Renovascular disease in the elderly: an analysis of 50 patients.

Fifty patients, 65 years of age or older, with renovascular disease were evaluated and treated between 1979 and 1981. Twenty-one patients were treated medically, 21 surgically and 8 with percutaneous transluminal angioplasty of the renal arteries. The age, sex, target organ involvement, initial blood pressure and serum creatinine were similar among the three groups. Sixty-six percent of the medical group demonstrated lower blood pressure. Ninety percent of the surgical group demonstrated a cure or improved blood pressure, and 43% of the patients with percutaneous transluminal angioplasty had improved blood pressure. Renal function deteriorated in 50% of the medical group, 19% of the surgical group and 25% of patients in the percutaneous transluminal angioplasty group. There was one operative death in the surgical group and one death related to percutaneous transluminal angioplasty. The data demonstrate that old age itself is not a contraindication to surgery. If hypertension is resistant to medical therapy, if the patient experiences undesirable side effects from the medications or if renal function is jeopardized, surgical therapy should be considered. More experience with percutaneous transluminal angioplasty is necessary to determine its precise role in managing atherosclerotic renal vascular disease in the elderly.

Dilevalol in severe hypertension. A multicenter trial of bolus intravenous dosing.

Dilevalol, the R-R optical isomer of labetalol, a nonselective beta-antagonist with vasodilation from selective beta 2 agonism, was administered in sequential multiple bolus intravenous injections of 10 to 100 mg in total doses ranging from 35 to 585 mg (mean dose, 414 mg) to 101 patients with supine diastolic blood pressures above 120 mm Hg. Mean blood pressure was reduced from 200 (+/- 3)/129 (+/- 1) mm Hg to 149 (+/- 2)/101 (+/- 1) mm Hg, a mean reduction of 51/28 mm Hg. The therapeutic goal was established as a reduction in supine diastolic blood pressure to less than 100 mm Hg or a reduction of at least 30 mm Hg. This was achieved in 62 (61%) of 101 patients, with an additional 7 patients having a final supine diastolic blood pressure of 100 mm Hg. Treatment with dilevalol was less successful in black male patients than in the group at large. There was a tendency for older patients to respond better than younger patients. Prior recent treatment of patients with beta-adrenergic antagonists decreased the effectiveness of the drug. Significant orthostatic hypotension was not noted. Sixty-four patients were transferred to oral dilevalol treatment in combination with a diuretic, and blood pressure in this group averaged 160/100 mm Hg after 1 month of therapy. Dilevalol appears to be a safe and effective drug that can be used intravenously successfully in the majority of patients with severe hypertension and provides an alternative to therapy with other agents. It also is a useful agent for oral treatment of these patients after successful intravenous therapy.

The patient with resistant hypertension. Cations, volume, and renal factors.

Hypertension that is truly resistant to modern antihypertensive therapy is uncommon. In the majority of cases, apparent resistance is more likely associated with poor patient adherence, interacting drugs, drug interactions, and inappropriate drug dosages. Sodium and fluid volume play a major role in resistant hypertension. There is considerable evidence to support the role of dietary sodium restriction in successful nonpharmacological treatment of hypertension. Salt sensitivity in humans appears to represent at least one factor determining individual susceptibility to variable salt intakes. Sodium and water retention may lead to refractoriness to many antihypertensive agents, and there is evidence to suggest that extracellular fluid volume expansion also plays a role in many hypertensive patients. While retention of sodium and water is well established early in patients with renal parenchymal disease, hypertension associated with progression of renal parenchymal disease is complicated by other factors that include interactions between hemodynamic and humoral factors, functional changes in adrenergic responses, and structural vascular disease. The role of other cations such as potassium, calcium, and magnesium in resistant hypertension has yet to be established.

Clinical implications of primary aldosteronism with resistant hypertension.

