Urinary Beta 2-microglobulin Research Articles

The effect of triathlon on urinary excretion of enzymes and proteins.

In order to investigate the effect of triathlon and renal function of normal subjects, we evaluated the excretion of urinary enzymes and proteins before and after triathlon. From 6 subjects samples were obtained 24 hours after the first urine collection. We performed quantification of urinary total protein, beta2-microglobulin (beta2-M), N-acetyl-beta-D-glucosaminidase activity (NAG), and concentration of urinary creatinine from each participant. There was a significant increase in urinary total protein excretion immediately after triathlon (p<0.01). The urinary beta2-M and NAG excretions after triathlon were higher than the initial values. Post-exercise proteinuria in one subject persisted until the next morning, whereas the increased excretion of urinary beta2-M and NAG returned to the pre-exercise level at least 24 hours after triathlon. It appears to be reasonable to presume that glomerular damage may persist in some subjects who do heavy exercise.

Concentration of cadmium in rice and urinary indicators of renal dysfunction.

OBJECTIVES: (1) To examine the relation between concentrations of cadmium (Cd) in rice and urinary concentrations of indicators of renal dysfunction and the prevalence of abnormalities in urine in areas...

Biological monitoring of cadmium exposure and renal effects in a population group residing in a polluted area in China

In an area of China, not previously studied in detail concerning cadmium pollution and possible adverse effects on the kidney of exposed populations, concentrations of cadmium in urine as an indicator of renal accumulation of cadmium was studied and related to indicators of renal dysfunction in order to examine if a relationship could be documented. Cadmium concentrations in urine were analysed by graphite furnace atomic absorption spectrometry and urinary beta-2 microglobulin (UBM) and albumin (UALB) were measured as indicators of renal dysfunction. Rice samples and urine samples were obtained from three areas in Zhejiang province, China, representing a highly exposed area, a medium exposed area and a control area, respectively. Cadmium concentrations in rice were 3.70, 0.51 and 0.072 mg/kg for the heavily, medium polluted areas and the control area, respectively. Cadmium concentrations in urine (geometric means) were 10.7, 1.62 and 0.40 μg/l in the high, medium and control areas respectively. There was a clear increase in UBM and UALB in the heavily exposed group in comparison to the control group and a slight increase in the medium exposed group. There was a statistically significant dose-response relationship between cadmium in urine and β 2-microglobulin excretion in urine, which is similar to what has previously been reported in other countries. The findings constitute the first report concerning a dose-response relationship in this population group in Zhejiang province in China.

Proximal tubular reabsorption of growth hormone and sodium/fluid in normo- and microalbuminuric insulin-dependent diabetes mellitus.

Proximal tubular dysfunction may be implicated in the pathogenesis of diabetic nephropathy. An investigation of proximal tubular function was carried out by assessing proximal tubular sodium-reabsorption and low molecular weight protein excretion in a group of patients with type 1 diabetes mellitus. Normoalbuminuric [group A, n = 6, albumin excretion rate (AER) mean (range) 4 (0-10) micrograms/min], and microalbuminuric [group B, n = 6, AER 88 (35-198) micrograms/min] patients with type 1 diabetes were compared with matched controls. Simultaneous lithium and growth hormone (GH) clearance and urinary beta 2-microglobulin excretion were assessed. Fasting plasma glucose at the start of the study was [median (range)] 13 (10.2-15.1), 9.3 (5.9-15) and 4.1 (4.0-5.0) mmol/l in groups A, B and controls, respectively, with a mean coefficient of variation during the study of 3.9% (group A) and 5.2% (group B). There was no significant difference in plasma glucose levels between patients in groups A and B. Urinary GH excretion was raised in the patients with microalbuminuria (group B; P < 0.05), although there was no difference in serum GH clearance rate between the patient groups and controls. Urinary GH correlated with B 2-microglobulin in the diabetic subjects (r = 0.665, P < 0.05) and with the degree of microalbuminuria in group B patients (r = 1, P < 0.01). Urinary GH was also greater than 10 microU, the median value observed in the controls, in 5 of 6 (83%) patients in group A. Glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) measured by constant infusion of 51Cr-ethylene diamine tetra-acetic acid (EDTA) and I125-para-amino hippuric acid (PAH), respectively, showed relative hyperfiltration in the normoalbumiruric group compared with controls (P < 0.05) and group B (P < 0.05). Absolute proximal reabsorption of sodium and of water (APRNa and APRH2O) was significantly higher in group A patients (P < 0.05). Although GFR was significantly higher in group A patients, no differences were found in fractional proximal reabsorption of sodium and water (FPRNa+H2O) or end proximal delivery between the patient groups and controls. Therefore, the measurement of protein reabsorptive capacity provides a more sensitive marker of renal tubular impairment in type 1 diabetes than sodium/fluid reabsorptive capacity. In patients with microalbuminuria, both glomerular and tubular damage may coexist. Our results stress the usefulness of markers of renal tubular function in monitoring the course of diabetic nephropathy. This study also shows that assessment of GH clearance has promise as a marker of renal tubular protein reabsorptive capacity.

