Urinary excretion of albumin beta2-microglobulin and free light chains during lithium treatment.

Albumin, beta2-microglobulin and free light chains were determined in urine in nine manic-depressive patients before and at intervals during three months of lithium treatment (longitudinal study). The same determinations were carried out in twenty-seven manic-depressive patients who had been treated with lithium for 3 months to 20 years and also in a control group (transversal study). There were no statistically significant changes in urinary excretions of albumin, beta2-microglobulin and free light chains during the longitudinal study. In one patient albumin excretion gradually increased during the study and remained elevated on reexamination 1 year later. No significant differences were found between the lithium treated patients and control subjects in the transversal study in either albumin, beta2-microglobulin or free light chain excretion. It is not clear whether the increased and sustained albumin excretion in one of the patients was due to lithium or was conincidental. The study shows that in most patients lithium treatment does not affect renal protein excretion.     

Urinary excretion of beta 2-microglobulin in myeloma patients

The levels of beta 2-microglobulin in urine and serum were determined in 39 patients with myelomatosis. In 25 patients the serum beta 2-microglobulin was elevated, and in seven of the patients with increased serum beta-microglobulin the urinary excretion of the protein was also increased. It was concluded that the increased urine beta-microglobulin indicates a renal tubular disorder.     

Urinary alpha 1 microglobulin levels in surveys of Balkan endemic nephropathy

The urinary alpha 1-microglobulin (alpha 1m) concentration was measured in 644 adults living in districts where Balkan nephropathy (BEN) is endemic. Comparison of alpha 1m with other indicators of tubular proteinuria, which is a classical sign of BEN, showed alpha 1m was a satisfactory marker. Using a cut-off of 20 mg alpha 1m/L none of 102 normal UK residents had a positive level. Whilst a raised level of alpha 1m was present in 85.7% of definitive cases of BEN and in 8.1%, 10.2% and 50% of subjects previously classified as normal, at risk and suspicious respectively according to the criteria used for epidemiological surveys of BEN.     

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).     

Alanine aminopeptidase and beta 2-microglobulin excretion in patients receiving vancomycin and gentamicin.

The effects of vancomycin, gentamicin, and combination vancomycin-gentamicin treatments on alanine aminopeptidase (AAP) and beta 2-microglobulin (beta 2M) elimination in 30 hospitalized patients were assessed and compared with elimination in a control group. Twenty-four-hour urine excretion values for AAP and beta 2M were determined on treatment day 1 and day 5 for patients receiving the three treatment regimens and for the control group. AAP excretion values for the vancomycin-treated group were not found to be statistically different from those of the control group. Both the gentamicin and the vancomycin-gentamicin groups had statistically higher AAP excretion values on treatment day 1 as well as on treatment day 5 when compared with the vancomycin and control groups. AAP excretion on day 5 of treatment was highest for the vancomycin-gentamicin group. Overall, beta 2M elimination was variable in all treatment groups. Although the beta 2M values were elevated as early as day 1 in all treatment groups, they were significantly elevated only in the vancomycin-gentamicin group on day 1 and only in the gentamicin group on day 5 compared with the vancomycin and the control groups. AAP appears to be a sensitive indicator of renal tubular damage. The combination of vancomycin and gentamicin results in greater AAP excretion than does either agent alone.     

Urinary albumin excretion in a population based sample of 1011 middle aged non-diabetic subjects

Jensen JS, Feldt-Rasmussen B, Borch-Johnsen K, Jensen G and The Copenhagen City Heart Study Group. Urinary albumin excretion in a population based sample of 1011 middle-aged non-diabetic subjects. Scand J Clin Lab Invest 1993; 53: 867-872

