Alpha1-microglobulin Levels Research Articles

Urinary excretion of pancreatic stone protein in diabetic nephropathy.

Urinary pancreatic stone protein (PSP) levels were measured in 68 diabetic patients and 170 healthy controls to investigate the relationship between the progression of diabetic nephropathy and PSP excretion. Urinary albumin, N-acetyl-beta-glucosaminidase (NAG), alpha1-microglobulin, creatinine clearance, and the blood PSP level were also determined in the diabetic patients. The urinary glucose level and glycemic control did not influence the urinary PSP level. In patients with normoalbuminuria (urinary albumin <20 mg/gCr, n=31), microalbuminuria (20-200 mg/Cr, n=19), and macroalbuminuria (>200 mg/gCr, n=18), the mean urinary PSP level was 347, 507, and 860 microg/gCr, respectively. These levels were significantly higher than the level in normal volunteers (168 microg/gCr, p<0.01). A significant positive correlation was observed between the urinary PSP level and the NAG or alpha1-microglobulin levels (p<0.01). There was a stronger correlation with alpha1-microglobulin. Blood PSP levels were also elevated in patients who had renal impairment with a decreased creatinine clearance. In conclusion, urinary PSP excretion was increased from the initial stage of diabetic nephropathy and this increase became more marked as nephropathy progressed. Increased PSP excretion may reflect renal tubular dysfunction.

Metabolic Alterations at Different Levels of Renal Function Following Continent Urinary Diversion Through Colonic Segments

Purpose We evaluated the influence of renal function on electrolyte and acid-base homeostasis in patients with colonic reservoirs for urine and the ability of these patients to handle an acute acid load. Materials and Methods The 19 patients studied were divided into 2 groups according to preservation of the glomerular filtration rate at last followup: group 1-well preserved glomerular filtration rate (mean 100 ml. per minute per 1.73 m. 2) with an average followup of 8.5 years and group 2-slight to moderate decrease in glomerular filtration rate (mean 55 ml. per minute per 1.73 m. 2) with a mean followup of 10.5 years. Renal tubular function was evaluated by urinary levels of protein alpha 1-microglobulin. Baseline serum and urine samples were analyzed for metabolic parameters, and baseline arterial blood gas was measured. Immediately thereafter ammonium chloride loading was performed. Results Some difference in acid-base homeostasis was found with slight hyperchloremic metabolic acidosis noted in 4 patients in group 2. Moreover, calcium homeostasis was influenced, with lower levels of ionized calcium noted in group 2. However, no difference was found in the ability of the patients in both groups to handle an acute acid challenge. Conclusions Patients with a glomerular filtration rate of approximately 55 ml. per minute per 1.73 m. 2 have sufficient renal function to compensate for the chronic endogenous acid load noted after urinary diversion and they can also handle an acute acid load adequately. Further studies are necessary to evaluate the long-term effects of a chronic endogenous acid load, for example on bone metabolism, in patients with impaired renal function after urinary intestinal diversion.

Nullification of a positive correlation between urinary levels of alpha 1-microglobulin and ulinastatin by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in mice.

The relationships between urinary levels of alpha 1-microglobulin (alpha 1M) and ulinastatin (UT) were investigated in C57BL/6J mice, a species which reportedly possesses the gene similar to that of humans for synthesizing the precursor protein of alpha 1M and UT. A positive correlation was established in normal mice. However, repetitive administrations (20 mg/kg, IP, four administrations/12 h) of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) nullified the positive correlation. A similar phenomenon was induced by ICV-administered MPTP (18 and 36 micrograms) in the animals. Furthermore, L-dopa administration (50 mg/kg, IV) in MPTP-treated (1 week after the final IP administration of MPTP) mice reversed the tendency of MPTP, although the agent alone did not affect the positive correlation in normal mice. These results suggest that nullification of the positive correlation probably was induced by the central effects of MPTP. We have found previously that the lack of a positive correlation between urinary levels of alpha 1M and UT distinguishes Parkinson's disease from other neuropsychiatric diseases such as dementia (Alzheimer-type and vascular dementia), schizophrenia and mood disorders. Our present results displayed a phenomenon that the lack of correlation between urinary levels of alpha 1M and UT in patients with Parkinson's disease is reproducible in MPTP-treated mice.

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.

