Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011881 (diabetic nephropathy)
 10,836 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The D allele of the angiotensin-converting enzyme (ACE) gene has been linked with diabetic nephropathy and IgA glomerulonephritis and with faster renal disease progression. The association of this allele with nephroangiosclerosis has been scarcely investigated. We have tested this association in 45 hypertensive patients (all whites) with well defined nephroangiosclerosis (diagnosis established on the basis of renal biopsy in all cases) and moderate to severe renal failure. As studies of genetic association of small size often produce conflicting results, besides a control group of 343 Italian patients with essential hypertension and normal renal function, we elected to use also a very large control group of race-matched subjects taken from a meta-analysis of 27,565 whites. The proportion of patients with the D allele (64%) was higher in patients with nephroangiosclerosis than that in Italian hypertensives (54%) and in whites (54%). DD and DI genotypes were more prevalent in patients than in control groups. The dominant model (DD and DI v II: nephroangiosclerosis v Italian controls: chi2 = 6.19, P = .012; nephroangiosclerosis v whites chi2 = 6.86, P = .009) fitted the data better than the codominant and the recessive model (P < or = .022). The D allele is associated with nephroangiosclerosis with a dominant effect in the sample of patients studied. Although intervention studies are needed to see whether these findings imply a causal association, our data suggest that this allele may at least act as disease marker in nephroangiosclerosis.
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PMID:The deletion polymorphism of the angiotensin-converting enzyme is associated with nephroangiosclerosis. 1082 48

In the United States, blacks are more frequently diagnosed than whites with end-stage renal failure (ESRF) from primary hypertension or diabetic nephropathy. We performed a validation retrospective case-note study of all blacks with ESRF who started renal replacement therapy (RRT) at three teaching hospitals in London, England, during 1991 to 1995 to investigate and validate the causes of primary renal disease using standard criteria. We identified 144 black patients with a mean age of 52.0 +/- 16.0 (SD) years; 59% were men and 32% had renal histological data. One hundred forty-four whites who were matched for age, sex, and onset of RRT (42% with renal histological data) underwent a similar validation exercise. Before the validation, the principal working diagnosis in the black patients had been diabetic nephropathy in 35% (89%, type 2; 11%, type 1); primary hypertension, 19%; glomerulonephritis (GN), 18%; and uncertain cause, 15%. After validation analysis, this changed to diabetes, 38% (16% biopsy proven); uncertain, 24%; GN, 20%; and primary hypertension, only 10% (28% biopsy proven). Among the uncertain cases (n = 34), 19 patients had hypertension, but this could not be established as the primary disease; 94% of all blacks had hypertension, accelerated in 21%. Among whites, only 3.5% had primary hypertension, and this proportion was not changed by the validation study. Type 2 diabetes is the most common single cause of ESRF in black patients in London, and although hypertension is more common and more severe in blacks, the proportion of renal failure attributed to primary hypertension is overestimated, and the diagnosis is often made using inadequate criteria.
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PMID:Causes of end-stage renal failure in black patients starting renal replacement therapy. 1092 8

Cigarette smoking has adverse effects on health causing ischemic heart disease, stroke, chronic obstructive lung disease and cancers of the respiratory and upper digestive tract, pancreas, kidney and urinary tract. Smoking causes an acute increase in mean arterial pressure and heart rate mediated by catecholamines and beta-adrenergic mechanisms. Chronic cigarette smoking reduces renal plasma flow, probably increasing synthesis of the vasoconstrictor endothelin and reducing generation of the vasodilatory endothelial nitric oxide. There is clinical evidence that cigarette smoking has important adverse effects on renal outcome in primary hypertension, diabetic nephropathy, primary glomerular diseases, systemic diseases involving the kidney and in patients on chronic hemodialysis, or after renal transplantation.
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PMID:Cigarette smoking and kidney involvement. 1128 41

Complications of insulin-dependent diabetes mellitus (IDDM) are a major cause of morbidity and mortality; however, the mechanisms of their development are still to be elucidated. Genetic susceptibility contributes to the pathogenesis of nephropathy in IDDM. Enhanced G-protein activation, a cellular phenotype observed in cultured cells from patients with essential hypertension, was recently documented in IDDM subjects with nephropathy. A C825T polymorphism was recently described in GNB3, the gene encoding the beta 3 subunit of heterotrimeric G-proteins. This genetic variant has been associated with enhanced G-protein activation. The 825T allele was observed more frequently in a group with essential hypertension. We analyzed the role of the C825T polymorphism in the predisposition to diabetic complications in IDDM. In this study, we investigated the frequency of this polymorphism in a large case-control study and found no association of the 825T allele with diabetic nephropathy, retinopathy, and neuropathy.
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PMID:The C825T polymorphism in the G-protein beta3 subunit gene and diabetic complications in IDDM patients. 1132 58