Followup Study of Renal Function in Children With Reflux Nephropathy After Resolution of Vesicoureteral Reflux

We evaluated data collected for 10 years on children with reflux nephropathy to identify a means of predicting the prognosis. A total of 15 boys and 13 girls were enrolled in this study at least 2 years after surgical and spontaneous resolution of vesicoureteral reflux in 25 and 3 patients, respectively. They were followed for more than 10 years and renal function was periodically evaluated. Urinary beta 2-microglobulin, alpha 1-microglobulin, N-acetyl-beta-D-glucosaminidase, microalbumin and 99mtechnetium dimercapto-succinic acid uptake were measured. Of the 28 patients 12 had high levels of urinary alpha 1-microglobulin during followup, including all 7 in whom renal function deteriorated. In 3 children with elevated alpha 1-microglobulin urinary microalbumin gradually increased after puberty. Although elevated levels of urinary beta 2-microglobulin, N-acetyl-beta-D-glucosaminidase and microalbumin were also observed, they were less predictive of renal function than alpha 1-microglobulin. These results suggest that elevated urinary levels of alpha 1-microglobulin may predict the risk of abnormal renal function in children with reflux nephropathy even before the appearance of significant proteinuria.

Use of urinary beta-2-microglobulin to predict severe renal damage in fetal obstructive uropathy.

Establish a clinically relevant threshold for urinary beta 2-microglobulin (beta 2m) to predict the presence of several renal damage in fetuses with obstructive uropathies. Retrospective review was conducted of urinary beta 2m levels, clinical outcomes, and pathological findings in 36 fetuses evaluated for presumed obstructive uropathy. Patients were divided into those free of renal injury (group 1, n = 13) and those with clinical or pathological evidence of severe irreversible renal injury (group 2, n = 23). Including all patients, a threshold beta 2m value of > 6 was able to predict the presence of severe renal damage with a 83% sensitivity and 71% specificity. beta 2m levels tended to decrease with increasing gestational age among those patients without renal injury (group 1), while beta 2m levels increased among those with severe renal damage (group 2). There was no difference in mean beta 2m levels in those < 20 weeks (p = 0.065) while there was a high degree of difference in those > 20 weeks of gestation (p < 0.001). In those > 20 weeks, a threshold of > 10 predicted the presence of severe renal damage with 100% sensitivity and specificity. Urinary beta 2m, especially in the fetus > 20 weeks, may be a clinically useful marker to detect the presence of severe renal damage due to obstructive uropathy and thus be an important adjuvant in the proper selection of fetuses for antenatal intervention.

In fetuses with isolated hydronephrosis, urinary beta 2-microglobulin and N-acetyl-beta-D-glucosaminidase (NAG) have a limited role in the prediction of postnatal renal function.

