Arylsulfatase A activity of urine in patients with various genitourinary tract disorders

Arylsulfatase A activity was measured in urine from patients with various genitourinary tract disorders such as bladder tumor and inflammation. No significant difference in enzyme activity was found between normal and affected urine on the basis of either the volume or protein content of urine, a finding which differed from previous results. However, it was demonstrated that urine from affected patients was more labile to heat treatment in comparison with the control. Upon pretreatment of urine arylsulfatase A at 62.5 degrees C for 10 min, an average of 57% of the original activity was lost in samples from patients with bladder tumor, 58% in those with testicular tumor and 62% in cystitis and urethritis, respectively, while the enzyme activity in the control urine lost only 27% with similar heat treatment. These results were statistically significant with p < 0.001. The arylsulfatase A from patients with advanced bladder tumors demonstrated the presence of a variant form (pI 5.3) which was not detected in normal urine. This variant of arylsulfatase A was also demonstrated in nephrostomy urine from patients with congenital obstruction of the pelvi-ureteric junction.     

Radioimmunoassay for arylsulfatase A in urine

Purified arylsulfatase A (EC 3.1.6.1) from human urine was radioiodinated under conditions that caused no significant loss of antigenic activity. We used this labeled arylsulfatase A (specific radioactivity 4-7.5 Ci/g) together with nonlabeled enzyme and rabbit antiserum produced against homogeneous enzyme to develop a radioimmunoassay for arylsulfatase A in urine. A solid-phase, second-antibody technique (Immunobead Second Antibody; Bio-Rad Laboratories) was used to separate free enzyme from antigen-antibody complexes. The working range of the assay was 0.1-4.0 ng of enzyme; within- and between-assay CVs were around 10%, and the analytical recovery was 105.5% (SD 7.7%). The lower limit of detection was 0.08 ng of arysulfatase A per assay, substantially less than that of typical activity-based assays. Over a wide range of urinary arylsulfatase A activities, results by this method agreed well (r = 0.99) with those obtained by activity assays. We measured the enzyme in urines of 59 healthy volunteers and 92 patients with different diseases, including a group of colorectal cancer cases, to determine whether this could serve as a reliable marker for cancer of the colon; however, urinary excretion of arylsulfatase A by most patients with colon cancer was within normal limits.     

A modified radioimmunoassay for arylsulfatase A in human serum and urine

A radioimmunoassay was developed for the determination of arylsulfatase A (EC 3.1.6.1) in human serum and urine. An isoenzyme of arylsulfatase A purified from human urine was used as a standard antigen. The enzyme was radioiodinated with 125I using the Chloramine T method and was stable for about 4 wk. Antibody-bound enzyme was separated from free enzyme by means of a double antibody technique in the presence of polyethylene glycol (PEG). The working range of the method was 0.15-5.0 ng of arylsulfatase A per assay. The within-assay CV was about 8% for both biological fluids and the between-assay CV for serum was 14.1%. Analytical recoveries were 93.2 +/- 9.1% and 97.8 +/- 5.5% for serum and urine, respectively, and the sensitivity was 0.040 ng of arylsulfatase per assay. Serum samples of 50 healthy blood donors were assayed to establish the normal serum level of immunoreactive enzyme, which was found to be 8.3 ng/ml +/- 1.8 ng/ml of serum. Storage of frozen serum was shown to have no significant effect on results obtained using this RIA.     

Arylsulfatase A activities in urine and tissues taken from bladder cancer patients

Urinary arylsulfatase A activity expressed as units/mg of urinary creatinine was significantly increased in bladder cancer patients, but not in patients with other genitourinary tract disorders, such as cystitis, urethritis and prostatic cancer, nor in patients with non-urological malignant diseases. The urinary enzyme activity was positively correlated with the stage of the bladder cancer, while post surgical follow-up revealed a marked decrease of the activity. Arylsulfatase A activity was also shown to be higher in malignant than in normal bladder tissue, demonstrating the activity to be a function of the grade of the tumor. Furthermore, the isoelectric point (pI 5.2-5.3) of the tissue enzyme in the bladder tumor coincided with that of the urine enzyme from the same cancer patients; the pI of the enzyme in urine from normal subjects was 4.7. These results suggest that most of the urinary arylsulfatase A in bladder cancer originates from tumor tissue.     

