Sodium intake and furosemide administration in hypertensive patients with renal insufficiency

The effects of various levels of sodium intake and loop diuretic (furosemide) administration upon arterial pressure and renal function were studied in 11 patients with impaired renal function and essential hypertension. The patients were hospitalized in a metabolic ward and continued taking their usual antihypertensive medications. After a stabilization period, all patients followed the following regiments for 5 to 7 days: period I, 20 mEq sodium diet without diuretic administration; period II, 80 mEq sodium diet and furosemide, 80 mg daily; and period III, 200 mEq sodium diet and furosemide, 240 mg daily. Supine diastolic pressure was lower (P is less than 0.05) during period II than during period I and both supine and standing systolic and diastolic pressures were significantly lower in period III than in period I (P is less than 0.01). No significant differences in the renal clearance of inulin were noted between any of the study periods. In patients with essential hypertension and impaired renal function, consumption of a moderate or liberal sodium diet combined with administration of a loop diuretic agent (furosemide) appears to result in better control of arterial pressure without significant changes in renal function than does strict sodium restriction without diuretic administration.     

Withdrawal syndromes and the cessation of antihypertensive therapy

A review of the available literature concerning sudden withdrawal of antihypertensive drugs shows that withdrawal syndromes after cessation of such agents have occurred with beta-blockers, methyldopa, clonidine hydrochloride, guanabenz, and bethanidine sulfate. Most commonly, these syndromes are limited to nervousness, tachycardia, headache, and nausea 36 to 72 hours after cessation of the drug. In rare cases, serious exacerbation of myocardial ischemia (beta-blockers) or hypertension (clonidine, methyldopa) may occur in the posttreatment period. The withdrawal syndromes generally respond promptly to reinstitution of antihypertensive therapy. The infrequent occurrence of withdrawal syndromes should not discourage use of these efficacious agents.     

Effects of guanethidine and methyldopa on a standardized test for renin responsiveness.

A standardized test for renin responsiveness, employing the dual stimulus of upright posture and the loop diuretic furosemide, was applied to 19 hypertensive patients in the untreated state and during therapy with the antihypertensive agents guanethidine and methyldopa. During therapy with guanethidine, 6 of 10 patients with "low-renin essential hypertension" experienced elevations of plasma renin activity to levles ordinarily diagnostic of "normal-renin" hypertension (P less than 0.05), whereas methyldopa had no significant effect on plasma renin activity in either "low-renin" or "normal-renin" patients. It is suggested that methyldopa has a negligible influence on renin responsiveness when stimulated under the above conditions and that it may be used during assessment of plasma renin activity in hypertensive patients whose blood pressure is too severely elevated for temporary withdrawal of therapy.     

A clinical approach to the management of a patient with suspected renovascular disease who presents with leg ischemia.

Atherosclerotic renal artery stenosis (ARAS) may cause hypertension, progressive renal failure, and recurrent pulmonary edema. It typically occurs in high risk patients with coexistent vascular disease elsewhere. Most patients with ARAS are likely to die from coronary heart disease or stroke before end-stage renal failure occurs. Recent controlled trials have shown that most patients undergoing angioplasty to treat renovascular hypertension still need antihypertensive agents 6 or 12 months after the procedure. Nevertheless, the number of antihypertensive agents required to control blood pressure adequately is lower following angioplasty than for medication alone. Trials assessing the value of revascularization for preserving renal function or preventing clinical events are only in the early recruitment phase. Revascularization should be undertaken in patients with ARAS and resistant hypertension or heart failure, and probably in those with rapidly deteriorating renal function or with an increase in plasma creatinine levels during angiotensin-converting enzyme inhibition. With or without revascularization, medical therapy using antihypertensive, hypolipidemic and antiplatelet agents is necessary in almost all cases.     

Gynecomastia and hypertension

Palpable dense and mobile subareolar tissue in the male breast defines the presence of gynecomastia. For the hypertension specialist, breast enlargement in men provides a clue to a secondary cause of hypertension or an adverse antihypertensive drug reaction. Hyperthyroidism, chronic renal failure, adrenal hyperplasia or tumors, amphetamine, cyclosporine, and anabolic steroids are secondary causes of hypertension associated with gynecomastia. Reserpine, methyldopa, and spironolactone are older drugs associated with gynecomastia; however, calcium antagonists (more commonly), angiotensin-converting enzyme inhibitors, and alpha1 blockers may also be associated with this finding. Treatment is directed to removal of the underlying cause.     

