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)

A patient with congenital generalized lipodystrophy developed nephrotic syndrome with progressive renal glomerulosclerosis attributed to diabetic nephropathy. Renal transplantation was performed and the patient was discharged with normal renal function. Marked hyperlipidemia (17,500 mg/dl) persisted. One month later renal malfunction developed, and an open renal biopsy was performed when there was no response to antirejection therapy. Massive lipid deposition in renal tubular cells with tubular necrosis and hemorrhage was present but only minimal evidence of graft rejection. Rejection therapy was tapered and renal function stabilized. Death occurred 2 months later because of pulmonary sepsis. Patients with generalized lipodystrophy and severe hyperlipidemia may be at an unusually high risk for renal homograft destruction.
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PMID:Renal transplantation in a patient with lipoatrophic diabetes. A case report. 36 May 16

Dahl salt-sensitive (S) rats fed a high salt diet develop hypertension, hyperlipidemia, and progressive renal disease. Previous studies have suggested that lipids may be important in the pathogenesis of glomerulosclerosis in Dahl S rats. To investigate this possibility, Dahl S rats fed 4% NaCl chow were treated chronically with the cholesterol synthesis inhibitor lovastatin. After 22 weeks, lovastatin-treated rats had a 38% reduction in serum cholesterol, a 76% reduction in urine albumin excretion, and one-sixth the incidence of focal glomerulosclerosis compared with vehicle-treated control rats. Blood pressure in lovastatin-treated rats was significantly (p < 0.05) lower than that in vehicle-treated rats both early in the study (4 weeks of treatment) and at the end of the protocol. Lovastatin had no effect on glomerular filtration rate or glomerular ultrafiltration dynamics. The efficacy of angiotensin converting enzyme inhibitors in attenuating proteinuria and experimental glomerular disease may be dependent on sodium intake. Thus, we also investigated the effects of long-term enalapril treatment on glomerular injury in Dahl S rats fed high salt chow. Enalapril treatment (50 or 200 mg/l drinking water) significantly lowered blood pressure in Dahl S rats, but did not significantly affect albuminuria or glomerulosclerosis. Enalapril also had no effect on glomerular hemodynamics. These results suggest that lipids may be important in the development of both glomerular disease and hypertension in Dahl S rats and that angiotensin converting enzyme inhibition may not affect the course of renal disease in a setting of high salt intake.
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PMID:Lovastatin but not enalapril reduces glomerular injury in Dahl salt-sensitive rats. 142 16

Hyperlipidemia may contribute to the progression of focal glomerular sclerosis (FGS) in humans and obese Zucker rats. Zucker rats undergo an increase in their plasma low density lipoprotein (LDL), very low density lipoprotein (VLDL) and oxidized lipids, resulting in the development of FGS. We examined the effects of such hyperlipidemic serum on thymidine uptake into cultured mesangial cells. LDL and VLDL both stimulated the overnight uptake of 3H-thymidine at a concentration of below 10 micrograms/ml and inhibited this uptake at over 50 micrograms/ml in the medium. Modified LDL and VLDL after oxidation, however, inhibited this uptake at a concentration of 1 microgram/ml in the medium. Although 20% serum-containing medium stimulated the thymidine uptake by the mesangial cells, the lipoprotein fraction inhibited the uptake, while the lipoprotein-free fraction markedly stimulated it. We conclude therefore that the lipoproteins in hyperlipidemic serum suppress and the lipoprotein-free fraction stimulates mesangial growth. Both may play a role in the development of FGS in rats.
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PMID:Effect of hyperlipidemic serum on cultured mesangial cells. 147 36

The pathology of male Syrian hamsters of APA strain which were injected intraperitoneally with 40 mg/kg body weight of streptozotocin (SZ) at 2 months of age was examined. It showed long-lasting prominent hyperglycaemia and hyperlipidaemia with glucosuria and the development of glomerular lipidosis from 1 month after SZ-injection (1 MAI). Glomerular lesions were restricted to the juxtamedullary cortex at 1 MAI and then extended to the subcapsular cortex. At 3 MAI, glomerular lesions were characterized by focal segmental glomerulosclerosis showing segmental expansion of the mesangial area due to an increase of basement membrane-like material and mesangial cells with lipid droplets and foam cells. SZ-induced diabetic APA hamsters will be a useful model for the investigation of glomerular lipidosis and focal segmental glomerulosclerosis.
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PMID:Rapid induction of glomerular lipidosis in APA hamsters by streptozotocin. 153 31

