Differing effects of antihypertensive agents on urinary albumin excretion

Skeletal muscles in an animal model of genetic hypertension (the spontaneously hypertensive rat. SHR) exhibit significant deficits in contractile performance. These deficits appear to be unrelated to the rise in blood pressure. Slow-twitch soleus muscles show a decrease in specific muscle tension and a reduced resistance to muscle fatigue during prolonged contractile activity. We tested the hypothesis that the reduced fatigue resistance occurs as a consequence of an impaired ability to maintain or restore Na+ and K+ balance across the sarcolemma during repeated contractions. This may result from a genetically based increase in the Na+ permeability of SHR muscles, coupled with a reduction Na+, K+ pump capacity as the animals mature. Soleus muscles in adult SHR exhibit a significant increase in intracellular Na+ content and a significant decrease in intracellular K+ content at rest. B6RB+ uptake in Na(+)-loaded hypertensive muscles is 45% less than predicted from the number of ouabain-binding sites available. Activation of Na+, K+ pumps using adrenaline or insulin produces a significantly smaller hyperpolarization in hypertensive soleus than in control muscles. Control soleus muscles are hyperpolarized for at least 10 min after a 4 min period of high-frequency activity, but hypertensive soleus muscles remain at resting polarity. Nonetheless, the number of ouabain-binding sites in hypertensive muscle is significantly greater than in control soleus, and binding affinities are similar. This apparent deficit in pump capacity might lead to a greater and more prolonged increase in extracellular K+ during repetitive contractions,and an associated decline in tension. Recently, we have been able to prevent the abnormal decrease in hypertensive soleus fatigue resistance by long-term treatment (8 weeks) with the Ca2+ blocker amlodipine. The therapy prevented or reversed the contractile deficits, but did not restore the responsiveness of the Na+, K+ pump to hormonal stimulation. The current data suggest that both a reduction in Na+, K(+)-pump capacity and changes in Ca2+ distribution play a role in the development of contractile deficits in hypertensive muscles.     

Prognostic value of urinary albumin excretion rate and other risk factors in elderly diabetic patients and non-diabetic control subjects surviving the first 5 years after assessment

In 1981-1982 urinary albumin excretion rates were determined in 211 diabetic and 216 non-diabetic subjects aged 60-74 years. By April 1992 122 diabetic and 58 non-diabetic probands had died. Dividing the two study populations at an albumin excretion rate of 15 micrograms/min showed that 69.3% of diabetic subjects with values at or above the limit, and 49.9% of those with values below (log rank test p = 0.0082) had died. The corresponding values for non-diabetic subjects were 44.4% and 21.0%, respectively (log rank test p = 0.0002). In single factor log rank tests ischaemic heart disease and a low value of HDL were also predictive of death in the diabetic population during a 10-11-year observation period. In the non-diabetic population ischaemic heart disease, hypertension, and a serum creatinine level above the median value were predictive. In further log rank analyses probands dying during the first years, (e.g. the first 2 years) were removed from the calculations. The prognostic value of the above-mentioned factors diminished with time. In a Cox Regression analysis we found that the predictive value of urinary albumin excretion rate to mortality had disappeared when subjects who had died during the first 5 years were removed from the analysis, whereas HDL in the diabetic patients and blood pressure and serum creatinine in non-diabetic subjects were still of significant predictive value. We therefore conclude that urinary albumin excretion rate is a more short-term predictor of mortality than previously thought, in contrast to HDL, hypertension and serum creatinine.     

Effect of antihypertensive treatment on urinary albumin excretion, glomerular filtration rate, and renal plasma flow in patients with essential hypertension

In 20 patients with essential hypertension the urinary albumin execretion, glomerular filtration rate (GFR),and renal plasma flow (RPF) were examined before and after antihypertensive treatment. Albumin excretion measured by radioimmunoassay was increased before treatment, and there was a significant fall during treatment. In patients responding well to therapy (diastolic pressure below 100 mm Hg), albumin excretion was significantly lower than in patients responding poorly to therapy. There was a positive correlation between albumin excretion before treatment and diastolic pressure during treatment, indicating that the albumin excretion rate may be used to predict the result of antihypertensive treatment. Patients with excretion rates below 25 mug/min generally respond well to the treatment used. No definite changes in GFR and RPF were found during treatment, and there was no correlation between albumin excretion and GFR and RPF. It is suggested that the increased albumin excretion in essential hypertension is due both to functional and morphological alterations in the glomerulus, namely increased glomerular filtration pressure and vascular damage.     

