Minoxidil, nadolol, and a diuretic. Once-a-day therapy for resistant hypertension.

We tested a once-a-day antihypertensive regimen using minoxidil, nadolol, and a diuretic in 55 patients with resistant hypertension. Forty-seven patients had evidence of end-organ damage. Twelve had mild renal insufficiency (serum creatinine concentration, 2.5 +/- 0.3 mg/dL). In 34 patients, treatment with nadolol and a diuretic was started with minoxidil added one to four weeks later. In the remainder, minoxidil, nadolol, and a diuretic were begun simultaneously because of severe hypertension. Initial supine and standing blood pressure (BP) in the 55 patients were 186 +/- 4/111 +/- 2 and 180 +/- 4/108 +/- 2 mm Hg, respectively. After 7 +/- 1 weeks, BP was controlled in 46 patients (84%) with the supine and standing BP reduced to 140 +/- 3/80 +/- 1 and 134 +/- 3/80 +/- 1, respectively. In six patients, BP was controlled but intolerable side effects occurred, making the regimen therapeutically successful in 40 patients (73%). The BP remained controlled during a follow-up of 43 +/- 5 weeks. In 31 patients, BPs measured 24 hours after the last dose were not different from random measurements. Mean serum creatinine levels remained stable in the 12 patients with renal insufficiency.

Comparison of nifedipine and propranolol used in combination with diuretics for the treatment of hypertension.

One hundred patients participated in a double-blind, randomized study to compare the antihypertensive efficacy of sustained-release nifedipine and propranolol in hypertensive patients whose diastolic blood pressure exceeded 95 mm Hg while receiving diuretic therapy. Nifedipine (mean dose, 79.6 mg per day) decreased blood pressure by 11.4/10.5 mm Hg; propranolol (mean dose, 198.4 mg per day) decreased blood pressure by 13.5/10.3 mm Hg. Reduction of diastolic blood pressure to below 90 mm Hg was achieved in 63 percent of nifedipine-treated patients and in 57 percent of propranolol-treated patients. Nifedipine therapy was associated with an increase in high-density lipoprotein cholesterol levels and a decrease in serum triglyceride levels. In contrast, propranolol therapy was associated with a decrease in high-density lipoprotein cholesterol levels and an increase in serum triglyceride levels. Nifedipine is as effective as propranolol in the treatment of patients with mild to moderate hypertension whose blood pressure is inadequately controlled by diuretic therapy.

Remission of nephrotic syndrome in type 1 diabetes: long-term follow-up of patients in the Captopril Study.

In 1994, we reported a 3.4 +/- 0.8 year follow-up of the eight patients who experienced remission of nephrotic syndrome during the Collaborative Study Group-sponsored, multicenter trial of captopril therapy in patients with type 1 diabetes with nephropathy (Captopril Study). Of the 409 patients randomized to treatment on the Captopril Study, 108 had nephrotic syndrome (24-hour proteinuria >/= 3.5 g of protein) at baseline. Of these 108 patients, 8 experienced remission of nephrotic syndrome (proteinuria

Use of oral clonidine for rapid titration of blood pressure in severe hypertension.

In 20 patients with severe hypertension, rapid oral clonidine titration was employed for control of blood pressure, with 0.2 mg as the initial dose followed by 0.2 or 0.1 mg at one hour and then 0.1 mg/hour, for a total dose of 0.8 mg. All 20 patients had a successful response, defined as a decrease in mean arterial pressure (MAP) of 30 mm Hg or more or attainment of a diastolic pressure of 100 mm Hg or lower. Baseline MAP was 160 +/- 4 (SEM) mm Hg (212 +/- 7/134 +/- 3) and decreased to 120 +/- 3 mm Hg (151 +/- 5/104 +/- 3). The mean dose was 0.32 +/- 0.02 mg, and mean response time 1.8 +/- 0.2 hours. Side effects were minimal, except for one patient who died of a cerebral infarct, which developed after the blood pressure was lowered with clonidine. Eighteen patients were treated in our emergency room; 14 were sent home after rapid titration. In ten who returned for a follow-up visit three to seven days later, blood pressure was reasonably well controlled, with clonidine and a diuretic only. Rapid oral clonidine titration can be effectively and, for the most part, safely used for treating severe hypertension even in an ambulatory setting. As with any other hypotensive drug, we recommended proceeding with caution, particularly in patients with symptomatic arteriosclerotic disease.

Immune reconstitution renal-limited sarcoidosis presenting as acute kidney injury.

An HIV-infected asymptomatic woman developed acute kidney injury six weeks after initiation of combination antiretroviral therapy (cART). A renal biopsy revealed both renal-limited sarcoidosis and HIV nephropathy. The acute renal injury reversed with glucocorticoid therapy.

Treatment of hyperlipidemia in the nephrotic syndrome: the effects of pravastatin therapy.

The hyperlipidemia of the nephrotic syndrome is characterized by an elevation of total cholesterol (TC) and low-density lipoprotein cholesterol (LDLC), with a normal or low high-density lipoprotein cholesterol (HDLC), and an increase in triglycerides (TGs) later in the course of the disease. If sustained, this lipid profile probably places these patients at increased risk for cardiovascular disease. Despite extensive trials of diet and drug therapy in patients with primary hyperlipidemias, few such trials exist in patients with the nephrotic syndrome. We conducted a randomized, prospective, double-blind, placebo-controlled trial to investigate the efficacy and safety of pravastatin, the newest cholesterol synthesis inhibitor, in the treatment of the hyperlipidemia of the nephrotic syndrome. After dietary modification was implemented, 13 patients received pravastatin and eight received placebo. All patients were maintained on a low-fat, low-cholesterol diet for the duration of the trial (24 weeks). The dose of pravastatin was increased from the initial 20 mg/d to 40 mg/d at week 10 or 18 if TC remained elevated (> 50th percentile). A bile acid sequestrant was added at week 18 if TC remained elevated and if the patient was already receiving the maximal pravastatin dosage. Dietary modification did not significantly change the lipid profile. Pravastatin (20 mg/d) reduced TC by 22% from a baseline of 301 +/- 28 mg/dL (P < 0.05) and LDLC by 28% from a baseline of 222 +/- 28 mg/dL (P < 0.05). When used at 40 mg/d (in six patients) no further change in the lipid profile was observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Inner medullary hemodynamics in chronic salt-depleted dogs.