Seventy-one fetal urine samples were taken from the bladder or renal pelvis of 33 fetuses at 13-36 weeks' gestation with a diagnosis of urinary tract anomaly. Severe isolated hydronephrosis in the absence of an enlarged bladder was the indication for sampling in 12/33 fetuses (26 samples), who were retrospectively classified into three groups: normal, intermediate, and dysplastic, based on the evaluation of postnatal renal function or histology. For all samples, urinary sodium (Na+), calcium (Ca2+), creatinine, beta 2-microglobulin, and N-acetyl-beta-D-glucosaminidase (NAG) were measured. Among the 71 fetal urine samples, both beta 2-microglobulin and NAG correlated inversely with gestational age, Na+, and Ca2+, but not with creatinine concentrations. However, the correlation of urinary beta 2-microglobulin with gestational age was dependent on the Na+ and Ca2+ concentrations, whereas urinary NAG correlated significantly with urinary Na+ and Ca2+, and also with gestational age. In fetuses with isolated hydronephrosis, only Na+, and not Ca2+, was significantly related to both beta 2-microglobulin and NAG. Only Na+ and beta 2-microglobulin were significantly, and similarly, higher in both dysplastic and intermediate kidneys when compared with fetuses with normal postnatal function. If only the last urine sampled was considered, there was overlapping of all parameters in the three groups. In isolated hydronephrosis, only the most extreme forms of renal failure might be suggested by elevated levels of Na+, Ca2+, beta 2-microglobulin, and NAG, without an obvious superiority of any of these parameters.

Change of renal function during vancomycin therapy in extremely low birthweight infants.

Twenty extremely low birthweight infants were treated with vancomycin (VCM). Their gestational age was 26.3 +/- 1.4 weeks (range 24.0-28.7 weeks) and their birthweight was 829 +/- 133 g (range 562-900 g). At the time of initial administration of VCM, postnatal age was 29.5 +/- 15.8 days (range 5-54 days). Vancomycin was administered in a dose between 9.3 and 11.0 mg/kg every 12 h for a period of 6.3 +/- 2.4 days (range 4-13 days). Serum and urinary specimens were obtained before and after (within 24 h following the last dose) VCM therapy. Serum creatinine and sodium, and urinary N-acetyl-beta-D-glucosaminidase (NAG) activity, creatinine, sodium, and beta-2-microglobulin (BMG) concentrations were measured. Fractional excretion of sodium (FENa) and NAG index (NAG:creatinine ratio) were calculated. There were no significant differences between the before and after VCM treatment in serum creatinine, urinary BMG concentration, FENa and NAG index. No infant showed any symptoms of renal insufficiency. However, the NAG index and FENa increased after treatment in 1 of 20 infants. Vancomycin is effective and safe in the treatment of serious infections in extremely low birthweight infants.

Relationship between pharmacokinetics of unchanged cisplatin and nephrotoxicity after intravenous infusions of cisplatin to cancer patients.

The relationships between pharmacokinetic parameters of unchanged cisplatin (CDDP) and several markers for nephrotoxicity after CDDP infusion (80 mg/m2) over 2 and 4 h were quantitated in patients with various cancers (lung, stomach and colon cancers and mediastinal tumor). Plasma and urinary levels of unchanged CDDP were measured using a specific high-performance liquid chromatography method. Pharmacokinetic parameters were calculated according to the model-independent method. The nephrotoxicity markers, blood urea nitrogen (BUN), serum creatinine (SCr), plasma and urinary beta2-microglobulin (BMGp and BMGu), urinary N-acetyl-beta-D-glucosaminidase (NAG) and creatinine clearance (CCR) were monitored for 30 days following CDDP administration. The maximum plasma concentration (Cmax), maximum urinary excretion rate (dAe/dt(max)), area under the plasma concentration-time curve from time zero to infinity (AUC), cumulative amount excreted in urine from time zero to infinity (Ae), total clearance (Clt), renal clearance (Clr) and plasma half-life (t1/2) of unchanged CDDP were not significantly different between the 2-h and 4-h infusion schedules. The values of the nephrotoxicity markers changed significantly following CDDP administration, suggesting that CDDP chemotherapy (80 mg/m2) caused nephrotoxicity. The Cmax of unchanged CDDP was the most informative pharmacokinetic parameter for nephrotoxicity. Cmax was related to maximum BUN, maximum SCr and minimum CCR levels in 27 CDDP treatments according to an exponential model. In order to attain more effective CDDP chemotherapy with minimum nephrotoxicity, the present pharmacokinetic and pharmacodynamic studies suggest that the Cmax or steady-state plasma level of unchanged CDDP should be maintained between 1.5 and 2 microg/ml in a standard continuous infusion schedule over 2 h and 4 h.

