Urinary albumin excretion in normal and diabetic subjects

Using an albumin radio-immuno-assay, urinary albumin concentration and excretion rate have been measured in diabetics and control subjects overnight, after several hours ordinary activity and during two successive one hour periods of recumbency. The urine albumin concentration was relatively constant throughout each of the four collection periods. Variations in albumin excretion rate were directly related to changes in urine flow. In assessing changes in urinary albumin, concentration and urine flow should be reported as well as the calculated albumin excretion rate.In the diabetics, selected for absence of clinical proteinuria, the mean concentration of albumin did not differ significantly from that of the controls. The overnight albumin excretion rate was higher in the diabetics, but this was due to the greater volume of urine.     

Urinary excretion of hyaluronan in man

A specific assay for hyaluronan (hyaluronic acid) has been applied to the determination of the polysaccharide in urine. The excretion in 22 healthy subjects was 330 micrograms/24 h (SD 77). The excretion was correlated with body weight and was therefore somewhat higher in males than in females. The molecular weight of the main fraction of urinary hyaluronan was in the range of 4000 to 12,000 in accordance with the hypothesis that it originates from blood and arises by glomerular filtration. A small fraction was of higher molecular weight and could have been produced in the urinary tract. Hyaluronan in male and female urine displayed the same molecular weight distributions. Patients with rheumatoid arthritis and primary biliary cirrhosis showed a two-fold and three-fold increase, respectively, of hyaluronan in urine with concurrently high levels of the polysaccharide in serum. A patient with Werner's syndrome displayed a ten-fold increase of the polysaccharide in both serum and urine.     

Urinary excretion of carnitine in man.

A convenient assay procedure for urinary carnitine is described. Urinary excretion of carnitine is determined in human subjects in various experimental states. Average excretions by this procedure were 59.3+/-3.3 mg. per day in men and 44.1+/-2.9 mg. per day in women. Carnitine excretion had a wide variation in women during the menstrual cycle and reached a maximum at the time of ovulation, but the excretion was relatively constant in men. Marked increases in carnitine excretion were observed in the states with increased lipolysis induced by fasting or ACTH injection. This finding suggests that lipid mobilization might be reflected in the excretion of carnitine in urine.     

Endocrine and renal response to water loading and water restriction in normal man

1. Nine normal subjects (eight male, one female) on a fixed daily intake of 150 mmol of sodium and 80 mmol of potassium, were randomized to receive either 3 days of 1.0 litre total water intake/24 h (food + fluid) or 4 days of 6.8 litres total water intake/24 h, and were then crossed over after a 3 day control period (2.7 litres water/24 h). 2. During water restriction, urine volume fell from 1.94 litres/24 h to less than 1 litre/24 h by the first day and was 0.77 litre/24 h on the final day. Plasma atrial natriuretic peptide levels were unchanged from baseline despite a large increase in plasma vasopressin and plasma and urine osmolality. Urinary sodium was unaltered throughout, while urinary potassium was increased on the final 2 days of water restriction. 3. During water loading, urine volume increased from 1.85 litres/24 h to 5.44 litres/24 h on the first day and remained at approximately 6 litres/24 h for the final 3 days. Plasma atrial natriuretic peptide showed no change. Plasma vasopressin and plasma and urine osmolality were reduced. Urinary sodium and potassium output were unchanged from baseline. 4. These results suggest that changes in plasma atrial natriuretic peptide are unlikely to be involved in the normal homoeostatic response to changes in water balance in man.     