Peptic ulcer and gastritis in uraemia, with particular reference to the effect of Helicobacter pylori infection

AIMS: To determine: (i) the prevalence of histological gastritis and peptic ulcer; and (ii) the clinical features of peptic ulcer, in patients with end-stage renal failure. METHODS: Upper endoscopy was performed by a single observer in 268 patients with end-stage renal failure over a 6-year period. Gastric histology and Helicobacter pylori status were studied in 40 consecutive subjects in whom there were no contraindications for gastric biopsy and who had not used antibacterial drugs in the preceding 4 weeks. As there are only limited data for healthy volunteers in Singapore, 33 age-, sex- and race-matched patients with functional dyspepsia from an earlier drug trial and 18 healthy volunteers who were not age-matched were used as controls. The clinical features of 43 consecutive uraemic patients with peptic ulcer were compared with those of 118 consecutive non-uraemic peptic ulcer patients seen by the same author. RESULTS: Among uraemic patients, histological gastritis was less common, compared with healthy volunteers and functional dyspepsia patients. Helicobacter pylori infection as assessed by histology was also less common among uraemic patients compared with functional dyspepsia patients, but the difference was not statistically significant on serological assessment. Uraemic patients with ulcer had an equal sex ratio, in contrast to a male preponderance among peptic ulcer patients with normal renal function. Uraemic patients with ulcer were more likely to be pain-free, to present with haemorrhage, to have multiple ulcers and postbulbar duodenal ulcers, but were less likely to have H. pylori infection. Among uraemic subjects, the prevalence of H. pylori infection was similar whether or not peptic ulcer was present. CONCLUSIONS: The prevalence of histological gastritis was lower in uraemic patients when compared with patients with functional dyspepsia and healthy volunteers. Peptic ulcers in uraemic subjects have different clinical characteristics from peptic ulcer in non-uraemic subjects.     

2017年ACC/AHA高血压指南对贵阳城区40~79岁不同糖代谢状态人群高血压患病情况的可能影响

目的探讨2017年美国心脏病学会/美国心脏协会(ACC/AHA)指南提出的新的高血压诊断标准下贵阳城区40~79岁不同糖代谢状态人群的高血压患病情况,为高血压的诊断标准及高血压的治疗策略提供线索。方法回顾性分析了中国2型糖尿病患者肿瘤发生风险的流行病学(REACTION)研究贵阳分中心的10140名40~79岁居民,根据糖尿病病史及口服葡萄糖耐量试验结果分为血糖正常组、空腹血糖受损(IFG)组、糖耐量受损(IGT)组、IFG+IGT组、既往诊断糖尿病组及新诊断糖尿病组,计算在美国预防、检测、评估与治疗高血压全国联合委员会第七次报告(JNC 7)及2017年ACC/AHA的高血压指南标准下不同糖代谢状态人群的高血压患病情况。结果在JNC 7标准下,贵阳城区40~79岁血糖正常人群、糖尿病前期人群、糖尿病人群的高血压标准化患病率分别为8.19%、9.57%、8.19%。在2017年ACC/AHA标准下,高血压的标准化患病率分别为20.27%、16.35%、11.59%。相比之下,以血糖正常及IGT人群的高血压患病率增加最为显著。新增的高血压患者共1739例,其中25.8%需应用降压药物治疗。根据2010年第六次人口普查贵州省人口数据,估计贵阳市40~79岁糖尿病前期人群中新增的高血压患者约12.3万人,新增需治疗人数约2.0万人;糖尿病人群中新增高血压患者约6.8万人,新增需治疗人数约2.1万余人。结论2017年ACC/AHA高血压指南会使贵阳市城区40~79岁不同糖代谢状态人群的高血压患病率明显增加,糖尿病及糖尿病前期的高血压人群的需治疗比例也会相当高,社会医疗负担加重。     

The rational use of diuretics in the treatment of arterial hypertension.

