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)

The awareness, treatment, and control of hypertension has risen steadily over the past three decades, until the early 1990s. However, blood pressure control to < 140/90 mmHg is attained in fewer than 25% of all hypertensive patients and fewer than 50% of drug-treated hypertensive patients, except for white women. Two special populations, African-Americans and diabetics, share several important attributes. First, they both have a high prevalence of hypertension, including stage 3 hypertension (as defined by the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of Hypertension VI: > or =180/110 mmHg), relative to other subgroups. African-Americans have an approximate 8% prevalence of stage 3 hypertension, and elevated systolic blood pressure is highly prevalent among diabetic people, particularly older African-American women. Second, both groups have high levels of blood-pressure-related target-organ damage, which contributes to their inordinately high absolute risk for cardiovascular disease complications (i.e. stroke, congestive heart failure, renal failure) at a given level of blood pressure. Moreover, the reduced natriuretic capacity common to each group contributes to the attenuated efficacy of antihypertensive drug monotherapy, particularly for drug classes other than diuretics and calcium antagonists. These two special populations are also typically salt-sensitive, an intermediate blood pressure phenotype that raises blood pressure medication requirements. This phenomenon has been associated with an attenuation in the normal nocturnal fall in blood pressure. The high absolute risk for cardiovascular disease among diabetics led to the formulation of more aggressive treatment recommendations for antihypertensive drug therapy. In diabetics, blood pressure therapy is initiated at blood pressures > or = 130/85 mmHg, and treatment goals are at least to this level, unless proteinuria is > or = 1g/day (in which case the goals are < 125/75 mmHg). The more aggressive treatment targets for diabetics will not be reached with most currently available single antihypertensive agents in many African-Americans. While at best only 50-60% of hypertensive patients can be controlled with single drug therapy, that percentage falls dramatically in persons with stage 3 hypertension and renal insufficiency, thereby necessitating the use of combination drug therapy. Treatment alone is not enough; treatment to goal blood pressure is an essential first step towards optimal target-organ protection. While circulating levels of renin are suppressed, in general, in these special populations, each group manifests an inordinate burden of blood-pressure-related target-organ damage that has been linked to excessive levels of angiotensin II or a reduced bradykinin and nitric oxide tissue effect. The renin-angiotensin-aldo-sterone-kinin system is therefore an attractive therapeutic target that might conceivably provide target-organ protection over and above that attributable solely to lowering the blood pressure.
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PMID:Difficult-to-treat hypertensive populations: focus on African-Americans and people with type 2 diabetes. 1034 Aug 40

Diabetes mellitus and hypertension is often associated, but with a different type of development in type 1 and type 2 diabetes. Type 1 diabetes, renal disease, starting with microalbuminuria, is associated with increasing blood pressure or hypertension, whereas the patient without renal disease is most often normotensive. Poor metabolic control is a predictor of microalbuminuria or incipient nephropathy, but with microalbuminuria hypertension is an important risk factor for progression along with poor glycemic control. The same is the case for overt renal disease, and metabolic control is important in all stages of renal disease in type 1 diabetes. It has also been shown that good metabolic control as well as antihypertensive treatment, especially with ACE-inhibitors, often combined with other agents is quite effective in preventing progression in renal disease in all its stages. In type 2 diabetes, blood pressure elevation is often found as early as at the actual diagnosis, and blood pressure significantly increases according to the degree of albuminuria, normo-microalbuminuria and clinical proteinuria (macroalbuminuria). Elevated blood pressure is an important risk for renal disease but more importantly so also for cardiovascular disease. Several studies document that antihypertensive treatment in particular with ACE-inhibitors is important in preventing microalbuminuria, in treating microalbuminuria and thus preventing progression, also in overt renal disease. Near-normalization of blood pressure is vital. Regarding cardiovascular disease, a series of studies now document that antihypertensive treatment with various antihypertensive agents is able to significantly reduce a number of major cardiovascular complications in diabetes, such as cardiac disease, stroke, and also microvacular disease, including retinopathy. Several studies show that antihypertensive treatment should be started at a level higher than 140-150/90. The blood pressure to be achieved during treatment is probably around 140/85 mmHg or even 130/80 mmHg as a pragmatic goal. However, there is no sign of a J-shaped curve in any of the studies, and therefore even lower blood pressure could be advantageous. Even mortality, at least from diabetes-related causes can be effected by antihypertensive treatment. With more advanced renal disease, normalization of blood pressure is increasingly difficult, especially systolic blood pressure, and therefore it is recommendable to screen patients much earlier on with focus on blood pressure recordings and measurements of albuminuria, including microalbuminuria, and to treat early.
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PMID:Drug treatment for hypertensive patients in special situations: diabetes and hypertension. 1042 11