Increased urinary albumin excretion rate (UAER) especially in the range of 20-200 μg min^?1, termed microalbuminuria, has been proposed as a risk marker and predictor for cardiovascular disease in non-diabetic subjects. Thus it would be of importance to describe the distribution of UAER in the non-diabetic population. Among 1011 30-70-year-old subjects without diabetes mellitus or urinary tract infection, who were invited to participate in a population based epidemiological study, the albumin concentration was measured in an overnight urine sample. The measurement was performed by an ELISA method. The UAER was calculated in units of μgmin^?1 as urinary albumin concentration × urine volume/urine collection time. The distribution of UAER was positively skewed with a median value of 2.3μgmin^?1 and a 5-95 inter-percentile range of 0-11.0μgmin^?1. The UAER held constant with age, but males had higher UAER than females, 2.6 (0-13.5)μgmin^?1 vs 2.2 (0-8.3)μgmin^?1; p < 0.005. The prevalence of microalbuminuria, defined as an UAER in the range of 15-150μgmin^?1 in an overnight urine sample, was 3% (95% C.I. interval: 1.9-4.0). These findings suggest, that the level of UAER which might notify increased cardiovascular risk, is lower than in patients with diabetes mellitus, if it is considered to be of any clinical relevance.     

Urinary excretion of albumin and beta-2-microglobulin in hypertensive and normotensive renal transplant recipients during urinary diluting and concentrating tests

Urinary excretion of albumin and beta-2-microglobulin was measured in nine hypertensive and nine normotensive renal transplant recipients and 10 healthy control subjects before and after an oral water load of 20 ml (kg body weight)-1 (study 1) and in eight hypertensive and 11 normotensive renal transplant recipients and 11 healthy control subjects during 24-h water deprivation (study 2). In both studies 1 and 2 urinary albumin excretion was significantly higher (p less than 0.01) in the hypertensive renal transplant recipients that in the normotensive patients and the control subjects (levels before loading; hypertensives: 23.9 micrograms/min (median), range 7.5-58.7; normotensives: 3.4 micrograms/min, range 1.0-49.3; controls: 2.9 micrograms/min, range 1.3-10.3). Urinary albumin excretion was significantly positive correlated to both systolic, diastolic and mean blood pressure (for mean blood pressure: rho = 0.625, n = 18, p less than 0.01) in transplanted patients. Albumin excretion tended to increase after water loading and to decrease during water deprivation in all groups. Beta-2-microglobulin excretion was approximately the same in all groups in both studies 1 and 2 and was not correlated to blood pressure. During a follow-up period of at least 18 months, none of the renal transplant recipients developed signs of chronic graft failure. Increased urinary albumin excretion in hypertensive renal transplant recipients thus appears to be caused by increased glomerular permeability that may be due to glomerular damage induced by arterial hypertension corresponding to the findings in essential hypertension.     

Urinary alpha1-microglobulin as a marker of nephropathy in type 2 diabetic Asian subjects in Singapore

OBJECTIVE: This study examines urinary alpha(1)-microglobulin as a marker of early nephropathy in type 2 diabetic Chinese, Malays, and Asian Indians in Singapore. RESEARCH DESIGN AND METHODS: A cross-sectional study was performed on 590 consecutive type 2 diabetic patients (296 males, 294 females) who were on routine follow-up at a primary care clinic. Information was obtained from interviews, case notes, and blood and urine samples. Because the distribution of urinary alpha(1)-microglobulin levels was highly skewed, these levels were log-transformed, and geometric means were calculated. There was correction for variability in urine flow by dividing by urine creatinine levels, given as mg/mmol urine creatinine, and adjustment for confounding variables. RESULTS: Urinary alpha(1)-microglobulin was higher in men than in women and was directly related to age, but no ethnic differences were apparent. It was directly related to duration of diabetes, with adjusted geometric means of 1.19 and 1.43 mg/mmol urine creatinine for a duration of <10 and > or =10 years, respectively (P = 0.07). Urinary alpha(1)-microglobulin was highest in patients on insulin, followed by those on oral medication and then those on diet alone (adjusted geometric means: 1.47, 1.36, and 0.86 mg/mmol urine creatinine, respectively; P = 0.01). Levels were also higher in patients with poor glucose control, as measured by HbA(1c), fasting plasma glucose, and 2-h postprandial plasma glucose (P < 0.01 for each). Urinary alpha(1)-microglobulin was directly related to albuminuria, with adjusted geometric means for normoalbuminuria, microalbuminuria, and macroalbuminuria of 1.06, 1.47, and 4.72 mg/mmol urine creatinine, respectively (P < 0.01). However, of patients with normoalbuminuria, 33.6% had raised urinary alpha(1)-microglobulin. Likewise, of patients with normal urinary alpha(1)-microglobulin, 27.6% had albuminuria. CONCLUSIONS: Urinary alpha(1)-microglobulin was related to duration, severity, and control of diabetes. Urinary alpha(1)-microglobulin and albumin were directly related, but in some patients, one was present in the absence of the other. Hence, in addition to albuminuria (which measures glomerular dysfunction), urinary alpha(1)-microglobulin (which measures proximal tubular dysfunction) is useful for the early detection of nephropathy in diabetic subjects.     