Urinary excretion of arylsulfatases in malnourished/vitamin A deficient children.

Serum vitamin A (retinol) levels were generally low in all malnourished children (6-15 microgram/100 ml) compared with control children (50 microgram/100 ml). A significant increase in vitamin A after appropriate therapy was observed in all malnourished groups. Dietary supplements of proteins and calories even without extra vitamin A supplements increased serum vitamin A levels in cases of kwashiorkor indicating active mobilization of liver vitamin A. Total urinary arylsulfatase A activity excreted in 24-h or within 8-h in the morning (6 a.m. to 2 p.m.) was significantly reduced in cases of malnutrition with or without mild vitamin A deficiency symptoms. The excretion of arylsulfatase B was not altered. In cases of severe vitamin A deficiency coupled with malnutrition increased excretion of both arylsulfatases A and B was evident. These results on urinary arylsulfatases excretory pattern have been obtained either in samples collected for 24-h or specifically for 8-h (morning) and it is suggested that this test on urinary arylsulfatases may prove useful for detection of acute vitamin A deficiency with malnutrition in field studies. A ratio of arylsulfatases A/B of 2.0 or less seems to indicate mild malnutrition, the normal ratio being 3.4. Furthermore a low ratio coupled with increased excretion of both arylsulfatases A and B may be considered specific for acute vitamin A deficiency.     

Diurnal variations of urinary enzyme excretion.

Variations in the urinary excretion of arylsulphatase A, beta-galactosidase, alpha-glucosidase and beta-glucuronidase throughout a 24-h period were studied in 8 healthy subjects. Urine was collected at 3-h intervals and enzyme activities were assayed after gelfiltration of the urine specimens. Significant intra-individual changes of the excretion of all 4 enzymes during the 24-h period were found. Enzyme output was high between 3 a.m. and 9 a.m. and low during the afternoon and evening hours. The most striking pattern was seen for arylsulphatase A. Diurnal variations of urinary enzyme excretion seemed not to be flow dependent. Both modes of expression of enzyme output (mU/min or U/g creatinine) gave corresponding results. It is concluded that for the measurement of the excretion of these enzymes urine should be collected during a fixed time interval, e.g. from 6 a.m. to 9 a.m.     

Protein-to-creatinine ratio in spot urine samples as a predictor of quantitation of proteinuria

BACKGROUND: Normal individuals usually excrete very small amounts of protein in the urine. Persistently increased protein excretion is usually a marker of kidney damage. Quantifying protein in urine is commonly used in the diagnosis of kidney diseases, detection of treatment effects and evaluation of prognosis. We evaluated the use of the total protein-to-creatinine ratio (P/C) in spot urine specimens as a predictor of urine protein excretion in 24-h collections. METHODS: The correlation between P/C in first morning and random urine specimens and urinary protein excretion in 24-h collections were analyzed. The cutoff value of P/C in first morning urine specimens for screening urinary protein excretion of 1 and 3 g in 24-h collections was determined by receiver operating characteristics (ROC) curve. RESULTS: For patients with Ccr 10 ml/min, the correlation was highly significant. Similar results were obtained for random urine specimens. By ROC curve analysis, the P/C of 0.94 and 2.84 g/gcr in first morning urine specimens represent the best threshold to detect urine protein excretion of 1 and 3 g in 24-h collections, respectively. There is a good correlation between P/C in first morning urine specimens and random urine specimens from inpatients and outpatients. But the P/C in random specimens is significantly higher than that in first morning specimens in outpatients. CONCLUSION: The P/C in spot urine samples could be used as an alternative to urine protein excretion in 24-h collections in patients with Ccr>10 ml/min. The P/C in first morning urine samples is better than that in random specimens, especially for outpatients.     