High lipoprotein(a) (Lp(a)) serum concentrations and the underlying apolipoprotein(a) (apo(a)) phenotypes are risk factors for cardiovascular disease in the general population as well as in patients with renal disease. Lp(a) concentrations are markedly elevated in patients with end-stage renal disease. However, nothing is known about the changes of Lp(a) depending on apo(a) size polymorphism in the earliest stages of renal impairment. In this study, GFR was measured by iohexol technique in 227 non-nephrotic patients with different degrees of renal impairment and was then correlated with Lp(a) serum concentrations stratified according to low (LMW) and high (HMW) molecular weight apo(a) phenotypes. Lp(a) increased significantly with decreasing GFR. Such an increase was dependent on apo(a) phenotype. Only renal patients with HMW apo(a) phenotypes expressed higher median Lp(a) concentrations, i.e., 6.2 mg/dl at GFR >90 ml/min per 1.73 m2, 14.2 at GFR 45 to 90 ml/min per 1.73 m2, and 18.0 mg/dl at GFR <45 ml/min per 1.73 m2. These values were markedly different when compared with apo(a) phenotype-matched control subjects who had a median level of 4.4 mg/dl (ANOVA, linear relationship, P < 0.001). In contrast, no significant differences were observed at different stages of renal function in patients with LMW apo(a) phenotypes when compared with phenotype-matched control subjects. The elevation of Lp(a) was independent of the type of primary renal disease and was not related to the concentration of C-reactive protein. Multiple linear regression analysis found that the apo(a) phenotype and GFR were significantly associated with Lp(a) levels. Non-nephrotic-range proteinuria modified the association between GFR and Lp(a) levels. In summary, an increase of Lp(a) concentrations, compared with apo(a) phenotype-matched control subjects, is seen in non-nephrotic patients with primary renal disease even in the earliest stage when GFR is not yet subnormal. This change is found only in subjects with HMW apo(a) phenotypes, however.
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PMID:Lipoprotein(a) serum concentrations and apolipoprotein(a) phenotypes in mild and moderate renal failure. 1061 46

