Α1-microglobulin Research Articles

Possible effects of environmental cadmium exposure on kidney function in the Japanese general population

To examine whether the current level of environmental exposure to cadmium (Cd) is associated with kidney dysfunction among general populations in Japan. A nationwide survey was conducted in Japan from 1991 to 1997 at 30 survey sites (with no known environmental heavy metal pollution), by the collection of 24-h food-duplicate samples, peripheral blood specimens and morning spot urine samples. In practice, 607 non-smoking adult women provided these samples. After being wet-ashed, the samples were analyzed for Cd in food duplicates (Cd-F), in blood (Cd-B) and urine (Cd-U) by inductively-coupled plasma mass spectrometry (ICP-MS). Urine samples were also analyzed for alpha 1-microglobulin (alpha 1-MG), beta 2-microglobulin (beta 2-MG) and retinol-binding protein (RBP), creatinine (cr) and specific gravity. Possible tubular dysfunction in association with Cd exposure was examined by simple, multiple and logistic regression analyses, and comparison among three different Cd-dose groups. To minimize the confounding effects of aging, 367 women from 41 to 60 years old were selected and subjected to the same statistical analyses. The analysis of a whole population of 607 women showed that alpha 1-MG and possibly beta 2-MG increased as a function of Cd-F, Cd-B and Cd-U. When the analysis was repeated with the selected population of 367 women aged 41-60, the Cd dose-dependent changes in alpha 1-MG and beta 2-MG became less evident. The distribution of the selected population with alpha 1-MG above two low cut-off values of > 4.9 and > 8.4 mg/g cr or with beta 2-MG above the lowest cut-off value of > 400 micrograms/g cr, was biased toward the group with higher Cd-Ucr, but such bias was not significant for both alpha 1-MG and beta 2-MG when higher cut-off values were employed. No bias was detected with RBP. Logistic regression analysis with alpha 1-MG, beta 2-MG and RBP (with cut-off values given above) in combination with age, Cd-F, Cd-B and Cd-Ucr gave essentially the same results. The evidence for kidney dysfunction was of borderline significance in the present study population for which geometric mean Cd-F, Cd-B and Cd-U were 24.7 micrograms/day, 1.76 micrograms/l, and 3.94 micrograms/g cr, respectively. The findings might suggest at the same time that the safety margin is small for the Japanese general population regarding environmental Cd exposure.

Age-related reference limits for urine levels of albumin, orosomucoid, immunoglobulin G and protein HC in children

Urine levels of albumin, orosomucoid (alias alpha1-acid glycoprotein), immunoglobulin G (IgG) and protein HC (alias alpha1-microglobulin) were determined in 247 healthy Swedish infants and children aged 1 day to 15 years. Urine samples were collected and stored in conditions known to guarantee stable protein levels. The protein levels were measured both as mass concentrations (mg l(-1)) and as protein-creatinine ratios (mg mmol(-1)). In an effort to arrive at practically useful upper reference limits, the variability with age for both units was analysed. The variability with age for the levels of three of the four proteins was considerably lower when the levels were expressed as creatinine ratios rather than as mass concentrations. The results allowed suggestion of the following upper reference limits, expressed as mg mmol(-1) creatinine, for use in clinical practise: IgG, 1 month to 15 years: 1.0; protein HC, 1 month to 15 years: 0.8; orosomucoid, 1 month to 15 years: 0.5; albumin, 1 month to 1 year: 3.8; 1-5 years: 3.3; 6-10 years: 2.7; 11-15 years: 2.1. In the immediate neonatal period the urine levels of all proteins were high and very variable.

The occurrence of renal involvement in primary Sjögren's syndrome: a study of 78 patients.