Twenty-eight patients with resistant hypertension were found to have primary aldosteronism; 25 had solitary adenoma and 3 had adrenal hyperplasia. All were severely hypertensive despite receiving three or more antihypertensive agents, including conventional doses of diuretics, sympatholytics, and vasodilators. Hypervolemia (24 patients) or normovolemia (2 patients) despite severe diastolic hypertension was the hallmark in 26 patients. Adequate salt and water depletion alone with spironolactone (200 mg/day) and hydrochlorothiazide (50-100 ng/day) reduced arterial pressure in all. Twenty-two patients had surgical removal of a solitary adenoma. Over 1 to 2 years of follow-up, 13 were normotensive without medication, and six required hydrochlorothiazide and three hydrochlorothiazide plus a beta-blocker to normalize blood pressure. Blood pressure response to surgery had no relation to either duration or severity of hypertension. Six patients (three with hyperplasia, three with adenoma) have continued diuretic therapy and are normokalemic and normotensive. These results indicate that primary aldosteronism can be associated with sever and drug-resistant hypertension, that maintained hypervolemia is the reason for resistance to therapy, that sustained volume depletion is the most important therapeutic goal for these patients, and that cure can be achieved despite prolonged and severe hypertension.

Blood pressure regulation in pheochromocytoma.

Two sets of studies were performed in 13 patients with proved adrenal pheochromocytoma to test the hypothesis that the sympathetic nervous system (SNS) is active and might contribute to the hypertensive state. Similar studies were performed in 15 additional patients considered to have essential hypertension. In the first set, 13 patients with pheochromocytoma were subjected to head-up tilt to assess the activity of the SNS. This maneuver decreased diastolic blood pressure in only two; heart rate increased appropriately in all except one. Changes in plasma norepinephrine (NE) were variable and did not correlate with changes in blood pressure (BP) and heart rate (HR). In the second set, 10 patients with pheochromocytoma were given a single oral dose of clonidine (0.3 mg) to evaluate what role, if any, the SNS might contribute to the hypertensive state. Fifteen patients with essential hypertension were studied similarly for comparison. Clonidine produced significant decreases in BP and HR but left plasma renin activity unchanged in both groups. In essential hypertension, the cardiovascular responses were accompanied by significant reductions in plasma NE. By contrast, plasma NE was unchanged in patients with pheochromocytoma, despite similar reductions in BP and HR. These results suggest that the sympathetic reflexes are intact in pheochromocytoma, and that much of the hypertension associated with these tumors may be related to increased sympathetic activity.

Early hemodynamic and humoral effects of lofexidine.

Hemodynamic and humoral effects of lofexidine were assessed in 11 patients with essential hypertension after a total of 1.5 mg were given orally over 24 hr. Heart rate (bpm) slowed (-12 +/- 6 [SEM], p less than 0.05) and cardiac output (liters per minute) was reduced (-0.78 +/-0.18, p less than 0.01) irrespective of blood pressure response; the latter was related to changes in systemic resistance (TPR) (r = 0.72, p less than 0.01). Cardiac performance judged from ejection fraction (0.61 +/- 0.03 to 0.59 +/- 0.03, NS) and mean transit time (8.73 +/- 0.53 sec to 9.20 +/- 0.35, NS) were not altered. Plasma volume was expanded more than 10% in two patients but not changed in the others. Supine plasma catecholamines determined in five patients were reduced in all but one with no correlation to changes in either TPR or diastolic blood pressure. On the other hand, there was an increase in plasma catecholamines during head-up tilt in four of five patients, indicating normal catecholamines release. Orthostatic hypotension occurred de novo in three patients; two of them had simultaneous slowing of heart rate (vasovagal attack). Results suggested that reduction of blood pressure by lofexidine depended on lack of increase in TPR in response to reduction of cardiac output; the hemodynamic pattern of this centrally acting adrenergic blocker closely resembled that reported for beta blockers.

The changing clinical spectrum of primary aldosteronism.

In a prospective study of 80 patients with primary aldosteronism (70 with adenoma and 10 with hyperplasia), "refractory" hypertension, hyperkinetic circulation, and hypovolemia were frequent occurrences. We found that measurements of serum potassium concentration and plasma renin activity were inadequate screening tests because of high rates of false-positive and false-negative results. The demonstration of excessive aldosterone production after three days of salt loading provided the best sensitivity (96 percent) and specificity (93 percent) in identifying patients with primary aldosteronism. Severe, persistent hypokalemia, increased plasma 18-hydroxycorticosterone values, and an anomalous postural decrease in the plasma aldosterone concentration, when present, provided the best indicators of the presence of an adenoma. Of three localizing procedures (selective adrenal venography, adrenal computed tomographic scan, and adrenal venous sampling for plasma aldosterone concentration) the measurement of adrenal venous plasma aldosterone concentration yielded 100 percent accuracy. These results indicate a wider clinical spectrum in primary aldosteronism than previously described. They also show that nonsuppressible aldosterone production is its most important diagnostic hallmark and the single best diagnostic screening procedure, and that adrenal venous sampling for plasma aldosterone concentration remains the most precise technique for identification and localization of tumors.