Membranous nephropathy is a worldwide problem that accounts for about 20% of the cases of the adult-onset nephrotic syndrome. This disease places many patients at risk for both end-stage renal failure and the complications of hyperlipidemia. Immune-mediated injury to the glomerular capillary wall in patients with membranous nephropathy is characterized by subepithelial immune complex formation and generation of the membrane attack complex of complement. Glomerular capillary hypertension, hyperlipidemia, and possibly cytokines could contribute to the glomerular sclerosis seen in the advanced stages of the disorder. In some cases, production of pathogenic antibody can be suppressed by treating the underlying condition. The mechanisms of action of immunosuppressive agents are being investigated and treatments are being tested in clinical trials to optimize the balance of efficacy and toxicity. Alternate-day treatment with corticosteroids is often recommended for nephrotic patients with idiopathic membranous nephropathy, but this approach has not been proved beneficial. Ongoing studies are evaluating whether cytotoxic drugs or cyclosporin A combined with prednisone is more effective than treatment with corticosteroids alone. Lipid-lowering drug therapy is warranted in cases of the persistent nephrotic syndrome to avert the cardiovascular sequelae of hyperlipidemia.
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PMID:NIH conference. Membranous nephropathy. 154 69

A prospective study was performed in order to evaluate the efficacy of oral cyclophosphamide and chlorambucil in inducing a remission in children with steroid-resistant primary nephrotic syndrome (NS). Out of 215 children with steroid-resistant primary NS, 164 had been followed from one to 10 years. The children had a mean age of 8.2 years, with a range from one to 16 years. Steroid resistance was more common in children over six years of age compared with the other age groups. Hematuria was seen in 68 of the 164 children (41%); hypertension in 41 (25%); and hyperlipidemia in 112 (68%). Hypocomplementemia was noted in 24 of the 65 (37%) children in whom complement concentrations were determined. Renal biopsy was performed in 117 of the children. Pathologic changes consisted of minimal change nephrotic syndrome (MCNS) in 14 children (12%), membranoproliferative glomerulonephritis (MPGN) in 45 (38%), focal segmental glomerulosclerosis (FSGS) in 20 (25%), mesangial proliferation (MP) in 23 (20%), and membranous glomerulonephritis in six children (5%). Cyclophosphamide (2 mg/kg/day) was given to 164 patients, with complete remission and partial remission rates of 20.7% (34 of 164 children) and 24.4% (40 of 164 children), respectively. In this group, sustained remission and sustained partial remission rates were found in 20% (32 children) and 13% (21 children), respectively. Chlorambucil was given to 40 children with steroid- and cyclophosphamide-resistant nephrotic syndrome, with total remission and partial remission rates of 20% (eight children), and 12.5% (five children), respectively. These rates did not change during the follow-up. Thus, cyclophosphamide is valuable in the treatment of children with steroid-resistant NS with a variety of histologic changes.
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PMID:Long-term follow-up in children with steroid-resistant nephrotic syndrome. 158 94

We have recently reported that a lipid-lowering agent, probucol, reduces proteinuria in puromycin aminonucleoside (PA)-induced nephrotic rats (PAN). In this study, we examined whether a long-term treatment of hyperlipidemia with probucol can suppress the development of focal and segmental glomerulosclerosis (FSGS) in chronic PAN. A chronic PAN model was made with repeated intraperitoneal injections of PA (initially 100 mg/kg body weight followed by 25 mg/kg 5 times at 2-week intervals). Two weeks after the first injection of PA, either normal rat chow with or without 1% probucol was given to the nephrotic rats for 10 weeks. Chronic PAN exhibited remarkable proteinuria, hypoalbuminemia and severe hyperlipidemia with all lipoprotein fractions increased. Probucol treatment significantly reduced the lipid concentration in all major lipoproteins, significantly reduced proteinuria and increased plasma albumin concentration. Plasma albumin inversely correlated with cholesterol or phospholipid in low-density and high-density lipoproteins, suggesting that the lipid-lowering effect of probucol may ameliorate the hypoalbuminemia associated with nephrosis. In light microscopic examination, various degrees of FSGS with tubulointerstitial lesions were observed in the renal cortex from chronic PAN. The degree of FSGS was scored from grades 1 to 4 according to severity. One half of the untreated PAN (4/8) was classified into grade 4 and the other into grades 2 or 3, whilst one half of treated PAN (4/8) was classified either into grade 1 or 2. The grading of FSGS correlated negatively with plasma albumin concentration. These results demonstrate that probucol is highly effective upon nephrotic hyperlipidemia and suggest that a long-term treatment of secondary hyperlipidemia can suppress progressive renal injury associated with chronic nephrosis.
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PMID:Treatment of hyperlipidemia with probucol suppresses the development of focal and segmental glomerulosclerosis in chronic aminonucleoside nephrosis. 158 21