To ascertain the occurrence of renal involvement in patients with primary Sjögren's syndrome (pSS). Urinary total protein excretion from 24 h urine collection, as well as urinary excretion rates of albumin, alpha-1 microglobulin (alpha1m) and IgG from overnight 8 h collections, were determined from 78 pSS patients (75 females, three males). Urine acidification capacity after oral ammonium chloride load was tested in 55 of these patients. Mild proteinuria (0.15-0.42 g/24 h) was observed in 34 patients (44%). Increased urinary excretion rates of albumin (>/=20 microgram/min), alpha1m (>/=7.0 microgram/min) or IgG (>/=5.0 microgram/min) were detected in nine (12%), nine (12%) and 11 patients (14%), respectively. Latent or overt distal renal tubular acidosis (dRTA) was observed in 18 out of 55 patients with pSS (33%). These patients had a longer duration of the disease (10+/-4 vs 8+/-4 yr; P</=0.05); they also had proteinuria (67 vs 27%; P</=0.025) and hypertension (44 vs 14%; P</=0.05) more frequently, and significantly higher serum creatinine (92+/-39 vs 78+/-13 micromol/l; P</=0.025) and serum beta-2 microglobulin (beta2m) levels (3.3+/-1.6 g/l vs 2.6+/-0. 6 g/l; P</=0.025) as compared to patients with normal urine acidification capacity. Inadequate renal acidification capacity, as well as mild proteinuria, were frequently found in patients with pSS. Those with dRTA had longer disease duration, a higher level of serum beta2m, and they had proteinuria and hypertension more frequently than those with normal renal acidification capacity.

Serum glucagon concentration and hyperinsulinaemia influence renal haemodynamics and urinary protein loss in normotensive patients with central obesity.

Insulin-resistance syndrome and hyperinsulinaemia are linked with cardiovascular disease (CVD) in the obese population. In particular, cardiovascular risk is more frequent in central obesity and is associated with microalbuminuria (MA). MA and changes of glomerular permeability to proteins in obesity might be related with renal haemodynamic modifications (that is glomerular hyperfiltration). Since glucagon is physiologically involved in renal haemodynamic regulation, the purpose of this study was to examine whether changes of circulating glucagon levels might haemodynamically induce MA and proteinuria in patients with central obesity. Forty normotensive obese out-patients, 22 with central (CO group) and 18 with peripheral (PO group) body fat distribution and 11 healthy subjects. Serum insulin and glucagon concentrations (fasting and after oral glucose tolerance test (OGTT)) by radio immuno assay (RIA); glomerular filtration rate (GFR, isotopic); total clearances and urinary excretion rates of albumin (AER), IgG (IgGER) and alpha1 microglobulin (computerized immunonephelometry). GFR and insulin concentrations (fasting and during OGTT) were higher in the CO than the PO group. Fasting glucagon concentrations were increased, and not physiologically suppressed during OGTT in patients with CO (fasting, P<0.05; OGTT 60 and 120 min, P<0.001 vs PO group). Moreover, glucagon concentrations were significantly correlated with GFR in the CO group (fasting, r=0.49, P<0.05; 60 min after OGTT, r=0.58, P<0.01); whereas no correlations were found in the PO group. Higher AER (P<0.001), IgGER (P<0.001) and alpha1 microglobulin (P<0.05) urinary concentrations were found in patients with CO than in the PO group. The increase of serum glucagon concentrations may be associated with the enhancement of GFR in patients with central obesity. Glomerular hyperfiltration might influence the development of MA and of proteinuria by means of a haemodynamic mechanism so contributing to increase the risk of renal microvascular complications and of CVD in central obesity.

Sex- and age-related changes in urinary contents of alpha 1-microglobulin and ulinastatin in mice.

1. Using two murine strains, ICR/Jcl and senescence-accelerated-prone inbred mouse 1 (SAMP1), age-associated changes in urine indices (e.g. urine volume, creatinine contents, contents of alpha 1-microglobulin (alpha 1M) and ulinastatin (UT) and the relation of urinary contents of alpha 1M and UT were investigated. 2. Sex-related differences in the indices were not observed in ICR nor in SAMP1 mice. 3. Urine indices per 24 h of ICR mice at 6 and 14 months of age were higher than those at 3 months of age, although indices of SAMP1 mice did not change with ageing. Urinary contents of alpha 1M and UT in ICR mice at 6 and 14 months of age were higher than those in SAMP1 mice. However, contents of alpha 1M and UT expressed as the contents per creatinine did not differ between these two strains. 4. In the relation between urinary contents of alpha 1M and UT, a positive correlation was displayed both in ICR and SAMP1 mice, and the regression slope did not significantly differ with ageing in these two strains. 5. These results suggest that ageing per se is not a factor which affects the relation of urinary contents of alpha 1M and UT.