Urinary albumin excretion rate and glomerular filtration rate in single-kidney type 2 diabetic patients

OBJECTIVE: To evaluate the urinary albumin excretion rate (UAER) and the glomerular filtration rate (GFR) of single-kidney type 2 diabetic patients (SKD) and of single-kidney non-diabetic patients (SKN). RESEARCH DESIGN AND METHODS: Patients who had only one kidney for at least 5 years, with no renal disease or hypertension at the time of the nephrectomy and with no calculus or systemic disease at the time of the evaluation, were included in this controlled cross-sectional study A total of 20 SKD (8 men, age 62 +/- 9 years; diabetes duration 8.5 +/- 7 years), 17 SKN (2 men, age 57 +/- 13 years), and 184 type 2 diabetic patients who were matched to the single-kidney diabetic group for age, sex, and BMI were studied. UAER was measured by immunoturbidimetry in timed 24-h sterile urine, and GFR was determined by the 51Cr-EDTA single-injection method. RESULTS: SKD patients presented a higher proportion (8 of 20, 40%) of microalbuminuria (UAER 20-200 microg/min) than SKN patients (3 of 17, 17.6%) and type 2 diabetic patients (37 of 184, 20%). SKD patients presented a higher proportion of macroalbuminuria (UAER >200 microg/min; 6 of 20, 30%) than SKN patients (1 of 17, 6%) but were similar to type 2 diabetic patients (43 of 184, 23%). The GFRs of normoalbuminuric SKN (71.7 +/- 21.4 ml x min(-1) x 1.73 m(-2)) and SKD patients (73.0 +/- 21.5 ml x min(-1) x 1.73 m(-2)) were similar but higher than the one-kidney GFR (GFR / 2) of the age-, sex-, and BMI-matched normal individuals (50.5 +/- 9.0 ml x min(-1) x 1.73 m(-2)) and normoalbuminuric type 2 diabetic patients (54.0 +/- 11.6 ml x min(-1) x 1.73 m(-2)). CONCLUSIONS: Increased GFR related to single-kidney status confers an increased risk of developing renal disease in the presence of diabetes.     

Indomethacin but not metoprolol reduces exercise-induced albumin excretion rate in type 1 diabetic patients with microalbuminuria

The effects of a single oral dose of indomethacin (1 mg kg-1) metoprolol (1.5 mg kg-1) and placebo on exercise-induced albumin excretion rate (AER) were compared in a randomized, crossover design in 14 normotensive, young Type 1 diabetes patients, nine of them with microalbuminuria (AER > 15 micrograms min-1) and five without microalbuminuria at rest. The albumin excretion rate, blood pressure, heart rate, blood glucose, and plasma concentrations of indomethacin and metoprolol were determined before and after 30 min submaximal physical exercise. In microalbuminuric patients the rise in albumin excretion rate after exercise on indomethacin (7 micrograms min-1) was lower than after placebo (29 micrograms min-1, p < 0.001) whereas the rise in albumin excretion rate with metoprolol during exercise (18 micrograms min-1) did not differ from placebo (p = 0.48), in spite of the expected less marked increase in blood pressure. In normoalbuminuric patients no significant increase in albumin excretion rate was noted by exercise in any of the treatment periods. A tendency to a linear correlation (r = -0.54, p = 0.07) was seen between the plasma concentration of indomethacin and the inhibition of exercise-induced increase in albumin excretion rate. No correlations were observed between exercise-induced changes in albumin excretion rate and systolic blood pressure, heart rate or blood glucose. In conclusion, acute indomethacin treatment, presumably through inhibition of renal prostaglandin synthesis, reduces the exercise-induced rise in albumin excretion rate in Type 1 diabetic patients with microalbuminuria.(ABSTRACT TRUNCATED AT 250 WORDS)     

Low urinary dopamine excretion associated to low sodium excretion in normotensive Piaroa Amazonian ethnia compared to urban subjects