Urinary albumin excretion and blood pressure in the general population

1. Twenty-four hour urinary albumin excretion rate was measured by a sensitive radioimmunoassay in 99 male and 100 female randomly selected factory workers, aged between 20 and 60 years. 2. The median (range) albumin excretion rates for men and women of 4.67 (1.0-25.8) and 5.25 (0.2-33.0) mg/24 h, respectively, were not significantly different. 3. No correlation was established between diastolic, systolic or mean arterial blood pressure and albumin excretion rate for the whole group. 4. Twenty-eight subjects with systolic and/or diastolic blood pressures greater than or equal to 140/90 mmHg (18.7/12.0 kPa) showed a positive correlation between mean arterial blood pressure and albumin excretion rate (r = 0.412, P less than 0.01). 5. There was no significant relationship between number of cigarettes smoked, age or alcohol intake and albumin excretion rate. 6. The data suggest that in the general population albumin excretion rate is variable and not dependent on blood pressure, but at blood pressures greater than 140/90 mmHg (18.7/12.0 kPa) albumin excretion rate may become pressure dependent, although high albumin excretion rates were sometimes found in subjects with blood pressures less than 140/90 mmHg (18.7/12.0 kPa).     

Urinary albumin excretion in normal subjects and in diabetic patients measured by a radioimmunoassay: methodological and clinical aspects

We have developed a radioimmunoassay method (RIA) to measure urinary albumin excretion. We determined the albumin excretion rate (AER) (micrograms/min) of 122 healthy subjects and 145 diabetic patients (115 type I, 30 type II). The results indicate that the RIA is sensitive (0.39 +/- 0.08 mg/L), precise (CV 5-8%), and gives reliable results on previously frozen urine samples. The distribution of the AER values in healthy subjects and diabetic patients was not normal. It was normalized by log or square-root transformation of the data. Seventy-three percent of diabetic patients lay within the normal range (0.6-10.6 micrograms/min). Twenty percent could be considered "at risk" to develop overt diabetic nephropathy because their albuminuria exceeded a threshold level of 15 micrograms/min chosen previously as the cutoff value for microalbuminuria. We found no correlation between AER and glycated hemoglobin, and only a weak correlation between AER and diabetes duration in type I diabetic patients.     

Urinary excretion of bile acids during acute administration in man

Six healthy subjects, 45-72 years old, received a 10-day feeding of 750 mg of two of the following bile acids: deoxycholate (DCA), chenodeoxycholate (CDCA), cholate (CA), hyodeoxycholate (HDCA), ursodeoxycholate (UDCA), and ursocholate (UCA). The urinary excretion of total bile acids was low during administration of lipophilic bile acids (DCA and CDCA), when serum levels show low postabsorption peaks. Instead, hydrophilic bile acids (UDCA and above all HDCA) were heavily excreted in the urine as sulphates and glucuronides, and serum levels reach high values. Only UCA, strongly hydrophilic, was predominantly excreted as unconjugated fractions. Thus, the physicochemical properties of bile acids (as measured by both the partition between octanol and water, and the water solubility) were factors that influenced the route of bile acid elimination from the body, whereas their conjugation was not always requested for urinary excretion.     

Urinary excretion of heroin and its metabolites in man.

The purpose of this study was to investigate the kinetics of urinary excretion of heroin and its metabolites in human subjects. Heroin and its metabolites were determined with gas-liquid chromatography. Two studies were conducted, each using 10 subjects. After i.v. administration of heroin HC1, 10 mg/70 kg, urine was collected every 8 hours and ad libitum for 1 week in the first study and every 2 hours in the first 8 hours and then at less frequent intervals for 24 hours in the second study. Heroin, 6-acetylmorphine, morphine, the sum of conjugates (morphine plus 6-acetylmorphine) and total normorphine were determined in the first 24-hour urine and accounted for 0.5, 1.5, 7.2, 52 and 4%, respectively, of the administered dose. Conjugated morphine could be detected in the urine 96 hours after drug administration. Eighty-eight percent of the free morphine and 84% of the total morphine found in the urine were excreted in the first 8 hours. The half-lives of urinary excretion of free morphine, 6-acetylmorphine, the sum of conjugates (morphine plus 6-acetylmorphine) and total normorphine were 1.28, 1.31, 2.76 and 2.72 hours, respectively. It was concluded that heroin in the body was rapidly metabolized and its metabolites were rapidly excreted in the urine.     

