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Renal dysfunction and hypertension are closely associated. Hypertension causes approximately 25% of end-stage renal disease (ESRD) and develops in virtually every patient with advanced renal insufficiency from any cause. Although normalization of blood pressure can reduce mortality from uremia and ameliorate the progression of renal impairment in patients with established renal insufficiency from hypertension and diabetes, antihypertensive therapy alone is not totally effective in preventing progressive compromise of renal function--especially in blacks and diabetics, who are at high risk for developing ESRD. Of particular promise is the rapidly increasing understanding of the intrarenal autocrine and paracrine functions of angiotensin II produced locally by a tissue renin-angiotensin system. Consistent and convincing experimental data have demonstrated that angiotensin II plays many roles in the control of renal function and the kidney's response to injury. The intrarenal effects of angiotensin II include: 1) increase in the efferent arteriolar tone, resulting in increased glomerular capillary pressure, 2) promotion of mesangial cell contraction, 3) stimulation of proximal tubular Na+ reabsorption, and 4) possible growth hormone effects leading to hypertrophy or hyperplasia of vascular smooth muscle. Because of their favorable intrarenal hemodynamic effects (particularly reduction of glomerular capillary pressure), ACE inhibitors may provide a renal protective effect in addition to their systemic antihypertensive effects. Clinical trials evaluating the effect of ACE inhibition on the progression of renal insufficiency in hypertensives and diabetics are currently under way. Favorable results could lead to a significant decrease in the morbidity and mortality associated with hypertension.
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PMID:Renal protective effects of angiotensin converting enzyme inhibitors. 226 Nov 45

The drug treatment of mild hypertension has been shown to afford protection against fatal and nonfatal strokes, congestive heart failure, progression to more severe levels of hypertension, and all-cause mortality, but not against the complications of coronary artery disease. The lack of benefit against coronary artery disease may result from failure to reduce other risk factors or because the drugs employed increased coronary risk. It can be taken as axiomatic that effective preventive antihypertensive therapy is more likely with drugs with mechanisms and sites of action that are focused on the underlying pathophysiology than with drugs that lower blood pressure by means unrelated to the hypertensive process. Adrenergic predominance plays a major role in the initiation and maintenance of essential hypertension and, consequently, the alpha-adrenergic receptor inhibitors were among the first substances to receive serious consideration as antihypertensive agents. However, since these drugs are nonselective, feedback control of transmitter norepinephrine was lost and, consequently, the clinical expectations of the early alpha-adrenergic receptor inhibitors in the treatment of high blood pressure were not fulfilled. The discovery of selective postjunctional alpha 1-adrenergic-receptor inhibitors, such as prazosin and doxazosin, which preserve feedback control of transmitter norepinephrine release, was the crucially important step in the development of specific drugs to combat the hyperactivity of adrenergic vasoconstrictor nerves in hypertension. These drugs have been shown to normalize hemodynamics in hypertensive patients. They lower blood pressure through a reduction in peripheral resistance at rest and during exercise, independent of changes in heart rate and blood pressure, with minimal reflex activation or tolerance development. Alpha 1-adrenergic-receptor inhibitors, such as prazosin and doxazosin, represent an attractive choice for initial therapy in all grades of hypertension and are especially appropriate in hypertensive patients with congestive heart failure, asthma and chronic obstructive airways disease, renal impairment, diabetes mellitus, hyperlipidemia, benign prostatic hyperplasia, or gout, and in those involved in vigorous work, sports, or exercise. There are no known contraindications to these drugs, except in patients who are sensitive to quinazolines.
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PMID:Pharmacologic basis for the use of doxazosin in the treatment of essential hypertension. 256 23

Surveys that evaluated antihypertensive drug-prescribing patterns were mailed to 150 family physicians and 150 primary care internists. The initial mailing was followed by a telephone follow-up and a second mailing. Forty-seven percent of family physicians and 41.9% of the internists who were still in practice returned the questionnaire. When asked about their choice of antihypertensive drug therapy for specific patients (based upon age, race, sex, and coexisting disease), the responses of the two specialties were similar. The only statistically significant difference was observed in the responses for a 58-year-old obese white woman with diabetes and renal impairment. In this example, the family physicians were more likely than internists to recommend an angiotensin converting enzyme inhibitor or a beta-blocker (P = .036). This study demonstrates that the majority of physicians individualized initial therapy for hypertension to the specific patient rather than strictly following a stepped-care approach with diuretics or beta-blockers as initial therapy.
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PMID:Antihypertensive drug-prescribing patterns of internists and family physicians. 257 Jan 21

