Urinary Beta 2-microglobulin Research Articles

Dose-response relationship between total cadmium intake and prevalence of renal dysfunction using general linear models.

To determine the maximum allowable intake limits for chronic dietary exposure to cadmium (Cd), the dose-response relationship between total Cd intake and prevalence of renal dysfunction was examined using general linear models considering the effect of age as a confounder. The target population comprised 1850 Cd-exposed and 294 non-exposed inhabitants of Ishikawa, Japan. They were divided into 96 subgroups by sex, age (four categories) cadmium concentrations in rice (three categories) and length of residence (four categories). As indicators of the cadmium-induced renal dysfunction, glucose, total protein, amino nitrogen, beta 2-microglobulin and metallothionein in urine were employed. General linear models were fitted statistically to the relationship among prevalence of renal dysfunction, sex, age and total Cd intake. Prevalence of abnormal urinary findings other than glucosuria had significant associations with total Cd intake. When total Cd intake corresponding to the mean prevalence of each abnormal urinary finding in the non-exposed subjects was calculated using general linear models, total Cd intakes corresponding to glucosuria, proteinuria, aminoaciduria (men only) and proteinuria with glucosuria were determined to be ca. 2.2-3.8 g and those corresponding to prevalence of metallothioneinuria were calculated as ca. 1.5-2.6 g. The low-molecular-weight protein in urine was confirmed to be a more sensitive indicator of renal dysfunction, and these total Cd intake values were close to those calculated previously by simple regression analysis, suggesting them to be reasonable values as the maximum allowable intake of Cd.

Effect of prior, low-level cadmium exposure in vivo on metallothionein expression in cultured lymphocytes.

Exposure to cadmium (Cd) is currently monitored by measurement of the metal in blood or urine, or by observation of excreted compounds such as beta 2-microglobulin or N-acetyl-beta-D-glucose. Whilst these approaches are useful for the detection of acute exposure to Cd, their applicability in the management of long-term, low-level exposure is less clear. Metallothioneins are ubiquitous proteins that are synthesized in response to heavy metal ions and may offer themselves as being a biologically sensitive indicator of Cd exposure. We have examined both basal and Cd-induced metallothionein mRNA levels in cultured lymphocytes from groups with different exposures to Cd, attempting to assess their potential as an indicator of Cd exposure and the suitability of such an assay for routine analysis. We found that induced metallothionein mRNA levels, rather than basal mRNA levels, increased in groups known to have received elevated body burdens of Cd, although these increases were not significant between groups. There was, however, a significant correlation between induced metallothionein mRNA levels and urinary beta 2-microglobulin. These results suggest that further work on the in vitro lymphocyte response to Cd as a diagnostic tool is warranted.

Indicators of renal effects of exposure to cadmium: N-acetyl-beta-D-glucosaminidase and others.

The renal effects of cadmium (Cd) have been studied in industrial workers exposed to Cd and inhabitants of Cd-polluted districts, as the kidney is a critical organ in exposure to Cd. Several biological indicators of Cd have been proposed including N-acetyl-beta-D-glucosaminidase (NAG) and beta 2-microglobulin (BMG) in urine for the detection of early renal effects. The average concentrations of Cd in urine samples were over 10 micrograms/g.creatinine in classic researches. Even in the industrial field, this exposure level is now hardly observed in Japan and western countries. The situation is the same with inhabitants in general living in a Cd-polluted district. From the viewpoint of consistency of the association, the relationship between Cd and NAG has become fairly definite. Stability in the pH change, simplicity, low cost and the reliability of measurements were also satisfactory. NAG is one of the recommended tools for detecting minimum renal effects under 10 micrograms/g.creatinine of Cd.

Dose‐response relations between urinary cadmium and tubular proteinuria in cadmium‐exposed workers

Cadmium in urine reflects the body burden in cadmium-exposed individuals. Urinary beta 2-microglobulin is frequently used as a marker of tubular proteinuria with an arbitrarily chosen value (34 micrograms/mmole creatinine) as the cut-off limit. Both this cut-off level and a lower limit (25 micrograms/mmole creatinine) were used in a study of the relationship between urinary cadmium and beta 2-microglobulin in 561 cadmium-exposed battery workers. There was a clear dose-response relation between the urinary cadmium level and the prevalence of tubular proteinuria ranging from 0.8% in the lowest exposure group, excreting less than 1 nmole cadmium/mmole creatinine, to 46.4% (50.0 for the lower cut-off level) in the highest exposure group with a mean urinary cadmium of 15 nmole/mmole creatinine. The relation between urinary cadmium and tubular proteinuria was also assessed using probit analysis. There was a 10% response at a urinary cadmium of 3 nmole/mmole creatinine. The impact of age on the dose-response relation was explored in two age groups with the cut-off point at 60 years of age, showing a 10% prevalence of tubular proteinuria at urinary cadmium levels of 1.5 nmole/mmole creatinine in this older age group and 5.0 nmole/mmole creatinine in the category under 60 years of age. The study thus indicates that the present health-based limit (10 nmole/mmole creatinine) proposed by the World Health Organization (WHO) is too high and it is suggested that a new limit should be set to 3 nmole/mmole creatinine.