Urinary excretion of hydroxyprolines in man under the influence of cold.

Urinary hydroxyproline excretion was studied in human subjects exposed to cold stress and was related to urine flow and tubular reabsorption of calcium and phosphate. The results indicate the occurrence of a calcium release from the bones, which does not seem to be caused by changed activity or immobilization. The cold-induced changes--calcium excretion, dehydration, and demineralization - are the same as those reported under space-flight conditions. Furthermore, it has also been possible to induce a similar response with psychological stress agents. These findings, together with recent observations on renal stone formation and hyperparathyrodism, indicate that different types of stress might have a direct influence on calcium homeostasis, possibly mediated by the adrenergic nervous system.     

Urinary excretion of N-acetyl-beta-D-glucosaminidase in normal and complicated pregnancy

The urinary excretion of N-acetyl-beta-D-glucosaminidase activity, a sensitive indicator of renal tubular injury, was monitored during and after pregnancy. During normal pregnancy, enzymuria increased progressively to levels 3-4 times above normal in the third trimester. In diabetic mothers, enzyme excretion followed a similar pattern, but was generally higher than in uncomplicated pregnancies. Also in preeclampsia, enzymuria tended to be higher than in normal pregnancy. Enzyme excretion normalized about a year after normal pregnancies, but remained elevated in diabetic subjects and in patients who had developed preeclampsia. This latter finding indicates that marginal persistent renal damage may occur during preeclampsia.     

Urinary albumin excretion: a predictor of glomerular findings in adults with microscopic haematuria

BACKGROUND: Microscopic haematuria without proteinuria is a common clinical finding. When urological causes are excluded, usual findings on renal biopsy are IgA nephropathy (which can progress to end-stage renal failure) or thin basement membrane nephropathy (which has an excellent prognosis). A non-invasive test to discriminate between the two would be useful. Aim: To examine the value of measurement of urinary albumin excretion in discriminating glomerular causes of microscopic haematuria in patients without proteinuria on urine dipstick tests. DESIGN: Single-centre retrospective cross-sectional observational study. METHODS: Adult patients who underwent renal biopsy for microscopic haematuria over a 6-year period from January 1994 were identified. Study entry required normal renal function, no proteinuria detected by dipstick, and urinary albumin excretion <300 mg/24 h. Patients with IgA nephropathy had follow-up for a mean of 58 months after biopsy. RESULTS: Of 169 patients fulfilling study criteria, 119 (70%) had normoalbuminuria (<30 mg/24 h); 52 (30%) had microalbuminuria (30-299 mg/24 h). Of those with normoalbuminuria, 106 (89%) had thin basement membrane nephropathy or no glomerular abnormality. Thirteen (11%) had IgA nephropathy, and of 12 of these followed-up for a mean 64 months, none developed overt, dipstick-positive proteinuria. In contrast, 24 (48%) of those with microalbuminuria had IgA nephropathy, and of 22 followed-up for a mean 55 months, five developed overt proteinuria. DISCUSSION: Urinary albumin excretion is an indicator of likely glomerular findings in microscopic haematuria, and may influence whether a renal biopsy is necessary.     

Low-dose dopamine infusion, renal haemodynamics and urinary albumin excretion rate in insulin-dependent diabetics and in normal man

