Beta 2M Excretion Research Articles

Theophylline for renal function in term neonates with perinatal asphyxia: A randomized, placebo-controlled trial

To study whether prophylactic theophylline can reduce the incidence and/or severity of renal failure in term infants with perinatal asphyxia. Term neonates with severe perinatal asphyxia were randomized to receive a single dose of either theophylline (study group, n = 40) or placebo (control group, n = 30) during the first hour of life. Daily weight, output/input ratio, 24-hour fluid intake, and urine volumes were recorded during the first 5 days of life. Those infants with asphyxial renal failure were followed up for 1 year. The incidence of severe renal dysfunction was increased in the control group. Creatinine clearance was higher and excretion of beta 2 microglobulin (beta2M) was lower in the theophylline group. Conversely, the glomerular filtration rate was lower in the control group. In infants with renal failure, serum creatinine and creatinine clearance returned to normal in the neonatal period, and the increased beta2M excretion normalized by age 6 weeks. A single dose of theophylline within the first hour of birth in term neonates with perinatal asphyxia results in a significant decrease in serum creatinine level and urinary excretion of beta2M, along with an increase in creatinine clearance.

130 Urinary Beta2-Microglobulin as an Indicator of Renal Lesion in Asphyxiated Neonates

BACKGROUND: Perinatal asphyxia can cause transient renal impairment or acute renal failure in neonates. Proximal tubular cells are extremely vulnerable to hipoxia.The ischemic injury results in elevated concentration of beta2microglobulin (beta2M) in urine.Urinary beta2M concentration increases with degree of tubular dysfunction.The aim of the study was to determine a concentration of beta2M in urine of asphyxiated and healthy neonates of varying gestational and postnatal age. STUDY AND THE CONTROL GROUPS: The study and the control groups were 141 neonates.The study group were 66 asphyxiated neonates,16 term and 50 preterm. Mean [SD] gestational age (GA) of term newborns was 38 (37 to 42) with mean [SD] birth weight 3290 g [703] and mean GA [SD] of preterm was 32 (30 to 36) mean [SD] birth weight 2070 g [548]. Criteria for inclusion were umbilical cord arterial pH less than 7.1 and BE less than minus 12 mmol/l. The control group were 75 neonates clinically stable 14 term (GA 37–42 mean [SD] 39 [1] mean birth weight [SD] 3440 g [500] and 57 preterm (GA 30- 36 mean [SD] 33 [2] mean [SD] birth weight 2061 g [552]. Both study and control group were divided into three subgroups of different maturation (A > 35, B-33–35, C 30–32 GA). METHODS: Urine samples were frozen at minus 20 C until assay. Beta2M was estimated in five samples on day 1, 3, 7, 14, 28 using competitive radioimmunoasay. RESULTS: We found statistically significant elevation of mean values of beta2M in urine of asphyxiated neonates compared to controls in all samples.The level of beta2M in preterm infants was significantly higher than that in term ones, both in study and control group during the entire first month of life.The highest values were observed in most immature neonates (GA 30–32). In group of asphyxiated and most immature neonates very high level of beta2M was still detected on day 28 while in fullterm it was almost normal.The beta2M excretion in asphyxiated neonates showed an increase on 1 and 3 day with a peak level at 7 day of age and than a slow decrease.Transient elevation of urinary beta2M were noted also in control group on day 3 with no significant differences between values of beta2M in the other samples in control group. We observed also correlation of beta2M with severity of perinatal asphyxia. The levels of beta2M were significantly increased in severe asphyxia group (pH less or equal 6.9) compared to mild asphyxia group. CONCLUSIONS: Measuring of beta2M can be non invasive method for determining a severity of perinatal asphyxia and renal maturation as well.

Urinary beta-2 microglobulin in renal dysfunction associated with hypothyroidism.

Hypothyroidism is associated with a number of functional renal disorders primarily affecting water and salt handling. In this study, we aim to investigate functional renal disorders in overt and subclinical hypothyroidism. We utilised urinary beta-2 microglobulin (beta2M) as a sensitive marker of tubular dysfunction. Urinary beta2M excretion and tests for renal functions were repeated before and after T4 replacement therapy. Forty-four patients (28 with overt disease, 16 with subclinical disease) and 31 healthy control subjects were involved in the study. There was a significant increase in urinary beta2M in both overt and subclinical hypothyroidism (p < 0.05 in both). TSH levels were correlated with beta2M excretion. Effects of hypothyroidism on renal functions were readily reversible by 3 weeks of thyroid hormone replacement therapy. Urinary beta2M was a sensitive marker of renal tubular dysfunction associated with overt and subclinical hypothyroidism.