Urinary prolactin excretion in children with renal disease

The contribution of the kidney to the metabolism of prolactin has not yet been established. In the present study, urinary prolactin concentrations in 30 children with renal disease were measured by a newly devised, highly sensitive, time-resolved immunofluorometric assay. Median prolactin concentrations in the urine of children with renal disease, were 1.86 pmol/L-1 of urine (range: 0.17-546.31 pmol/L-1. By stepwise regression analysis, change in urinary prolactin levels as a function of the urinary beta 2-microglobulin concentrations was detected. These results indicate that prolactin urinary excretion in children with renal disease is dependent on the renal proximal tubular function.

Clinical significance of urinary enzymes and beta 2-microglobulin following ESWL.

To examine the renal damage caused by shock waves, urinary excretion of enzymes and beta 2-microglobulin were determined before and after ESWL. Urine samples were obtained from 35 patients with renal stone and 26 patients with ureteric stone treated with ESWL. Urinary lactate dehydrogenase (LDH) levels significantly increased on day 0, just after ESWL, in both groups. In the ureteric stone group the kidneys received less shock waves than in the renal stone group. Increased urinary lactate dehydrogenase was considered to have derived from erythrocytes in urine. Elevated urinary N-acetyl-beta-D-glucosaminidase (NAG) levels were also observed on day 0 after ESWL in both groups, due to unknown reasons. Indirect effect of ESWL through the sympathetic nervous system or humoral factors may contribute to increases in the urinary excretion of NAG. No significant increase was found in urinary gamma-glutamyl-transpeptidase (GGTP) levels for 5 days after ESWL. Urinary beta 2-microglobulin (BMG) levels increased on day 0 in the renal stone group alone. In our present study, the clinical significance of urinary enzymes and BMG was not well evaluated, because urinary excretion of these indicators following ESWL were transient and mild.

Early detection of nephrotoxic effects in thalassemic patients receiving desferrioxamine therapy

Nineteen transfusion-dependent beta-thalassemia major patients were included in the study. Six of these patients underwent chelation therapy with desferrioxamine by subcutaneous infusion (50 mg/kg/12 hr) and 13 received intravenous infusion (50 mg/kg/6 hr or 100 mg/kg/24 hr). BUN, creatinine, creatinine clearance, beta 2-microglobulin, urinary beta 2-microglobulin and urinary growth hormone excretion were evaluated during desferrioxamine treatment. Thirteen out of nineteen patients presented tubular damage indicated by increased excretion of urinary beta 2-microglobulin. 85% (11 of 13) of these patients showed more serious tubular damage, as demonstrated by concurrent increased urinary growth hormone excretion. Moreover, a positive correlation between urinary growth hormone excretion and urinary beta 2-microglobulin was observed (P < 0.05).

Concentrations of cadmium in air and urine in an alkaline battery works.

Concentrations of cadmium in air are available for exposed workers in an alkaline battery factory from 1965, and of cadmium in urine concentrations from rather later. Using simple statistical methods annual data sets have been analysed by department, job or other classification. Summary results of concentrations of cadmium in air from 1965 and in urine from 1970 are examined, and show a steady annual reduction. No attempt is made to relate changes in concentrations to changes in manufacturing practice or control measures, although the effects of one major change are noted. Relations between concentrations of cadmium in air and in urine since 1970 are reported. Those between cadmium in air and recent concentrations of cadmium in blood and of beta 2-microglobulin in urine are commented on. The kinetics of cadmium absorption, partition and excretion are not considered in any depth.