The objective of this work was to compare urinary dopamine, noradrenaline, adrenaline, sodium and potassium excretion in a group of normotensive Piaroa Amazonic ethnia who do not use salt in their regular food intake, against a group of urban normotensive citizens known to have a high salt intake in their regular meals. Twenty adult normotensive Piaroa subjects living in the Amazonas forest, 11 men and 9 women, 23-72 years old, and 33 normotensive urban citizens, 25-70 years old, 17 men and 17 women, were included in the study. After a 10 min. rest, an average of three supine systolic (SBP) and diastolic (DBP) blood pressure recordings was obtained. Piaroas subjects SBP and DBP were 111.3 +/- 2.9 mmHg and 62.7 +/- 1.9 mmHg respectively; urban subjects SBP and DBP were 111.8 +/- 2.2 mmHg and 70.3 +/- 1.6 mmHg respectively. Supine heart rate was lower in Piaroas (58.0 +/- 1.8 beats/min) than in urban subjects (76.5 +/- 1.9 beats/min), p < 0.05. Sodium urinary excretion was much lower in Piaroas (12.6 +/- 5.2 mmol/24 h) when compared to urban subjects (210.7 +/- 24.5 mmol/24 h), p < 0.01. No difference was found in daily urinary potassium excretion between Piaroas and urban subjects (50.4 +/- 7.2 mmol/24 h vs 45.1 +/- 7.4 mmol/24 h). Urinary dopamine excretion was lower in Piaroas (314.7 +/- 40.1 micrograms/24 h) in comparison to urban subjects (800.4 +/- 59.2 micrograms/24 h), p < 0.05. Daily urinary noradrenaline and adrenaline excretion were 67.9% and 85.4% respectively lower in Piaroas than in urban subjects. In conclusion, lower amounts of sodium daily intake are associated to lower kidney dopamine production in Piaroas as compared to urban subjects. Apparently indigenous tribes might require less kidney dopamine synthesis to excrete the very small amounts of salt they consume in their regular food intake. The opposite was found in urban subjects; more kidney dopamine synthesis would be required for larger amounts of urinary sodium excretion. In this population, essential hypertension has been associated to a failure of the natriuretic mechanism triggered by dopamine onkidney tubules.     

Thrombogenic factors are related to urinary albumin excretion rate in type 1 (insulin-dependent) and type 2 (non-insulin-dependent) diabetic patients

Parameters of haemostasis, endothelial cell markers and lipid peroxide levels were studied in 64 Type 1 (insulin-dependent) and 94 Type 2 (non-insulin-dependent) diabetic patients according to their urinary albumin excretion rate in comparison with age-matched control subjects. We determined plasma levels of fibrinogen (Clauss' method), coagulation factor VII:activity (clotting assay), factor VII antigen, protein C and S antigen, von Willebrand factor antigen, D-dimer concentration (ELISA), and lipid peroxide levels (thiobarbituric acid) in relation to urinary albumin excretion rate (RIA). Significant positive correlations were found between urinary albumin excretion rate and plasma fibrinogen (p < 0.005, p < 0.02), factor VII activity (p < 0.0002, p < 0.002), factor VII antigen (p < 0.0001, p < 0.001), protein C (p < 0.003, p < 0.05), and lipid peroxides (p < 0.02, p < 0.004) in Type 1 as well as in Type 2 diabetes. Von Willebrand factor (p < 0.001) and protein S (p < 0.0005) correlated with albuminuria only in patients with Type 1 diabetes. Although most of the haemostatic abnormalities are already found in normoalbuminuric patients, the significant positive correlations to urinary albumin excretion indicate that endothelial cell damage and coagulation disorders deteriorate with the progression of diabetic nephropathy.     

Effect of diet on urinary MHPG excretion in depressed patients and normal control subjects

The authors studied the effect of a catecholamine-controlled diet on the urinary level of 3-methoxy-4-hydroxyphenylglycol (MHPG) of 6 depressed patients and 6 normal volunteers. The normal subjects showed no change in MHPG levels on or off the diet; the depressed patients showed a significant increase in MHPG while off the diet.     

Comparison of urinary excretion of UV-absorbing constituents in healthy subjects and patients with rheumatoid arthritis using analytical isotachophoresis

Analytical isotachophoresis has been applied to the separation of urinary constituents in healthy controls and patients with rheumatoid and osteoarthritis. Various methods of comparing isotachograms have been investigated. Significant differences have been demonstrated between the pattern of UV-absorbing components in patients with rheumatoid arthritis and healthy subjects.     

