Combination of enalapril and low-dose thiazide reduces normoalbuminuria in essential hypertension

OBJECTIVE: To examine the effect of the combination of enalapril with a very low dose of hydrochlorothiazide versus atenolol on urinary albumin excretion in normoalbuminuric patients with mild to moderate essential hypertension. A secondary objective was to compare the effects of the two regimens in patients with different levels of albuminuria. DESIGN: A 12 weeks, randomized, double-blind, double-dummy, multicenter, comparative study with two parallel groups. SETTING: General practices in Denmark and Finland. PATIENTS: The subjects comprised 174 patients with mild to moderate essential hypertension, normal serum creatinine and no proteinuria. INTERVENTIONS: Enalapril/hydrochlorothiazide (20/6 mg) daily or atenolol (50 mg) daily. MAIN OUTCOME MEASURES: Urinary albumin: creatinine ratio and blood pressure. RESULTS: At baseline, normoalbuminuria was found in 74 and 85 patients in the enalapril/hydrochlorothiazide and atenolol groups, respectively. Blood pressure was reduced similarly by both treatments. The ratio of urinary albumin to creatinine in normoalbuminuric patients was significantly reduced during treatment with enalapril/hydrochlorothiazide at 20/6 mg (from geometic mean x/divided by antilog SD of 0.53 x/divided by 1.77 to 0.47 x/divided by 1.58 mg/mmol, P=0.02) but was unchanged during atenolol treatment (0.55 x/divided by 1.74 and 0.58 x/divided by 1.87 mg/mmol). The difference between the two treatments was statistically significant (P=0.03) and was predominantly achieved through a reduction of albuminuria in the upper-normal range during enalapril/hydrochlorothiazide treatment. CONCLUSIONS: Therapy with enalapril/hydrochlorothiazide at 20/6 mg and atenolol at 50 mg once daily reduced blood pressure similarly in patients with essential hypertension. Suppression of urinary albumin excretion within the normoalbuminuric range was observed during treatment with enalapril/hydrochlorothiazide at 20/6 mg.     

Age-race subgroup compared with renin profile as predictors of blood pressure response to antihypertensive therapy. Department of Veterans Affairs Cooperative Study Group on Antihypertensive Agents

CONTEXT: Renin profiling and age-race subgroup may help select single-drug therapy for stage 1 and stage 2 hypertension. OBJECTIVE: To compare the plasma renin profiling and age-race subgroup methods as predictors of response to single-drug therapy in men with stage 1 and 2 hypertension as defined by the Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure. DESIGN: The Veterans Affairs Cooperative Study on Single-Drug Therapy of Hypertension, a randomized controlled trial. SETTING: Fifteen Veterans Affairs hypertension centers. PATIENTS: A total of 1105 ambulatory men with entry diastolic blood pressure (DBP) of 95 to 109 mm Hg, of whom 1031 had valid plasma and urine samples for renin profiling. INTERVENTIONS: Randomization to 1 of 6 antihypertensive drugs: hydrochlorothiazide, atenolol, captopril, clonidine, diltiazem (sustained release), or prazosin. MAIN OUTCOME MEASURE: Treatment response as assessed by percentage achieving goal DBP (<90 mm Hg) in response to a single drug that corresponded to patients' renin profile vs a single drug that corresponded to patients' age-race subgroup. RESULTS: Clonidine and diltiazem had consistent response rates regardless of renin profile (76%, 67%, and 80% for low, medium, and high renin, respectively, for clonidine and 83%, 82%, and 83%, respectively, for diltiazem for patients with baseline DBP of 95-99 mm Hg). Hydrochlorothiazide and prazosin were best in low- and medium-renin profiles; captopril was best in medium- and high-renin profiles (low-, medium-, and high-renin response rates were 82%, 78%, and 14%, respectively, for hydrochlorothiazide; 88%, 67%, and 40%, respectively, for prazosin; and 51%, 83%, and 100%, respectively, for captopril for patients with baseline DBP of 95-99 mm Hg). Response rates for patients with baseline DBP of 95 to 99 mm Hg by age-race subgroup ranged from 70% for clonidine to 90% for prazosin for younger black men, from 50% for captopril to 97% for diltiazem for older black men, from 70% for hydrochlorothiazide to 92% for atenolol for younger white men, and from 84% for hydrochlorothiazide to 95% for diltiazem for older white men. Patients with a correct treatment for their renin profile but incorrect for age-race subgroup had a response rate of 58.7%; patients with an incorrect treatment for their renin profile but correct for age-race subgroup had a response rate of 63.1% (P = .30). After controlling for DBP and interactions with treatment group, age-race subgroup (P<.001) significantly predicted response to single-drug therapy, whereas renin profile was of borderline significance (P= .05). CONCLUSIONS: In these men with stage 1 and stage 2 hypertension, therapeutic responses were consistent with baseline renin profile, but age-race subgroup was a better predictor of response.     