Urinary N-acetyl-beta-glucosaminidase and beta-2-microglobulin in the diagnosis of urinary tract infection in febrile infants

Urinary N-acetyl-beta-glucosaminidase (NAG) and beta-2-microglobulin (B2M) concentrations were measured in 24 pediatric patients with febrile urinary tract infection (UTI) and compared with the technetium-99m-labeled dimercaptosuccinic acid (DMSA) renal scan results, in order to evaluate a noninvasive means to localize the site of UTI. Increased urinary B2M and NAG were not associated with renal inflammation (pyelonephritis), as defined by positive dimercaptosuccinic acid scan. Median NAG concentrations were 114.2 mumol/hour/mg creatinine (CR) (range, 5.7 to 305.4) in 17 febrile UTI patients vs. 13.8 (range, 3.4 to 104.3) in 17 age and sex-matched febrile controls with negative urine cultures, P = 0.0001. The sensitivity and specificity of NAG > or = 40 mumol/hour/mg of CR in predicting UTI in febrile patients, regardless of the site of infection, were 88 and 88%, respectively. Increased urinary NAG is associated with UTI in febrile patients regardless of the level of infection (scan status), and may be an informative indicator of UTI.

URINARY INDICES OF RENAL DYSFUNCTION IN NEONATAL ASPHYXIA

N-acetyl-glucosaminidase ( NAG ) & Beta-2-microglobulin ( B2M ) were measured in urine of term newborns to assess effects of asphyxia on renal tubular function. NAG is an enzyme found in proximal tubular cells. Its urinary concentration reflects tubule cell breakdown. B2M is produced by the liver, filtered at the glomerulus & reabsorbed by proximal tubular cells. Urine B2M levels reflect tubular dysfunction. 32 neonates made up the study group with an equal number of controls. Study babies fulfilled a diagnosis of Posthypoxic Encephalopathy according to the system of Sainat. NAG & B2M were assayed at 24–48 hours of life & at 4-6 days. There was significant difference (P<0.05) between control & study subjects for both analytes in both measurement periods. Both NAG & B2M appear to be sensitive indices of renal tubular dysfunction in asphyxiated neonates. NAG levels were high immediately & fell slightly toward the end of the first week of life, whereas B2M though significantly elevated at 24-48 hours, continued to rise. Control (Normal) values are consistent between days 1 & 6. Dabies, will be further assessed at 4-6 weeks.

Serum concentration and urinary excretion of beta 2-microglobulin and microalbuminuria in familial Mediterranean fever.

Familial Mediterranean fever is characterised by recurrent and self limited attacks of fever and polyserositis and its devastating complication is the development of renal amyloidosis. In order to detect the presence of early glomerular and tubular damage in patients with familial Mediterranean fever and to assess the possible role of beta 2-microglobulin in the inflammatory attacks of this disease, serum and urine beta 2-microglobulin concentrations and microalbuminuria were evaluated in these patients. A total of 20 patients with familial Mediterranean fever were studied on and off colchicine treatment; seven of these patients developed a familial Mediterranean fever attack when they were off treatment. During the familial Mediterranean fever attacks serum beta 2-microglobulin concentrations decreased, whereas fractional excretion of beta 2-microglobulin, urine beta 2-microglobulin creatinine, and urine albumin/creatinine ratios increased. We conclude that glomerular and tubular functions deteriorate during the attacks. Further studies are needed to discover the effector(s) causing these transient glomerular and tubular disorders.

A study of thyroid hormone levels of inhabitants of the cadmium-polluted Kakehashi River basin

We compared thyroid hormone levels of inhabitants (19 men and 16 women) of the cadmium (Cd)-polluted Kakehashi River basin in Ishikawa Prefecture, with those of subjects (23 men and 47 women) living in a non-polluted area. In addition, we investigated the relationships between the thyroid hormone levels and indices of renal dysfunction induced by Cd exposure. The following results were obtained: 1) The free T4 level of females was significantly lower than that of controls. 2) The T3 level of inhabitants of both sexes was significantly higher than that of controls. 3) The level of free T4 among females became lower with the increases of urinary beta 2-microglobulin (beta 2-MG), urinary protein, urinary sugar, urinary amino acids and serum creatinine (Cr) levels, and with decreases of creatinine-clearance (CCr) and %TRP. 4) We could not find any relationship between the increase of T3 and the indices of renal dysfunction induced by Cd exposure in either sex.

Urinary beta 2- and alpha 1-microglobulin levels in normal subjects in Singapore.

Differing normal values for urinary beta 2-microglobulin have been reported for different countries. In this study, we have attempted to establish the urinary beta 2- and alpha 1-microglobulin levels of apparently healthy subjects in Singapore. Urine samples collected from 271 subjects were analysed. The subjects ranged from 19 to 62 years old, with a mean age of 36.8 years. The majority (84.5%) were non-smokers. Urine samples with a pH level < 5.5 were excluded from the analysis. The urinary beta 2- and alpha 1-microglobulin values followed log normal distributions. Their 95th percentiles were 288 micrograms/g creatinine and 7.35 mg/g creatinine, respectively. Statistically significant differences were found between sexes and ethnic groups for urinary beta 2-microglobulin values. Both alpha 1- and beta 2-microglobulin values increased significantly with age. Smokers had significantly higher urinary alpha 1-microglobulin values.