Associations between blood pressure and dietary intake and urinary excretion of electrolytes in a Chinese population

OBJECTIVE: The effect of age on energy expenditure was studied. DESIGN: Case-control study. SETTING: Respiration chamber at the University of Maastricht. SUBJECTS: Thirteen young men (27 +/- 4 years) and ten elderly men (74 +/- 5 years), were recruited with advertisements in local media. METHODS: In a 36 h experiment, 24 h energy expenditure (EE), sleeping metabolic rate (SMR), diet-induced thermogenesis (DIT) and energy expenditure of physical activity (EEact) were measured while subjects performed an activity protocol in a respiration chamber under strictly controlled conditions. RESULTS: SMR as a function of fat-free mass (FFM) was not different between both age groups. 24 h EE during a standardized activity protocol was significantly higher for the young men (young men: 12.85 +/- 1.53 MJ/d; elderly men: 10.90 +/- 1.12 MJ/d; P = 0.011). The DIT expressed as MJ/d was significantly higher for the young subjects but similar when expressed as percentage of energy intake (young men: 13.10 +/- 5.44%; elderly men: 9.88 +/- 3.86%). The resulting figure for EEact (24 h EE--SME--DIT) was the same for young and elderly men (young men: 3.11 +/- 0.71 MJ/d; elderly men: 3.05 +/- 0.64 MJ/d). CONCLUSION: The results indicate that mean energy costs for low intensity daily activities (some daily household activities and a bench stepping exercise) were the same for young and elderly men.     

Plasma homocysteine is related to albumin excretion rate in patients with diabetes mellitus: a new link between diabetic nephropathy and cardiovascular disease?

The high risk of cardiovascular disease in patients with diabetes mellitus, particularly in those with nephropathy, is not completely explained by classical risk factors. A high plasma homocysteine concentration is an independent risk factor for cardiovascular disease but information on its association with diabetes is limited. Fasting homocysteine concentrations were measured in the plasma of 165 diabetic patients (75 with insulin-dependent [IDDM]; 90 with non-insulin-dependent diabetes [NIDDM]) and 56 non-diabetic control subjects. Other measurements included the prevalence of diabetic complications, glycaemic control, lipid and lipoprotein levels, vitamin status and renal function tests. Patients with NIDDM had higher homocysteine levels than control subjects, whereas IDDM patients did not (9.2 +/- 4.5 vs 7.7 +/- 2 micromol/l, p < 0.01; and 7.0 +/- 3 vs 7.4 +/- 2 micromol/l, NS). Univariate correlations and multiple regression analysis showed albumin excretion rate to be the parameter with the strongest independent association with homocysteine. Patients with both types of diabetes and nephropathy had higher plasma homocysteine concentrations than those without nephropathy. Increases of homocysteine in plasma were related to increases in the severity of the nephropathy. Fasting hyperhomocysteinaemia was considered as the mean of the plasma homocysteine for all control subjects (7.5 +/- 2.1 micromol/l) + 2 SD (cut-off = 11.7 micromol/l). Nephropathy was present in 80 % of diabetic patients with fasting hyperhomocysteinaemia. In conclusion, increases in fasting homocysteine in diabetic patients are associated with increased albumin excretion rate, especially in those with NIDDM, thus providing a potential new link between microalbuminuria, diabetic nephropathy and cardiovascular disease.     

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.     

Increased 24-hour endothelin-1 urinary excretion in patients with chronic obstructive pulmonary disease

Abnormalities in endothelin-1 (ET-1) pulmonary metabolism have been reported in patients with pulmonary hypertension, asthma and chronic obstructive pulmonary disease (COPD). In this study we have evaluated the 24-hour urinary excretion of ET-1 in COPD patients both during acute exacerbation and stable phase of the disease. ET-1 plasma and urinary levels were measured in 13 COPD patients on admission to the hospital for an acute exacerbation and at the recovery period. Ten healthy volunteers were also studied. Determination of plasma and 24-Hour urinary ET-1 levels were carried out with a radioimmunoassay test. Plasma ET-1 levels in COPD patients were similar during exacerbation and recovery and were not significantly different from those in the healthy subjects. 24-hour urinary excretion of ET-1 was increased in COPD patients during acute exacerbation; it decreased during recovery, but remained elevated when compared to normal subjects. A negative correlation was found between arterial oxygen pressure and ET-1 excretion; no correlation was found between plasma and urinary ET-1 values. In conclusion, COPD patients excrete higher amounts of ET-1 compared to healthy subjects. Urinary ET-1 values are further increased during acute exacerbation of the disease.     