Biological monitoring results for cadmium exposed workers.

As part of a settlement agreement with the Occupational Safety and Health Administration (OSHA) involving exposure to cadmium (Cd), a battery production facility provided medical surveillance data to OSHA for review. Measurements of cadmium in blood, cadmium in urine, and beta 2-microglobulin in urine were obtained for more than 100 workers over an 18-month period. Some airborne Cd exposure data were also made available. Two subpopulations of this cohort were of primary interest in evaluating compliance with the medical surveillance provisions of the Cadmium Standard. These were a group of 16 workers medically removed from cadmium exposure due to elevations in some biological parameter, and a group of platemakers. Platemaking had presented a particularly high exposure opportunity and had recently undergone engineering interventions to minimize exposure. The effect on three biological monitoring parameters of medical removal protection in the first group and engineering controls in platemakers is reported. Results reveal that both medical removal from cadmium exposures and exposure abatement through the use of engineering and work practice controls generally result in declines in biological monitoring parameters of exposed workers. Implications for the success of interventions are discussed.

Urinary beta 2-microglobulin as a marker for vesicoureteral reflux.

To determine whether urinary beta 2-microglobulin (beta 2 M) excretion would be elevated in patients with severity of vesicoureteral reflux, urinary beta 2 M/creatinine (Cr) ratios were measured on random urine samples in 56 children with various grades of reflux. Results were compared with ratios of 39 nonrefluxing patients matched for age and gender. Patients with evidence of renal insufficiency or urinary tract infection were excluded. Bladder urine was obtained at the time of the vesicoureterogram. Reflux was graded using the International Reflux Classification System. The mean urinary beta 2 M/Cr ratio was higher in the refluxing group (1.82 +/- 0.6 micrograms/mg Cr) than in the nonrefluxing control group (0.54 +/- 0.09 microgram/mg Cr. P < 0.01). When the mean urinary beta 2 M/Cr ratios were compared for each grade of reflux with the nonrefluxing control group, patients with grade IV and V reflux had significantly higher urinary beta 2 M/Cr values than the nonrefluxing patients (2.83 +/- 0.71 micrograms/mg Cr and 4.61 +/- 0.65 micrograms/mg Cr, P < 0.001, respectively). No patient with grade I, II, or III reflux had a urinary beta 2 M/Cr ratio above 0.92 microgram/mg Cr. Statistical analysis revealed no significant differences among the mean beta 2 M/Cr ratio for grade I (0.53 +/- 0.08), II (0.51 +/- 0.09), or III (0.59 +/- 0.17) refluxers or the nonrefluxing controls. Therefore, urinary beta 2 M/Cr ratios are increased in children with a high grade of reflux. Such values may be useful in the early detection of tubular damage in patients with vesicoureteral reflux.

Inorganic fluoride kinetics and renal tubular function after sevoflurane anesthesia in chronic renal failure patients receiving hemodialysis.

Although sevoflurane is used in clinical anesthesia, its effects on renal function and inorganic fluoride (F-) kinetics in patients with chronic renal failure (CRF) have not been determined. We investigated F- kinetics and renal tubular function in sevoflurane anesthesia in CRF patients having hemodialysis. Five patients dialyzed and five with normal renal function undergoing parathyroidectomy or thyroidectomy were anesthetized with sevoflurane (1.0%-2.5%) and nitrous oxide in oxygen. Serum and urine levels of F-, blood urea nitrogen (BUN), serum creatinine (Cr), serum and urine beta 2-microglobulin (BMG) levels, and urine N-acetyl-beta-D-glucosaminidase (NAG) level were measured. BUN, Cr, and serum and urine BMG levels were significantly higher in the CRF patients than in the controls. There were no differences in serum F- level, rate of elimination, and area under the curve of serum F- levels between the two groups. However, the CRF patients had a significantly lower level of urine F- than control subjects. These data suggest that the F- kinetics in the CRF patients is different from that in normal renal function subjects. This clinical study with a limited number of patients may facilitate further studies to define the mechanisms of differences in the F- kinetics between normal subjects and CRF patients having hemodialysis after sevoflurane anesthesia.