Decreased insulin requirement and improved control of diabetes in pregnant women given a high-carbohydrate, high-fiber, low-fat diet

Five quantitative measures of diabetic control [HbA1c determinations, mean 24-h plasma glucose values, mean amplitude of glycemic excursions (MAGE), mean 24-h urinary loss of glucose, and daily exogenous insulin requirement] were compared in 20 pregnant women who were randomly assigned to either a high-carbohydrate, high-fiber diet (HCF) that was low in fat or to a control diet commonly prescribed for pregnancy. Eleven women followed the HCF diet and nine subjects, the control diet, from baseline entry into the study until delivery. Dietary compliance was excellent, with 78% of the women in each group rated good or acceptable. HbA1c values were similar in both groups at baseline (HCF: 11.0 +/- 0.5% versus control: 10.2 +/- 0.6%), with no different predelivery values (8.6 +/- 0.4%). Mean 24-h plasma glucose levels improved in patients on both diets, with lower values noted in the HCF group at predelivery. MAGE values and standard deviations did not differ significantly in the two groups. Glycosuria decreased markedly in both dietary groups, but differences between groups were not significant. Improved control of diabetes on the HCF diet was achieved with significantly lower increments in insulin dose during gestation (HCF baseline: 32 +/- 8 U/24 h to 66 +/- 10 U/24 h versus control baseline: 27 +/- 9 U/24 h to 108 +/- 12 U/24 h, P less than 0.03). Outcome of pregnancy did not differ in the two groups of patients, but women on the HCF diet gained less weight than those on the control diet (26 +/- 3 lb versus 35 +/- 5 lb, P less than 0.05). Mean newborn gestational age was similar in the two groups (HCF: 37.2 +/- 0.7 wk versus control: 36.5 +/- 0.7 wk). Mean birth weight in infants of HCF mothers was 3809 +/- 248 g versus 3313 +/- 278 g in infants of control mothers (P less than 0.05). We conclude that although marked improvement of diabetic control occurred on both regimens, patients on the HCF diet achieved better control of diabetes with significantly lower increments in exogenous insulin.     

Effects of chronic administration of an angiotensin-converting enzyme inhibitor on angiotensin-converting enzyme activity in the pars recta of rabbits

1. To determine whether chronic angiotensin-converting enzyme inhibition induces a decrease in proximal tubular angiotensin-converting enzyme activity, urine and blood samples were collected in conscious New Zealand rabbits before and after 16 days administration in drinking water of low doses of captopril (2.6 +/- 0.6 mg 24 h-1 kg-1), high doses of captopril (7.6 +/- 0.9 mg 24 h-1 kg-1) or no captopril (controls). The kidneys were then removed and angiotensin-converting enzyme activity was determined in isolated pars recta of microdissected nephrons as pmol of tritiated hippurylglycylglycine substrate hydrolysed min-1 of incubation and mm-1 of tubule. 2. Both low and high doses of captopril significantly decreased plasma angiotensin-converting enzyme activity and increased plasma renin activity, thus indicating an effective inhibition of circulating angiotensin-converting enzyme. Both low and high doses of captopril also significantly decreased mean arterial pressure and increased water intake and urine flow rate. Neither dose modified creatinine clearance and absolute and fractional sodium excretion. 3. None of the doses altered urinary kallikrein excretion. Urinary excretion of kinins was increased by 98.7% compared with control rabbits by the high dose of captopril (402 +/- 152 vs 251 +/- 104 ng/24 h, P less than 0.01) but was unchanged by the low dose of captopril. 4. Angiotensin-converting enzyme activity in the pars recta was lower in rabbits given the high dose of captopril than in control rabbits (17.6 +/- 7.2 vs 37.3 +/- 9.0 pmol min-1 mm-1, P less than 0.01) but was not decreased in rabbits given the low dose of captopril (40.4 +/- 5.0 pmol min-1 mm-1).(ABSTRACT TRUNCATED AT 250 WORDS)     