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 benefit of good blood pressure control in patients with arterial hypertension has been repeatedly demonstrated. In high-risk patients, a good blood pressure control is one of the main prerequisites for the reduction of morbidity and mortality. However, as has been shown in population-based studies, the quality of blood pressure control both in patients with essential hypertension and in hypertensive diabetic patients is still unsatisfactory. Only a minority of patients achieve target blood pressure values below 140/90 mm Hg. This situation has not changed within the recent years, although the prescriptions of antihypertensive drugs have continuously increased. This paper describes a structured hypertension treatment and teaching program (HTTP) which was developed and evaluated during the last 16 years and which aims at intensification of antihypertensive therapy by active involvement of the patients in their own treatment. This programme primarily focuses on the improvement of the patients' long-term treatment compliance by means of information about non-pharmacological and pharmacological therapies and instructions to regular blood pressure self-measurements. The efficacy and feasibility of the HTTP has been evaluated in several studies which unanimously show considerable benefits not only concerning blood pressure control but, most importantly, regarding reduction in the incidence and progression of hypertension-associated diseases as cerebro- and cardiovascular events and diabetic nephropathy. Therefore, it seems essential to implement the HTTP in the German health care system in order to finally achieve the desired quality of care for patients with arterial hypertension.
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PMID:[Optimized therapy for hypertension]. 1148 99

The amiloride-sensitive Na+/H+ exchanger (NHE) mediates uphill H+ extrusion and thus causes intracellular alkalinization. The NHE plays a major role in pH homeostasis, Na+ absorption, cell volume regulation, and cell proliferation; it is activated by growth factors, mitogens, neurotransmitters, tumor promoters, and others. At intracellular pH (pHi)>7.2-7.4, the system is quiescent; when pHi falls, the rate of H+ - efflux increases in an allosteric manner to reach a maximum around pHi=6.0. The kinetics for external Na+ follows the Michaelis-Menten model with a single, binding site. The effect of intracellular H+ best fits an allosteric model with at least two binding sites. According to the postulate that erythrocyte sodium-lithium countertransport (NLCT) might be one mode of operation of the ubiquitous NHE, and following the trail of previous investigations of NLCT association with hypertension and diabetic nephropathy, several studies have confirmed elevated NHE activity in different cell types in patients with essential hypertension. However, the relation between NHE and either NLCT or hypertension remains unclear and the usefulness of NLCT activity as a risk marker for the development of essential hypertension has been now excluded. On the contrary, few publications have dealt with the physiologic NHE in diabetic nephropathy, and contrasting results have been reported. We have observed an accelerated NHE in essential hypertension and in Type 1 diabetes, however without any relationship with urinary albumin excretion rate. Furthermore, NHE activity increased in non-diabetic first-degree relatives of Type 1 diabetic patients, yet no difference could be observed between relatives of probands with diabetic nephropathy and relatives of probands with normoalbuminuria. Unlike erythrocyte NHE activity, abnormal albumin excretion was a distinctive feature of non-diabetic first-degree relatives of Type 1 diabetic patients with nephropathy. The lack of agreement among Authors, even using both the same cell and the same method, testifies to the difficulty in performing a correct patient selection and uniformly reproducible NHE measurement. We compare individual clinical characteristics among different study populations confirming previous conclusions regarding NLCT in essential hypertension: main determinant for the flux values of NHE seems to be patient selection rather than methodology. A common effort is advisable to collaborate, standardise, compare methodologies, and unify criteria of subject recruitment.
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PMID:Sodium/hydrogen exchange activity in type 1 diabetes mellitus: the never-ending story. 1171 94

Proteinuria is the hallmark of renal disease and proteinuria exceeding 1 gm a day in patients with renal disease augers a poorer prognosis. Proteinuria has been shown to be tubulotoxic and directly contributes to renal deterioration. Patients with non-selective proteinuria are more likely to have progressive renal disease. Diabetic patients with persistent microhaematuria have about 20 times the risk of developing diabetic nephropathy. In essential hypertension, the onset of de novo proteinuria after years of adequate BP control is a marker of subsequent decline in renal function. In glomerulonephritis, more severe proteinuria is associated with faster rate of progression. Even though the initial phase of proteinuria in patients with glomerulonephritis is usually of immunological origin, in the vast majority of patients with established disease, the latter progressive phase of proteinuric glomerulopathy is the result of glomerular hyperfiltration which shifts glomerular non-selective pores to larger dimensions resulting in excessive leakage of protein in the urine. Endothelial injury resulting from glomerular hyperfiltration causes increase in local generation of Angiotensin II in the kidney as part of the hemodynamic response. ACE inhibitors and angiotensin II receptor antagonists (ATRA) can improve glomerular pore-selectivity by remodelling the glomerular basement membrane. In addition, these agents also have beneficial effects by decreasing TGF-beta production therapy decreasing mesangial cell proliferation, hence ameliorating disease progression in patients with diabetic nephropathy and IgA nephropathy. A number of recent clinical trials have shown that ACEI and ATRA therapy can retard the progression of renal deterioration in patients with NIDDM and those with IgA nephropathy and even restore normal renal function in those with mild renal impairment. Treatment and control of proteinuria in patients with renal disease should be regarded as important as treatment of hypertension as it can prevent renal failure.
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PMID:Proteinuria: clinical signficance and basis for therapy. 1176 58