Assessment of Renal Effects of Sevoflurane in Elderly Patients Using Urinary Markers

To the Editor: Although sevoflurane anesthesia has been shown not to cause nephrotoxicity in adults with normal renal function, its effect in patients with impaired renal function or in the elderly has not been thoroughly investigated. Recently, urinary albumin has gained attention as a marker of postanesthetic renal injury in surgical patients [1], but there is no agreement on how the results of studies should be interpreted. At our institution, we have investigated the effects of inhaled anesthetics on renal function in elderly patients. We present the data of our study, in which urinary albumin, alpha1 microglobulin (MG), beta2 MG, and N-acetyl- beta-D-glucosaminidase (NAG) were used as markers of renal injury in elderly patients anesthetized with sevoflurane. Thirteen patients aged >or=to70 yr undergoing gastrectomy were randomly assigned to receive either sevoflurane anesthesia (n = 7; mean age 77.6 yr) or isoflurane anesthesia (n = 6; mean age 78.5 yr). We used routine anesthetic techniques for our institution in this study, i.e., local epidural anesthesia combined with inhaled anesthesia (3 L/min air, 2 L/min oxygen, and either sevoflurane or isoflurane). A urine sample was collected via a catheter before anesthesia, and cumulative urine samples were then collected during and after anesthesia (immediately before surgery; 2 h after the start of surgery; at the end of surgery; and 3 h and Days 1, 3, and 7 after anesthesia). There were no significant differences in patient demographics. The mean minimum alveolar anesthetic concentration-hour was 5.1 for the sevoflurane group and 3.7 for the isoflurane group. The mean urinary albumin excretion was 65.0 mg/g creatinine (gCr) and 44.4 mg/gCr before anesthesia, which significantly increased to 147.9 mg/gCr and 196.9 mg/gCr 2 h after the start of surgery, sustained similar values 3 h after anesthesia, and returned to close to the preanesthetic values on Postanesthesia Day 1 in the sevoflurane group and the isoflurane group, respectively. No significant difference was found between the two groups, and the increase in urinary albumin excretion indicated that transient glomerular injury occurred with both anesthetics. The mean urinary alpha1 and beta2 MG levels were 9.3 mg/gCr and 0.81 mg/gCr in the sevoflurane group and 7.4 mg/gCr and 0.70 mg/gCr in the isoflurane group before anesthesia, showed a gradual but significant increase in both groups during anesthesia, and reached 31.4 mg/gCr and 6.20 mg/gCr in the sevoflurane group and 44.1 mg/gCr and 10.9 mg/gCr in the isoflurane group by 3 h after anesthesia. The values of alpha (1) and beta2 MG then temporally dropped on Postanesthesia Day 1, but they increased again on Day 3 in both groups and decreased again on Day 7 (cause unknown). The mean urinary NAG also began to increase during anesthesia to significantly higher levels than the preanesthetic values (18.9 mg/gCr in the sevoflurane group and 16.9 mg/gCr in the isoflurane group), reached a peak 3 h after anesthesia (40.6 mg/gCr in the sevoflurane group and 35.7 mg/gCr in the isoflurane group), but returned to almost the preanesthetic values on Postanesthesia Day 1. The changes in the urinary enzyme levels indicated the presence of transient renal tubular injury in both groups. In conclusion, using urinary markers, we found that sevoflurane and isoflurane anesthesia in combination with epidural anesthesia resulted in similar degrees of mild, transient, glomerular, and tubular functional impairment in elderly surgical patients undergoing gastrectomy. Kokichi Hase, MD Kazuko Meguro, MD Takako Nakamura, MD Department of Anesthesiology; Tokyo Metropolitan Geriatric Hospital; Tokyo 173-0015, Japan

PROTEINURIA AND RENAL FUNCTION DURING AND AFTER ACUTE URINARY RETENTION

Purpose Benign prostatic hyperplasia is the most common neoplasm as well as the main cause of bladder outlet obstruction in men. It may progress to involve a risk of urinary retention. We investigated the effects of acute urinary retention on renal function. Materials and Methods We evaluated renal function using biochemical markers in 25 men with a mean age of 69 years in whom an episode of acute urinary retention a mean of 31 hours in duration was due to bladder outlet obstruction. Patients were followed for 6 months after acute retention was relieved. Patients were not known to have had any renal disease previously. Results During acute urinary retention at presentation, and after 1 and 6 months we noted albuminuria in 100, 92 and 54% of patients, elevated alpha 1-microglobulin excretion in 54, 39 and 58%, and elevated beta 2-microglobulin excretion in 17, 19 and 9%. Serum creatinine or creatinine clearance did not predict proteinuria. All parameters became normal at 6 months in only 2 cases. Conclusions Acute urinary retention affects glomerular and tubular renal function. After acute urinary retention was relieved increased glomerular permeability and tubular damage persisted in the majority of patients. This condition may have been partially due to previous long-term bladder outlet obstruction. Our findings stress the importance of the rapid recognition and treatment of acute urinary retention.