The prevalence of hypertension in adult Nigerians is about 20% and hypertension remains a significant risk factor in cardiovascular morbidity and mortality. In Africans, hypertension carries a dismal prognosis, has a late clinical presentation and certain antihypertensives may be less effective. We therefore conducted a therapeutic audit in order to assess the initial cardiovascular risk profile of Nigerian patients as well as the safety and efficacy of different antihypertensive agents. A cross-sectional survey of 367 patients (M:F:2:1) modal age 25-44 years, mostly WHO II, enrolled in our clinic was undertaken. 56% had been on treatment for up to one year and 2% for longer than ten years. 12.5% had concomitant diabetes mellitus. Statistical analyses of drug efficacy were done by Spearman correlation and Analysis of Variance (ANOVA). The rank order of hypertensive efficacy was as follows: Thiazides (T) (r = 0.57, P less than 0.05), T + Methyldopa (M) (r = 0.91, P less than 0.001) T + M + Hydralazine (r = 0.92, P less than 0.001). Neither propranolol, nor frusemide showed significant overall efficacy. However, propranolol appeared efficacious in hypertensives with renal impairment. Postural dizziness was occasionally reported. Total mortality was 6% occurring mostly in the modal age group. Diabetic hypertensives had a 5 fold enhanced risk of a fatal outcome (X2 P less than 0.001). Our findings support a rational stepped care approach to pharmacotherapy of hypertension in black Africans, a cost-effectiveness analysis of common antihypertensives; it elucidates the associated adverse effects to patients, and draws attention to the lethality of concomitant hypertension and diabetes. Prospective large scale studies of the treatment of hypertension in Africans are required.
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PMID:A therapeutic audit in the management of hypertension in Nigerians. 260 27

Hypertensive diabetic patients are particularly prone to renal function impairment. A total of nine out-patients with diabetes and hypertension were, therefore, entered into this single-blind uncontrolled study on the effects of 50 mg/day atenolol on reducing blood pressure and preserving normal kidney functioning. Treatment and evaluations were continued for 12 months. Serum beta 2-microglobulin concentration was used as the index for measuring renal impairment. Atenolol significantly reduced heart rate, systolic and diastolic blood pressure, and serum beta 2-microglobulin concentrations compared with baseline. Plasma glucose and glycosylated haemoglobin levels were unchanged, and blood urea nitrogen levels were increased slightly (non-significant). Serum creatinine showed a tendency (non-significant) to reflect the changes in beta 2-microglobulin concentration. Ways in which atenolol may act to improve kidney functioning are suggested. It is concluded that atenolol is a favourable choice for the treatment of hypertension in diabetic patients with normally functioning kidneys since, even in long-term use, normal renal functioning is preserved.
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PMID:A 1-year follow-up study on the effect of atenolol on serum beta 2-microglobulin level in hypertensive diabetic patients. 265 32

Contrast nephropathy can be defined as an acute impairment of renal function that follows exposure to radiocontrast materials and for which alternative explanations for renal impairment have been eliminated. Based on reported studies, the incidence of contrast associated nephropathy (CAN) varies from 0 to 22%. This wide variation can be traced to differences in study design and the criteria used to designate significant renal impairment. Irrespective of the exact incidence, 2 defined risk factors have been identified: preexisting renal disease and diabetes mellitus. Whereas preexisting renal insufficiency is the single most influential risk factor for CAN, when diabetes coexists the incidence approaches 100%. The clinical presentation of CAN is distinct, having a temporal relation between the performance of the contrast study in the high-risk patient and the onset of an increase in serum creatinine levels within the next 24 hours. Serum creatinine values greater than 50% of baseline or rising 1 mg/dl or more is diagnostic. The peak serum creatinine level occurs within 3 to 5 days of the contrast study and oliguria is associated in approximately 30% of the cases. Monitoring serum creatinine is the most useful clinical procedure in high-risk patients after angiography. At least 5 potential pathophysiologic mechanisms of CAN have been proposed: interference with renal perfusion, altered glomerular perm-selectivity, direct tubular injury, intraluminal obstruction, and immunologic mechanisms. Support for each mechanism, either singularly or in combination, can be found in published reports; however, none has achieved universal acceptance. The single most important clinical axiom regarding the prevention and management of CAN is, "Always use the least invasive diagnostic procedure available."(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Contrast-associated nephropathy. 267 65