Low concentrations of intravenous polygelines promote low‐molecular weight proteinuria

Previously we observed that atrial natriuretic peptide (ANP)-induced albuminuria was accompanied by an increase in urinary excretion of the low-molecular weight protein (LMW protein) beta2-microglobulin (beta2-m), suggesting that the albuminuria may at least partly be the result of blockade of tubular protein reabsorption. However, in our experiments ANP was dissolved in the polygeline Haemaccel (Hoechst, Behring-Werke, Marburg Germany) to prevent adhesion of ANP to the infusion system. Anecdotal reports have shown that high dosages of polygelines such as Haemaccel or Gelofusine (Braun NPBI Oss, the Netherlands) may influence tubular protein handling. In the present study we have evaluated the effect of a low and high doses of the polygeline Haemaccel on proteinuria. In addition, we have reassessed the effects of ANP. We measured urinary beta2-microglobulin (beta2-m) and albumin excretion in healthy volunteers after infusion of a high-dose pure Haemaccel (0.04 mL kg(-1) min(-1) for 60 min), a low-dose Haemaccel (0.01 mL kg(-1) min(-1) for 60 min followed by infusion of 0.02 mL kg(-1) min(-1) for 60 min) and a low-dose Gelofusine (dose comparable to the low-dose Haemaccel). In addition we performed similar studies using ANP dissolved in saline and Haemaccel. Infusion of Haemaccel caused a dose-dependent increase in urinary excretion of beta2-m. There were no differences between Haemaccel and Gelofusine. After infusion of ANP dissolved in Haemaccel urinary beta2-m excretion increased from 0.05 +/- 0.03 microg min(-1) to 27 +/- 10 microg min(-1) and urinary albumin excretion increased from 4.5 +/- 1.1 microg min(-1) to 9.7 +/- 6.3 microg min(-1) (P<0.05). During ANP + saline infusion, urinary beta2-m excretion did not change, whereas the urinary albumin excretion increased from 5.3 +/- 1.5 microg min(-1) to 7.9 +/- 2.4 microg min(-1) (P<0.05). Our study demonstrates that even low doses of the polygelines Haemaccel and Gelofusine profoundly attenuate the tubular reabsorption of the low-molecular weight protein beta2-m. Atrial natriuretic peptide does not affect tubular protein reabsorption. Therefore, the rise in albuminuria during ANP infusion most likely reflects alterations in glomerular permeability.

Beta2-microglobulin in hypertensive pregnancies

Beta2-Microglobulin (beta2-m) is a polypeptide that is freely filtered and then mostly reabsorbed and degraded in the proximal renal tubule. Beta2-m is a marker of glomerular filtration (GFR) in renal failure, whereas urinary beta2-m is a marker of proximal renal tubular dysfunction. Preeclampsia (PE) (ie, de novo hypertension in pregnancy with accompanying renal, cerebral, or liver disease or thrombocytopenia) often has renal involvement characterized by proteinuria, decreasing glomerular filtration, or renal tubular dysfunction. The aim of this study was to determine whether serum beta2- m concentration or urinary beta2-m excretion were greater in women with PE than in women with gestational hypertension (GH) (ie, isolated de novo hypertension in the second half of pregnancy) and normal pregnant women. Seventy-five pregnant women (35 with PE, 22 with GH, and 18 normotensives) were studied prospectively. Serum creatinine and beta2-m concentrations, 24-hour proteinuria, and fractional excretion (FE) of beta2-m were measured. Preeclamptics had similar serum creatinine but higher serum beta2-m (3.26+/-0.99 mg/L) than gestational hypertensives (2.44+/-0.77 mg/L; P = 0.016), and both groups had higher serum beta2-m than controls (1.62+/-0.54 mg/L; P = 0.001). FE of beta2-m was similar amongst groups (PE: 0.27%; interquartile range [IQR]: 0.20-0.86; GH: 0.21%; IQR: 0.11-0.40; controls: 0.26%, IQR: 0.12-0.69). PE is characterized by higher serum beta2-m but similar serum creatinine to GH. Because FE beta2-m is similar in these groups, this implies reduced filtering of beta2-m in PE rather than altered tubular handling of beta2-m. Further studies are now necessary to assess whether measurement of serum beta2-m is helpful in the clinical management of the hypertensive disorders of pregnancy. (Am J Kidney Dis 1998 Feb;31(2):308-12)