Peripheral blood progenitor cell reinfusion (PBPC) in patients undergoing high-dose chemotherapy (HDC) for poor prognosis malignancies, has been described as causing possible acute gastrointestinal (nausea, vomiting), allergic (oedema, bronchospasm, anaphyl- axis), renal (proteinuria, haematuria) and/or cardiovascular (hypotension, arrhythmia, conduction disturbances, transient ischaemic phenomena) toxicities. To establish the clinical relevance of these observations and the possible relationship with different HDC regimens used, we performed a clinical and instrumental evaluation on 33 patients with advanced breast cancer, non-Hodgkin's lymphoma, Hodgkin's disease, relapsed ovarian cancer, Ewing's sarcoma, extragonadal germinal tumour and small cell lung cancer. They underwent at least one reinfusion each for a total of 51 studied procedures. No patient had a previous history of cardiovascular disease or significant intercurrent illness such as diabetes or liver, renal or neurologic impairment. All patients had totally implanted central venous catheters, through which the transplants had been collected and reinfused without technical consequences. To evaluate cardiovascular function, we continuously monitored 12-lead ECGs, with arterial pressure (AP) measurements every 5 min from the beginning of the procedure to 15 min after the reinfusion ended. We did not observe any significant differences between basal and subsequent steps in AP, heart rate, PQ and QTc time, P wave and QRS complex duration or P wave and QRS electrical axes. No patient showed any ST-T tract pathological abnormality, but one patient developed a transient ectopic atrial rhythm, without any haemodynamic disfunction and with spontaneous reversion to sinus rhythm. No patient complained of symptoms of haemodynamic failure. Gastrointestinal side-effects appeared to be strictly related to speed of reinfusion and to the number of packs reinfused, probably reflecting on the amount of dimethylsulphoxide infused. In one patient a tonic-clonic seizure occurred during a vomiting episode, but no patient developed allergic or renal toxicities. We conclude that PBPC reinfusion, if managed according to the procedure we propose in patients without organic impairment, is a safe procedure not associated either with increased risk of acute arrhythmias or ischaemic or significant systemic acute toxicities. Bone Marrow Transplantation (2000) 25, 173-177.
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PMID:Evaluation of acute toxicities associated with autologous peripheral blood progenitor cell reinfusion in patients undergoing high-dose chemotherapy. 1196 Feb 81

In patients with essential hypertension and in those with diabetes mellitus, the presence of increased amounts of urinary protein or albumin has been shown to be an important and independent risk for an increased incidence of cardiovascular morbidity and mortality. A constellation of cardiovascular risk factors has been described in these individuals, as well as evidence for diffuse endothelial cell dysfunction, which suggests these individuals are particularly susceptible to the development of extensive vascular disease. Recent studies have also suggested that proteinuria is not only a marker for renal disease but it also predicts those patients at greatest risk for the development of chronic and progressive renal insufficiency. This effect of proteinuria was evident in patients in whom urinary protein excretion rates exceeded 1 g/24 hours, but probably is true even in patients with smaller amounts of proteinuria. This effect of proteinuria on progression of renal disease is independent of other risk factors such as level of renal function, blood pressure, and dyslipidemia. Recent clinical studies have demonstrated that modification of proteinuria by the use of angiotensin-converting enzyme (ACE) inhibitors independent of reductions in systemic blood pressure results in slowing of the rate of loss of renal function and even stabilization of renal function over longer periods of treatment. In patients with renal disease, the totality of evidence suggests that multiple pharmacological and dietary modifications will be necessary to achieve the optimal slowing of the progression of renal disease. In addition, strategies will be required to reduce risks involved in the development of cardiovascular disease to ensure optimal patient survival. The similarity of risk factors involved in cardio-renal disease progression should allow us to achieve this goal with our current therapeutic armamentarium.
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PMID:Proteinuria: its clinical importance and role in progressive renal disease. 1076 8

Elevated plasma levels of fibrinogen and activated coagulation pathways are risk factors of cardiovascular disease in the general population. In a cross-sectional study of a case series, we investigated the relationship between fibrinogen and hemostatic markers with target-organ damage (TOD) in patients with arterial hypertension. Prothrombin time, partial thromboplastin time, fibrinogen, fibrin D-dimer, prothrombin fragment 1+2 (F1+2), and antithrombin III were measured in 352 untreated patients with mild to moderate essential hypertension and 92 normotensive controls. Staging of TOD was assessed according to W.H.O. guidelines by clinical evaluation and laboratory tests including measurements of creatinine clearance, proteinuria, ophthalmoscopy, electrocardiography, echocardiography, and ultrasound examination of major arteries. F1+2 concentrations were significantly greater in hypertensive patients than normotensive controls and were positively correlated with blood pressure. Age, blood pressure levels, duration of hypertension, smoking, HDL-cholesterol, triglycerides, and plasma fibrinogen, fibrin D-dimer, and F1+2 levels were significantly related to the presence and severity of TOD in univariate analysis. Plasma fibrinogen and D-dimer levels were related to organ damage independent of age, blood pressure, duration of hypertension, and smoking status. Separate analysis indicated significant association of fibrinogen and D-dimer levels with cardiac, cerebrovascular, peripheral vascular, and renal damage. In conclusion, elevated plasma levels of fibrinogen and a prothrombotic state are associated with the presence and severity of TOD in patients with essential hypertension and may contribute to the development of atherosclerotic disease in these patients.
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PMID:Relationship of fibrinogen levels and hemostatic abnormalities with organ damage in hypertension. 1111 10