Single-void urine samples can be used to estimate quantitative microalbuminuria

The excretion of small quantities of urinary albumin (microalbuminuria) may predict renal failure in diabetes. The measurement of microalbuminuria with radioimmunoassays has been based on 24-h, overnight, and 3- to 4-h collections. To determine whether single-void urine samples can be used to estimate 24-h excretion, we compared the results of 24-h outpatient urine collections with single-void samples corrected for creatinine from diabetic and nondiabetic subjects. The overall correlation of single-void sample results expressed as microgram albumin per milligram creatinine with 24-h excretion (mg/24 h) was excellent (r = .82, P less than .001). More important, in the diabetic patients the sensitivity and specificity of detecting 24-h microalbuminuria in the abnormal range were at least 94 and 96%, respectively. Single-void urine specimens adjusted for creatinine discriminate between normal and abnormal levels of microalbuminuria, as determined in 24-h urine collection, with high specificity and sensitivity.     

Elevated serum levels of angiotensin-converting enzyme in patients with diabetic retinopathy

Serum levels of angiotensin-converting enzyme (ACE) were measured in 53 patients with type II (non-insulin-dependent) diabetes (25 without ophthalmologic complications, 20 with background retinopathy, and eight with proliferative retinopathy) and in 33 healthy nondiabetic subjects. Diabetic subjects were excluded if they had hypertension, ischemic heart disease, peripheral vascular disease, or an elevated urine albumin level. After an overnight fast, blood was taken for determination of ACE, blood glucose, glycosylated hemoglobin (HbA1), and C peptide levels. Data were analyzed according to the nonpaired Student's t test and linear regression analysis. Levels of ACE were significantly elevated in the whole diabetic group as compared with control subjects (334.0 U/L +/- 97.0 vs 250.5 U/L +/- 85.5, P less than .001). This elevation was more marked in those diabetics with background retinopathy (344.6 U/L +/- 96.8, P less than .001) and proliferative retinopathy (357.3 U/L +/- 93.2, P less than .01); no significant difference was found between ACE levels of diabetics without complications and those of control subjects. No correlation was found between ACE levels and HbA1, blood glucose, or C peptide values. We conclude that ACE levels are elevated in type II diabetes, chiefly in patients with retinopathy. This finding may reflect microvascular damage caused by secretion of ACE by the vascular endothelial cells.     

Effect of intranasal histamine on nasal mucosal blood flow and the antidiuretic activity of desmopressin.

The effects of exogenous histamine on nasal mucosal blood flow and the systemic activity of intranasally administered desmopressin, a vasopressin analogue, were studied in normal volunteers. Ten subjects received either saline or histamine (1, 20, 100, and 500 micrograms) by intranasal spray. Maximal nasal mucosal blood flow response, determined by laser doppler velocimetry, demonstrated a significant (P less than 0.05) linear relationship to histamine dose. Eight additional subjects received each of the following intranasal treatments: 20 micrograms histamine followed by 10 micrograms desmopressin; normal saline followed by 10 micrograms desmopressin; 20 micrograms histamine followed by vehicle; or normal saline and vehicle. Nasal blood flow was determined before and after each treatment. Desmopressin activity was assessed by measuring urine osmolality, flow rate, electrolyte, and creatinine concentration for 24 h after each treatment. The effect of histamine and desmopressin was greater than desmopressin alone, with respect to nasal blood flow response (103 +/- 24 vs. 4 +/- 17%, mean +/- SEM, P less than 0.02), initial urine osmolality (520 +/- 123 vs. 333 +/- 75 mosM, P less than 0.03), urine electrolyte (potassium, 45 +/- 11 vs. 28 +/- 7 meq/liter; sodium, 68 +/- 21 vs. 36 +/- 8 meq/liter, P less than 0.03) and creatinine concentrations (95 +/- 23 vs. 60 +/- 13 mg/dl, P less than 0.03), and the duration of decrease in urine flow rate compared with saline and vehicle. These results suggest that the systemic activity of intranasal desmopressin is enhanced by increasing local nasal blood flow and are consistent with increased transnasal absorption of the peptide.     