The angiotensin converting enzyme (ACE) inhibitors are widely used in the management of essential hypertension, stable chronic heart failure, myocardial infarction (MI) and diabetic nephropathy. There is an increasing number of new agents to add to the nine ACE inhibitors (benazepril, cilazapril, delapril, fosinopril, lisinopril, pentopril, perindopril, quinapril and ramipril) reviewed in this journal in 1990. The pharmacokinetic properties of five newer ACE inhibitors (trandolapril, moexipril, spirapril, temocapril and imidapril) are reviewed in this update. All of these new agents are characterised by having a carboxyl functional groups and requiring hepatic activation to form pharmacologically active metabolites. They achieve peak plasma concentrations at similar times (t(max)) to those of established agents. Three of these agents (trandolapril, moexipril and imidapril) require dosage reductions in patients with renal impairment. Dosage reductions of moexipril and temocapril are recommended for elderly patients, and dosages of moexipril should be lower in patients who are hepatically impaired. Moexipril should be taken 1 hour before meals, whereas other ACE inhibitors can be taken without regard to meals. The pharmacokinetics of warfarin are not altered by concomitant administration with trandolapril or moexipril. Although imidapril and spirapril have no effect on digoxin pharmacokinetics, the area under the concentration-time curve of imidapril and the peak plasma concentration of the active metabolite imidaprilat are decreased when imidapril is given together with digoxin. Although six ACE inhibitors (captopril, enalapril, fosinopril, lisinopril, quinapril and ramipril) have been approved for use in heart failure by the US Food and Drug Administration, an overview of 32 clinical trials of ACE inhibitors in heart failure showed that no significant heterogeneity in mortality was found among enalapril, ramipril, quinapril, captopril, lisinopril, benazepril, perindopril and cilazapril. Initiation of therapy with captopril, ramipril, and trandolapril at least 3 days after an acute MI resulted in all-cause mortality risk reductions of 18 to 27%. Captopril has been shown to have similar morbidity and mortality benefits to those of diuretics and beta-blockers in hypertensive patients. Captopril has been shown to delay the progression of diabetic nephropathy, and enalapril and lisinopril prevent the development of nephropathy in normoalbuminuric patients with diabetes. ACE inhibitors are generally characterised by flat dose-response curves. Lisinopril is the only ACE inhibitor that exhibits a linear dose-response curve. Despite the fact that most ACE inhibitors are recommended for once-daily administration, only fosinopril, ramipril, and trandolapril have trough-to-peak effect ratios in excess of 50%.
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PMID:Clinical pharmacokinetics and selective pharmacodynamics of new angiotensin converting enzyme inhibitors: an update. 1192 21

The benefit of good blood pressure control in patients with arterial hypertension has been repeatedly demonstrated. In high risk patients, a good blood pressure control is one of the main prerequisites for the reduction in morbidity and mortality. However, as shown in population-based studies, the quality of blood pressure control both in patients with essential hypertension and in hypertensive diabetic patients is still unsatisfactory. Only a minority of patients achieve target blood pressure values below 140/90 mm Hg. This situation has not changed within the recent years, although the prescriptions of antihypertensive drugs have continuously increased. This paper describes a structured hypertension treatment and teaching programme (HTTP) which was developed and evaluated during the last 16 years and which aims at intensification of antihypertensive therapy by active involvement of the patient in his own treatment. This programme primarily focuses on the improvement of the patients' long-term treatment compliance by means of information about non-pharmacological and pharmacological therapies and instructions to regular blood pressure self measurements. The efficacy and feasibility of the HTTP has been evaluated in several studies which unanimously show considerable benefits not only concerning blood pressure control but, most importantly, regarding reduction in the incidence and progression of hypertension associated diseases as cerebro- and cardiovascular events and diabetic nephropathy. Therefore, it seems essential to implement the HTTP in the German health care system in order to finally achieve the desired quality of care for patients with arterial hypertension.
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PMID:[Results of a structured hypertension teaching and treatment programme]. 1193 Feb 87


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