Non-Invasive coronary investigations are positive in 12 to 52% (average 22%) of type II diabetics, and 11 to 30% (average 17%) of type i diabetics. These statistics vary according to bias of recruitment. Haemodynamic lesions are found at coronary angiography in 35 to 80% of patients who have at least one positive non-invasive investigation. Nine to 12% of diabetics have silent myocardial ischaemia (SMI) confirmed by coronary angiography, compared with 1.3 to 5.3% of non-diabetic controls paired for age and sex. The higher frequency of SMI in diabetics seems to be mostly due to the increased frequency of ischaemic heart disease in diabetics. The importance of cardiac autonomic neuropathy (CAN) in SMI is controversial. The risk factors associated with SMI are those usually associated with coronary artery disease: age, masculine gender, hypercholesterolaemia, hypertriglyceridaemia, hypertension, smoking, a family history of cardiovascular disease, insulin therapy (for type II diabetes), proteinuria, retinopathy, peripheral occlusive arterial disease.... The French recommendations for investigating SMI seem to be contradictory. A single risk score in a given patient could help codify the investigation of SMI in diabetics, but this type of score has not yet been validated.
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PMID:[Silent ischemic cardiopathy: which diabetics to examine?]. 1129 59

Based on many epidemiological studies, hypertensive diabetics have been regarded as high risk for cardiovascular disease. The sixth Joint National Committee guideline (JNC VI) recommended to start hypotensive agents even at high normal blood pressure, i.e. over 130/85 mmHg and lower their blood pressure to less than 130/85 mmHg. If patients are associated with renal dysfunction (proteinuria of more than 1 g/day), the target blood pressure would be less than 125/75 mmHg. These target blood pressures were supported Hypertension Optimal Treatment study and/or UKPDS. ACE inhibitors, Ca-antagonists or alpha-blockers were regarded as one of the first line drugs. Japanese Society of Hypertension has established the guideline for hypertension treatment, in which almost the same recommendation has been made for diabetics except one point, i.e., at high normal blood pressure, lifestyle modification might be the initial treatment followed by hypotensive agents if their blood pressure dose not go down to less than 130/85 mmHg during the next 3-6 months. Based on these guidelines, more vigorous antihypertensive treatment would be recommended in diabetics to reduce micro- and macrovascular disease.
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PMID:[Antihypertensive treatment in diabetics]. 1139 99