Inhibitory effect of bikunin on calcium oxalate crystallization in vitro and urinary bikunin decrease in renal stone formers

Two proteins of 17 and 24 kDa, respectively, which were immunologically related to bikunin, were purified from urine of healthy men, using in the last step a trypsin CNBr-sepharose affinity column. These proteins strongly inhibited calcium oxalate (CaOx) crystallization in two in vitro models. In the first model, the presence of 8 microg/ml protein in a medium containing 0.76 mM CaCl2 (with 45Ca) and 0.76 mM ammonium oxalate inhibited the crystallization process by 80%, as estimated by supernatant radioactivity after 60 min of incubation. A similar inhibition was observed in the second turbidimetric model, where the CaOx crystallization kinetics were followed for 10 min at 620 nm in a medium containing 4 mM CaCl2 and 0.5 mM Na2Ox. These proteins were used as standard protein for the development of an enzyme-linked immunosorbent assay (ELISA) in urine. Mean (+/-SEM) urinary bikunin concentration in 18 healthy subjects was 5.01 +/- 0.91 microg/ml. This was a concentration range of strong inhibitory activity in vitro. Bikunin values were nearly 50% lower (2.54 +/- 0.42 microg/ml, P=0.007) in 31 CaOx renal stone formers (having weddelite crystals in their first morning urine) than in the healthy volunteers. A correlation was found between urinary bikunin and alpha-1 microglobulin concentrations in the control group (y=0.73x + 1.09, r2=0.8) while no such correlation existed in the lithiasis group. In conclusion, bikunin exerts a strong inhibitory action of CaOx crystallization in vitro. Its involvement in urinary CaOx crystallization of stone formers is highly probable, based on the significant decrease in its urinary concentration in the majority of stone formers studied.

Histologie Distribution and Biochemical Properties of α1‐Microglobulin in Human Placenta

The embryo is protected from immunologic rejection by the mother, possibly accomplished by immunosuppressive molecules located in the placenta. We investigated the distribution and biochemical properties in placenta of the immunosuppressive plasma protein alpha 1-microglobulin. Placental alpha 1-microglobulin was investigated by immunohistochemistry and, after extraction, by electrophoresis, immunoblotting and radioimmunoassay. alpha 1-Microglobulin staining was observed in the intervillous fibrin and in syncytiotrophoblasts, especially at sites with syncytial injury. Strongly stained single cells in the intervillous spaces and variably stained intravillous histiocytes were noted. Solubilization of the placenta-matrix fraction and placenta membrane fraction released predominantly the free form of alpha 1-microglobulin, but, additionally, an apparently truncated form from the placenta-membrane fraction. The soluble fraction of placenta contained two novel alpha 1-microglobulin complexes. The biochemical analysis indicates the presence in placenta of alpha 1-microglobulin forms not found in blood. The histochemical analysis supports the possibility that alpha 1-microglobulin may function as a local immunoregulator in the placenta.

Biomarkers of nephrotoxicity in children environmentally exposed to lead in Poland

Nephropathy has been reported in children with overt lead intoxication. Only recently low-level lead exposure has been associated with renal effects, especially with regard to tubular function. The objective of the present study was to investigate the relation between lead exposure and renal function in children in the Katowice region, an industrial area in Poland. This cross-sectional study involved 157 children, aged 4–14 years. Blood lead concentration was used as an index of lead exposure. Glomerular filtration rate was estimated using the height adjusted serum creatinine calculation (crea-GFR) and measurement of cystatin C in serum. The renal tubular function was evaluated by measuring the urinary concentration of protein HC. The median blood lead concentration was 0.35 μmol/L (72 μg/L) with a range of 0.09–1.36 μmol/L. Crea-GFR (n = 143) decreased significantly (p = 0.002) with increasing concentrations of lead in the blood. Serum cystatin C (n = 84) increased with blood lead (p = 0.004). There was an association (p = 0.002) between blood lead and urinary concentration of protein HC (n = 49). In summary, the present findings indicate that the association between blood lead and the markers of renal function on both a glomerular and a tubular level may be caused by environmental lead exposure. Copyright © 1999 John Wiley & Sons, Ltd.