Limitations of urinary telomerase activity measurement in urothelial cancer

The reported frequency of detectable telomerase activity in spontaneously voided urine samples from patients with urothelial cancer varied from 0 to 85%. We examined stasis in the bladder and specimen storage as interfering conditions in this assay. Telomerase activity in exfoliated cells was measured by a polymerase-chain-reaction-based assay in spontaneously voided urine from urothelial cancer patients. Effects of retention in the bladder and specimen storage from voiding to measurement of telomerase activity were modeled by suspending 10(6) cells from the cancer-derived T24 line in normal urine (pH 6.5) at 37 degrees C and 25 degrees C, respectively. Hematuria was modeled by adding hemoglobin. In T24 cells suspended in urine at 37 degrees C, telomerase activity had decreased to approximately 20% of preincubation activity after 1 h, and had disappeared after 3 h. In urine at 25 degrees C, telomerase activity in T24 cells had decreased to approximately 40% of preincubation activity at 1 h and to <10% at 6 h. When we examined telomerase activity in exfoliated cells in spontaneously voided urine from urothelial cancer patients (excluding first-voided morning specimens), telomerase activity was detected in only 21% of samples (four of 19) despite measurement with 1 h of voiding and steps to avoid hemoglobin interference. Measurement of telomerase activity in spontaneously voided urine is insufficiently sensitive and reliable for the diagnosis of urothelial cancer.     

Urine C-peptide after recovery from diabetic ketoacidosis: an index of insulin dependency

C-peptide immunoreactivity (CPR) in 24-h urine was assayed in 13 diabetic patients during and after recovery from ketoacidosis. In 10 patients who remained insulin-dependent on discharge and in the subsequent follow-up period, urine CPR was low (18 micrograms/day or less), while in three patients who were ultimately controlled by diet or sulfonylureas, urine CPR was normal (59-92 micrograms/day, normal value 74 +/- 26 micrograms/day). In the latter group, urine CPR in one patient assayed during ketoacidosis was 6 micrograms/day and, in another patient, it was 22 micrograms/day on the 3rd day of the admission. This may imply that in the latter group, B-cell function was decompensated in ketoacidosis, but was restored after recovery. Clinical courses suggested that these patients were not in the remission phase of IDDM, but belonged to NIDDM. Among other groups of diabetic patients, urine CPR in those treated with diet or sulfonylureas was 72 +/- 30 micrograms/day and always higher than 20 micrograms/day. The prevalence of urine CPR less than 20 micrograms/day was more frequent in those with younger onset of diabetes, higher insulin dosage, unstable diabetes, or previous history of ketoacidosis among insulin-treated patients. We suggest that urine CPR less than 20 micrograms/day is an index of insulin dependency, although in a state of extreme decompensation of B-cells such as in ketoacidosis, urine CPR can be decreased low even in NIDDM.     

Regulation of nitric oxide synthesis by proinflammatory cytokines in human umbilical vein endothelial cells. Elevations in tetrahydrobiopterin levels enhance endothelial nitric oxide synthase specific activity.