Microalbuminuria (MA) is defined as persistent elevation of albumin in the urine, of 30-300 mg/day (20-200 microg/min). These values are less than the values detected by routine urine dipstick testing, which does not become positive until protein excretion exceeds 300-500 mg/day. Use of the albumin-to-creatinine ratio is recommended as the preferred screening strategy for all diabetic patients. MA is measured in spot morning urine obtained from the patient in the office and sent for measurement of both albumin and creatinine. A value above 0.03 mg/mg suggests that albumin excretion is above 30 mg/day and therefore MA is present. MA should be checked annually in everyone, and every 6 months within the first year of treatment to assess the impact in patients started on antihypertensive therapy. MA is an established risk factor for renal disease progression in type 1 diabetes and its presence is the earliest clinical sign of diabetic nephropathy. In addition, a number of studies suggest that MA is an important risk factor for cardiovascular disease and defines a group at high risk for early cardiovascular mortality in both type 2 diabetes and essential hypertension. MA also signifies abnormal vascular permeability and the presence of atherosclerosis. Among nondiabetic patients with essential hypertension, MA is associated with higher blood pressures, increased serum total cholesterol, and reduced serum high-density lipoprotein cholesterol. Thus, taken together these data support the concept that the presence of MA is the kidney's notice to the physician/patient that there is a problem with the vasculature. MA can be reduced, and progression to overt proteinuria prevented, by aggressive blood pressure reduction. The National Kidney Foundation recommends that blood pressure levels be maintained at or below 130/80 mm Hg in anyone with diabetes or renal disease. This should be accomplished with antihypertensive agents that prevent the rise in MA and hence prevent development of proteinuria. Such agents are angiotensin-converting enzyme inhibitors, angiotensin receptor blockers and, to a lesser extent, Beta blockers, non-dihydropyridine calcium antagonists, and diuretics. In summary, the presence of MA is a marker of endothelial dysfunction and a harbinger of markedly enhanced cardiovascular risk. All patients with diabetes and/or hypertension should be screened for the presence of microalbuminuria with use of spot morning urine. To maximize prevention of MA development, the following goals should be instituted: 1) blood pressure should be maintained at less than 130/80 mm Hg and a low-salt, moderate-potassium diet instituted; 2) in diabetics, HbA1c should be kept at less than 7%; 3) in obese patients, a weight loss program should be implemented, with a goal BMI of less than 30; and 4) the physician and patient, working together, should maintain low-density lipoprotein cholesterol at less than 120 mg/dL, and less than 100 mg/dL if diabetes is present. (c)2001 by Le Jacq Communications, Inc.
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PMID:Microalbuminuria: what is it? Why is it important? What should be done about it? 1141 91

The aim of this study was to evaluate the relations between left ventricular (LV) functional abnormalities, microangiopathy, and autonomic dysfunction in patients with non-insulin-dependent diabetes mellitus (NIDDM). We studied 66 normotensive patients with NIDDM of > or =4 years' duration (age, 51 +/- 4.5 years; 35 men) and no clinical evidence of cardiac disease. Twenty-one healthy subjects matched for age and sex served as a control group. Echocardiography and Doppler studies were performed to assess LV systolic and diastolic function. Microangiopathy was assessed by fundus examination. Autonomic function was assessed by standing blood pressure and heart rate response to Valsalva maneuver. Patients with NIDDM had a lower ejection fraction (58% +/- 11% versus 66% +/- 4%, P <.0001), E-F deceleration slope (382 +/- 75 versus 427 +/- 31 cm/s(2), P <.05), and E velocity (55 +/- 11 vs. 58 +/- 6 cm/s, P =.02) of the mitral diastolic flow, compared with control subjects, respectively. Patients with ejection fraction <50% had a higher prevalence of retinopathy (65% versus 29%, P <.005), abnormal blood pressure response to standing (53% versus 8%, P <.0005), and proteinuria (65% versus 27%, P =.006). An inverse correlation was found between the duration of diabetes and both the ejection fraction (r = -0.53, P <.05) and E/A ratio (r = -0.4, P <.005). E/A ratio <1 was associated with a higher prevalence of retinopathy (49% versus 20%, P =.01) and abnormal blood pressure response to standing (29% versus 4%, P <.005). Patients with NIDDM and no symptoms of cardiovascular disease have a reduced LV systolic and diastolic function as compared with healthy subjects. LV systolic and diastolic abnormalities are correlated with the duration of diabetes and with other diabetic microangiopathies such as diabetic retinopathy and neuropathy.
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PMID:Left ventricular systolic and diastolic functional abnormalities in asymptomatic patients with non-insulin-dependent diabetes mellitus. 1154 74


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