Urine protein excretion and swimming events

To determine total urinary protein, albumin (ALB), and beta 2-microglobulin (beta 2m) excretion rates in relation to different speeds, 12 males were studied while swimming distances of 100, 600, and 2,000 m at maximal speed. Venous blood lactate concentrations rose to 16.1, 11.6, and 4.5 mmol.l-1 after the 100, 600, and 2,000 m events, while plasma volumes were reduced by 11.3, 7.7, and 5.5%, respectively. ALB urine excretion increased to 110-120 micrograms.min-1 after the 100 and 600 m swims and to 56 micrograms.min-1 after 2,000 m (resting values: 9 micrograms.min-1). In the meantime, the beta 2m excretion rate increased 21 and 10 times the resting values, respectively, for the two shorter swims, with no change for the longer one. Progressive plasma volume reduction was associated with the increase of the protein excretion rate. As evidenced by the creatinine clearance, the glomerular filtration rate did not change for the 100 m swim but dropped by 23 and 35% for the 600 and 2,000 m ones, respectively. On the other hand, the ALB clearance increases were elevated for the three swims, while the beta 2m clearance increases were inversely related to the swimming speeds. The data showed a relationship between the rate of protein excretion and the speed of the swim, and the reduction of plasma volume. The findings could indicate a renal glomerular alteration, with an additional dysfunction of the tubular reabsorption process when the exercise load is high during swimming events.

Renal tubular dysfunction in primary Sjögren's syndrome: Clinical studies in 27 patients

Kidney involvement in Sjögren's syndrome (SS) including renal tubular disorders are well recognized but little is known about frequency and extent of such dysfunction in the general population of patients with primary SS, due to a lack of group studies. We studied 27 patients with primary SS and without other possible causes of tubular dysfunction. Increased urinary beta 2M excretion, due to proximal tubular dysfunction, was present in 26% of patients. Inadequate urine acidification after oral NH4 Cl, proving distal tubular dysfunction, was found in 12% of the patients studied. Concentrating ability, tested by thirst, was decreased in 44% of patients studied. Abnormal renal tubular tests correlated with presence of ANA (p = 0.05) but not with other clinical parameters. In conclusion demonstrable renal tubular dysfunctions occur in over half the patients with primary SS. Literature concerning this subject is discussed.

Fractional Excretion of Beta-2-Microglobulin in the Urine of Patients with Normal or Reduced Renal Function and Hepatic Coma

The purpose of this prospective study was to evaluate beta-2-microglobulin (beta 2m) as a differential diagnostic indicator between hepatic nephropathy (HN) and acute tubulointerstitial nephropathy (ATIN) in patients with reduced renal function and hepatic coma, and to determine whether beta 2m excretion could be used as a marker of renal impairment before increased serum creatinine (S-Cr) concentration or decreased creatinine clearance (Cr-Cl). Finally, the use of beta 2m as a prognostic indicator was investigated. Eighteen patients in hepatic coma grade III-IV were entered in the study and were divided into two groups in accordance with their renal function (serum creatinine above/below 180 mumol/l). The fractional excretion of beta 2m (FE-beta 2m) was used to monitor beta 2m elimination. The study failed to show any distinction in FE-beta 2m between HN and ATIN patients, presumably owing to the small number of patients. FE-beta 2m could not predict the development of renal failure earlier than the increase in S-Cr or decrease in Cr-Cl. However, a few patients who survived paracetamol intoxication had increased FE-beta 2M in the beginning of the coma and normal S-Cr and Cr-Cl. Patients who died as a result of paracetamol intoxication had both abnormal FE-beta 2m and abnormal S-Cr and Cr-Cl, suggesting that if therapy had been initiated earlier, when only FE-beta 2m was affected, these patients might have survived. All patients who survived, except three paracetamol- and one aminoglycoside-intoxicated patient, had normal FE-beta 2m in the beginning of the coma.(ABSTRACT TRUNCATED AT 250 WORDS)

Renal handling of beta-2-microglobulin in neonates treated with gentamicin.

Increased levels of urinary beta 2-microglobulin (beta 2M) have been used as a marker of proximal tubular dysfunction in human neonates. To assess the value of beta 2M in the detection of early stages of tubular damage caused by gentamicin, renal handling of beta 2M was studied sequentially in 18 gentamicin-treated neonates with idiopathic respiratory distress syndrome (mean birth weight 1,781 g, mean gestational age 33.7 weeks) during the first 7 days of life. These data were compared with those obtained from 10 control infants matched for gestational and postnatal ages. In addition, follow-up studies of renal function were conducted in 14 of 18 study infants 1 week after termination of therapy, on day 14 postpartum. The (+/- SD) fractional tubular excretion of beta 2M (FE beta 2M) tended to decrease significantly in the control infants from 10.3 +/- 1% on day 1 to 6.5 +/- 0.8% on day 7 postpartum (p less than 0.05). In infants treated with gentamicin, the mean FE beta 2M rose from 10.5 +/- 2% on day 1 to 17.1 +/- 1% on day 7 (p less than 0.01), followed by a decrease to 8.2 +/- 0.5% over the next 7 days (p less than 0.001). Compared with the control infants, values for the infants receiving gentamicin were significantly higher on postpartum days 3,5, and 7 (p less than 0.001). No significant differences in serum creatinine, creatinine clearance, or fractional tubular excretion of sodium were observed between the two groups during the study period.(ABSTRACT TRUNCATED AT 250 WORDS)

