Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Schimke-immuno-osseous dysplasia (SIOD) is a multisystem disorder caused by a mutation of the chromatin remodeling protein. The main clinical findings are spondyloepiphyseal dysplasia with disproportional growth deficiency, nephrotic syndrome with focal and segmental glomerulosclerosis, and defective cellular immunity. Transitory ischemic attacks due to vaso-occlusive processes are still an untreatable and life-limiting complication in patients with SIOD. The underlying pathophysiology of vaso-occlusive processes in SIOD is unclear. We report the clinical and pathological findings of the eldest published patient with the severe form of SIOD, who died at the age of 23 years due to pulmonary hypertension with subsequent right heart failure. The autopsy revealed a severe generalized atherosclerosis including the brain, heart, and pulmonary arteries. However, the kidney that was transplanted at the age of 5 years showed a good graft function without glomerular sclerosis and with only minimal nephrosclerosis on histology. Thus, the absence of severe vaso-occlusive processes in the transplanted organ and in the severely atherosclerotic host may indicate that the vaso-occlusive processes in SIOD are not caused by post-transplant cardiovascular morbidity such as arterial hypertension and hyperlipidemia. Instead, vascular factors of the host such as endothelial dysfunction may explain the pathophysiology of atherosclerosis in SIOD.
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PMID:Generalized atherosclerosis sparing the transplanted kidney in Schimke disease. 1505 43

Disturbances of lipid metabolism are a constant feature of nephrotic syndrome. In patients with NS they compose a significant risk factor of atherosclerosis and progression of renal insufficiency. However, mechanisms leading to these disturbances are still not fully understood. The paper presents summary of hitherto published studies, experimental, as well as clinical trying to elucidate the patomechanism of lipid disturbances in the course of nephrotic syndrome.
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PMID:[Lipid disturbances in the nephrotic syndrome]. 1505 52

In 1989, we encountered a 68-year-old male patient with marked hyperlipoprotein(a)emia (hyperLp(a)emia), who was being treated for hypertension and arteriosclerotic obliterans (ASO) at an outpatient clinic of our hospital. He began to develop leg edema in 2002 and was referred to the Department of Internal Medicine. It was determined that he had severe hyperlipidemia (total cholesterol, 362 mg/dl), proteinuria, and hypoalbuminemia, suggesting the presence of nephrotic syndrome. On lipoprotein analysis, he was found to have very high levels of Lp(a) in the plasma (329 mg/dl). Severe atherosclerosis was also found: that is, abdominal aortic aneurysm (AAA) and coronary artery disease (CAD) were detected, in addition to ASO. After remission of the nephrotic syndrome, the plasma Lp(a) level decreased to 204 mg/dl and the total cholesterol concentration decreased to 179 mg/dl, while very high levels of Lp(a) persisted. We estimate that the markedly elevated Lp(a) plasma levels in this patient may have played some role in the progression of atherosclerosis.
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PMID:A case of marked hyperlipoprotein(a)emia associated with nephrotic syndrome and advanced atherosclerosis. 1614 4

Cardiovascular risk is dramatically increased in patients with end-stage renal disease (ESRD). However, even minor dys-functions such as microalbuminuria or a mild increase in serum creatinine (Cr) have a major impact on cardiovascular risk. Increased cardiovascular risk is present in multiple populations, including general populations, patients with moderate risk such as hypertensives, and high-risk patients including patients with heart failure and myocardial necrosis. There are many mechanisms underpinning the increased cardiovascular risk. Regarding atherosclerosis, the kidney can be victim or villain. On the one hand, both kidney disease per se and renal insufficiency can induce vascular damage, thereby increasing cardiovascular risk. Kidney disease without renal insufficiency can cause an increased prevalence in hypertension, dyslipidemia (nephrotic syndrome), sympathetic system hyperactivity, and in renin angiotensin system hyperactivity. A moderate-severe renal insufficiency can induce an increase in many vasculotoxic substances such as ADMA, lipoprotein(a), homocysteine, disturbances in calcium and phosphate metabolism, anemia and left ventricular hypertrophy. A more severe renal insufficiency can induce the ominous malnutrition-inflammation-atherosclerosis (MIA) syndrome. On the other hand, the kidney can be the victim of atherosclerosis. Ischemic nephropathy, caused by atherosclerotic renal artery disease and atheroembolism from abdominal aorta are two examples. Finally, it is important to consider that the kidney, being an organ with a wide vasculature, could be a sophisticated sensor of subclinical cardiovascular damage.
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PMID:[Hypertension, atherosclerosis and kidney]. 1578 9