The effects of feeding 2 or 10% fat on glucose tolerance, blood lipids, life span and tissue pathology of male BHE/cdb rats were studied. Six groups of 30 rats were fed from weaning diets containing 1% corn oil plus either 1 or 9% corn oil (CO diets). Animals that became ill and died were necropsied and their tissues were examined histologically. Glucose tolerance and blood lipids were determined at 300 and 600 d of age. At 300, 500, 600 and 700 d of age subsets of rats were killed and heart, aorta, lungs, liver, pancreas and kidneys collected for histological examination. The experiment was terminated at 700 d. Feeding the high level MO or BT diet delayed the development of glucose intolerance and lipemia. Longevity was shorter in the rats fed the high MO diet. There were few differences among the groups of rats fed the 2% fat diets with respect to glucose tolerance and lipemia. Glomerulosclerosis was observed in all rats but was more severe and appeared earlier in rats fed the high MO diet than in those fed the high CO or BT diets. In rats with severe renal lesions, mineralized foci were observed in soft tissue, notably the aorta and heart. The results of this study indicate that the source and amount of the dietary fat can influence age-related tissue changes and longevity.
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PMID:Life span is shortened in BHE/cdb rats fed a diet containing 9% menhaden oil and 1% corn oil. 158 49

The mesangium constitutes the core of the renal glomerulus. It consists of the matrix, composed of mucopolysaccharides and glycoproteins, and two cell types. The predominant cell type is the mesangial cell, resembling a vascular smooth muscle cell. Up to 15% of the mesangial cell population additionally consists of resident mesangial phagocytes. These are derived from the bone marrow and belong to the family of mononuclear leukocytes. They are phagocytic, express Fc and C3 receptors, and display membrane Ia antigens. They syngeneically stimulate lymphocyte proliferation via antigen presentation. They are equally potent allogeneic stimulating cells in mixed lymphocyte culture. The mesangium is also the preferred locus of the induced migration of monocytes in inflammatory and proteinuric states. The presence of both normally resident and inflammation-associated mesangial phagocyte is lipid dependent. Hyperlipidemia increases the population of mesangial phagocytes. Lipid restriction decreases their number and, as a result, diminishes the allogenicity of renal transplants and blunts the progression of glomerulonephritis. One signal regulating the infiltration of the mesangium by mononuclear phagocytes appears to be a complex neutral lipid that is highly and specifically chemotactic for monocytes. It is released by the contractile mesangial cell in response to the stimulation of its Fc receptor and to the mesangial deposition of macromolecules. Both resident and inflammatory mesangial phagocytes secrete factors that remodel the mesangial matrix, stimulate mesangial cell proliferation, alter glomerular basement membrane permeability, and regulate blood flow. The persistence of mononuclear phagocytes in an activated state within the mesangium contributes to the marked alteration in mesangial structure that eventuates in glomerulosclerosis in both immune and nonimmune models of glomerular injury.
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PMID:The mesangial phagocyte and its regulation of contractile cell biology. 160 Jan 40

Diabetic patients who develop proteinuria show a marked increase in cardiovascular morbidity and mortality. The precise pathogenesis of human diabetic kidney disease and the factors responsible for the susceptibility to it remain, in part, obscure. However, there is now evidence that renal disease clusters in families and that genetic factors may be of central importance in determining susceptibility. Predisposition to arterial hypertension has been suggested as playing a contributory role in the development of kidney disease. Hypertrophic processes may be implicated in the susceptibility to arterial wall damage and glomerular injury in diabetes. Interestingly, fibroblasts of patients with diabetic nephropathy show a higher Na+/H+ antiport activity and a greater 3H-thymidine incorporation into DNA than fibroblasts of diabetic patients without nephropathy. The first clinical signs of renal involvement are the appearance of microalbuminuria and a small elevation in arterial pressure. Mesangial expansion accompanies these changes. Microalbuminuria is associated with abnormalities of lipoprotein profiles and higher Na+/Li+ countertransport rates. The environmental changes brought about by diabetes could lead in susceptible individuals to increased systemic and intraglomerular pressures on the one hand and to mesangial expansion on the other. These two processes would cause proteinuria and glomerulosclerosis. Lipid abnormalities may further aggravate the renal histological damage and, in combination with hypertension, contribute to the accelerated atherosclerosis typical of patients with diabetic kidney disease. A vicious circle would thus be triggered, involving reduction in renal function, further hypertension, proteinuria, glomerular obsolence and hyperlipidaemia, and eventually end-stage renal failure or premature cardiovascular death.
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PMID:Risk factors for renal and cardiovascular disease in diabetic patients. 165 64


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