Diagnostic Potential of Urinary Enzymes and β2‐Microglobulin in Acute Urinary Tract Infection

Urinary excretions of beta 2-microglobulin (beta 2M), N-acetyl-beta-D-glucosaminidase (NAG), alanine aminopeptidase, beta-glucuronidase, acid and neutral alpha-glucosidase as indicators of proximal tubular dysfunction were measured in patients with acute upper and lower urinary tract infection (UTI) and fever of non-renal origin. The sensitivity of beta 2M was 67% and of NAG 49% as assessed in more than 100 episodes of acute pyelonephritis. Combined use of beta 2M and NAG increased the sensitivity to 75%. The degree of beta 2-microglobulinuria and enzymuria was comparable in patients with acute pyelonephritis and fever due to non-renal infections. The excretion of beta 2M and the various enzymes was too variable and unpredictable in individual cases to be useful as diagnostic indicator. In localizing an acute UTI, tests for proximal tubular dysfunction seem to be of no more clinical value than properly measured body temperature.

Beta 2-microglobulin clearance in neonates: Index of tubular maturation

Serum and urinary beta 2-microglobulin (beta 2M) were studied by enzyme immunoassay in 28 normal neonates at day 1 and day 4 of life in relation to gestational age (GA) and postnatal age (PNA). The infants were grouped according to GA; 10 with GA ranging from 32 to 35 weeks (mean 33.5 weeks) and 18 with GA ranging from 36 to 41 weeks (mean 38.3 weeks). Serum beta 2M varied directly with both GA and PNA. When values for serum beta 2M were related to conceptional age (CA), a significant positive correlation was present for all the infants studied (r = 0.68, P less than 0.01). Fractional excretion of beta 2M (FE beta 2M) decreased as a function of both GA and PNA. When a comparison of FE beta 2M was made in infants of all CA, a significant inverse correlation was noted for infants with CA less than or equal to 35 weeks (r = -0.89, P less than 0.001). The fall in FE beta 2M reached a plateau by 36 weeks. The highest FE beta 2M (33%) was observed in infants of 32 weeks CA who had the lowest filtered beta 2M (F beta 2M). No statistically significant relationship between changes in FE beta 2M and fractional urine flow rate was observed within each of the CA categories (infants less than or equal to 35 weeks, r = 0.21, P = 0.28; infants greater than or equal to 36 weeks, r = 0.25, P = 0.18).(ABSTRACT TRUNCATED AT 250 WORDS)

Renal tubular absorption of β2 microglobulin

125Iodinated human beta 2 microglobulin (beta 2m, 5 to 30 mg) was administered to anesthetized rats. Clearance studies showed a low threshold of excretion of injected beta 2m and a high Tm of 400 to 600 micrograms X min-1 X kg-1. A glomerular sieving coefficient of 0.97 was calculated as the slope of the curve: beta 2m excretion rate = F (plasma beta 2m X glomerular filtration rate) for values above saturation. Electrophoresis analysis of proteinuria in agarose gel and sodium dodecyl sulfate polyacrylamide gel showed that injection of saturating doses of beta 2m induced the excretion of proteins of similar size but different charge and that of other proteins of different size. Among the latter, some were excreted transiently in association with beta 2m, whereas others had a delayed excretion suggesting existence of a complex mechanism of reabsorption whose steps remain to be elucidated.

Failure of sodium aurothiomalate and triethyl phosphine gold to cause renal tubular injury in rheumatoid arthritis: implications for the aetiology of gold-related nephropathy.