The development of modern pharmacologic diuretic agents has revolutionized the therapy of arterial hypertension. The diuretics currently available are easily administered orally, are effective in the presence of alkalosis or acidosis, are non-toxic and have a low incidence of side effects which are readily circumvented or treated. Loop diuretics such as furosemide have the capacity to be effective in patients with diminished renal function or clinical situations that have a powerful stimulus to sodium retention. In clinical circumstances when renal potassium loss is to be prevented such as in patients receiving digitalis, the addition of a potassium-sparing diuretic to either a thiazide or furosemide will achieve the clinical goal of providing an effective diuresis while inhibiting potassium excretion. The mechanism of antihypertensive activity of the diuretic agents appears to be the reduction of extracellular fluid volumes and plasma volumes. Hence, the clinical dictum that to be effective as an antihypertensive agent, diuretics should be administered in diuretic doses. Besides being the cornerstone of initial antihypertensive therapy, diuretics also play an important role in antihypertensive therapy of patients with moderate to severe hypertension who are receiving potent antihypertensive drugs of the vasodilator or sympatholytic class of compounds. Indeed, one of the most important steps in the successful therapy of these patients receiving multiple drugs, is the re-assessment of the diuretic agent. The sodium retention and consequent fluid volume expansion associated with the administration of these potent antihypertensive agents may often cause these patients to develop apparent drug resistance since the thiazide diuretics are not potent enough to counteract the powerful stimulus to sodium retention caused by these antihypertensive agents. The re-evaluation of the diuretic agent at this point will usually necessitate the substitution of furosemide for thiazide or the doubling of the dose of the present loop diuretic. A working knowledge of the physiology of urine formation and the sites of action of currently available diuretic agents will enable the clinician to tailor the diuretic agent to the clinical circumstances of an individual patient and allow the clinician to rationally select a diuretic for the treatment of arterial hypertension.     

The short term effects of oral labetalol in patients with chronic renal disease and hypertension.

This double-blind, controlled, crossover study compared the effects on blood pressure control, glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) of labetalol, methyldopa and placebo in patients with chronic renal disease and hypertension. When compared with placebo, BP was significantly lower during treatment with both labetalol and methyldopa (P greater than 0.05) but did not differ significantly between the two active treatment periods; post-exercise heart rates were also significantly lower on labetalol than placebo (P less than 0.05). After treatment with labetalol, ERPF was significantly greater than with the placebo (P less than 0.05) but did not differ significantly between the active treatments. GFR did not differ significantly between the three groups. No significant differences were observed in haematology or liver function test results on labetalol compared with placebo. Labetalol is a safe and effective antihypertensive in patients with hypertension associated with chronic renal disease. In the short term it leads to an increase in ERPF which may be beneficial for such patients.     

The Use of Diuretics in Varying Degrees of Renal Impairment: An Overview

Administration of diuretics during acute renal failure in animals has been demonstrated to be of value with mannitol and/or loop-blocking diuretics, furosemide or ethacrynic acid. There is evidence that if these drugs are given very early in the controlled experimental environment that there will be some beneficial effect in maintaining renal function. However, in man the temporal relationship between the acute onset and the successful response to the administration of the drugs is, at best, coincidental and the use of diuretics in acute renal failure may not produce the same results as seen in the laboratory. One of the best guides to the underlying disease when there is acute decompensation in renal function is the utility of the renal failure index which utilizes urine and plasma sodium and urine and plasma creatinine ratios.

Large doses of loop-blocking diuretics can be of benefit in patients with mild to moderate chronic renal insufficiency and fluid retention and/or hypertension. When renal insufficiency is severe in the pre-dialysis setting, furosemide, bumetanide or muzolimine may be of some benefit; however, as renal failure worsens the response of the kidney is sluggish and it is wise to begin to dialyze when glomerular filtration deteriorates below 5 ml per minute.     

The effect of treatment on health-related quality of life in patients with hypertension and renal artery stenosis

The quality of life in patients with hypertension is considered to be impaired mainly by side effects of antihypertensive drug therapy. Since balloon angioplasty for renal artery stenosis has a medication-sparing effect, it may lead to an improvement in quality of life. The objective of the study is to compare the effect of antihypertensive drug therapy and balloon angioplasty on quality of life in patients with hypertension and renal artery stenosis. We compared the quality of life in 56 patients randomised to balloon angioplasty to that in 50 patients randomised to antihypertensive drug therapy after 3 and 12 months of follow-up. Quality of life was measured using a questionnaire on physical symptoms associated with hypertension and antihypertensive drugs, and two generic health questionnaires (MOS Survey and EuroQol instrument). After follow-up, the patients who underwent angioplasty used less antihypertensive drugs than the patients who were treated with antihypertensive drugs only (mean+/-s.d., 1.9+/-0.9 vs 2.5+/-1.0 drugs after 3 months, P=0.002). They reported similar physical complaints, however, and a similar quality of life. The results after 12 months of follow-up were the same. In conclusion, for patients with hypertension and renal artery stenosis, the decrease in antihypertensive medication after intervention is too small to lead to a detectable improvement in quality of life.     