Light chain nephropathy.

In 13 specimens of renal tissue from 11 patients, deposits of monoclonal immunoglobulin light chains and continuous granular electron-dense material within tubular basement membranes and in association with the glomerular basement membrane were identified. All but one patient were men n the fifth to seventh decades of life, and each presented with azotemia and features of glomerular rather than tubulointerstitial disease. Osteolytic bone lesions occurred in only three patients, and a bone marrow plasmacytosis greater than 30 percent consistent with plasma cell myeloma was identified in only four patients. Light chain distribution in the nephron was confirmed with immunoelectron microscopy and was not associated with deposition of other serum proteins such as immunoglobulin heavy chains, complement, transferrin, alpha 2 macroglobulin and albumin. The electron dense deposits differed in distribution and character from those associated with membranoproliferative glomerulonephritis type II (dense deposit disease), amyloidosis, cryoglobulinemia, macroglobulinemia and benign monoclonal gammopathy. Serum from six of these patients did not bind to normal human or rat renal parenchyma in vitro. Kappa light chain nephropathy was characterized by predominant linear tubular basement membrane kappa deposits, and nodular mesangial and linear glomerular basement membrane kappa immunostaining. Lambda light chain nephropathy was characterized by linear lambda glomerular basement membrane and tubular basement membrane immunostaining. Manifestations of glomerular dysfunction dominated the clinical presentation of light chain nephropathy, and most patients did not have typical features of multiple myeloma. The diagnosis was predicated upon thorough immmunohistologic assessment of renal biopsy material.

Intravenous labetalol in the treatment of severe hypertension and hypertensive emergencies.

The antihypertensive effects of intravenous labetalol were evaluated in 59 patients with hypertensive crises or severe hypertension in need of rapid lowering of blood pressure in a multicenter study. Patients appearing with a supine diastolic blood pressure 125 mm Hg or greater, or a supine systolic blood pressure of more than 200 mm Hg received an initial mini-bolus injection (20 mg) of labetalol. This was followed by repeated incremental doses of 20 to 80 mg given at 10 minute intervals to achieve a supine diastolic blood pressure of less than 95 mm Hg or decrease 30 mm Hg or greater, or a satisfactory decrease in systolic blood pressure. Patients were stratified into those who had taken antihypertensive medication within 24 hours and those who had not. The initial mini-bolus injection caused rapid but not abrupt reduction in blood pressure; the baseline mean blood pressure decreased 23/14 mm Hg. Further injections were needed in the majority of patients (mean: 197 mg). The blood pressure reduction after the last dose of labetalol was 55/33 mm Hg. In pretreated patients and in those who had no medication for 24 hours prior to the intravenous labetalol, the response was similar. Heart rate decreased 10 beats per minute in the total population. In patients pretreated with beta-adrenergic blockers, blood pressure response was similar to that in the total group (59/35 versus 55/33 mm Hg), but heart rate remained essentially unchanged. The dose required to achieve the therapeutic effect was less in pretreated patients than in untreated patients, but the duration of action was shorter. No serious adverse effects were encountered even in patients with concomitant diagnoses of acute left ventricular failure, myocardial infarction, stable congestive heart failure, atrial fibrillation, angina pectoris, acute stroke, transient ischemic attack or encephalopathy. Labetalol is a safe and effective treatment for a rapid blood pressure reduction in hypertensive emergencies.

A critical look at survival of diabetics with end-stage renal disease. Transplantation versus dialysis therapy.