The early lesions of atherosclerosis begin in childhood, and are related to antecedent cardiovascular disease risk factors. Environmental and genetic factors such as diet, obesity, exercise, and certain inherited dyslipidemias influence the progression of such lesions. The identification of youth at risk for atherosclerosis includes an integrated assessment of these predisposing factors. Treatment starts with a diet low in total and saturated fat and cholesterol, the use of water-soluble fiber and plant sterols, weight control, and exercise. Drug therapy, for example, with inhibitors of hydroxymethylglutaryl CoA reductase, bile acid sequestrants, and cholesterol absorption inhibitors, can be considered in those with a positive family history of premature coronary artery disease and a low-density lipoprotein cholesterol above 160 mg/dL, after dietary and hygienic measures. Candidates for drug therapy often include those with familial hypercholesterolemia, familial combined hyperlipidemia, the metabolic syndrome, polycystic ovarian syndrome, type I diabetes, and the nephrotic syndrome. We review the safety and efficacy of dietary and drug therapy, and propose an updated diagnostic and therapeutic algorithm that includes the metabolic syndrome. The early identification and treatment of youth with dyslipidemias is likely to retard the atherosclerotic process.
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PMID:Treatment of dyslipidemia in children and adolescents. 1625 15

Familial hypercholesterolemia (FH) is characterised by elevated plasma LDL-cholesterol levels and premature ischemic heart disease. Statin therapy is mandatory in order to prevent atherosclerosis in patients with heterozygous FH. Both genetic and environmental factors affect the statin-induced LDL-cholesterol lowering effect in patients with heterozygous FH. Recently published data suggest that plasma lipoprotein(a) levels may affect the efficacy of statin therapy in patients with nephrotic syndrome. However, no data are available concerning the effect of lipoprotein(a) levels on the efficacy of statin therapy in patients with heterozygous FH. This report demonstrates negative correlation between plasma lipoprotein(a) levels and the LDL-cholesterol lowering effect of statin therapy in 49 patients with heterozygous FH.
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PMID:Plasma lipoprotein(a) levels and LDL-cholesterol lowering response to statin therapy in patients with heterozygous familial hypercholesterolemia. 1695 Dec 79

Schimke-immuno-osseous dysplasia (SIOD) is an autosomal recessive disorder with the main clinical findings of spondyloepiphyseal dysplasia, nephrotic syndrome, and defective cellular immunity. Vaso-occlusive processes, especially generalized atherosclerosis, are a life-limiting complication in patients with severe SIOD. The nitric oxide synthase (NOS) oxidizes L-arginine to nitric oxide (NO). NO is a potent vasodilator with inhibitory effects on platelet aggregation and the development of atherosclerosis. We hypothesized that reduced NO production due to antagonism of NOS by asymmetric dimethylarginine (ADMA) would be a possible pathophysiological mechanism for vaso-occlusion in SIOD. We tested this hypothesis in 10 patients with SIOD and 10 age-matched healthy controls. Plasma and urine levels of nitrite and nitrate, the indicators of NO synthesis, and of ADMA, an endogenous NOS inhibitor, in children suffering from SIOD were not significantly different from those in the age-matched healthy controls. Our results suggest that the L-arginine/NO pathway is not altered in SIOD. Antagonism of NOS by ADMA does not seem to be the cause of premature general atherosclerosis in SIOD. The underlying pathology of vaso-occlusion in SIOD still remains unclear.
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PMID:Vaso-occlusion in Schimke-immuno-osseous dysplasia: is the NO pathway involved? 1707 78