Urinary excretion of proinflammatory cytokines and transforming growth factor beta at early stages of diabetic nephropathy

AIM: To examine correlations between urine excretion of proinflammatory cytokines, transforming growth factor beta (TGF-b) and changes in renal structure and function, quality of glycemia control in patients with type 1 diabetes mellitus. MATERIAL AND METHODS: Urinary excretion of interleukine 1-beta (IL-1b), monocytic chemoattractive protein-1 (MCP-1), RANTES and TGF-b was measured with enzyme immunoassay in 57 patients including 22 patients with normal albuminuria, 23--with microalbuminuria, 12--with macroalbuminuria. Creatinine clearance was subnormal in 8 patients with macroalbuminuria. The control group consisted of 10 healthy persons. Morphological examination of renal biopsies was performed in 8 patients with normoalbuminuria and 10 patients with microalbuminuria. RESULTS: Patients with normoalbuminuria had excretion of MCP-1 significantly higher than in controls. Microalbuminuria patients showed high excretion of IL-1b, MCP-1 and TGF-b. Excretion of IL-1b, MCP-1, RANTES and TGF-b in patients with macroalbuminuria was higher than in controls and other groups of patients. Excretion of cytokines and TGFb correlated inversely with glomerular filtration rate and hemoglobin level. Positive correlations were detected between excretion of IL-1b, MCP-1, TGFb and glycated hemoglobin A(1c). In patients with normo- and microalbuminuria cytokine and TGFb excretion correlated with thickness of glomerular and glomerular basal membrane. CD68-positive macrophages were detected in the intersticium of 1 patient with normoalbuminuria and 6 patients with microalbuminuria. CONCLUSION: Urinary excretion of proinflammatory cytokines and TGF-b was elevated in patients with DM-1 having micro- and macroalbuminuria suggesting participation of inflammation in development of diabetic nephropathy.     

Urinary albumin excretion rate is associated with increased ambulatory blood pressure in normoalbuminuric type 2 diabetic patients

OBJECTIVE: To evaluate the 24-h blood pressure profile in normoalbuminuric type 2 diabetic patients. RESEARCH DESIGN AND METHODS: A cross-sectional study was conducted in 90 type 2 diabetic patients with a urinary albumin excretion rate (UAER) <20 microg/min on two occasions, 6 months apart (immunoturbidimetry). Patients underwent clinical and laboratory evaluations. Ambulatory blood pressure monitoring and echocardiograms were also performed. RESULTS: UAER was found to correlate positively with systolic doctor's office blood pressure measurements (r = 0.243, P = 0.021) and ambulatory blood pressure (24 h: r = 0.280, P = 0.008) and left ventricular posterior wall thickness (r = 0.359, P = 0.010). Patients were divided into four groups according to UAER (<5, > or =5-10, > or =10-15, and > or =15-20 microg/min). Systolic blood pressure parameters for the 1st, 2nd, 3rd, and 4th groups, respectively, were 123.0 +/- 10.6, 132.5 +/- 15.0, 139.0 +/- 23.4, and 130.7 +/- 8.0 mmHg for 24-h blood pressure (ANOVA P = 0.004) and 48.4 +/- 6.0, 54.5 +/- 11.2, 58.8 +/- 15.6, and 57.6 +/- 8.0 mmHg for 24-h pulse pressure (ANOVA P = 0.003). A progressive increase in the prevalence of diabetic retinopathy was observed from the 1st to the 4th UAER group: 27.3, 43.8, 45.5, and 66.7% (P = 0.029 for trend). CONCLUSIONS: In type 2 diabetic patients, UAER in the normoalbuminuric range is positively associated with systolic ambulatory blood pressure indexes, left ventricular posterior wall thickness, and diabetic retinopathy, suggesting that intensive blood pressure treatment may prevent diabetes complications in these patients.     