Capillarovenous angioma of the maxillary sinus. Apropos of a case with review of the literature

Metabolic side-effects of antihypertensive drugs may increase the risk of coronary heart disease despite an adequate blood pressure reduction. Since combinations of different antihypertensive drugs are often necessary and frequently used, we performed a randomized study comparing the effects of a fixed combination of hydrochlorothiazide and sotalol (group A), or hydrochlorothiazide and captopril (group B) on blood pressure and on lipid and glucose metabolism in 40 men with essential hypertension over 1 year. Significant blood pressure reductions (p < 0.001) were achieved in both treatment groups: from 160/105 to 128/88 mmHg in group A (mean doses: hydrochlorothiazide 33 and sotalol 197 mg) and from 162/106 to 135/89 mmHg in group B (hydrochlorothiazide 33 and captopril 64 mg) after 12 months, respectively. No significant changes in body weight were observed in either treatment group. Triglycerides increased (p < 0.05) in both treatment groups (from 183 to 262 mg/dl in A, and from 160 to 196 mg/dl in B) and HDL cholesterol decreased (p < 0.001 and < 0.05) in both groups (from 45.1 to 35.7 mg/dl in A, and from 49.3 to 46.3 mg/dl in B), whereas LDL cholesterol increased significantly (p < 0.05) only in group A from 153 to 164 mg/dl. No significant changes were observed in total cholesterol nor in lipoprotein(a) concentrations in either treatment group. Fasting plasma glucose and hemoglobin A1 increased significantly (p < 0.05) only in group A after 1 year of treatment (from 91.6 to 98.0 mg/dl, and from 6.3 to 6.9%, respectively). Serum levels of creatinine and potassium decreased, and uric acid increased significantly under either combination. Our data show that the diuretic/beta-blocker combination has adverse effects on lipid and glucose metabolism after long-term therapy. The effects of the diuretic/ACE inhibitor combination on lipid metabolism are less pronounced and there are no adverse effects on glucose metabolism. However, the ACE inhibitor component could not completely counteract the metabolic effects of the diuretic. Both combinations have no effects on Lp(a). We conclude that the combination of hydrochlorothiazide with an ACE inhibitor has a better metabolic profile for the treatment of essential hypertension than the combination with a beta-blocker.     

The effect of angiotensin-converting enzyme inhibitors on proteinuria in chronic glomerulonephritis

The effect of two angiotensin-converting enzyme (ACE) inhibitors, lisinopril and captopril, on proteinuria and renal haemodynamics was investigated in 11 hypertensives (9 men, 2 women; mean age 46 +/- 16 years) with proteinuria (> 1.5 g/24 h) due to chronic glomerulonephritis and impaired renal function (glomerular filtration rate < 75 ml/min). In a randomized and double-blind cross-over trial the patients received, each time for six weeks, either lisinopril (5 mg/d, sometimes increased to 10 mg/d after 3 weeks) or captopril (twice daily 12.5 mg, sometimes increased to twice 25 mg after 3 weeks). Initially and between the individual treatment phases they were on a placebo phase for 4 weeks. The following were measured: protein excretion, including fractional clearance of albumin and IgG, plasma-renin activity and renal haemodynamics. Protein excretion was not significantly reduced by either drug (placebo: 7.1 +/- 4.0 g/d; lisinopril: 5.1 +/- 2.8 g/d; captopril: 5.4 +/- 3.0 g/d). Albumin excretion and fractional albumin clearance were significantly decreased only by lisinopril (P < 0.05), not by captopril. Plasma-renin activity was increased more by lisinopril than captopril (Placebo: 1.0 +/- 0.9 ng/ml.h; lisinopril: 5.2 +/- 2.8 ng/ml.h [P < 0.05]; captopril: 1.8 +/- 1.3 ng/ml.h [P < 0.05]). The renal haemodynamics was only slightly influenced by either drug, but captopril significantly decreased the filtration fraction in the presence of chronic glomerulonephritis and renal failure. - Resulting from their influence on the renin-angiotensin-aldosterone system, ACE inhibitors have, in addition to their known action on renal haemodynamics, an independent effect on the loading barrier of the basal membrane of the kidney.     