The effect of prostaglandin E 1 on renal function after cardiac surgery involving cardiopulmonary bypass

This study was performed to evaluate the effect of prostaglandin E 1 (PGE 1) on renal function after cardiac surgery in patients undergoing cardiopulmonary bypass (CPB). Haemodynamic and renal functional response to low dose PGE 1 (0.02 ug kg −1 min −1) (group A) or saline (group B) infusion via peripheral vein during CPB was evaluated in 20 patients who underwent cardiac surgery. The perfusion pressure was maintained at about 60 mmHg during CPB in both groups. Urine beta 2-microglobulin (UBMG) (P < 0.01), and urine N-acetyl-beta-D-glucosaminidase (NAG) (P < 0.05) demonstrated significantly high values after CPB in both groups compared with the presurgical value. Free water clearance (C H 2O ) decreased significantly at the first postoperative day compared with the pre-surgical value in both groups (P < 0.01). Statistical analysis of NAG, UBMG and C H 2O demonstrated significant differences between both groups, in C H 2O values at the third (P < 0.05) and fifth days (P < 0.05) after surgery, in NAG values at the fifth (P < 0.01) and seventh days (P < 0.01), and in UBMG values at the first (P < 0.05) and third (P < 0.05) postoperative day, respectively. Cardiac output (co) did not change in either group throughout this study. Pulmonary capillary wedge pressure (PCWP) in group A decreased significantly at 30 and 60 min after CPB, but in group B did not change throughout the study. Cardiac index (CI) decreased significantly at 60 min after CPB in group A (P < 0.05) and at 30 min in group B (P < 0.05). These results suggest that PGE 1 may be a useful drug for prevention of renal dysfunction after CPB.

Abnormal renal function in isolated systolic hypertension correlation with ambulatory blood pressure

Does ambulatory blood pressure correlate with the renal function damage better than clinic blood pressure in isolated systolic hypertension, as has been reported in other target organ involvement in combined systolic/diastolic hypertension? We investigated the correlation of serum beta-2 microglobulin concentration and both 24-h urine beta-2 microglobulin concentration and excretion as measures (suggestive) of glomerular filtration rate and tubular reabsorption, respectively with both ambulatory and clinic blood pressure in 19 health normotensive (68 ± 4.9 years) and 50 isolated systolic hypertensive elderly individuals (69 ± 5.4 years). Serum beta-2 microglobulin concentration and 24-h urine beta-2 microglobulin concentration and excretion were higher in the isolated systolic hypertension than in the normotensive group ( P < 0.05). In isolated systolic hypertensive patients, 24-h urine beta-2 microglobulin concentration and excretion were related to ambulatory blood pressure ( r = 0.32–0.40, P < 0.05), but not to clinic blood pressure; waking systolic blood pressure had the strongest correlation with both 24-h urine beta-2 microglobulin concentration and excretion among derivatives of ambulatory blood pressure ( r = 0.35 and 0.40, P < 0.05). We conclude that ambulatory blood pressure, especially waking systolic blood pressure, is superior to clinical blood pressure in predicting renal function impairment, in isolated systolic hypertensive patients.

Renal tubular function after reduction of environmental cadmium exposure: a ten-year follow-up.

A prospective follow-up study was carried out to assess the prognosis of renal tubular function after reduction of environmental cadmium exposure. Time-related changes in urinary beta 2-microglobulin and cadmium excretion were followed from 1979 to 1989 in 102 residents of a cadmium-polluted area in Nagasaki, Japan. The average dietary cadmium intake among the study population was more than 200 micrograms/d in 1969, which decreased to approximately half that amount in 1983 because cadmium-polluted paddy fields were replaced with new soil in 1981. The geometric mean urinary beta 2-microglobulin concentration for 28 subjects aged 40 y or older in 1979 increased from 1,135.8 micrograms/g creatinine in 1979 to 1,999.7 micrograms/g creatinine in 1989. A similar tendency was also observed in 16 subjects with urinary beta 2-microglobulin concentrations greater than 1,000 micrograms/g creatinine in 1979, although the statistical significance of the difference did not reach the 5% level, probably because of the small sample size. In 48 persons examined in 1982, 1986, and 1989, the geometric mean of urinary cadmium concentration decreased from 8.49 micrograms/g creatinine in 1982 to 6.03 micrograms/g creatinine in 1989. The tendency for increasing beta 2-microglobulin excretion observed in the present study could not be explained by aging alone. Thus, it was concluded that renal tubular dysfunction caused by environmental cadmium was irreversible and slowly progressive, even after reduction of exposure. Six of 8 subjects who had severe renal dysfunction and who were included in the study died before 1986 and could not be followed. The implication of loss of subjects because of death is also discussed.