We have examined cytokine regulation of nitric oxide synthase (NOS) in human umbilical vein endothelial cells (HUVEC). 24-h treatment with IFN-gamma (200 U/ml) plus TNF (200 U/ml) or IL-1 beta (5 U/ml) increased NOS activity in HUVEC lysates, measured as conversion of [14C]L-arginine to [14C]L-citrulline. Essentially, all NOS activity in these cells was calcium dependent and membrane associated. Histamine-induced nitric oxide release, measured by chemiluminescence, was greater in cytokine-treated cells than in control cells. Paradoxically, steady-state mRNA levels of endothelial NOS fell by 94 +/- 2.0% after cytokine treatment. Supplementation of HUVEC lysates with exogenous tetrahydrobiopterin (3 microM) greatly increased total NOS activity, and under these assay conditions, cytokine treatment decreased maximal NOS activity. IFN-gamma plus TNF or IL-1 beta increased endogenous tetrahydrobiopterin levels and GTP cyclohydrolase I activity, the rate-limiting enzyme of tetrahydrobiopterin synthesis. Intracellular tetrahydrobiopterin levels were higher in freshly isolated HUVEC than in cultured cells, but were still limiting. We conclude that inflammatory cytokines increase NOS activity in cultured human endothelial cells by increasing tetrahydrobiopterin levels in the face of falling total enzyme; similar regulation appears possible in vivo.     

Prostatic inhibin-like peptide quantified in urine of prostatic cancer patients by enzyme-linked immunosorbent assay

This is a highly specific enzyme-linked immunosorbent assay (ELISA) for measuring prostatic inhibin-like peptide (PIP) in urine, in which we use penicillinase (EC 3.5.2.6) conjugated with PIP and, as solid phase, a polystyrene microtiter plate. We used this ELISA to measure PIP in 24-h urine specimens from men with prostatic cancer (PCa) and from age-matched controls. For prostatic cancer patients the mean +/- SEM urinary PIP of 36.1 +/- 5 micrograms/24 h was significantly (P less than 0.001) lower than the mean of 127.1 +/- 9 micrograms/24 h for the age-matched controls. PIP values for 30 samples measured by both ELISA and RIA correlated well (r = 0.985). We could detect as little as 1.56 ng of PIP in a sample. Analytical recovery of added PIP ranged from 91% to 104%. Mean CVs were 8.9% within-assay and 12.7% between-assay. We believe that this ELISA will be useful in assessing the status of PIP in men with normal and diseased prostates and in examining the function of the hypothalamus-pituitary-prostate axis.     

Effects of amlodipine and fosinopril on heart rate variability and left ventricular mass in mild-to-moderate essential hypertension

The differences between long-acting dihydropyridines and angiotensin-converting enzyme inhibitors with regard to their long-term effects on 24-h heart rate variability (HRV) and left ventricular (LV) mass are less clear in mild-to-moderate essential hypertension. We studied the long-term effects of amlodipine and fosinopril on 24-h HRV and LV mass in mild-to-moderate essential hypertension. In this study, 27 patients with never treated mild-to-moderate essential hypertension were randomised to receive either amlodipine or fosinopril once daily as monotherapy. At baseline and at the end of the third and sixth months, each of the patients underwent 24-h HRV and ambulatory systolic (SBP) and diastolic (DBP) blood pressure analysis. LV mass index was calculated from echocardiographic examination at baseline and at the end of the sixth month. In amlodipine group (n = 14), 24-h SBP/DBP (mmHg) decreased from 144 +/- 8/94 +/- 4 to 128 +/- 6/83 +/- 3 at the end of the third month and to 125 +/- 5/81 +/- 2 at the end of the sixth month (p < 0.0001). In fosinopril group (n = 13), the respective changes were 143 +/- 9/97 +/- 7, 132 +/- 6/87 +/- 5 and 127 +/- 6/82 +/- 3 (p < 0.0001). At the end of the sixth month, LV mass index (g/m(2)) decreased from 122 +/- 26 to 105 +/- 21 in amlodipine group (p < 0.0001) and from 118 +/- 23 to 101 +/- 14 in fosinopril group (p < 0.0001). There were no significant changes in HRV parameters in both the groups. It was concluded that both drugs caused significant decrease in SBP and DBP, and LV mass in patients with mild-to-moderate essential hypertension did not have significant long-term effects of either amlodipine or fosinopril on 24-h HRV parameters reflecting sympathetic or parasympathetic activity in these patients.     