Renal and metabolic effects of 1-year treatment with ramipril or atenolol in NIDDM patients with microalbuminuria

The clinical importance of selection of different antihypertensive drugs for the treatment of diabetic patients is still unclear. Thus we performed a randomised, controlled study in 105 hypertensive non-insulin-dependent diabetic (NIDDM) patients with microalbuminuria over 1 year. Patients received either the angiotensin converting enzyme (ACE) inhibitor ramipril (2.5-5.0 mg/day; in addition 24% of patients also received felodipine) or the beta blocking agent atenolol (50-100 mg/day; in addition 24% of patients also received hydrochlorothiazide). Blood pressure, metabolic control, lipid levels and albumin excretion rate were studied during the follow-up. After 1 year an almost identical fall (p < 0.001) in blood pressure was observed with ramipril (170/100 vs 150/ 85 mmHg, median) and atenolol (180/100 vs 150/ 80 mmHg, median). With ramipril a reduction of total cholesterol (6.3 vs 5.9 mmol/l), of LDL cholesterol (3.8 vs 3.6 mmol/l) and HDL cholesterol (1.3 vs 1.2 mmol/l) was found, whereas triglycerides slightly increased (1.8 vs 2.0 mmol/l). With atenolol a similar reduction of total cholesterol (6.3 vs 5.9 mmol/l), LDL cholesterol (3.8 vs 3.7 mmol/l) and HDL cholesterol (1.4 vs 1.2 mmol/l) and an increase of triglycerides (1.4 vs 1.7 mmol/l) was noted. Metabolic control of the patients was maintained with both ramipril and atenolol treatment. With ramipril treatment urinary albumin creatinine ratio (14.4 vs 13.8 mg/mmol) and creatinine clearance (82 vs 84 ml/min) were constant, but with atenolol an increase of albumin creatinine ratio (13.9 vs 19 mg/mmol, p < 0.001) and a slight decrease of creatinine clearance (80 vs 66 ml/min, p < 0.05, not significant after Bonferroni correction) was observed. In conclusion: 1-year treatment of NIDDM patients with ramipril or atenolol does not influence metabolic control, the changes in serum lipids were similar. Despite almost identical blood pressure reduction in both groups the albumin creatinine ratio was constant under ramipril, but increased under atenolol treatment.     

Renal proximal disfunction based on activity of n-acetyl-beta-d-glucosaminidase in urine of patients with kidney failure

N-acetyl-beta-D-glucosaminidase (NAG) urine activities of 63 patients with stable and unstable chronic renal failure have been investigated. The values of NAG activity obtained from these patients were compared with NAG activity of 33 normal controls. Abnormal NAG values (> 70 nmol/mg of creatinine) were found in 60 (95.2%) patients with chronic renal failure and the median of all values was 327.8 nmol/mg of creatinine. It was 14-fold greater than the median of values for normal controls. There were any significant differences of NAG values between the patients with massive proteinuria (> 1.5 g/24 h), moderate proteinuria and those without 24 hour proteinuria or non-significant proteinuria (respectively 423.5 +/- 286.3 vs 414.4 +/- 334.8 vs 453.0 +/- 451.3 nmol/mg of creatinine). There was no significant difference between the two subgroups of patients with NAG values above and below 280 nmol/mg of creatinine in age, gender, serum urea and uric acid levels. However, the incidence of patients with NAG values higher than 280 nmol/mg of creatinine was statistically significant in unstable course of renal insufficiency and raised serum creatinine levels. It is suggested that the measurement of NAG excretion may be helpful to monitor unstable process in renal failure.     