Biomarkers of nephrotoxicity in children environmentally exposed to lead in Poland

Nephropathy has been reported in children with overt lead intoxication. Only recently low-level lead exposure has been associated with renal effects, especially with regard to tubular function. The objective of the present study was to investigate the relation between lead exposure and renal function in children in the Katowice region, an industrial area in Poland. This cross-sectional study involved 157 children, aged 4–14 years. Blood lead concentration was used as an index of lead exposure. Glomerular filtration rate was estimated using the height adjusted serum creatinine calculation (crea-GFR) and measurement of cystatin C in serum. The renal tubular function was evaluated by measuring the urinary concentration of protein HC. The median blood lead concentration was 0.35 μmol/L (72 μg/L) with a range of 0.09–1.36 μmol/L. Crea-GFR (n = 143) decreased significantly (p = 0.002) with increasing concentrations of lead in the blood. Serum cystatin C (n = 84) increased with blood lead (p = 0.004). There was an association (p = 0.002) between blood lead and urinary concentration of protein HC (n = 49). In summary, the present findings indicate that the association between blood lead and the markers of renal function on both a glomerular and a tubular level may be caused by environmental lead exposure. Copyright © 1999 John Wiley & Sons, Ltd.

Pathological excretion patterns of urinary proteins in renal cell cancer patients exposed to trichloroethylene

A study was carried out to investigate urinary protein excretion patterns by means of SDS-polyacrylamide-gel-electrophoresis (SDS-PAGE) in renal cell cancer patients who had previously been exposed to high levels of trichloroethylene. Thirty-eight out of 41 (93%) renal cell cancer patients investigated had former extensive trichloroethylene exposure, but only 23 out of 50 (46%) renal cell cancer patients without a history of occupational exposure to trichloroethylene revealed urinary protein patterns indicative of toxic effects on the tubular system. One hundred controls without histories of overt renal disease and not occupationally exposed to trichloroethylene were examined in the same way; only 11 (11%) of them displayed protein excretion patterns indicative of damage to the renal tubule. These results are supported by alpha 1-microglobulin excretion data. The following conclusions are drawn: (1) Substantially more cases of tubular damage are found amongst renal cell carcinoma patients having been exposed to substantial levels of trichloroethylene over many years as compared with renal cell carcinoma patients not exposed to trichloroethylene. (2) The results support the view that chronic tubular damage is a precondition for the nephrocarcinogenic effect of trichloroethylene. (3) The findings indicate that urine protein patterns, on the basis of the SDS-PAGE methodology, represent a 'biological effect parameter' for the medical surveillance of persons occupationally exposed to trichloroethylene.

Binding of rat alpha 1-inhibitor-3-methylamine to the alpha 2-macroglobulin signaling receptor induces second messengers.

Binding of receptor-recognized forms of tetrameric human alpha 2-macroglobulin (alpha 2M*) to a macrophage signaling receptor induces cAMP synthesis, increases in inositol 1,4,5-triphosphate (IP3) synthesis, and a concomitant rise in cytosolic free calcium ([Ca2+]i). The alpha 2M* signaling receptor is coupled to a pertussis-toxin insensitive G protein. Binding of alpha 2M* also occurs to the low density lipoprotein receptor-related protein/alpha 2M receptor (LRP/alpha 2MR), but this binding does not induce signal transduction. Rat alpha 1-inhibitor-3 (alpha 1I3) is a monomeric member of the alpha-macroglobulin/complement superfamily. Like alpha 2M, it can react with proteinases or methylamine which induces a conformational change causing activated alpha 1I3 to bind to LRP/alpha 2MR. We now report that alpha 1I3-methylamine binds to the macrophage alpha 2M* signaling receptor inducing a rapid rise in the synthesis of IP3 with a subsequent 1.5- to 3-fold rise in [Ca2+]i. alpha 1I3-methylamine binding to macrophages also caused a statistically significant elevation in cAMP. Native alpha 1I3, like alpha 2M, was unable to induce signal transduction. alpha 1I3 forms a complex with alpha 1-microglobulin, which has a distinct conformation from alpha 1I3 and is recognized by LRP/alpha 2MR. This complex also induces an increase in [Ca2+]i comparable to the effect of alpha 1I3-methylamine on macrophages. It is concluded that activation of alpha 1I3 by methylamine or binding of alpha 1-microglobulin causes similar conformational changes in the inhibitor, exposing the receptor recognition site for the alpha 2M* signaling receptor, as well as for LRP/alpha 2MR.