Effect of venovenous bypass on perioperative renal function in liver transplantation: Results of a randomized, controlled trial

Although venovenous bypass (VVBP) has been suggested to protect the kidneys during liver transplantation and its systematic use has therefore been recommended, this beneficial effect of VVBP has not been clearly demonstrated. In a prospective, randomized, controlled trial, 77 patients receiving liver transplants for chronic liver disease were allocated to be supported with VVBP (group 1, 38 patients) or not (group 2, 39 patients). Both groups were similar in relation to preoperative clinical and laboratory data and operative transfusion requirements. Inulin clearance and urinary beta2-microglobulin and N-acetyl-beta-D-glucosaminidase (NAG) excretion (to determine glomerular filtration rate and tubular damage, respectively) were measured at different perioperative periods (anesthesia induction, hepatectomy, anhepatic phase, biliary anastomosis, and 24 hours after surgery). A significant decrease in inulin clearance and increase in tubular damage markers were observed in the anhepatic phase, which only partly improved in the subsequent phases. No significant differences were observed between groups 1 and 2 at any perioperative phase, except during the anhepatic phase, in which a more marked renal function impairment occurred in group 2 patients. However, renal function on the 7th postoperative day and the need for hemodialysis/ hemofiltration during the 1st week were similar in both groups. Among 40 variables analyzed, only low mean arterial pressure at anesthesia induction was identified as an independent predictor for early postoperative severe renal failure (inulin clearance < 10 mL/min/1.73 m2 at the 24th postoperative hour), with no significant relationship between this complication and the use of venovenous bypass. Renal function markedly deteriorates during liver transplantation, and renal impairment persists during the early postoperative period. Because VVBP support is not associated with any clear benefit in renal function, its systematic use does not seem to be justified. (Hepatology 1996 Jun;23(6):1418-28)

Serum sodium imbalance in the bedridden elderly. Part One: Realities and problem of management

Symptoms and other abnormalities associated with serum sodium imbalance were studied in bedridden elderly and healthy elderly subjects. 1. A significantly higher number of the bedridden elderly suffered from chronic wasting disease. 2. The average serum sodium concentration in bedridden elderly subjects was significantly lower than in healthy subjects, as was the sodium intake and the sodium content in urine, which indicate that the bedridden elderly subjects suffered from chronic sodium deficiency. 3. The bedridden elderly subjects had high levels of plasma PRA and antidiuretic hormone, and their aldosterone levels were low, which indicate that their condition was associated with a decrease in available circulating plasma, hypersecretion of antidiuretic hormone, and a decline in the ability to retain sodium. 4. Measurement of 24-hr creatinine clearance, albumin, and beta 2-microglobulin in urine revealed that bedridden elderly subjects had high levels of renal dysfunction, the result of which may a disturbance in water excretion. Abnormalities in serum sodium levels in the bedridden elderly subjects were related to a chronic deficiency in sodium intake, which reduced their ability to maintain sodium levels and impaired their renal function. Iatrogenic factors are likely to play an important role in the genesis of this condition, and should be taken into account in during management.

Nephrotoxic effects of unleaded petrol in female rats.

Female Wistar rats were exposed to 4 g m-3 unleaded petrol for 8 h a day, 5 days a week for 60 days. Urinary beta 2-microglobulin (beta 2-m), lactate dehydrogenase (LDH) and lysozyme were used as markers of tubular dysfunction. Urinary excretion of albumin and the glomerular filtration rate (GFR) were used as indicators of glomerular impairment. There were no statistically significant changes in the GFR or urinary albumin concentrations in the exposed group. Petrol exposure induced an increase of beta 2-m, total proteins, lysozyme and LDH excretion, but only beta 2-m was increased significantly. Our results show that subchronic exposure to high levels of unleaded petrol induced only a mild proximal tubular dysfunction in female rats.