The survival of 100 consecutive patients with diabetic nephropathy after treatment with hemodialysis, peritoneal dialysis, or renal transplantation was reviewed at our institution from 1976 to 1982. Standard actuarial survival analysis revealed an overall survival of 83% and 61% at one and two years, respectively. Coronary angiography was used as a screening procedure for renal transplantation. In the dialysis group, 27 patients were considered acceptable transplant candidates on the basis of the coronary angiography but were not transplanted for other reasons. When the survival analysis was limited to those "transplant candidates" the survival rates were 78%, 51%, and 8% at 1, 2, and 5 years, respectively. In comparison, survival after transplantation was 81%, 67%, and 45%, at 1, 2, and 5 years, respectively. In order to eliminate bias, survival comparisons were subsequently made using the Cox Proportional Hazard Model to take into account the time the transplant patients spent on dialysis prior to renal transplantation. When this analysis was performed, there was no significant difference in survival between transplantation and dialysis for the first two years, but overall survival after five years was significantly better after renal transplantation even when the comparison was limited to acceptable transplant candidates who remained on dialysis (P = .04). Survival for patients with significant coronary disease (greater than 70% stenosis of a coronary vessel or moderate to severe left ventricular dysfunction) was analyzed according to therapeutic modality. Although overall prognosis was poor in this group as a whole (1, 2, and 5 year survivals were 76%, 45%, and 19%, respectively), the cardiac patients had a trend to better survival after renal transplantation than when maintained on dialysis (P = .22). In addition to other factors such as quality of life, rehabilitation, and progression of other diabetic complications, the benefit of renal transplantation on patient survival must be considered when deciding between renal transplantation and maintenance dialysis therapy for diabetic patients with renal failure.

Mechanism of antihypertensive action of dilevalol compared with that of "cardioselective" beta-blocking agents.

The hemodynamic effects of dilevalol, a nonselective beta-adrenergic blocking agent with vasodilating properties, were evaluated in 34 hypertensive patients and compared with those of the "cardioselective" beta blockers atenolol and metoprolol in 21 patients. Hemodynamic measurements were obtained at baseline, after acute treatment (first dose) with dilevalol (400 mg) and atenolol (50 mg) or metoprolol (100 mg), and again after subchronic treatment with these agents. After both acute and subchronic treatment (mean daily dose 1,042 mg), dilevalol significantly reduced mean arterial pressure (MAP, p less than 0.0001), by significantly reducing systemic vascular resistance index (SVRI, p less than 0.001), and by not significantly altering cardiac index (CI). In contrast, atenolol and metoprolol significantly reduced MAP (p less than 0.002) by significantly reducing CI (p less than 0.0001), with a concomitant increase in SVRI (p less than 0.007). Heart rate (HR) was reduced significantly less (p less than 0.006) with dilevalol than with the cardioselective agents. Correlation of the decrease in MAP with other hemodynamic parameters revealed that the effects on MAP of acute treatment with the cardioselective drugs are related to a decrease in HR (r = 0.63, p = 0.002), whereas those of subchronic treatment are correlated to a decrease in CI (r = 0.59, p = 0.01). The decrease in MAP after acute and subchronic dilevalol treatment is correlated primarily with SVRI (r = 0.46 to 0.49, p less than 0.01) and only secondarily with HR (r = 0.34, p less than 0.05). Therefore, the main mechanism of antihypertensive action for dilevalol is vasodilation, in contrast to the cardioselective agents, which is beta blockade.

Celiprolol in systemic hypertension.

The safety and efficacy of orally administered celiprolol, a new beta 1-selective adrenergic blocking drug with peripheral beta 2-agonist properties, were assessed in 91 patients with mild to moderate systemic hypertension (supine diastolic blood pressure [BP] 95 to 114 mm Hg without medication) using a placebo-controlled, double-blind, randomized, titration-to-effect study design. All patients received placebo for 4 weeks and were then randomized to receive placebo (n = 46) or once-daily celiprolol (n = 45), which was titrated every 2 weeks (200, 400, 600 mg/day) over a 6-week period to achieve a reduction in supine diastolic BP to less than or equal to 90 mm Hg. Plasma lipids and lipoproteins were also assessed at baseline, during placebo and after randomization to active therapy in a subgroup of patients. Compared with placebo, celiprolol reduced supine and standing BP (reduction of supine BP -0.4/-2.1 mm Hg with placebo, -5.7/-6.4 with celiprolol, p less than 0.05; reduction of standing BP -1.7/-1.0 with placebo, -7.2/-4.9 with celiprolol, p less than 0.05). Supine heart rate was reduced by 6.8 beats/min with celiprolol compared with 2.0 beats/min with placebo (p less than 0.05). No differences were seen when the effects of placebo and celiprolol on plasma lipoproteins were compared. Celiprolol is a safe, effective and well tolerated once-daily antihypertensive drug and has no detrimental effects on plasma lipids.

Abdominal bruits in renovascular hypertension.