Sexual symptoms in hypertensive patients. A clinical trial of antihypertensive medications

The effects of captopril, methyldopa, and propranolol hydrochloride on reported distress over sexual symptoms over a 24-week treatment period were examined as part of a multicenter, randomized, double-blind clinical trial in which 626 men with mild to moderate hypertension participated. On entry into the clinical trial, 58% of patients taking antihypertensive medications and 44% of men not receiving antihypertensive drugs reported distress over one or more sexual symptoms. Among 304 patients treated with monotherapy who completed the trial, total symptoms distress scores of treatment groups did not differ from each other in change from baseline to week 24, but in particular, problems of maintaining an erection were significantly worsened with propranolol therapy. Among 177 patients treated with monotherapy plus a diuretic, total sexual symptoms distress scores worsened among the groups taking methyldopa or propranolol, with significant worsening in all individual symptoms among patients taking propranolol, and problems in maintaining an erection and in ejaculation among patients receiving methyldopa. Among patients treated with captopril plus a diuretic, no change from baseline appeared in scores for any of the sexual symptoms. The findings underline the importance of taking an adequate sexual history and document that selection of antihypertensive drugs may significantly affect the incidence of sexual symptoms.     

Pharmacodynamic effects and clinical use of alpha methyldopa in the treatment of essential hypertension

The availability of decarboxylase inhibitors provides a new biochemical means for controlling blood pressure in patients with diastolic hypertension. The decarboxylase inhibitor, alpha methyldopa, is a potent antihypertensive agent which produces a predominant orthostatic response. The hypotensive action of the drug appears due to peripheral arteriolar relaxation and accompanying reduction in cardiac output. Its ability to reduce renal vascular resistance suggests potential usefulness in the hypertensive patient with renal functional impairment as well.     

Helicobacter pylori and perforated peptic ulcer. Prevalence of the infection and role of non-steroidal anti-inflammatory drugs

AIMS: To study the prevalence of Helicobacter pylori infection in patients with perforated peptic ulcer, to compare it with the prevalence in patients with uncomplicated ulcer, and to assess the role of non-steroidal anti-inflammatory drugs in this prevalence. METHODS: Consecutive patients with perforated peptic ulcer were included in this retrospective study. As a control group, patients undergoing elective outpatient evaluation for the investigation of dyspepsia during the same time period and found to have a peptic ulcer at endoscopy were included. A 13C-urea breath test was carried out in all patients to diagnose H. pylori infection. RESULTS: Sixteen patients with perforated peptic ulcer and 160 with non-complicated peptic ulcer were included. Sixty-two percent of the patients with perforated peptic ulcer were infected by H. pylori, while the microorganism was detected in 87% of the patients without this complication (P = 0.01). Non-steroidal anti-inflammatory drugs intake was more frequent (P = 0.012) in patients with perforated peptic ulcers (56%) than in those without perforation (26%). H. pylori prevalence in perforated peptic ulcers was of 44% in patients with non-steroidal anti-inflammatory drugs intake, but this figure increased up to 86% when only patients not taking non-steroidal anti-inflammatory drugs were considered (P = 0.09). In the multivariate analysis, non-steroidal anti-inflammatory drugs intake was the only variable that correlated with peptic ulcer perforation [odds ratio, 3.6 (95% confidence interval, 1.3-10); P = 0.016]. CONCLUSION: The mean prevalence of H. pylori infection in patients with perforated peptic ulcer is, overall, of only about 60%, which contrasts with the 90-100% figure usually reported in non-complicated ulcer disease. However, the most important factor associated with H. pylori-negative perforated peptic ulcer is non-steroidal anti-inflammatory drugs use, and if this factor is excluded, prevalence of infection is almost 90%, similar to that found in patients with non-perforating ulcer disease.     

Review of Therapeutic Modalities Acting Directly Via Central Pathways

The brain influences arterial pressure through central mediation of a variety of neurotransmitters, including norepinephrine, and translates this action into changes in peripheral autonomic tone. Two opposed adrenergic systems have been described in brain: a hypothalamic pathway in which adrenergic receptor stimulation raises arterial pressure and a brainstem pathway related to the baroreflex arc in which adrenergic receptor stimulation lowers arterial pressure. Antihypertensive drugs with primarily central effects, including clonidine and alpha methyldopa, act as alpha₂ adrenoceptor agonists. The central receptor involved in their antihypertensive action is of the alpha₂ type but is located postsynaptically. Activation of this receptor by either clonidine or alpha methylnorepinephrine, a metabolite of alpha methyldopa, engages the depressor pathway in the brainstem and leads to a decrease in norepinephrine release and a reduction in peripheral sympathetic tone. Clonidine and alpha methyldopa share a similar pattern of peripheral effects, including reductions in preganglionic sympathetic nerve traffic, bradycardia, decreases in plasma renin activity, reductions in blood pressure in the supine position and adverse effects such as depression, sedation and bad dreams. Because of the frequency and severity of these side effects, there is an ongoing search for new centrally acting antihypertensive agents which might be better tolerated.     