Factors relating to urinary protein excretion in children with autosomal dominant polycystic kidney disease

Adults with autosomal dominant polycystic kidney disease (ADPKD) who have overt proteinuria (>300 mg/d) have higher mean arterial pressures, lower creatinine clearances, larger renal volumes, and a more aggressive course of renal disease than ADPKD patients without proteinuria. This study examines the relationship between proteinuria and microalbuminuria and similar factors in ADPKD children. A total of 189 children from 81 ADPKD families was included in the analysis. The ADPKD children (n = 103) had significantly greater urine protein excretion rates than the non-ADPKD children (n = 86) (3.9+/-0.3 versus 2.8+/-0.2 mg/m2 per h, P < 0.001). Children with severe renal cystic disease (> 10 cysts; n = 54) had greater protein excretion than those with moderate disease (< or = 10 cysts; n = 49) (4.4+/-0.5 versus 3.3+/-0.2 mg/m2 per h, P < 0.05). The ADPKD children had significantly greater albumin excretion rates than the non-ADPKD children (32+/-6 versus 10+/-2 mg/m2 per 24 h, P < 0.001), and a higher percentage of ADPKD children had significant microalbuminuria (>15 mg/m2 per 24 h in boys and >23 mg/m2 per 24 h in girls) than their unaffected siblings (30% versus 10%, P < 0.05). Thirty percent of ADPKD children had albuminuria and 23% had overt proteinuria. For all ADPKD children, there was no correlation between proteinuria and hypertension. However, there was a significant correlation between urinary protein excretion and diastolic BP among children diagnosed after the first year of life (r = 0.23, P < 0.05). Therefore, proteinuria and albuminuria occur early in the course of ADPKD and may be markers of more severe renal disease.     

Evaluation of the antihypertensive efficacy of lisinopril and captopril associated with hydrochlorothiazide by ambulatory measurement of arterial pressure

The objective of this study was to evaluate the efficacy, particularly in terms of the 24-hour cover, and the safety of lisinopril 20 mg + hydrochlorothiazide 12.5 mg 5L/HCTZ) and captopril 50 mg + hydrochlorothiazide 25 mg (C/HCTZ) in patients with essential HT requiring two-agent therapy. Twenty patients with a diastolic blood pressure (DBP) between 95 and 120 mmHg after 2 weeks of placebo were randomised to receive, under double-blind conditions, either L/HCTZ or C/HCTZ as a single daily dose for 4 weeks. Clinical examination, laboratory tests and 24-hour ambulatory blood pressure monitoring (ABPM) were performed at the end of the placebo and active treatment periods. L/HCTZ and C/HCTZ significantly lowered SBP and DBP on occasional recordings and on ABPM. The mean fall in blood pressure on ABPM (SBP, DBP, mean of 24-hour recording, diurnal and nocturnal) at 4 weeks was greater with L/HCTZ than with C/HCTZ. Both treatments were effective for 24 hours and did not alter the circadian cycle. The clinical and laboratory safety was good. The blood pressure figures obtained by ABPM were lower than on occasional recordings, emphasising the value of this technique in the evaluation of a patient's poor response to antihypertensive treatment.     

Overt proteinuria and microalbuminuria in autosomal dominant polycystic kidney disease

The amount of proteinuria is a prognostic indicator in a variety of glomerular disorders. To examine the importance of urinary protein excretion in autosomal dominant polycystic kidney disease, this study determined the clinical characteristics of autosomal dominant polycystic kidney disease patients with established proteinuria and the frequency of microalbuminuria in hypertensive autosomal dominant polycystic kidney disease patients without proteinuria. In 270 autosomal dominant polycystic kidney disease patients, mean 24-h urinary protein excretion was 259 +/- 22 mg/day. Forty-eight of 270 autosomal dominant poly-cystic kidney disease patients had over proteinuria (> 300 mg/day). The patients with established proteinuria had higher mean arterial pressures, larger renal volumes, and lower creatinine clearances than did their nonproteinuric counterparts (all P < 0.0001), a greater pack year smoking history (P < 0.05), and the projection of a more aggressive course of renal disease (P < 0.05). All autosomal dominant polycystic kidney disease patients with established proteinuria were hypertensive, as compared with 67% without established proteinuria (P < 0.001). Forty-nine patients with hypertension and left ventricular hypertrophy without established proteinuria were examined for microalbuminuria; 41% demonstrated microalbuminuria. Those with microalbuminuria had higher mean arterial pressure, larger renal volumes and increased filtration fraction. Therefore, established proteinuria and microalbuminuria in autosomal dominant polycystic kidney disease patients are associated with increased mean arterial pressure and more severe renal cystic involvement.     

