Edward T. Zawada

Comparison of hydrochlorothiazide and sustained-release diltiazem for mild-to-moderate systemic hypertension.

The safety and efficacy of sustained-release diltiazem, 120 to 180 mg twice daily, was compared with those of hydrochlorothiazide, 25 to 50 mg twice daily, in 207 patients with mild-to-moderate hypertension (supine diastolic blood pressure [BP] 95 to 114 mm Hg) using a baseline, placebo, parallel-design study protocol. All patients received placebo for 2 to 4 weeks, followed by either study drug during the double-blind phase, titrated over 8 weeks to achieve a goal of supine diastolic BP reduction of at least 10 mm Hg and/or a diastolic BP of less than 90 mm Hg. Patients not achieving the treatment goal with either drug alone received the other drug in combination. Both drugs produced significant decreases in supine and upright BP throughout the 26-week study. The magnitude of decrease in mean supine diastolic BP was similar for both drugs as monotherapy at week 14 (-11.4 and -12.1 mm Hg, respectively). Hydrochlorothiazide produced significantly greater reductions at week 14 in mean supine systolic BP than sustained-release diltiazem (-19.5 and -12.7 mm Hg, respectively). The difference in mean supine diastolic BP reduction with the 2 drugs diminished when hydrochlorothiazide (50 mg/day) was compared with sustained-release diltiazem. The BP effects were sustained for 6 months with both drugs. The 2 drugs appeared to lower BP more in patients older than 60 years and more in black than in white patients. The combination of the 2 drugs decreased supine diastolic BP to goal levels in about 56% of the patients not achieving goal with either drug alone. Adverse effects were minimal with either drug alone and in combination, except for hypokalemia, which increased with thiazide alone and in combination.

Clinical Course of Patients with Scleroderma Renal Crisis Treated with Captopril

Since it has been suggested that the renin-angiotensin axis may play an important role in the severe hypertension and in the acute renal deterioration in scleroderma, we sought to determine the effectiveness of angiotensin blockade in the treatment of this disorder. Captopril controlled blood pressure successfully and easily in 4 consecutive patients with scleroderma renal crisis. Mean serum creatinine was 3.5 mg/dl after scleroderma renal crisis immediately prior to captopril. The first patient required maintenance hemodialysis because of progression to advanced renal failure before captopril was available. However, in this patient oliguric renal failure was changed to nonoliguric renal failure immediately after beginning therapy. Serum creatine stabilized in the other 3 patients. Serum creatinine peaked at 4.7 mg/dl, but then progressively improved to 3.5 mg/dl 12 weeks after captopril was begun. None of the other 3 patients required any form of dialysis during the scleroderma renal crises. Mean survival of these 4 patients was significantly greater than that of the 9 previous patients with scleroderma crisis. These observations confirm that angiotensin blockade with captopril is effective therapy to prevent renal deterioration, to control blood pressure and prolong survival in scleroderma patients with renal crisis.

Hyponatremia in spinal cord injury.

Hypoosmolar hyponatremia (serum Na+ less than 130 mmol/L) has proven a common and incompletely explained phenomenon in the spinal cord injured patient. When present, it has generally been preceded by excessive fluid intake and environmental/dietary factors which reversibly restrict free water excretion. We have attempted to more fully characterize the determinants of SCI-associated hyponatremia by retrospectively analyzing its features and treatment response in a series of 14 hyponatremic SCI patients. In most instances, hyponatremia could be attributed to uncontrolled fluid intake in the presence of an acute or semiacute illness and thus stimuli for non-osmotic releases of arginine vasopressin. Treatment measures generally included administration of 3% saline, with all patients recovering uneventfully from their episode of hyponatremia.

Renal Parenchymal Malakoplakia Presenting as Acute Oliguric Renal Failure

A 47-year-old chronic alcoholic white male with previously normal renal function and no prior history of urinary tract infection developed the sudden onset of fever, bilateral flank pain, oliguria, and deterioration of renal function. Subsequent workup revealed massive pyuria, bilaterally enlarged kidney, and positive urine and blood cultures for E. coli. In spite of successful treatment with appropriate antibiotics and gradual improvement of the patients clinical status, pyuria and renal failure persisted, necessitating institution of hemodialysis. 8 weeks after admission a renal biopsy revealed renal parenchymal malakoplakia.