Urinary albumin excretion is correlated to fibrinogen levels and protein S activity in patients with type 1 diabetes mellitus without overt diabetic nephropathy

The aim of the study was to test the hypothesis that in diabetic patients without overt nephropathy there may be a correlation between the activity of natural anticoagulant proteins and glomerular dysfunction. Assays for functional activity of proteins S and C, measurements of urinary albumin excretion, lipid parameters and haemoglobin A1c were performed in 91 patients with type 1 diabetes mellitus and 85 patients with type 2. Patients with type 1 diabetes and microalbuminuria had significantly higher mean age (44.1 +/- 10.9 vs. 37.9 +/- 12.7 years; p<0.05), fibrinogen level (3.75 +/- 1.0 vs. 3.21 +/- 0.8 g/l; p<0.01), protein S activity (92.3 +/- 17.6 vs. 84.5 +/- 15.5%; p<0.05) and higher prevalence of retinopathy (p<0.01) and macrovascular disease (p<0.01) than those with normoalbuminuria. Albumin excretion was significantly correlated to age (r=0.25, p<0.05), fibrinogen level (r=0.39, p<0.01), protein S activity (r=0.27; p<0.05), total cholesterol (r=0.23; p<0.05), apoprotein B (r=0.22; p<0.05), retinopathy (r=0.33; p<0.01) and macrovascular disease (r=0.33; p<0.01). Patients with type 2 diabetes mellitus and microalbuminuria had significantly higher apoprotein B levels (1.17 +/- 0.3 vs. 1.06 +/- 1.2 mg/dl; p<0.05) than those with normoalbuminuria, and apoprotein B was significantly correlated to albumin excretion (r=0.22; p<0.05). In a multivariate model of type 1 diabetes mellitus with fibrinogen, protein S and C activity, cholesterol, triglycerides, haemoglobin A1c, retinopathy, and macrovascular disease as independent parameters (r=0.53; p<0.003), there was significant independent correlation of fibrinogen (beta=0.28; p<0.01), protein S activity (beta=0.27; p<0.05) and retinopathy (beta=0.21; p<0.01) with albumin excretion. We conclude that in type 1 diabetes, relative elevation of fibrinogen level and protein S activity appear in the early stages of development of diabetic nephropathy, and may be related to the pathogenesis of diabetic kidney disease.     

Serum beta2-microglobulin in controls and cancer patients.

Serum beta2-microglobulin levels have been measured in 210 cancer and control patients to assess the significance of this investigation in cancer patients. Subjects studied included patients with breast and gastrointestinal cancer, corresponding control patients in both categories, and healthy volunteers. The composition of these groups allowed an assessment of the relative importance of changes related to cancer, benign disease, age and sex. A significant rise in serum beta2-microglobulin levels with advancing age was demonstrated in the control subjects. Mean levels were also consistently higher in females than in males in each patient group. After statistical correction for these age and sex effects, mean values remained significantly higher in each of the various cancer groups than in their controls. Patients with more advanced breast cancer had higher levels than those with 'early' disease, as did patients with stomach cancer compared to those with colo-rectal cancer. One possible interpretation is that levels increase with increasing tumour bulk, and therefore the estimation of serum beta2-microglobulin may be useful as one of a battery of tests in the management of cancer patients.     

探讨同型半胱氨酸和β2-微球蛋白检测在糖尿病肾病早期诊断的意义

目的：通过对糖尿病肾病（DN）不同病期患者的血清同型半胱氨酸（Hcy）和β2-微球蛋白（β2-MG）的检测,探讨血清Hcy和β2-MG水平改变在DN诊断中的临床价值。方法：在美国贝克曼AU2700全自动生化分析仪上采用循环酶法和胶乳增强免疫比浊法检测实验组和对照组血液样本中Hcy和β2-MG的水平,同时检测与肾功能密切相关的血清学指标尿素（UREA）和肌酐（CREA）的含量。结果：实验组血清Hcy、β2-MG、UREA和CREA含量明显高于对照组,两组比较差异有统计学意义或高度统计学意义（p〈0.05或p〈0.01）;Ⅰ期、Ⅱ期、Ⅲ期、Ⅳ期检测Hcy和β2-MG浓度水平呈递增性升高,Ⅱ期、Ⅲ期和Ⅳ期患者血清中Hcy和β2-MG的含量明显高于Ⅰ期患者,与Ⅰ期患者检测结果比较,差异有统计学意义（P〈0.05）。结论：联合检测血清Hcy和β2-MG水平有助于DN的早期诊断,检测结果能够及早为临床治疗以及临床采取正确的治疗方案提供具有参考价值的诊断依据。     

Catabolism of rat beta2-microglobulin in the rat.