Antiproteinuric effect of angiotensin-converting enzyme inhibition and C5b-9 urinary excretion in membranous glomerulonephritis

BACKGROUND: Angiotensin-converting enzyme (ACE) inhibitors have an antiproteinuric effect in membranous glomerulonephritis (MGN). However, no studies have investigated whether this antiproteinuric effect is influenced by urinary C5b-9 excretion, a marker of immunological activity in this disease. METHODS: Eleven patients with biopsy-proven MGN were treated with captopril for 8 weeks. The evolution of several clinical and biochemical parameters, including 24-h urinary protein excretion was evaluated every 4 weeks. Urinary C5b-9 excretion was measured at the onset and at the end of captopril treatment. RESULTS: Patients with MGN had significantly higher C5b-9 excretions than a group of 14 healthy controls (89 +/- 23 vs 3.7 +/- 1.4 ng/mg UCr; P < 0.001). A significant correlation was found between urinary C5b-9 and the magnitude of proteinuria, both at the onset and at the end of treatment. After 8 weeks of captopril treatment, proteinuria had decreased from 8 +/- 1.8 to 5.2 +/- 1.3 g/day (P < 0.05). Four weeks after captopril discontinuation, proteinuria rose to 7.3 +/- 1.7 g/day (P < 0.05). A marked variability in the antiproteinuric response was observed, ranging from 0 to 85% with respect to baseline values. No correlation between decrease in proteinuria and baseline urinary C5b-9 levels was observed. Several patients with elevated urinary C5b-9 levels had captopril-induced decrease in proteinuria. CONCLUSIONS: ACE inhibition induces an antiproteinuric effect in patients with MGN. The urinary C5b-9 excretion does not predict the magnitude of this response.     

Clinical survey of congenital cytomegalovirus infection in Japan

Contrast media-induced nephropathy is one of the leading causes of hospital-acquired renal failure, occurring most frequently in patients with pre-existing renal insufficiency. We prospectively studied 55 patients with chronic renal insufficiency (serum creatinine concentration 1.4 to 3.5 mg/dl) who underwent abdominal aortography and arteriography of the lower extremities. The patients were randomized into two groups. Group 1, 28 patients, received dopamine 2.5 mcg/kg beginning 1 hour before arteriography and continuing for 12 hours. Group 2 received an equal volume of saline for the same period of time. Serum creatinine and 12-hour creatinine clearance were measured before arteriography and for 4 consecutive days afterward. Acute contrast-induced decrease in renal function was defined as increase in the baseline serum creatinine concentration > or = 0.5 mg/dl. On day 1 postarteriography the serum creatinine increased from baseline .193 mg/dl for controls while the dopamine group decreased slightly from baseline .018 mg/dl (p = 0.002). Excepting day 1 postarteriography, there was no statistical difference between groups, and serum levels for both groups increased linearly from baseline across time (dopamine p = 0.028, control p = 0.025). In patients with pre-arteriography baseline serum levels greater than or equal to 2.0 mg/dl, however, the increase in serum creatinine from baseline levels was consistently and significantly greater in the control group through the fourth day (0.012 < or = p < or = 0.049). Creatinine clearance did not change significantly from baseline after arteriography in the dopamine group (baseline versus days 1 through 4, 0.238 < or = p < or = 0.968); however, the control group showed a significant linear decrease in creatinine clearance from baseline through the fourth day after arteriography (p = 0.016). Dopamine infusion prevented a rise in serum creatinine 24 hours after angiography in patients with pre-existing renal insufficiency, and protected against contrast-induced decrease in renal function in patients whose baseline serum creatinine was > or = 2.0 mg/dl.     

Assessment of ventricular diastolic function in AIDS patients from Congo: a Doppler echocardiographic study

The aim of this study was to evaluate the effect of transdermal clonidine on hemodynamic and metabolic parameters in patients who have elevated blood pressure and non-insulin-dependent diabetes mellitus (NIDDM). After a 2-week run in placebo period, 20 NIDDM patients who had diastolic blood pressure in the range of 90 to 105 mm Hg underwent a randomized, single blind, placebo controlled, cross-over study of 4 week treatment with clonidine (transdermal patch 2.5 mg/week) or placebo (inactive patch). Compared with placebo, clonidine significantly reduced systolic (153 +/- 6 v 163 +/- 8) and diastolic (88 +/- 2 v 98 +/- 3.5 mm Hg, P = .001) blood pressure, left ventricular mass (94 +/- 11 v 99 +/- 12 g/m2, P < .01) and fasting glucose levels. Total glucose disposal (glucose clamp) was 6.5 +/- 1.5 with placebo and 7.1 +/- 1.6 mg/kg/min with clonidine (P < .01). Oxidative glucose disposal (indirect calorimetry) was also greater after clonidine. Plasma glucose, insulin, and C-peptide responses following oral glucose (75 g) were significantly lower after clonidine, as well as urinary albumin excretion. Transdermal clonidine is effective in reducing blood pressure in hypertensive NIDDM patients and is well tolerated. It may be useful to reduce the cardiovascular impact of hypertension in diabetes mellitus.     