Prevalence of positive urinary dipstick analysis (leucocyte esterase, nitrite, haemoglobin, or glucose) in a population of 3645 adult subjects--consequence for measurement of urinary albumin excretion rate

A 10-year-old boy presented with typical fundus findings of frosted branch angitis in both eyes. Fluorescein angiography showed late-phase hyperfluorescence in some active areas of vascular lesions. Indo-cyanine green (ICG) angiography showed similar but less extensive hyperfluorescence along the frosted vessels and in the disc. ICG angiography also showed filling delay in the choriocapillaris. These findings suggest that frosted branch angitis is a manifestation of inflammation in the retina and the choroid. Laboratory studies showed increase in the toxoplasma titer at 1:10,240 and in the serum levels of alpha 1 and alpha 2 globulin. Frosted branch angitis in this case seemed to be the consequence of local allergic reaction, or immune complex deposition, presumably due to toxoplasma infections.     

The effect of N-acetylcysteine on total serum anti-oxidant potential and urinary albumin excretion in critically ill patients

PURPOSE: Calcium channel blockers have been reported to increase the risk of gastrointestinal bleeding. We tested this hypothesis, and also assessed whether beta blockers decrease this risk. SUBJECTS AND METHODS: A nested case-control design within a population-based cohort of all 34,074 new users of beta blockers, angiotensin-converting enzyme (ACE) inhibitors, or calcium channel blockers in Saskatchewan, from 1990 to 1993 and followed up to March 1995, was used. We identified all 311 subjects hospitalized because of gastrointestinal bleeding during this period, each of whom was matched to 10 randomly selected controls. RESULTS: The rate of hospitalization for gastrointestinal bleeding was 3.0 per 1,000 per year. The adjusted rate ratio of gastrointestinal bleeding for current use of calcium channel blockers was 1.1 (95% confidence interval [CI] 0.8 to 1.4) and 0.66 (95% CI 0.44 to 0.98) for beta blockers compared with no current use of anti-hypertensive drugs. The adjusted rate ratio for ACE inhibitor use was 1.0 (95% CI 0.7 to 1.3) while that for diuretic use was 1.4 (95% CI 1.0 to 2.0). CONCLUSIONS: The use of calcium channel blockers does not appear to increase the risk of gastrointestinal bleeding in the first five years of treatment, while beta blockers may prevent this adverse event. The unexpected elevated risk associated with the use of diuretics needs to be investigated further.     

Effect of quinapril on the albumin excretion rate in patients with mild to moderate essential hypertension. Multicenter Study Group

The rising number of emergency admissions and the increasing specialisation of medicine sometimes cause problems in the organisation of care for patients admitted as emergencies to medical beds. A multidisciplinary working group from general practice and the hospital sector identified five main areas in which problems occurred-communication, appropriateness of referral, finding beds, waiting by patients, and the organisation of clinical care. Guidelines and standards were suggested. We then carried out an audit of acute care in 42 hospitals with 400 or more acute beds. The most significant problems that emerged were the suboptimal involvement of consultants in acute care, the frequent lack of appropriateness of the admitting specialty to the patient's condition, and confusion about policies for admitting elderly patients.     

Divergent association of apolipoprotein E polymorphism with vascular disease in patients with NIDDM and control subjects

We analysed a well-characterized group of 83 patients (43 men, 40 women; mean age +/- SEM: 65.5 +/- 0.6 years at the 10-year examination) with non-insulin-dependent (Type 2) diabetes mellitus (NIDDM) and in 123 control subjects (56 men, 67 women; mean age +/- 0.9 years) retrospectively for the relationship of apolipoprotein E (apo E) genotypes (E2/3, E3/3 vs E3/4, E4/4) to the incidence of clinical macrovascular disease and its risk factors and the incidence of microvascular complications of diabetes during the first 10 years of NIDDM, as well as carotid intima-media thickness measured by B-mode ultrasound at the 10-year examination. In patients with NIDDM, apo E4 genotype showed no relationship to clinical events or carotid intima-media thickness. However, in the control subjects with apo E4, the incidence of non-fatal myocardial infarction during the follow-up was increased (apo E4 positivity: 17.1%; apo E4 negativity 5.1%; p = 0.035) and they had higher common carotid intima-media thickness than those with apo E2/3 or apo E3/3 (1.15 +/- 0.05 mm vs 1.01 +/- 0.03 mm, p = 0.008). Apo E genotype groups showed no relationship to microvascular complications of diabetes, although control subjects with apo E4 positivity showed a higher frequency of microalbuminuria than those lacking apo E4. We conclude that apo E4 was a marker of vascular disease and increased atherosclerosis in non-diabetic subjects, whereas in the diabetic patients these relationships were absent. It is likely that NIDDM per se influences the vascular risk so overwhelmingly that the effects of other risk factors are obscured.