Evaluation of proximal tubular function in preterm infants by urinary alpha 1-microglobulin.

alpha 1-Microglobulin is a low molecular weight protein that is relatively stable in urine of low pH. There have been few reports on urinary alpha 1-microglobulin (U-A1M) excretion in preterm infants. This study was designed to establish the ranges for U-A1M in clinically stable preterm infants and to investigate changes observed in sick preterm infants. We measured U-A1M and urinary beta 2-microglobulin (U-B2M) levels at 1, 4, 7, 14, 28 and 90 days after birth in stable preterm infants (Group 1) and sick preterm infants who were depressed at birth and required immediate resuscitation (Group 2). In Group 1 infants, both parameters were high during the first 28 days and appeared to decline thereafter. U-A1M in Group 2 infants was only significantly increased compared with Group 1 on day 1, as was U-B2M. On each day of the study, U-A1M had significant positive correlations with U-B2M for all the infants studied. The changes of the two parameters observed in Group 1 probably reflect postnatal evolution of proximal tubular function in stable preterm infants. A comparison of groups 1 and 2 shows a high prevalence of acute tubular injury at birth in sick infants and also suggests that U-A1M as well as U-B2M may be a sensitive index for detecting acute tubular damage and for following its course in preterm infants.

Correlations of peritoneal interleukin-6, serum beta-2 microglobulin and urinary beta-2 microglobulin after elective abdominal surgery.

Postoperative peritoneal interleukin-6 (P-IL-6), serum beta-2 microglobulin (SBMG) and urinary beta-2 microglobulin (UBMG) concentrations were examined in 33 patients who underwent various types of abdominal surgery. Similar time-dependent changes in SBMG and UBMG were observed in five other patients who underwent abdominal surgery. SBMG decreased the first day after the operation (1POD), then increased and reached the preoperative level by the third day after the operation (3POD). UBMG started to increase 1POD, reached the maximum 3POD, then decreased. The 1POD SBMG concentration was significantly correlated with P-IL-6, and 3POD UBMG was also significantly correlated with P-IL-6. These findings indicate that serum and urinary beta-2 microglobulin concentrations are closely correlated with P-IL-6.

HLA tissue types in patients with acute tubulointerstitial nephritis accompanying uveitis

Four cases of idiopathic acute tubulointerstitial nephritis (TIN) associated with uveitis (so-called TINU syndrome) were experienced between 1986 and 1990. Patients' ages ranged from 14 to 42 years old and three were female and one was male. All cases showed general symptoms, such as general malaise, anorexia and weight loss. All patients had initially TIN and became ill uveitis four to eight months after the onset of TIN. All cases had mild proteinuria, mild anemia, the lower serum levels of potassium, hyper gamma-globulinemia and the reduced glomerular filtration rate with the increased beta 2-microglobulin in urine and serum. All renal biopsies specimens showed mild edema and diffuse infiltration of inflammatory mononuclear cells in the interstitium without any glomerular or vascular abnormalities. Furthermore, numerous CD4 positive cells, CD8 positive cells and CD11c positive cells were seen in the interstitium. Of four patients, three cases were treated with both oral administration and eye drop of prednisolone (PSL), another one case was therapied with eye drop PSL only. In all cases TIN had good prognosis, but two patients had recurrences of uveitis. All patients underwent tissue typing for HLA-A, B, C and DR antigens. Three patients had identical HLA-Cw3 and all four cases revealed identical HLA-A24(9). These results suggest that immunological mechanism, especially cell-mediated, and HLA system may play an important role in the occurrence of TINU syndrome.

Renal abnormalities in leprosy.

We have evaluated laboratory and clinical manifestations of renal disease in 96 patients with leprosy, looking for a sensitive and early marker for detection and possibly follow-up of nephropathy in these patients. Microscopic hematuria was observed in 21.9% of the cases (with dysmorphic erythrocytes in 71.4% of them). Abnormal microalbuminuria and urinary beta 2-microglobulin were found in 15.8 and 19.8% of the cases, respectively. We have observed a high frequency of hematuria, abnormal microalbuminuria and elevation of urinary beta 2-microglobulin in these patients still with normal serum creatinine.