In hypertension the primary pathophysiologic abnormality is a generalized increase in the peripheral vascular resistance as a result of concentric narrowing of the systemic arterioles, as a result of alpha 1-receptor stimulation. Such stimulation is attenuated by the selective alpha 1-inhibitor doxazosin. The pharmacologic attributes of doxazosin are translated into direct relaxation of the peripheral arteriolar resistance vessels and venous capacitance system, particularly those with a high alpha-adrenoceptor population. The direct effects of such vascular dilatation are immediately beneficial to the heart in reducing systemic and pulmonary vascular pressures that reduce left ventricular wall stress and myocardial oxygen consumption. In clinical studies doxazosin has been found to have a plasma half-life of 19 to 22 hours, of which a single daily dose is sufficient to control hypertension. The antiatherogenic changes in the blood lipid profile resulting from long-term treatment with doxazosin can also be expected to advance its primary prevention potential in hypertensive patients, which is in marked contrast to the potentially disadvantageous changes in the blood lipid profile that follow treatment with beta-blockers and thiazide diuretics. The therapeutic efficacy of doxazosin has been confirmed, irrespective of hypertension severity, age and race of the patient, or the presence of renal impairment or diabetes mellitus. Its side-effect profile is not substantially different from that of placebo or other antihypertensive drug treatment. Given its unique actions regarding antihypertensive efficacy, together with favorable effects on blood lipids, doxazosin probably holds more promise for the prevention of precocious coronary heart disease in hypertensive patients than any other currently available antihypertensive agent.
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PMID:Pharmacotherapeutic stature of doxazosin and its role in coronary risk reduction. 290 44

Between 1981 and 1986, 10 consecutive cases of melioidosis were seen at the University Hospital, Kuala Lumpur, Malaysia. They illustrate the amazing guises of melioidosis presenting as: abscesses of the supraspinatus muscle, psoas muscle, brain and liver; three different pulmonary forms; an acute suppurative dermal lesion; an acute septicaemia; and chronic lymphadenitis. The majority had underlying diseases: diabetes mellitus, the commonest, was present in six, out of whom three had previous pulmonary tuberculosis; other predisposing conditions were renal failure, corticosteroid therapy and malnutrition. Three patients who died had pre-existing renal impairment and developed renal failure later, suggesting that the former is a bad prognostic sign. Clinical diagnosis was difficult: all cases were diagnosed bacteriologically. A high level of clinical awareness is necessary, especially when presentation simulates pulmonary or extrapulmonary tuberculosis in patients with diabetes or other compromised states.
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PMID:Melioidosis, the great mimicker: a report of 10 cases from Malaysia. 318 45

From August 1974 to January 1985, 53 patients (26 men; seven Maoris) mean age 45 (SD 15) years, with diabetes mellitus for a mean of 12 (SD nine) years had a renal biopsy and were followed. Indications for biopsy were nephrotic syndrome, proteinuria, renal impairment (five) and hematuria (one). Mean plasma creatinine concentration was 0.22 (SD 0.18) mmol/L and protein excretion 3.4 (SD 2.5) g/24 h. Diabetic nephropathy was demonstrated in 39 patients and significantly associated with retinopathy and insulin dependent diabetes mellitus (IDDM). Of the 39 patients followed for 25.7 (SD 22.8) months, 18 had died (nine myocardial infarction, six uremia, two sepsis, one stroke) and nine had begun dialysis. The five-year cumulative renal survival was 28%. The presence of the nephrotic syndrome and the plasma creatinine concentration at presentation were the best predictors of survival. Diabetics with IDDM of 20 years duration, retinopathy and heavy proteinuria, who survive the other complications of their disease, are likely to have diabetic nephropathy requiring renal replacement therapy.
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PMID:Renal disease in diabetics--which patients have diabetic nephropathy and what is their outcome? 324 62

Heavy reversible proteinuria induced by antihypertensive treatment with low doses of captopril has recently been reported by our group in psoriatic patients. To ascertain whether an increased permeability of the glomerular basal membrane of psoriatics can lead to an enhanced urinary excretion of albumin independently from the presence or absence of coexisting diabetes or hypertension, the latter parameter was measured in 39 patients affected by diffuse psoriasis. A high prevalence of microalbuminuria was observed in diabetic and hypertensive psoriatics. Moreover, a direct correlation was found between the diastolic blood pressure (BP) values and the urinary excretion of albumin in the entire group of psoriatics, thus suggesting systemic hypertension as one of the factors responsible for proteinuria in these patients. However, more than 50% of normotensive psoriatics showed an enhanced excretion of albumin. Since microalbuminuria has been indicated as a reliable index to predict the development of renal impairment, the finding of an enhanced albumin loss in psoriatics represents a further risk factor in these patients, who are particularly susceptible to experience cardiovascular complications.
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PMID:High prevalence of microproteinuria, an early index of renal impairment, in patients with diffuse psoriasis. 328 Oct 46


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