A pathomorphological study on damage and repair process of tubuli after renal ischemia

To clarify the development of tubular necrosis and its healing process in ischemic renal failure observing degeneration, necrosis, cell proliferation and the involvement of apoptosis in the renal tubular epithelial cells before and after renal ischemia in rats through morphological examination. Eight week-old male rats were used for this study. The model for acute renal failure was by obstruction of bilateral renal arteries and veins for 45 minutes in several intervals (0 hr, 1 hr, 3 hr, 6 hr, 12 hr, 24hr, 48 hr, 96 hr, 1 week, 2 weeks and 4 weeks) each following reperfusion. Urinary beta 2-microglobulin (BMG) levels were measured to evaluate renal tubular function. In evaluating tubular necrosis and cell proliferation, observations of renal tubular tissue were made serially by use of light microscopy and immunological staining of proliferating cell nuclear antigen (PCNA) and bromodeoxyuridine (BrdU), respectively. The number of nuclei in the proximal tubular epithelium/circumference of the basement membrane (n/BM index) was calculated using a tissue measuring device. Transmission electron microscopy and the TdT-mediated dUTP-biotin nick end labeling (TUNEL) methods were used as indices of apoptosis. Maximal BMG values were obtained 24 hours after ischemia when injury in the proximal tubular epithelium was most prominent. The maximal number of PCNA and BrdU-positive cells were obtained 24 hours after ischemia and thereafter gradually decreased. The n/BM index in the disorder group was significantly increased 96 hours and 1 week after ischemia (p < 0.001). Electron microscopy revealed nuclear fragmentation and apoptosis in the tubular area indicating that there were significant differences. The number of positive cells for in situ nick end labelling increased 24 hours and 2 weeks after ischemia, exhibiting a two peak curve. However, the number of positive cells significantly decreased 4 weeks after ischemia. In the proximal kidney tubules damaged by reperfusion after ischemia, epithelial hyperplasia developed 3 to 6 days after the most active period of S-phase cells was noted. Thereafter, a decreasing number of epithelial cells was observed. It seemed that the decreasing number of these cells had been produced by apoptosis detected 2 weeks after ischemia.

Platelet-derived growth factor, interleukin (IL)-1 beta, IL-6R and tumor necrosis factor-alpha in IgA nephropathy. An immunohistochemical study.

We clarified the presence of platelet-derived growth factor (PDGF), interleukin (IL)-1 beta, IL-6, IL-6 receptor (IL-6R) and tumor necrosis factor-alpha (TNF-alpha) in renal biopsy specimens from 62 patients with IgA nephropathy, and discuss their relationship with mesangial cell proliferation, degree of histological damage and various clinical factors. Mesangial proliferation was determined histologically by PAS staining and the positive rate of proliferating cell nuclear antigen (PCNA). Renal biopsy specimens were stained using an enzyme-antibody method to determine the presence of cytokines and the receptor. PCNA-positive cells in the glomeruli significantly increased in patients positive for PDGF, IL-6, IL-6R and TNF-alpha. The degree of histological damage increased with the positive rates of PDGF, IL-6 or IL-6R and the number of PCNA-positive cells in the glomeruli. In the PDGF-A-positive patients, total urinary protein (TUP), urinary beta2-microglobulin (u-beta2-m) and systolic and diastolic blood pressure were significantly higher, and creatinine clearance (Ccr) was significantly lower than in the PDGF-A-negative patients. In the PDGF-B-positive patients, TUP, serum creatinine (s-Cr) and urinary and serum beta2-m increased significantly and Ccr decreased significantly. Il-1beta was not related to any clinical factors. In the IL-6-positive patients, TUP was significantly higher than in the IL-6-negative patients. In the IL-6R-positive patients, TUP, s-Cr, urinary beta2-m and systolic blood pressure were significantly higher than in the IL-6R-negative patients. In conclusion, PDGF, IL-6 and IL-6R may be closely related to mesangial cell proliferation, histological changes and deterioration of various clinical factors in patients with IgA nephropathy.

Measurement of beta 2-microglobulin in bovine serum and urine by radioimmunoassay.