Fixed combination verapamil SR/trandolapril

Urapidil is a peripheral postsynaptic alpha 1-adrenoceptor antagonist with central agonistic action at serotonin 5-HT1A receptors. It reduces blood pressure by decreasing peripheral vascular resistance. Oral urapidil decreases blood pressure in patients with mild to moderate essential hypertension and associated risk factors such as hyperlipidaemia or type 2 (non-insulin-dependent) diabetes mellitus with no effect on heart rate. The antihypertensive efficacy of urapidil is similar to that of most comparators in patients with mild to moderate essential or secondary hypertension and no concomitant risk factors. However, the antihypertensive efficacy of urapidil was lower than that of hydrochlorothiazide in a well designed trial. Lipid levels and glucose metabolism are not adversely affected and may improve with urapidil in patients with lipid or glucose abnormalities. Urapidil can be safely combined with other antihypertensive agents such as hydrochlorothiazide and nifedipine and improves blood pressure control in previous nonresponders to monotherapy. Intravenous urapidil reduces blood pressure in patients with pre-eclampsia or hypertension in pregnancy and in patients with hypertensive crises or peri- or postoperative hypertension. The decrease in blood pressure is similar to that observed after nifedipine, enalaprilat, sodium nitroprusside and dihydralazine, greater than that of ketanserin according to 1 larger study, and greater than that of sublingual nitroglycerin in 1 trial in patients with nonsurgical hypertensive crises and pulmonary oedema. However, more patients responded to treatment with urapidil than with enalaprilat or nifedipine. Heart rate is less likely to be altered by urapidil than with some comparator drugs. Urapidil appears to be well tolerated, with most adverse events being mild and transient. The incidence of adverse events with urapidil is similar to that with prazosin, metoprolol, atenolol, sodium nitroprusside and hydrochlorothiazide and less than that with nifedipine and clonidine. Urapidil may not be as well tolerated as captopril and, in 1 study, more urapidil than nitrendipine recipients discontinued treatment because of adverse events. Conclusions: urapidil reduces blood pressure without altering heart rate. The oral formulation is an effective choice in patients with hypertension and concomitant dyslipidaemia or type 2 diabetes mellitus, in whom the drug does not adversely affect and may improve lipid profiles and glucose metabolism. The intravenous formulation is effective in controlling various hypertensive crises and hypertension associated with pregnancy or surgery and is similar to or better than other first-line agents used in these conditions. Thus, urapidil may be a useful alternative to currently available antihypertensive agents.     

Effect of the angiotensin converting enzyme inhibitor, captopril, on proteinuria in chronic glomerular disease

The antiproteinuric effect of the angiotensin-I-converting enzyme inhibitor, captopril, was studied in 14 patients (10 men and 4 women, age range of 24 to 60 years) with chronic glomerulonephritis in whom IgA nephritis had been confirmed by renal biopsy. Eight of the 14 patients had received antihypertensive drugs such as calcium channel blockers, diuretics or beta-blockers. Captopril was added to these regimens at 25 mg twice daily in 3 patients, and 37.5 mg in 11 patients. Proteinuria decreased from 2.55 +/- 0.48 g/day to 1.58 +/- 0.35 g/day within three months after the start of administration. In 4 patients (28.6%), the extent of reduction was over 50%, and in 8 patients (57.1%), over 25%. Blood pressure, creatinine clearance and serum creatinine were not changed significantly. There was a positive linear correlation between the extent of reduction of proteinuria and the increase in plasma renin activity (r = 0.93, p < 0.001). We conclude that captopril reduces proteinuria in some patients with IgA nephritis whose plasma renin activity responds to the drug.     