Urinary lactate excretion in normal children and in children with enzyme defects of carbohydrate metabolism.

Urinary lactate was analyzed in 53 normal children, 7 children with glucose-6-phosphatase-deficient glycogenosis, 1 child with fructose-1,6-diphosphatase deficiency and 1 child with pyruvate dehydrogenase deficiency. Lactate in 24-h urine was expressed as concentration, total excretion, excretion per kg body weight and per 1.73 m2 body surface, and as lactate/creatinine quotient. Of these parameters, the lactate concentration in 24-h urine showed the smallest variation in normal children (0.155 +/- 0.053 mM), whereas in patients with one of the above mentioned enzymopathies 10-300-fold elevations were found. The lactate/creatinine quotient, normal range 0.010 to 0.058 (mM/mM) was also used to correct for unnoticed losses of urine. Both parameters, used in conjunction with blood lactate analysis, are suitable for a first screening of patients with enzymopathies of carbohydrate metabolism, and for the follow-up study of the steady or unsteady state of the patient with an enzyme defect of carbohydrate metabolism.     

Expression modes of urinary N-acetyl-beta-D-glucosaminidase in patients with chronic renal insufficiency

BACKGROUND: Urinary N-acetyl-beta-D-glucosaminidase (NAG) activity has emerged as potentially useful early marker of renal tubular injury. This activity is usually evaluated in random urine samples and is related to urinary creatinine concentration. Reports about the lack of correlation between NAG activity of 24-h urines and activity of random urine samples in some clinical and experimental situations led us to study the correlation existing between different procedures for expressing urinary NAG in patients with chronic renal insufficiency. METHODS: Thirty samples of 24-h urine and 30 random urine samples from chronic renal insufficiency patients were collected. The activity of urinary NAG was examined fluorimetrically. RESULTS: The following correlations were observed: (1) r = 0.431 (P = 0.017) for activity in random urine samples and total activity in 24-h urines); (2) r = 0.281 (P = 0.005) for activity in random samples and activity, expressed as U/l, in 24-h urines. CONCLUSIONS: The data show that collection of urine excreted over the whole day and evaluation of total daily excretion of NAG seems the method of choice, at least for patients with chronic renal insufficiency.     

Comparison of albumin excretion rate obtained with different times of collection

This study was undertaken to assess the usefulness of different techniques for determination of albumin excretion rate (AER). Ninety patients with type I (insulin-dependent) diabetes mellitus and 45 with type II (non-insulin-dependent) diabetes mellitus, with AER/24 h of less than 200 micrograms/min, were included. All patients were free of major systemic complications of diabetes and overt kidney disease (mean serum creatinine 1.1 +/- 0.1 mg/dl, range 0.4-1.2 mg/dl). We compared timed day, night, and 24-h specimens, as well as timed spot specimens during water-induced diuresis. Most patients with type I (75 of 90) and type II (30 of 45) diabetes had AER less than 20 micrograms/min and showed significant differences in AER that were dependent on the collection time. Differences were diminished or absent with AER less than 20 micrograms/min. Sensitivity, specificity, and prediction rates of AER in different specimens were evaluated against 24-h AER. Use of albumin concentrations and albumin-creatinine ratios did not improve test performance in comparison with AER. Sampling time and the overall rate of AER influenced measurement of urinary albumin excretion. Day or 24-h AER is most useful to determine the presence of abnormal AER. AER and albumin concentration in spot samples are of limited use for initial screening and frequently require day or 24-h specimens of AER for confirmation. Day or 24-h AER should be used for long-term follow-up of the diabetic patient.