Highly purified rat beta2-microglobulin (beta2m) as well as cytochrome c and lysozyme were radiolabeled and their catabolism studied in the rat. More than 90 percent of these low molecular weight proteins were removed from the serum within an hour and excreted into the urine by 24 hours. Except for the kidney in which the concentration of these protein is ten- to twentyfold greater than in the serum, there is little evidence that rat tissues are concentrating these proteins. The stomach was found to concentrate radioiodine. The catabolism of rat beta2m differed from that of cytochrome c and lysozyme in that the kidney contained twice as much labeled rat beta2m. In addition, the rat excretes 10 to 15 percent of the injected rat beta2m but only 1 to 5 percent of the cytochrome c or lysozyme. These studies established a basis for turnover studies of beta2m complexed with other cell membrane proteins, for example, HL-A or H-2 peptides.     

Determination of beta 2-microglobulin in serum by a microparticle-enhanced nephelometric immunoassay.

This fully automated nephelometric immunoassay to quantify beta 2-microglobulin in human serum measures the light-scattering signal produced by agglutination of commercially available latex microparticles (diameter 0.1 micron) coated with specific F(ab')2 against beta 2-microglobulin. The calibration curve, generated by serial dilutions of a beta 2-microglobulin standard of known concentration, is used to calculate beta 2-microglobulin concentrations in serum samples by the logit-log function and linear-regression analysis. The assay range (sample dilution 400-fold) extends from 0.3 to 40.0 mg/L. No antigen excess appears at beta 2-microglobulin concentrations up to 320 mg/L. Within-run CVs ranged from 1.0% to 3.4%, and between-days from 1.2% to 2.8%. Total imprecision (CV) was < 5%. Analytical recovery averaged 99.5% +/- 2.8%. Rheumatoid factor, complement, bilirubin (up to 340 mumol/L), and hemoglobin (up to 2.0 g/L) do not interfere. Strongly turbid lipemic samples must be cleared before analysis. Standard curve linearity was very good in samples covering the clinical useful range of concentrations. Results of the method correlated well with those of radioimmunoassay and microparticle enzyme-linked immunoassay (r = 0.979 and 0.975, respectively). The reference interval (nonparametric estimation) in apparently healthy adults (n = 303) was 0.87 (0.80-0.94) to 2.42 (2.28-2.45) mg/L; the median value was 1.54 mg/L.     

Measurement of serum beta 2-microglobulin by a latex nephelometric immunoassay.

A rapid and simple technique for the measurement of beta 2-microglobulin on the Behring nephelometer was developed using a commercially available latex-anti beta 2-microglobulin. This is a fully automated assay and no pretreatment of sample is necessary. An excellent correlation with radioimmunoassay (r = 0.972) and time-resolved fluoroimmunoassay (r = 0.914) was obtained. Haemolysis, lipemia, bilirubin, and rheumatoid factor do not cause interference because of the high dilution of samples and the use of Fab fragments of the antibody. The analytical range extends from 0.6 to 10.7 mg/L. Between-run imprecision (CV) ranged from 6 to 8%.     

Selection of Plasmodium falciparum pfmdr1 alleles following therapy with artemether-lumefantrine in an area of Uganda where malaria is highly endemic

Polymorphisms in the Plasmodium falciparum pfmdr1 gene were assayed in pretreatment samples and in samples from patients reinfected following therapy with artemether-lumefantrine. The pfmdr1 alleles 86N, 184F, and 1246D significantly increased in prevalence after treatment. All samples had a single pfmdr1 copy. Treatment with artemether-lumefantrine selects for polymorphisms that may alter antimalarial drug response.