Changes in the ratio of urinary α1‐microglobulin to ulinastatin levels in patients with Alzheimer‐type dementia and vascular dementia

Relationships between urinary levels of alpha 1-microglobulin (alpha 1M) and ulinastatin (UT) in patients with dementia were investigated. There were no significant differences in alpha 1M and UT levels and alpha 1M: UT ratios among three groups: age-matched control subjects, patients with either Alzheimer-type senile dementia (ATD) or vascular dementia (VD). Although a positive correlation was established between alpha 1M and UT levels in these groups, the regression of the demented patients differed significantly from that of controls (P < 0.05). A tendency towards a negative correlation between alpha 1M: UT ratios and the levels of severity or duration of the disease was displayed in the ATD group, whereas a tendency toward a positive correlation between alpha 1M: UT ratios and the levels of severity was observed in the VD group. These results suggest that changes in the relationships between urinary levels of alpha 1M and UT may provide a useful biochemical index for diagnoses of ATD and VD.

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.

Serum levels of alpha-1 microglobulin and beta-2 microglobulin in bone marrow transplant recipients treated with cyclosporin A

The levels of alpha-1 microglobulin (alpha 1m) and beta-2 microglobulin (beta 2m) in serum were estimated in 77 bone marrow transplant recipients. In comparison to pre-transplant levels, the highest levels of alpha 1m and beta 2m were found during impairment of renal function, i.e., during cyclosporin-induced nephrotoxicity and during treatment with other nephrotoxic drugs (P less than 0.001). The alpha 1m levels were less elevated during infections and acute graft-versus-host disease (P less than 0.01), while beta 2m levels were markedly elevated during the same conditions (P less than 0.001). The linear correlations between serum creatinine and alpha 1m and creatinine and beta 2m were r = 0.7 and 0.8, respectively (P less than 0.001). The overall correlation between alpha 1m and beta 2m was 0.4 (P less than 0.001). It is concluded that alpha 1m might be a complement to serum creatinine levels in monitoring renal function after bone marrow transplantation.

Transferrinuria in Type 2 Diabetes: The Effect of Glycaemic Control

Urinary excretion rates of transferrin, albumin, N-acetyl-beta-D-glucosaminidase (NAG) and alpha-1-microglobulin (A1M) were measured in type 2 (non-insulin-dependent) diabetic patients at diagnosis and after 6 and 12 weeks treatment. Initially 21 (53%) patients had elevated transferrin excretion rates. The proportion of patients with raised transferrin excretion rates fell to 30% at 6 weeks and 20% at 12 weeks with treatment of diabetes. At diagnosis 11 (28%) patients had elevated albumin excretion rates and 10 of these had elevated transferrin excretion rates. After 6 weeks treatment only six (15%) had elevated albumin excretion rates and by 12 weeks this number had fallen to four (10%). NAG and A1M levels also fell with treatment of diabetes. There were correlations between the transferrin excretion rate and albumin excretion rate (r = 0.86, P less than 0.0001), transferrin excretion rate and NAG (r = 0.46, P less than 0.0001), and transferrin excretion rate and A1M (r = 0.55, P less than 0.0001) at each visit. There were weaker correlations between the albumin excretion rate and A1M and NAG at each visit. The correlations between the transferrin excretion rate and markers of tubular function (NAG and A1M) suggest that tubular dysfunction may play a part in renal loss of transferrin in diabetes mellitus. There were no differences in transferrin excretion rates between patients with and without evidence of complications.

Serum levels of alpha-1 microglobulin and beta-2 microglobulin in bone marrow transplant recipients treated with cyclosporin A

Abstract. The levels of alpha-1 microglobulin (α1m) and beta-2 microglobulin (β2m) in serum were estimated in 77 bone marrow transplant recipients. In comparison to pretransplant levels, the highest levels of α1m and β2m were found during impairment of renal function, i. e., during cyclosporin-induced nephrotoxicity and during treatment with other nephrotoxic drugs (P< 0.001). The α1m levels were less elevated during infections and acute graft-versus-host disease (P < 0.01), while β2m levels were markedly elevated during the same conditions (P < 0.001). The linear correlations between serum creatinine and α1m and creatinine and β2m were r= 0.7 and 0.8, respectively (P < 0.001). The overall correlation between α1m and β2m was 0.4 (P< 0.001). It is concluded that α1m might be a complement to serum creatinine levels in monitoring renal function after bone marrow transplantation.