Changes in the surface conditioning of calcium-salt crystals treated with physiological and alkaline urine.

To study, using an in vitro model, the early phases of deposition of urinary components onto the surface of calcium-salt crystals treated with physiological and alkaline urine. Calcium carbonate, oxalate and phosphate crystals were incubated in either freshly collected 'physiological' urine (pH 5.5) or with urine at pH 8.0. The surface conditioning was characterized using sodium-dodecyl sulphate-polyacrylamide gel electrophoresis immunoblot profiles of the adsorbed proteins and by Fourier transform infrared spectroscopy. Crystal morphology and aggregation were assessed using scanning electron microscopy. The patterns of protein adsorption from physiological urine showed the ubiquitous adsorption of bands within 51-86 kDa, while Tamm-Horsfall protein (THP) and alpha 1-microglobulin were found only in calcium oxalate crystals. Less aggregation was detected in calcium oxalate and phosphate crystals treated in urine at pH 5.5, while a new crystalline phase was deposited on calcium carbonate surfaces. Incubation in alkaline urine led to changes in the protein electrophoretic profiles, with a significant variation in the morphology of the inorganic phase only in calcium phosphate crystals. The binding of urinary proteins onto crystals depends on the chemistry of the surface and on the physicochemical composition of the urine. THP, albumin, alpha 1-microglobulin and a 20 kDa protein were able to bind calcium crystals under different circumstances. Except for THP, there was no clear relationship between the adsorption of proteins on crystals and the re-arrangement of the inorganic phase.

Identification of proteins extracted from calcium oxalate and calcium phosphate crystals induced in the urine of healthy and stone forming subjects.

The purpose of our study was to identify the proteins and investigate the differences, if any, between protein components of the matrices of calcium oxalate (CaOx) and calcium phosphate (CaP) crystals induced in vitro in whole human urine of healthy individuals and kidney stone patients. In addition, preliminary studies were performed to understand the effect of centrifugation and filtration of urine on its protein contents. Crystallization in urine was induced by addition of an oxalate or phosphate load. Crystals were collected, washed, and analyzed by scanning electron microscopy, X-ray diffraction, and energy dispersive X-ray microanalysis. Matrix proteins were obtained by demineralization with ethylene diamine tetraacetic acid (EDTA), analyzed by polyacrylamide gel electrophoresis, and identified by western blotting technique. No significant differences were detected between protein components of the matrices of CaOx and CaP crystals and between the crystal matrices obtained from the urine of normal and stone forming subjects. Albumin (AB), inter-alpha-inhibitor (IalphaI) related proteins, alpha-1 microglobulin (alpha-1 m), osteopontin (OPN), prothrombin (PT)-related proteins and Tamm-Horsfall protein (THP) were identified in matrices of both CaOx and CaP crystals induced in urine from both the normal subjects and stone formers. AB, PT-related proteins and OPN were the main constituents. The other proteins were present in smaller but detectable amounts. However, CaP crystal matrix, contained a large amount of THP. In addition CaP crystals contained significantly more proteins than CaOx crystals. Centrifugation and/or filtration of the urine resulted in reduction of many high molecular weight proteins including THP, AB and OPN in the urine.

Apolipoprotein E polymorphism and renal function in German type 1 and type 2 diabetic patients.

To examine the association of renal function in diabetic patients with apolipoprotein (apo) E polymorphism. Apo E genotypes, lipid and lipoprotein serum levels, creatinine clearance (CCr), and excretion of marker proteins were determined in German type 1 (IDDM; n = 162) and type 2 (NIDDM; n = 124) diabetic patients. Albumin and immunoglobulin (Ig) G are considered to reflect charge-size permselectivity of the glomerular capillary basement membrane, and increased alpha 1-microglobulin (MG) excretion indicates compromised reabsorptive capacity of the renal tubules. Patients with NIDDM had higher lipid levels and lower CCrs than patients with IDDM. In patients with IDDM, age- and sex-adjusted analysis of variance showed an association between apo E genotypes and CCr, and the Jonckheere-Terpstra test demonstrated a decreasing glomerular filtration rate in the following order of genotypes: epsilon 4 epsilon 4/epsilon 4 epsilon 3 > epsilon 3 epsilon 3 > epsilon 2 epsilon 2/epsilon 2 epsilon 3. Multiple linear regression analyses revealed that in patients with IDDM, the epsilon 2 allele was a negative predictor of CCr and a positive predictor of urinary excretion of albumin, IgG and alpha 1-MG independent from HDL and LDL cholesterol, TG concentration, age, and sex. Apo E polymorphism influences serum lipoprotein levels in patients with IDDM and NIDDM. Apo E polymorphism may be a renal risk factor of clinical relevance in normolipidemic patients with IDDM.