The effect of experimental renal vasodilatation by means of low-dose (2.0 micrograms/kg/min) intravenous dopamine infusion was investigated in 28 insulin-dependent diabetes mellitus (IDDM) patients with normal basal urinary albumin excretion rate (UAE) (less than 15 micrograms/min), 9 IDDM patients with UAE between 15-200 micrograms/min (microalbuminuria), and 7 normal subjects. Glomerular filtration rate (GFR) (thalamate clearance) showed a small increase with dopamine infusion, in the normoalbuminuric IDDM patients from 140 +/- 20 to 146 +/- 20 ml/min (2p less than 0.01), in the microalbuminuric IDDM patients from 146 to 151 ml/min (NS), and in normal subjects from 115 +/- 16 to 122 +/- 15 (2p less than 0.05). A marked increase in renal plasma flow (RPF) (hippuran clearance) was seen in all three groups--533 +/- 82 to 724 +/- 120 ml/min (2p less than 0.01), 574 +/- 69 to 777 +/- 140 ml/min (2p less than 0.01) and 523 +/- 87 to 749 +/- 145 ml/min (2p less than 0.05), respectively. Urinary albumin excretion rate (radioimmunoassay) increased from 5.3 x/divide 1.5 (tolerance factor) to 6.5 x/divide 1.8 micrograms/min (2p less than 0.05) in the normoalbuminuric IDDM patients and from 6.1 x/divide 2.1 to 7.8 x/divide 2.3 micrograms/min (2p less than 0.05) in the normal subjects, while no significant change was seen in the microalbuminuric group of diabetics. Kidney volume (ultrasonic scanning) was significantly enhanced in IDDM patients (294 +/- 73 ml vs. 196 +/- 49 ml). There was no significant correlation between kidney volume and the renal haemodynamic response to dopamine.(ABSTRACT TRUNCATED AT 250 WORDS)     

Low dose infusion of atrial natriuretic peptide causes salt and water excretion in normal man

1. The effects of low dose infusion of atrial natriuretic peptide (ANP) were observed in double-blind, placebo-controlled study in six fluid-loaded volunteers. After baseline observations, hourly increments of 0.4, 2 and 10 pmol min-1 kg-1 were infused with continuous observation of heart rate, blood pressure and cardiac output. Plasma ANP, aldosterone, and catecholamines, and urinary volume and sodium excretion, were estimated at half-hourly intervals. 2. ANP infusion resulted in an increase of 35, 98 and 207% in urinary sodium excretion and of 10, 20 and 71% in urinary volume when compared with placebo. Plasma ANP was markedly elevated above placebo levels only during infusion of 10 pmol of ANP min-1 kg-1. 3. No change in heart rate of blood pressure was noted during the study, but a significant fall in stroke volume index was observed during active treatment. Plasma levels of aldosterone and catecholamines were not significantly different on the 2 treatment days. 4. The potent natriuretic and diuretic effects of this peptide at plasma concentrations not significantly elevated from physiological suggest a hormonal role for ANP in the homoeostasis of salt and water balance.     

The effect of potassium loading on sodium excretion and plasma renin activity in Addisonian man.

Potassium has been shown to suppress plasma renin activity (PRA). This study was designed to study the role of increased aldosterone production in the mediation of such a response. Five patients with adrenal insufficiency were placed on a diet of 60 meq potassium and 100-150 meq of sodium while receiving a constant amount of cortisone acetate and Florinef. Upright PRA was determined each day for 2-3 days in the control period and then for 3-4 days after potassium intake had been increased to 200-300 meq/day. Potassium loading induced a natriuresis. Hence, patients were either sodium replaced (six studies in four patients) or allowed to become sodium depleted (three patients). Potassium loading without replacement was associated with a decrease in weight, negative sodium balance, hyperkalemia, and a positive potassium balance. PRA rose during the experimental period. Potassium loading with sodium replacement was associated with little change in weight or sodium balance. Hyperkalemia and positive potassium balance were present to the same degree as found in the studies without sodium replacement. When all PRA values are considered (both morning and evening values) there was no significant change with potassium loading (+ 1.31 ng/ml per h; range + 6.9 to -2.0). We conclude that hyperkalemia or a positive potassium balance did not suppress PRA in Addisonian man in these studies when sodium balance was maintained, nor did it prevent a rise in PRA when sodium balance was negative.