Alpha1-microglobulin, beta2-microglobulin and retinol binding protein in childhood febrile illness and renal disease

Serum and urinary levels of alpha-1-microglobulin (A1M), beta-2-microglobulin (B2M) and retinol binding protein (RBP) were measured using a Mancini radial immunodiffusion technique in 52 children with renal disease, 36 with non-renal febrile illness and 29 controls. In controls the mean serum level for A1M was 25 +/- 4.6 (SD) mg/l for B2M 1.7 +/- 0.5 mg/l and for RBP 31 +/- 8 mg/l. A1M levels were not significantly altered by febrile illness while B2M was elevated and RBP markedly depressed. Serum A1M and B2M were elevated in the nephrotic syndrome, while serum B2M was also raised during infancy. Coefficients of log-transformed data with creatinine-derived glomerular filtration rate (GFR) were -0.87 for B2M, -0.71 for RBP, and -0.62 for A1M. In the urine A1M was always measurable in controls while B2M and RBP were undetectable in all but a small number. The urine levels of all three proteins increased in response to non-renal febrile illness, and rose invariably when GFR fell to below 40-50 ml/min per 1.73 m2. Of the three proteins A1M was most frequently elevated in the urine with febrile and renal illness. RBP was rarely detectable when the other two proteins were not. Urinary A1M was consistently elevated in the nephrotic syndrome in contrast to B2M, possibly as a reflection of the increased glomerular permeability. We conclude that serum B2M is superior to A1M and RBP as an index of glomerular filtration, although its levels should be interpreted with caution in febrile disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Serum levels of alpha-1 microglobulin in recipients of renal allografts

Serum levels of alpha 1 microglobulin (s-alpha 1 m) in 92 recipients of renal transplants were elevated during pretransplant uremia (P less than 0.001), acute rejection (P less than 0.01), and cyclosporin-induced nephrotoxicity (P less than 0.01). In patients with stable renal function, those treated with cyclosporin had higher s-alpha 1 m than those receiving azathioprine: 81 +/- 4 and 64 +/- 3 mg/l (mean +/- SEM), respectively (P less than 0.05). The serum creatinine levels were 127 +/- 5 and 115 +/- 7 mumol/l (mean +/- SEM), respectively (N.S.). Two of the patients with normal serum creatinine had normal s-alpha 1m levels. There were positive linear correlations between s-alpha 1m and serum creatinine levels during stable renal function, rejection, cyclosporin-induced nephrotoxicity, and cytomegalovirus infections (r = 0.7-0.8, P less than 0.01-0.001) and between s-alpha 1m and beta 2 microglobulin (beta 2m) during the same conditions (r = 0.5-0.8, P less than 0.01-0.001). During infections, serum creatinine and beta 2m increased (P less than 0.001), but s-alpha 1m did not. S-alpha 1m values did not distinguish between rejection and cyclosporin-induced nephrotoxicity. It is concluded that s-alpha 1m might be a valuable complement to serum creatinine levels in the evaluation of renal function in renal transplant recipients.

Serum levels of alpha-1 microglobulin in recipients of renal allografts

Abstract. Serum levels of α1 microglobulin (s-α1m) in 92 recipients of renal transplants were elevated during pretransplant uremia (P < 0. 001), acute rejection (P < 0. 01), and cyclosporin-induced nephrotoxicity (P < 0. 01). In patients with stable renal function, those treated with cyclosporin had higher s-αim than those receiving azathioprine: 81 ± 4 and 64 ± 3 mg/l (mean ± SEM), respectively (P < 0. 05). The serum creatinine levels were 127 ± 5 and 115 ± 7μmol/l (mean ± SEM), respectively (N. S.). Two of the patients with normal serum creatinine had normal s-α1m levels. There were positive linear correlations between s-α1m and serum creatinine levels during stable renal function, rejection, cyclosporin-induced nephrotoxicity, and cytomegalovirus infections (r= 0. 7–0. 8, P < 0. 01–0. 001) and between s-α1m and β2 microglobulin (β2m) during the same conditions (r= 0. 5–0. 8, P < 0. 01 -0. 001). During infections, serum creatinine and β2m increased (P< 0. 001), but s-α1m did not. S-α1m values did not distinguish between rejection and cyclosporin-induced nephrotoxicity. It is concluded that s-α1m might be a valuable complement to serum creatinine levels in the evaluation of renal function in renal transplant recipients.