Risk factors for contrast nephropathy in diabetic patients undergoing cardioangiography

Risk factors for contrast nephropathy were prospectively studied in 17 patients with non-insulin dependent diabetes mellitus undergoing cardioangiography. Contrast nephropathy, defined as a serum creatinine increase of greater than 25% at 3 day after angiography, occurred in 29.4% of diabetic patients. Patients who developed contrast nephropathy had significantly higher serum creatinine (Cr), fractional excretion of sodium (FENa), urinary albumin excretion rate (AER), and lower 24hr Ccr than patients who did not (Cr: 1.5 +/- 0.3 mg/dl vs. 0.8 +/- 0.1 mg/dl, FENa: 1.9 +/- 0.5% vs. 0.6 +/- 0.1%, AER: 522 +/- 335 micrograms/min vs. 27 +/- 13 micrograms/min, 24hr Ccr: 39.1 +/- 11.6 ml/min vs. 86.2 +/- 9.3 ml/min, P < 0.05). Contrast nephropathy developed in all of two patients with overt proteinuria (AER more than 200 micrograms/min), but none of eight patients with normoalbuminuria (AER below 15 micrograms/min). Three of seven patients with microalbuminuria developed contrast nephropathy, and two of them had advanced nephropathy. FENa obtained next day was significantly elevated over baseline in patients with contrast nephropathy (1.9 +/- 0.5% vs. 9.7 +/- 4.5%, P < 0.05), but unchanged in patients without contrast nephropathy. The rise in C beta 2-microglobulin/Ccr and enzymuria was noted in both group. Percentage decrease of Ccr on the next day was positively correlated with FENa before angiography (r = 0.645, p < 0.01). Of 24hr Ccr, AER, and FENa before angiography, FENa was revealed as a statistically significant discriminant factor for contrast nephropathy by stepwise discriminant analysis (p = 0.0008). These results suggest that contrast nephropathy develops predominantly in the stage not of incipient but of overt diabetic nephropathy indicated by a decline of glomerular filtration, overt proteinuria, and tubular dysfunction. Of them, tubular dysfunction may be the most important risk factor for contrast nephropathy.     

Risk factors for mortality in patients with insulin-dependent diabetes

The prognostic significance of microalbuminuria, macroalbuminuria and other putative risk factors for mortality in insulin-dependent diabetic patients were evaluated in a 10 year prospective study. We identified 939 insulin-dependent diabetic patients; 593 patients had normoalbuminuria (< or = 30 mg/24 h), 181 had microalbuminuria (31-299 mg/24 h), and 165 had macroalbuminuria (> or = 300 mg/24 h). Fifteen percent of patients with normoalbuminuria, 25% with microalbuminuria and 44% with macroalbuminuria at baseline died during follow-up (p < or = 0.01). Significant predictors of all-cause mortality were male sex, age, height, smoking, low social class, urinary albumin excretion, hypertension, serum creatinine, and HbA1c. Age, smoking, microalbuminuria, overt nephropathy, and hypertension were significant predictors of cardiovascular mortality. The mortality in patients with microalbuminuria was only slightly increased compared to patients with normoalbuminuria. Median survival after onset of overt diabetic nephropathy was 13.9 (11.8 to 17.2) years. Abnormally elevated urinary albumin excretion and other potentially modifiable risk factors such as hypertension, smoking, poor glycaemic control and social class predicts increased mortality in insulin-dependent diabetic patients.     

Centralized i.v. team provides inpatient and home-care treatment

AIM: The study of the effects of the inhibitor of angiotensin converting enzyme ramipril (tritace) on the 24-h profile of blood pressure (BP) in patients with mild and moderate arterial hypertension. MATERIALS AND METHODS: Ramipril was given to 21 males aged 45-68 years with essential hypertension stage II (WHO criteria) with stable elevated diastolic blood pressure (95-114 mm Hg) in a single dose 2.5-10 mg/day. Captopril controls received 100 mg twice a day. BP was monitored using "SpaceLabs Medical" unit (model 90207, USA). RESULTS: Compared to placebo, ramipril lowered systolic and diastolic blood pressure both for the 24-h period and in the day time; captopril lowered only diastolic BP in the day time. Side effects of long-term application of ramipril occurred 2 times less frequently than in application of captopril. CONCLUSION: Long-term treatment with ramipril in the above regimen provides more effective control of BP than captopril in the above doses in patients with mild and moderate hypertension.     