A study of 87 patients surgically treated for renal arterial stenosis revealed that upper abdominal bruits were heard more frequently in patients whose stenosis was due to fibrous disease than to atherosclerosis. A diastolic bruit in a patient with fibrous disease of the renal artery usually indicated a favorable surgical result. Conclusions regarding the prognostic value of diastolic bruits in atherosclerotic renal artery disease must be deferred until a larger number of patients with this finding can be studied. When hypertension of less than 3 year's duration was combined with presence of a diastolic bruit, 17 or 18 patients had a favorable surgical outcome. An abdominal bruit should be carefully sought for in all patients evaluated for hypertension; when found, should be characterized acurately, because of the important diagnostic and prognostic information it may provide.

The diagnostic dilemma: a clinician's viewpoint.

The prevalence of renovascular hypertension appears to be increasing, particularly in older patients with generalized arteriosclerosis, hypertension and impaired renal function. While clinical clues remain extremely useful in identifying patients at increased risk, older screening tests have been largely abandoned in favor of angiographic methods that provide visual identification of renal artery lesions. Renal scintigraphic techniques, with or without angiotensin-converting enzyme (ACE) inhibition, offer the potential for providing accurate measurements of renal function, and may be particularly useful in identifying critical renal arterial stenosis. In assessing the future role of scintigraphy, careful clinical validation of these correlations will be necessary, as will determinations of their usefulness in patients with renal insufficiency and those with bilateral renal artery stenosis. The role of adrenal scintigraphy in the localization of adrenal tumors is also reviewed. Their cost-effectiveness, limitations in sensitivity and specificity compared to current diagnostic technologies, and potential applications are discussed.

Current management of hypertensive emergencies.

A number of potent and rapidly acting pharmacological agents are available to achieve safe, rapid, and controlled blood pressure reduction in most hypertensive crises. While sodium nitroprusside remains the drug of choice in many hypertensive emergencies, several newer agents are now available that may prove to be acceptable alternatives in the management of certain cases. Glyceryl trinitrate (nitroglycerin) and labetalol may be advantageous in patients with significant coronary artery disease. When adequate facilities to monitor continuous infusion of sodium nitroprusside are not immediately available, the intermittent minibolus administration of diazoxide or labetalol or the use of sublingual or oral nifedipine prove useful. A thorough knowledge of the pharmacological properties and proper indications of the currently used agents is essential for optimum management of the critically ill hypertensive patient.

Captopril-induced cough.

Since the advent of angiotensin-converting enzyme inhibitors (captopril and enalapril), cough has been recognized sporadically as a side effect, but has received little attention in the pulmonary literature. To emphasize that angiotensin-converting enzyme (ACE) inhibitors should be considered among possible etiologies of cough, we report recent experience with two patients and review the available experience with ACE inhibitor-induced cough.

The diagnosis of renovascular hypertension. A clinician's viewpoint.

The sensitivity and specificity of screening and diagnostic studies for renovascular hypertension has been the focus of debate and disappointment for many years. The use of these studies has been further restricted by the insistence of clinicians that studies provide visual identification of the anatomy of the renal vasculature. Digital subtraction angiography continues to provide an increasingly attractive alternative offering visualization of the renal arteries. Reevaluation of screening and diagnostic studies is needed to determine their potential value, particularly in patients with atherosclerotic renovascular disease and renal insufficiency and in assessing the potential salvability of the ischemic kidney.

Differential effects of morning and evening dosing of nisoldipine ER on circadian blood pressure and heart rate.