Human α&lt;sub&gt;1&lt;/sub&gt;-Microglobulin and Its Relationship to Renal Function

To evaluate the clinical usefulness in terms of estimation for glomerular filtration rate (GFR), we determined the levels of alpha 1-microglobulin (alpha 1m) in the serum and urine of patients with various renal diseases and compared with those of beta 2-microglobulin (beta 2m) and creatinine. Serum and urinary alpha 1m levels were measured by using single-radial immunodiffusion method. 24-hour creatinine clearance (Ccr) was used as a indicator of GFR. There was a significant positive correlation between serum alpha 1m and creatinine levels (r = 0.75, p less than 0.001). Serum alpha 1m, beta 2m and creatinine inversely correlated and logarithmically correlated to Ccr as shown in the following equations: log alpha 1m = 2.30 - 0.42 X log Ccr (r = -0.74); log beta 2m = 2.06 - 0.91 X log Ccr (r = -0.92); log creatinine = 1.57 - 0.78 X log Ccr (r = -0.94). Both correlation coefficient and regression coefficient for alpha 1m were rather poor compared to those for beta 2m and creatinine. However, alpha 1m levels started to increase over normal range when Ccr fell below 80 liters/day, while beta 2m and creatinine remained within normal ranges. The daily urinary excretion of alpha 1m was increased in the patients whose Ccr was within normal limits compared to that of healthy control subjects (15.2 +/- 3.2 mg/day, n = 19, vs. 5.7 +/- 0.7, n = 7, p less than 0.001). Fractional clearance of alpha 1m increased proportionally to the decrease of Ccr. These data suggest that combined measurements of alpha 1m in the serum and urine seem to be useful to estimate GFR, especially to detect the mild reduction of CFR.

Human alpha 1-microglobulin in various hepatic disorders.

Human alpha 1-microglobulin (alpha 1-m) levels were studied in the sera and urine of patients with various liver diseases. In patients with acute hepatitis and chronic hepatitis it was almost within the normal range. A significant decrease of serum alpha 1-m, however, was demonstrated in patients with compensated liver cirrhosis (p less than 0.05) as well as in those with decompensated liver cirrhosis (p less than 0.001). The most striking decrease was noted in patients with fulminant hepatitis (p less than 0.001). Its concentration in hepatoma was generally within the normal range, but there was 1 hepatoma case with the high concentration of alpha 1-m. Serum alpha 1-m levels correlated significantly with serum albumin, plasma fibrinogen and cholinesterase activity. As compared with the level in normal individuals, the patients with decompensated liver cirrhosis had significantly low urinary alpha 1-m (p less than 0.005), reflecting the findings for sera. These results indicated that the liver plays an important role in alpha 1-m synthesis, and its quantitation may be used for evaluating severe liver damage.

Human alpha 1-microglobulin levels in various body fluids.

alpha 1-Microglobulin levels in serum and urine were estimated by using single radial immunodiffusion, resulting in the following mean values: umbilical cord blood serum, 40.6 mg/l; normal adult serum, 44.2 mg/l; and normal urine, 5.7 mg/24 h urine volume. Slightly higher levels of serum alpha 1-microglobulin were found in infants and the aged. Serum and urine alpha 1-microglobulin levels in patients with renal failure, however, were greatly increased, mean levels being 231.5 mg/l and 100.7 mg/24 h urine volume, respectively. Serum alpha 1-microglobulin levels in these patients correlated well with both serum creatinine and beta 2-microglobulin levels. Serum alpha 1-microglobulin level did not correlate positively with serum levels of other plasma proteins, such as alpha 1-antitrypsin, haptoglobin, complement, etc. Ouchterlony immunodiffusion also revealed the presence of alpha 1-microglobulin in synovial fluid, ascites, pleural effusion, amniotic fluid, cyst fluid, and cerebrospinal fluid. The levels of alpha 1-microglobulin in these fluids were measured by single radial immunodiffusion, except that its level in cerebrospinal fluid was measured by radioimmunoassay. Mean alpha 1-microglobulin concentration was 20.8 mg/l in synovial fluid, 28.7 mg/l in ascites, 21.5 mg/l in pleural effusion, 2.7 mg/l in amniotic fluid, 8.2 mg/l in cyst fluid, and 42.3 ng/ml in cerebrospinal fluid.