The effects of chronic salt depletion on medullary hemodynamics remain unknown. In the present study, sodium excretion, renal hemodynamics including papillary plasma flow, measured by the albumin-accumulation technique, and papillary tissue solute content were determined during hydropenia in 13 anesthetized sodium-replete and 10 sodium-depleted dogs. Salt depletion induced a significant rise in plasma renin activity and aldosterone without potassium depletion. Mean arterial pressure, GFR, and renal blood flow were similar in sodium-depleted and sodium-replete dogs. Despite a similar distribution of cortical blood flow (measured by the microsphere method) in the two groups, papillary plasma flow was markedly reduced in sodium-depleted dogs (8.8 +/- 1.7 vs. 22.8 +/- 1.9 ml X min-1 X 100 g-1 in sodium-replete dogs), associated with a significant decrease in renal sodium excretion. Furthermore, papillary osmolality and sodium concentration were significantly greater in sodium-depleted dogs. Ultrastructure examination revealed smooth muscle cells surrounding the efferent arterioles and pericytes with contractile potential encircling descending vasa recta. These results suggest that included in the complex hemodynamic adjustment to chronic sodium depletion is a significant reduction in inner medullary blood flow that may be important in maintaining enhanced papillary solute concentration. In addition, the anatomy of the medullary vasculature is compatible with regional regulation of medullary blood flow.

Effective hypertension control in inner city blacks.

A clinic for patients with "resistant" hypertension was established and patients were followed by one physician, nurse, and secretary. The records of 105 randomly chosen patients out of 700 were reviewed. In 86 of 105 (82%), diastolic blood pressure was controlled (less than 90 mm Hg) (group I), but in 19 patients, after 54 +/- 6 (mean +/- standard error) months, it remained greater than 90 mm Hg (group II) with substantial improvement in 53% (10 of 19 patients). The two groups were similar in age (57 +/- 1 vs 54 +/- 3 years), race (84% vs 74% blacks), and sex (75% vs 86% female). The entry blood pressures in groups I and II were similar, 170 +/- 3/101 +/- 1 and 167 +/- 6/105 +/- 3 mm Hg, respectively. Last visit blood pressure was 130 +/- 1/79 +/- 1 in group I, lower than 156 +/- 5/94 +/- 2 in group II (p less than 0.05). At entry into the clinic and at the last visit, dosing and type of medications were similar in both groups. Although patient visits averaged 6.7/yr in both groups, patients in group II missed 1.7 +/- 0.3 compared with 0.9 +/- 0.1 visits/year for group I (p less than 0.01). Group II patients were also less compliant with medications, primarily because of psychosocial problems. Medications, however, were more available to this group, since 16 of 19 (84%) were Medicaid recipients, compared with 46 of 86 (53%) in group I (p less than 0.025).(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of diuretics on inner medullary hemodynamics in the dog.

Although the hemodynamic effects of diuretics have been studied extensively, their effects on inner medullary blood flow remain unknown. In the present study, renal hemodynamics, including papillary plasma flow measured by the albumin accumulation technique, and associated alterations in papillary tissue solute content were determined in anesthetized, hydropenic dogs and during euvolemic diuresis induced by furosemide (3 mg/kg plus 2 mg/kg per hr, iv), ethacrynic acid (3 mg/kg plus 2 mg/kg per hr, iv) or chlorothiazide (10 mg/kg plus 10 mg/kg per hr, iv). Renal blood flow increased significantly after furosemide and ethacrynic acid and decreased significantly after chlorothiazide. Sixty minutes after diuretic administration, papillary plasma flow was 10.8 +/- 1.0 (mean +/- SE) in six furosemide- and 11.3 +/- 2.6 ml/min per 100 g in six ethacrynic acid-treated dogs, both significantly lower than in eight normal or eight chlorothiazide-treated dogs [26.4 +/- 2.6 and 26.7 +/- 2.7 ml/min per 100 g, respectively (P less than 0.01)]. A similarly low papillary plasma flow was also noted 10 minutes after diuretic administration in five furosemide and four ethacrynic acid dogs (13.6 +/- 2.3 and 13.4 +/- 1.8 ml/min per 100 g, respectively). In furosemide and ethacrynic acid dogs, papillary osmolality and sodium content were significantly lower than those in normal or chlorothiazide dogs. In normal and chlorothiazide dogs, papillary sodium content was similar, with a significantly reduced papillary osmolality in the latter. At the time papillary plasma flow was measured, extracellular fluid volume was similar among the four groups of dogs; however, plasma renin activity increased significantly in furosemide and ethacrynic acid dogs (P less than 0.01) and remained unchanged in normal and chlorothiazide dogs. Furthermore, papillary plasma flow was restored to normal (25.3 +/- 3.9 ml/min per 100 g) in five dogs in which furosemide was infused during angiotensin II blockage with saralasin, despite a similar diuresis and natriuresis as the other furosemide group. These data demonstrate that after administration of furosemide, ethacrynic acid and chlorothiazide, regulation of papillary plasma flow is independent of renal blood flow, and suggest that angiotensin II may play a role in the reduced papillary plasma flow in furosemide and ethacrynic acid dogs.