The urinary excretion of two proteins, B-2-microglobulin (beta 2M) and N-acetyl-B-D-glucosaminidase (NAG) was measured in 25 patients with rheumatoid arthritis (RA) on nonsteroidal anti-inflammatory drugs (NSAID). Although beta 2M excretion was normal NAG excretion was raised. As NAG excretion by a group of osteoarthritis patients receiving similar doses of NSAIDs was normal, it is concluded that rheumatoid disease per se may be associated with mild renal tubular dysfunction. Twelve of the above 25 patients were then given oral triethylphosphine-gold (auranofin) 6 mg daily and urinary beta 2M and NAG were measured after 6 months' treatment. Urinary excretion of beta 2M and NAG was also measured in 13 patients with RA established on intramuscular sodium aurothiomalate (MGST) and NSAIDs. Neither auranofin nor myocrisin were found to further significantly increase beta 2M and NAG excretion. These results suggest that gold compounds are not toxic to renal tubular epithelium.

Beta 2-Microglobulin instability in pathological urine.

Urinary excretion of beta 2-microglobulin (beta 2M) is a widely used test of renal proximal tubular function. beta 2M is known to be unstable in normal urine with a pH less than 5.5. The results of a study of beta 2M excretion in patients receiving gentamicin suggested that beta 2M might be more unstable in pathological urine. A series of experiments was designed to define the extent, variability, and mechanism of its instability in pathological urine. It was unstable in pathological urine with a pH of 6.0 at 37 degrees C and pH 5.5 at room temperature, but this varied in urines from different patients. The instability was abolished by heating the urine to 80 degrees C. These results suggest that the most likely explanation for the instability is enzymic degradation. Because enzymuria will vary among patients, investigators should test the stability of beta 2M in urine from the patients they wish to study before trying to define conditions for urine collection.

Patterns of urinary β2-microglobulin excretion by patients treated with aminoglycosides

Aminoglycoside antibiotics are relatively mild nephrotoxins, but their action is site-specific to the proximal tubule. Therefore, use of these drugs presents a unique opportunity to study the temporal relation between the damage to the cells lining the renal proximal tubule and the subsequent rise in the serum creatinine concentration. Our study of 52 aminoglycoside-treated patients included measurements of daily serum creatinine, daily 24-hour urinary beta 2-microglobulin (beta 2M) excretion, and determination of aminoglycoside tissue accumulation. An elevation in beta 2M excretion above the baseline value occurred in 37 of 52 (71%), whereas the serum creatinine concentration rose in only 17 of 52 (33%) of patients. Even fewer patients (10 of 52) demonstrated all three criteria for aminoglycoside nephrotoxicity. These 10 patients had elevated tissue accumulation, evidence of renal tubular damage, and a rise in serum creatinine concentration. The increased beta 2M excretion greater than 50 mg/day preceded the serum creatinine rise by 2 to 7 days. An abnormal baseline beta 2M was not a risk factor for a subsequent rise in creatinine concentration or vice versa. Although each test is primarily site specific, widespread and severe renal proximal tubular damage, regardless of cause, will eventually lead to an elevation of serum creatinine. Thus, serial monitoring of proximal tubular function with urinary beta 2M excretion has potential value in the assessment of insults to this site, but cannot be expected to explain all changes in serum creatinine.

Radioimmunoassay of beta2-microglobulin in monoclonal gammopathies (author's transl)

Serum concentration of beta2m were measured by radioimmunoassay in 78 healthy subjects and 80 patients with monoclonal gammopathies. The beta2m levels of normal sera were normally distributed with a mean concentration of 1610 microgram/l. 77% of values were between 1200 and 2000 microgram/l. The serum beta2m levels of patients with monoclonal gammopathies were significantly higher than those of the healthy subjects, but there was no significant difference when comparing the Ig class or the light-chain type. Urinary beta2m excretion of patients with monoclonal gammopathies (3--5400 microgram/l) were slightly higher than normal (15--113 microgram/l). Serum beta2m levels did not correlate with the serum levels of monoclonal immunoglobulins. This supports the hypothesis of the mutual independence of beta2m and Ig production.

Serum beta2-microglobulin in hemodialyzed patients.

beta2-Microglobulin (beta2-M) concentrations were measured by radioimmunoassay in 63 patients treated with maintenance hemodialysis. Serum levels ranged from 12.5 to 92 microgram/ml and were found stable upon sequential measurements over a 6-month period. Excretion of beta2-M was achieved through urinary loss (up to 150 mg/day) and to a lesser extent by ultrafiltration across acrylopolynitrile but not cellophane dialysis membranes. Proximal tubular cells being the major site of beta2-M catabolism, stable levels in anephric patients indicated a defective production of beta2-M in uremic patients. Serum beta2-M levels were not correlated with predialysis urea, creatinine, hematocrit or middle molecule material. In vitro experiments do not support a possible toxicity of purified beta2-M but do not rule out the contribution of other low molecular weight proteins to uremic toxicity.