Clinical practice in paediatric nephrology is continuously evolving to mirror the research output of the 21st century. The management of antenatally diagnosed renal anomalies, urinary tract infections, nephrotic syndrome and hypertension is becoming more evidence based. Obesity and related hypertension is being targeted at primary and secondary care. The evolving field of molecular and cytogenetics is discovering genes that are facilitating clinicians and families with prenatal diagnoses and understanding of disease processes. The progression of chronic kidney disease in childhood to end-stage renal failure (ESRF) can be delayed using medical treatment to reduce proteinuria and treat hypertension. Pre-emptive living-related renal transplantation has become the treatment of choice for children with ESRF, thereby reducing the morbidity and mortality associated with peritoneal and haemodialysis. Although peritoneal dialysis, which is performed in the patient's home, is the preferred modality for children for whom there is no living or deceased donor for transplantation, home nocturnal haemodialysis is becoming a feasible option. Imaging modalities with the use of magnetic resonance and computerised tomography are continuously improving. As mortality for renal and vasculitic diseases improves, the gauntlet is now thrown down to reduce morbidity with secondary prevention of longer-term complications such as atherosclerosis and hyperlipidaemia. Clinical and drug trials in the fields of hypertension, nephrotic syndrome, systemic lupus erythematosus, vasculitis and transplantation are producing more effective treatments, thereby reducing the morbidity resulting from the disease processes and the side effects of drugs.
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PMID:How have the past 5 years of research changed clinical practice in paediatric nephrology? 1737 45

Minimal change nephrosis, the main pediatric form of idiopathic nephrotic syndrome is usually a benign condition responsive to standard steroid treatment. However, relapses occur frequently leading to secondary steroid resistance in a small proportion of cases. Steroid resistant nephrotic syndrome presents mainly as focal segmental glomerulosclerosis. It represents about 8-10% of cases of pediatric idiopathic nephrotic syndrome. The prognosis of focal segmental glomerulosclerosis is bad, with the majority of cases evolving to terminal renal insufficiency within several years. Among the causes of idiopathic nephrotic syndrome are changes of cellular immunity, circulating plasma factors not fully identified yet and mutations of podocyte proteins. Podocyte mutations are responsible for the development of about one third of cases steroid resistant focal segmental glomerulosclerosis. Treatment of idiopathic nephrotic syndrome is determined by international guidelines. If initial steroid treatment is followed by multiple relapses, levamisole, cyclophosphamide and finally cyclosporine-A are used stepwise. In the case of steroid resistance podocyte mutations should be evaluated. If mutated, aggressive steroid treatment is contraindicated. Cases without mutations are candidates for an intensified steroid therapy and cyclosporine-A. Recurrence of focal segmental glomerulosclerosis following transplantation can be suspected in patients without podocyte mutations. Due to the crucial role of the presence of mutations in focal segmental glomerulosclerosis, genetic evaluation before aggressive immunosuppression and preceding transplantation should be introduced. Supportive treatment of idiopathic nephrotic syndrome consists of fluid and salt restriction, protein intake tailored to the protein losses, prevention of thrombosis and infection, and -mainly in steroid resistant cases--measures to prevent of premature atherosclerosis and deterioration of kidney function.
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PMID:[Nephrotic syndrome in childhood]. 1738 Jun 87

The collapsing variant of focal segmental glomerulosclerosis is a fulminant lesion characterized by rapid progression to end-stage renal disease. Substantial in vivo and in vitro evidence suggests that lipids, particularly low density lipoprotein (LDL), can contribute to the progression of glomerulosclerosis as they do in atherosclerosis. The nephrotic syndrome is typically associated with marked elevation of LDL and suppression of high density lipoprotein (HDL), abnormalities which may, accelerate both of these lesions. We report the case of a patient who presented with heavy proteinuria and hypertension and was found to have collapsing focal segmental glomerulosclerosis as well as, surprisingly, a markedly elevated HDL level. Despite the poor prognosis of this lesion, over a 3-year period the patient maintained normal renal function and has experienced a decline in her proteinuria to below-nephrotic levels while maintaining an elevated HDL level. Though this is only a single report, it may nevertheless be worthwhile to consider the possibility that HDL levels could potentially modulate the course of glomerular disease.
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PMID:Possible role of high density lipoprotein in the progression of glomerulosclerosis. 1768 14


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