Current therapy of hypertension. A pharmacologic approach.

Adequate treatment of hypertension requires that the physician understand the pharmacologic actions of antihypertensive agents. Although no drug is without adverse reactions, it should be possible to choose an agent or combination of agents which can effectively lower blood pressure and be tolerated by the patient. The indications, proposed mechanisms of actions and adverse effects of the following antihypertensive drugs are discussed: thiazide diuretics, spironolactone, triamterene, trimethaphan, Rauwolfia alkaloids. guanethidine, bethanidine, methyldopa, clonidine, pargyline, propranolol, hydrazaline, minoxidil, guancydine, diazoxide and sodium nitroprusside.     

Atherosclerotic renal artery stenosis: Surgery, percutaneous transluminal angioplasty, or medical therapy?

Atherosclerotic renal artery stenosis typically occurs in high-risk patients with coexistent vascular disease elsewhere. Patients with atherosclerotic renal artery stenosis may develop progressive renal failure but have a much higher risk of dying of stroke or myocardial infarction than of progressing to endstage renal disease. Recent controlled trials comparing medication to revascularization have shown that only a minority of such patients can expect hypertension cure, whereas trials designed to document the ability of revascularization to prevent progressive renal failure are not yet available. Revascularization should be undertaken in patients with atherosclerotic renal artery stenosis and resistant hypertension or heart failure, and probably in those with rapidly deteriorating renal function or an increase in plasma creatinine levels during angiotensin converting enzyme inhibition. With or without revascularization, medical therapy using antihypertensive agents, statins, and aspirin is necessary in almost all cases.     

Indapamide is superior to thiazide in the preservation of renal function in patients with renal insufficiency and systemic hypertension

The long-term effects of indapamide or hydrochlorothiazide on blood pressure and renal function were examined in patients with impaired renal function and moderate hypertension. Both drugs controlled hypertension and blood pressure remained normal during the 2 years of the study. Despite this comparable control of hypertension, indapamide therapy was associated with a 28.5 ± 4.4% increase in creatinine clearance, whereas treatment with hydrochlorothiazide was associated with a 17.4 ± 3.0% decrease in creatinine clearance. The results of the study indicate that indapamide is superior to hydrochlorothiazide in the treatment of patients with impaired renal function and moderate hypertension.     

Ambulatory blood pressure during diseases of the kidney.

During the last few years there has been a renewal of interest in blood-pressure-induced kidney damage due to a progressive increase in the incidence and prevalence of hypertension and vascular diseases as a cause of end-stage renal disease (ESRD). The need to prevent ESRD demands a continuation of effort to make the early identification of hypertensives who are at risk possible and to provide them with effective antihypertensive therapy. Since ambulatory blood pressure monitoring has been used successfully to assess blood pressure and identify risk markers for cardiovascular diseases, a logical approach would be to use it also to identify the risk markers for ESRD. Higher than normal percentages of non-dippers have been found among subjects with renal failure, during dialysis (haemofiltration, peritoneal dialysis and continuous ambulatory peritoneal dialysis), among cases of renovascular hypertension or cystic kidney disease and among cases of renal transplantation. Although this non-dipping pattern might be related to the presence of severe hypertension in some patients, such as those who have renovascular hypertension, in other cases the abnormal circadian variability is present with milder forms of hypertension or even in the absence of hypertension. Monitoring ambulatory blood pressure could offer advantages for protection of renal function during antihypertensive treatment of subjects with mild renal insufficiency. Furthermore, ambulatory blood pressure monitoring seems to have been prognostic for the development of proteinuria in a group of refractory hypertensives. Whether higher than normal nocturnal blood pressures and the non-dipping pattern are causes or consequences of renal disease should be addressed in prospective studies. The above notwithstanding, assessment of nocturnal blood pressure seems to be an important aid in the management of patients with hypertension-related renal disease and of patients who are susceptible to developing it.