Blood pressure lowering and potassium conservation by triamterene-hydrochlorothiazide and amiloride-hydrochlorothiazide in hypertension.

Effects of once‐daily doses of 50 mg triamterene with 25 mg hydrochlorothiazide and 5 mg amiloride with 50 mg hydrochlorothiazide were compared in a randomized, multicenter study of 84 adult subjects with mild to moderate hypertension (diastolic blood pressure 90 to 114 mm Hg). After a 3‐wk placebo lead‐in period, the subjects entered a 6‐wk treatment period. The two drug regimens were compared with respect to antihypertensive effects and effects on serum potassium and magnesium levels during the final week of drug therapy, with the use of the last week of placebo therapy as a covariate. Both drug regimens substantially reduced mean supine systolic and diastolic blood pressures to well within normal limits; there was no significant difference between the two groups. Twenty‐four of the 41 subjects receiving triamterene‐hydrochlorothiazide (59%) and 29 of the 43 patients receiving amiloride‐hydrochlorothiazide (67%) had diastolic blood pressure <90 mm Hg at week 9. Five subjects receiving amiloride‐hydrochlorothiazide (12%) and two subjects receiving triamterene‐hydrochlorothiazide (5%) had hypokalemia (serum potassium level <3.5 mEq/l) at week 9. The average decrease in serum potassium levels during amiloride‐hydrochlorothiazide therapy (−0.33 ± 0.08 mEq/l) was greater than that after triamterene‐hydrochlorothiazide (−0.08 ± 0.07 mEq/l). Serum magnesium levels were not changed by either regimen. Weight loss was greater in the amiloride‐hydrochlorothiazide group than in the triamterene‐hydrochlorothiazide group. It is reasonable to assume that the greater potassium loss during amiloride‐hydrochlorothiazide therapy than during triamterene‐hydrochlorothiazide therapy was a consequence of the larger dose of hydrochlorothiazide in the former (50 mg) compared with the latter (25 mg). Although the effect on lowering blood pressure by amiloride‐hydrochlorothiazide was slightly greater than that by triamterene‐hydrochlorothiazide (also consistent with the larger dose of hydrochlorothiazide), the difference was small and not significant. Triamterene‐hydrochlorothiazide at low doses is effective in the treatment of hypertension.

Hemodialysis. Basic principles and practice.

Hemodialysis removes uremic toxins and excess fluid from the blood by diffusion dialysis and ultrafiltration. The efficiency of this process depends on the size, shape, and type of semipermeable membrane used in the hemodialyzer. Although the hollow-fiber kidney remains popular, the parallel-plate hemodialyzer is reestablishing itself, partly because it can use newer types of membranes. With newer membranes, ultrafiltration can be performed without diffusion dialysis, which appears to have important clinical advantages. The dialysate bath used in the hemodialyzer resembles plasma water in composition, with electrolytes added to compensate for abnormalities of end-stage renal disease. Although the technical problems of hemodialysis have been largely overcome, an accurate, easy-to-use method of evaluating the adequacy of the hemodialysis prescription has yet to be devised.

Prostaglandin E2 excretion in spinal cord injury patients.

Hyponatremia has proven to be a common finding in spinal cord injured (SCI) patients. Mechanisms exist whereby SCI patients with either normal or impaired renal function may develop it. One such mechanism may be an impairment in prostaglandin (PGE2) excretion resulting in unopposed activity of antidiuretic hormone (ADH). Paired 24-hour urine collections for PGE2 were collected from SCI patients with varying degrees of renal dysfunction. There was a wide interpatient variability in the excretion of PGE2, with no significant correlation of PGE2 excretion in respect to either urine volume, urine sodium concentration, or the degree of renal dysfunction.