rejection is to avoid graft injury from both immune and nonimmune mechanism together with nonnephrotoxic maintenance immunosuppression.
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PMID:Chronic renal allograft rejection: pathophysiologic considerations. 1595 91

Obesity is one of the most frequently encountered medical problems of our time. Among the complications of this pathologic entity, renal disease is an important issue and its pathophysiologic mechanisms are a challenge for the physician, since a variety of etiologic factors are implicated in its genesis. For example, hypertension, hyperlipidemia and insulin resistance affect renal function, each one in a different way. Obesity seems to be a state in which kidneys demonstrate morphological and functional alterations, while hormonal and growth factors play a significant role. Among them, leptin, a recently discovered cytokine, has undergone extended investigation and has proven to be a factor that contributes to renal disease, mainly through mechanisms that involve activation of the TGF-beta system resulting in glomerulopathy and related clinical symptoms. Experiments in animals have revealed interesting aspects as far as the role of leptin in kidney function. Understanding the underlying mechanisms of obesity-related glomerulopathy may become a valuable aid in handling an obese patient with renal disease and associated problems.
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PMID:Obesity and renal disease: a possible role of leptin. 1661 10

The synthesis of extracellular matrix (ECM) in mesangial cells (MCs) plays important roles in the development and progression of renal diseases, including chronic allograft nephropathy. Mycophenolic acid (MPA), an inhibitor of inosine monophosphate dehydrogenase 2 (IMPDH2), suppresses MC proliferation and ECM synthesis. However, the exact inhibitory mechanism of MPA on MCs has not been clearly elucidated. In this study we compared the inhibitory effects of MPA and IMPDH2 reduction [by using small interfering RNA (siRNA)] on oleic acid (OA)-induced fibronectin secretion and cellular reactive oxygen species (ROS) in mouse MCs. Growth-arrested MCs were stimulated with OA in the presence or absence of MPA, IMPDH2 siRNA, N-acetylcysteine (NAC), transforming growth factor beta (TGF-beta) antibody or exogenous guanosine. Fibronectin secretion into the medium was examined by Western blot, dichlorodihydrofluorescein (DCF)-sensitive cellular ROS by fluorescence-activated cell scanning (FACS), TGF-beta levels in the media by enzyme-linked immunosorbent assay (ELISA). OA increased fibronectin secretion, TGF-beta and cellular ROS levels. A TGF-beta neutralizing antibody effectively suppressed OA-induced fibronectin secretion. NAC and MPA completely suppressed OA-induced fibronectin secretion and decreased the levels of TGF-beta and cellular ROS. However, IMPDH2 siRNA partly inhibited OA-induced MC activation. Exogenous guanosine successfully reversed the inhibitory effects of IMPDH2 siRNA on OA-induced MC activation. Pleiotropic inhibitory effect of MPA on OA-induced mouse MC activation was mediated via its antioxidant effect on cellular ROS production and partly via inhibition of IMPDH2 itself. Our results implicate ROS as an alternative therapeutic target for the prevention of hyperlipidemia-related glomerulopathy, chronic allograft nephropathy, and subsequent graft loss.
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PMID:Mycophenolic acid inhibits oleic acid-induced mesangial cell activation through both cellular reactive oxygen species and inosine monophosphate dehydrogenase 2 pathways. 1909 39

Despite improvements in immunosuppressive therapy, long-term allograft survival after kidney transplantation remains as low as 50%. Chronic allograft nephropathy (CAN) is a major cause of late graft loss in renal transplant recipients. The histopathologic signs of CAN-interstitial fibrosis, tubular atrophy, glomerulopathy and vasculopathy-are nonspecific; therefore, the 2007 Banff classification dispensed with the term CAN in favor of 'interstitial fibrosis and tubular atrophy without evidence of any specific etiology'. In this Review, however, the term CAN is used to describe a clinical syndrome that is characterized by progressive decline in renal function from 3 months after transplantation, accompanied by the development of proteinuria and hypertension. The pathogenesis of CAN is complex and incompletely understood, and involves several immunological and non-immunological factors. We discuss the contributory roles of acute rejection, donor age, anti-human-leukocyte-antigen antibodies, calcineurin inhibitor nephrotoxic effects, viral infection, hypertension and hyperlipidemia. The prevention and treatment of CAN needs multidisciplinary strategies. Early detection by means of protocol biopsy and calculation of glomerular filtration rate is the first step, followed by management of modifiable risk factors.
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PMID:The pathogenesis and treatment of chronic allograft nephropathy. 1963 33


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