The time of administration of once-daily antihypertensive agents may have a significant impact on blood pressure control during awake and sleep periods. Using 24-h ambulatory monitoring, we compared the effects of morning and evening dosing of the long-acting dihydropyridine calcium channel blocker, nisoldipine extended-release (ER), on circadian blood pressure (BP) and heart rate in patients with mild-to-moderate hypertension. After completing a 3-week placebo run-in period, 85 patients were randomized to morning versus evening nisoldipine ER treatment at a fixed 20-mg dose. Patients were treated for 4 weeks, followed by crossover to the alternate dosing regimen for 4 additional weeks. Twenty-four-hour ambulatory monitoring was performed at baseline and at 4 and 8 weeks after randomization. Awake and sleep times were determined by electronic activity recorders (Actigraphy). Similar least-squares (+/-SE) mean changes from baseline in 24-h BP (systolic BP/diastolic BP: -11.9/-7.4 +/- 0.6/0.5 v -11.6/-6.5 +/- 0.6/0.5 mm Hg) and heart rate (1.0/1.7 +/- 0.4/0.4 beats/min) occurred with morning and evening administration, respectively. A significantly greater effect on awake diastolic BP (systolic BP/diastolic BP: -12.6/-8.1 +/- 0.7/0.4 v -11.3/-6.4 +/- 0.7/0.4 mm Hg; P = .16/.01) was observed with morning dosing compared with evening dosing. In addition, small increases in sleep and early morning heart rate were seen with evening compared with morning administration of nisoldipine (sleep, 3.1 +/- 0.4 v 0.4 +/- 0.4 beats/min; P < .001; early morning, 3.5 +/- 0.7 v 0.5 +/- 0.7 beats/min; P = .002). These differential effects on awake BP and sleep heart rate were also observed in patients who had normal (dippers) and elevated (nondippers) BP values during sleep. Appropriate evaluation of the efficacy and safety of long-acting antihypertensive agents is essential when evening administration is being considered. In the present study, the timing of nisoldipine ER administration had no effect on mean changes in BP and heart rate over a 24-h period. However, nisoldipine ER had some differential effects during sleep and awake periods with morning relative to evening dosing.

Membranous glomerulonephritis associated with industrial mercury exposure. Study of pathogenetic mechanisms.

The nephrotoxicity associated with mercury may be manifested as either acute tubular necrosis or an immune complex glomerulonephritis, depending upon the conditions under which the patient is exposed to the metal. Two patients with industrial exposure to mercury developed the nephrotic syndrome due to membranous glomerulonephritis. A multidisciplinary approach was used to define more precisely the pathogenetic mechanisms involved in the production of the glomerular lesion. Although glomeruli were normal by light microscopy, immunohistochemical studies demonstrated confluent finely granular epimembranous deposits of IgG and C3. This distribution was confirmed at the ultrastructural level with immunoelectron microscopy. High resolution elemental analysis of electron dense inclusions in tubular epithelial phagolysosomes demonstrated energy dispersion spectra characteristic of coexisting mercury and selenium. Eluates from the biopsy material were not immunoreactive against normal rat or human kidney. There was no immunoreactivity of epimembranous deposits with antibodies having renal tubular epithelial antigen or urinary uromucoid specificity. These observations suggest that a distinctive immunopathologic lesion is associated with mercury-associated membraneous glomerulonephritis, that the role of the metal itself may only be coincidental, and that the involved antigen remains unknown. Prednisone therapy had no documented persistent beneficial influence upon the level of proteinuria in one patient who has been lost to follow-up. In one patient not treated with steroid therapy, withdrawal of exposure to the metal resulted in disappearance of mercury from body fluids and clinical remission.

Comparison of labetalol and hydrochlorothiazide in elderly patients with hypertension using 24-hour ambulatory blood pressure monitoring.

The safety and efficacy of labetalol and hydrochlorothiazide (HCTZ) were compared in a group of 34 patients aged 65 years or older with mild to moderate essential hypertension. After a 4-week placebo run-in period, during which all previous antihypertensive medication was discontinued, patients were randomized to receive either labetalol (100 mg bid) or HCTZ (25 mg bid). The patients' blood pressure and heart rate were evaluated biweekly and drug dosage was titrated (up to 400 mg and 50 mg bid of labetalol and HCTZ, respectively) to achieve a standing diastolic blood pressure less than 90 mm Hg. Patients underwent 24-hour ambulatory blood pressure monitoring at the end of the placebo run-in period and again after the 6-week titration period. Both labetalol and HCTZ significantly (P less than .01) reduced standing systolic (-19.4 vs -27.7 mm Hg) and diastolic (-14.0 vs -15.2 mm Hg) blood pressures following 12 weeks of treatment. Both antihypertensives effectively controlled the 24-hour ambulatory blood pressure, however, the labetalol group experienced a significantly lower rate of rise in diastolic blood pressure (P = .02) and mean arterial pressure (P = .02) during the acceleration period (400-1200) compared to the HCTZ group. HCTZ caused significant decreases in serum potassium (P less than .01) and alkaline phosphatase (P less than .05) and increases in uric acid (P less than .01) and urea nitrogen (P = .07). These results indicate that labetalol may offer some unique advantages over thiazide diuretics that may be particularly important in the treatment of elderly patients with hypertension.