A radioimmunoassay (RIA) system for quantification of bovine beta 2-microglobulin (beta 2-M) in serum and urine was developed. The protein isolated from bovine colostrum showed a single band in SDS-PAGE, and its molecular weight was approximately 11,600. Amino acid sequences for the first 24 residues and the amino acid composition of the protein were in agreement with those in the bovine beta 2-M of previous research works. In an Ouchterlony test, a single precipitation line was formed between the protein and the antiserum made by the protein. From these results, it was confirmed that the protein isolated from the colostrum was pure bovine beta 2-M. For creation of an RIA calibration curve for urine, a urine void of beta 2-M, as much as possible (beta 2-M-free urine), and a PBS were used as diluents. Intraassay (n = 10) and interassay (n = 3) variances were 1.7-4.6% and 7.1-11.5% in the PBS dilute method, and were 1.4-5.1% and 12.3-13.5% in the beta 2-M-free urine dilute method, respectively. Mean recoveries were 160 +/- 19% (mean +/- SD) and 98.4 +/- 7.9% in PBS and beta-M-free urine, respectively. It was found that the method using the beta 2-M-free urine as a diluent was more accurate than using PBS. The beta 2-M concentrations in serum and urine of healthy Holstein cows measured by this RIA system showed a logarithmic normal distribution for urine and a normal distribution for serum. The mean beta 2-M concentrations were 0.0305(+0.04443)(-0.0210) mg/l (Geometric mean +/- S.D., n = 43) in urine and 2.87 +/- 0.45 mg/l (Arithmetic mean +/- S.D., n = 26) in sera. Further, we could not observe the particular tendency of daily variation in urinary beta 2-M concentrations of healthy cows (Holstein, n = 3 x 2 days).

Albuminuria in untreated patients with primary aldosteronism or essential hypertension

The determinants and significance of urinary albumin excretion have been studied in normal subjects and in hypertensive patients; however, they are unknown in patients with primary aldosteronism. From a population of 114 patients with documented primary aldosteronism, we selected 23 never-treated patients (12 males, 11 females; 11 tumoral, 12 non-tumoral) and compared them to patients with never-treated essential hypertension with low renin (supine plasma renin activity <1 ng/ml per h, n = 23) or normal renin (supine plasma renin activity between 1 and 4 ng/ml per h, n = 23), matched for age, body mass index, mean arterial pressure, renal function and known duration of hypertension. The patients with primary aldosteronism had lower serum potassium and higher plasma aldosterone concentrations than those with essential hypertension. Urinary albumin and beta2-microglobulin excretion were greater in untreated patients with primary aldosteronism than in those with low- or normal-renin essential hypertension. Among the patients with essential hypertension, the renin activity was not a determinant of albuminuria. These findings indicate that primary aldosteronism is associated with excessive urinary albumin excretion. This albuminuria could be due to impairment of proximal tubular reabsorption caused by hypokalemic nephropathy and/or by high levels of circulating aldosterone; however, it could be an indicator of target-organ damage associated with primary aldosteronism.

Lead‐induced nephropathy: Relationship between various biological exposure indices and early markers of nephrotoxicity

Lead nephropathy in adults is silent and insidious, characterized by the absence of proteinuria in its early phase. Of the early markers of nephrotoxicity, urinary N-acetyl-beta-D-glucosaminidase (NAG) appears to be the only one that is elevated in early lead nephropathy. However, the elevation in urinary NAG activity may be a response to a sharp increase in renal burden of lead. Its usefulness as a marker of chronic lead nephropathy is thus in doubt. There is a need, then, to identify a reliable early biological indicator of lead-induced kidney damage. Furthermore, there is also a need to identify suitable markers of chronic exposure to describe meaningful dose-response and dose-effect relationships. Traditionally, blood lead (PbB) was used, but the current blood lead level (PbBrec) is more an indicator of recent exposure. Time-integrated blood lead indices (PbBint) derived from repeated serial PbB measurements can be used as indices of chronic exposure. In 128 lead-exposed workers, the PbBint was the most important exposure variable in describing the variability in urinary alpha 1-microglobulin (U alpha 1 m), urinary beta 2-microglobulin (U beta 2m), and urinary retinol binding protein (URBP). U alpha 1m was the only marker that was significantly higher in the exposed group, with a good dose-response and dose-effect relationship with PbBint. The lack of dose-response and dose-effect relationships in other studies may be due to inappropriate exposure markers as well as less sensitive response markers. PbBint has a better correlation than PbBrec. Furthermore, U alpha 1m may be the most sensitive of the markers because of its higher molecular weight.