Renal effects of losartan and amlodipine in hypertensive patients with non-diabetic nephropathy

BACKGROUND: The objective of this study was to examine the effects of angiotensin II receptor blocker losartan versus the calcium channel blocker amlodipine on proteinuria, renal haemodynamics, glomerular sieving and tubular function in hypertensive patients with non-diabetic nephropathy. METHODS: The study design was a prospective, double blind, placebo controlled, randomized crossover trial with amlodipine and losartan. Renal parameters were measured at baseline and at the end of each 4-week active treatment period. Fifteen patients with a diagnosis of non-diabetic renal disease and hypertension were included. RESULTS: Mean arterial blood pressure decreased from 123+/-13 mmHg at baseline to 113+/-10 mmHg (P<0.01) on losartan and to 114+/-10 mmHg on amlodipine (P<0.01). Urinary albumin excretion significantly decreased from 3510+/-2586 mg/24 h at baseline to 2684+/-2051 mg/24 h (P<0.01) on losartan and increased non-significantly to 3748+/-3355 mg/24 h on amlodipine. Filtration fraction significantly decreased from a baseline value of 22.8+/-9.3% to 21.2+/-10.2% (P<0.05) on losartan and increased to 23.6+/-8.9% (ns) on amlodipine. Either drug did not significantly alter glomerular sieving of neutral dextrans. CONCLUSION: Our results demonstrate that losartan, but not amlodipine, decreased albumin excretion in hypertensive patients with non-diabetic nephropathy.     

Double-blind, parallel, comparative multicentre study of a new combination of diltiazem and hydrochlorothiazide with individual components in patients with mild or moderate hypertension

OBJECTIVE: To compare the antihypertensive efficacy and tolerability of a new combination preparation of diltiazem (150 mg) and hydrochlorothiazide (12.5 mg) with the individual constituents in patients with mild/moderate hypertension. DESIGN: Multi-centre, double-blind, randomised parallel group study. PATIENTS: Seventy-one patients with essential hypertension were recruited to the study. TREATMENT: Following completion of the placebo run-in period 63 patients fulfilled the prerandomisation criteria and entered the 10 week treatment period. Patients were randomised to receive either the combination preparation (D 150 mg/H 12.5 mg), diltiazem (150 mg) or hydrochlorthiazide (12.5 mg). The dosage was increased in three patients who had not attained target blood pressure (BP) control after 6 weeks. OUTCOME MEASURES: Response to treatment assessed by change from baseline in clinic and 24 h ambulatory BP. RESULTS: The proportion of patients achieving target BP (a reduction in resting supine diastolic blood pressure (DBP) to below 90 mm Hg or a reduction of 10 mm Hg from baseline) was 80% in the combination group, 55% in the diltiazem group, and 38% in the hydrochlorothiazide group. The respective figures for reduction in supine DBP from baseline were 13.5 mm Hg, 11.2 mm Hg and 5.9 mm Hg. A similar treatment order appeared throughout each of the efficacy variables. BP control throughout the 24 h dosing interval was demonstrated by ambulatory BP monitoring. Each treatment was well tolerated. CONCLUSION: This study provides clear evidence of the efficacy of combination therapy with diltiazem and hydrochlorothiazide in the management of patients with hypertension.     

Multiple injuries in peacetime and wartime estimate of severity of injury by the Injury Severity Score and Polytraumaschlüssel

The aim of this study was to evaluate the efficacy and tolerability of valsartan, a new angiotensin II receptor antagonist, versus atenolol in the treatment of severe primary hypertension. A total of 103 adult out-patients were randomised to receive either valsartan 160 mg or atenolol 100 mg once daily for 6 weeks. If necessary, additional blood pressure (BP) control could be provided as add-on therapy. Both valsartan and atenolol decreased mean sitting diastolic BP (DBP) and mean sitting systolic BP (SBP): least squares mean change from baseline in DBP; valsartan, -20.0 mm Hg; atenolol, -20.4 mm Hg: in SBP; valsartan, -30.0 mm Hg; atenolol, -25.5 mm Hg. There was no statistically significant difference between the treatment groups. Add-on hydrochlorothiazide (HCTZ) 25 mg was required by 97.2% of patients receiving atenolol and 83.6% of patients receiving valsartan; additional verapamil SR 240 mg was also required by 58.3% of patients receiving atenolol and 64.2% receiving valsartan. Valsartan was well tolerated, with a comparable incidence of treatment-related adverse experiences in both groups. In conclusion valsartan 160 mg is as well tolerated and effective as atenolol 100 mg in lowering BP in severely hypertensive patients.