Acute kidney failure. Non-invasive diagnosis of acute kidney failure in operative intensive care patients

Acute renal failure is a common and severe complication in ICU. Renal laboratory examinations like creatinine and urea are late signs of renal dysfunction: Most of the functional abilities are reduced and there is no time for therapeutical interventions. The aim of this study was to find some earlier sensitive parameters of renal dysfunction and the order of appearance, the cause of acute renal failure and the value of the measured parameters. After agreement of the local ethic committee, 21 patients of the ICU were investigated. They were divided into two groups: 1st (n = 14) with no signs of renal dysfunction and were regarded as control group and 2nd (n = 7) were examined until the beginning of acute renal failure. For five days the glomerular filtration rate, proteinuria (immunoglobulin G, Tamm-Horsfall protein, alpha-1- and beta-2 microglobulin, lysozyme), the brush border enzymes angiotensinase A and the lysosomal enzyme N-acetyl-beta-d-glucosaminidase were daily measured and compared with clinical standards like the excretion of albumin, the clearances of creatinine and urea and the fractional excretion of sodium. Both groups were comparable with respect to drug therapy, APACHE-II-score (with the exception of the last day before ARF), and infusion therapy. There were differences in tubular functions between the 2 groups. Patients developing renal insufficiency showed an increased excretion of alpha-1-microglobulin, and decreased excretions of Tamm-Horsfall-protein, angiotensinase A as well as a low renal blood flow. Significant differences were also detectable in glomerular functions (glomerular filtration rate), albumin, and immunoglobulin G. Only a short time interval (1 to 2 days) between tubular and glomerular damage were detectable in patients with renal insufficiency. Renal failure must be due to circulatory problems because of the nearly simultaneous increase of tubular and glomerular parameters after RPF decreased. The parameters alpha 1-microglobulin, angiotensinase A and Tamm-Horsfall-protein gave early indications for the acute renal failure. They showed satisfactory sensitivity and specificity, but the positive predictive value was poor.

SOLUBLE INTERLEUKIN-2 RECEPTOR IN CHILDREN WITH REFLUX NEPHROPATHY

Purpose Serum soluble interleukin-2 receptor level is a sensitive and quantitative marker of lymphocyte activation. We determined levels of serum soluble interleukin-2 receptor in children with reflux nephropathy to evaluate its clinical significance in the prediction for the progression of renal injuries. Materials and Methods Serum soluble interleukin-2 receptor values were determined in 63 children with reflux nephropathy. The group consisted of 37 boys and 26 girls 10 to 18 years old. T cells (naive and memory), B cells and macrophages were evaluated immunohistochemically in the scarred kidneys of 4 other patients (3 boys and 1 girl 5 to 16 years old) who underwent nephrectomy due to severe reflux nephropathy with little function seen on 99m technetium-dimercapto-succinic acid (DMSA) renal scan. Levels of serum soluble interleukin-2 receptor were measured by an enzyme-linked immunosorbent assay. We simultaneously determined serum levels of creatinine and beta 2-microglobulin, and urinary levels of alpha 1-microglobulin and microalbumin. Individual functions of the right and left kidneys were estimated by renal dimercaptosuccinic acid uptake. Results Levels of serum soluble interleukin-2 receptor in the patients who had low total uptake of DMSA (right uptake plus left uptake) were significantly higher than those from patients with normal total uptake. Levels of serum soluble interleukin-2 receptor correlated significantly with levels of creatinine (r=0.616, p <0.0001) and beta 2-microglobulin (r=0.803, p <0.0001), and levels of urinary alpha 1-microglobulin (r=0.753, p <0.0001) and microalbumin (r=0.673, p <0.0001). A significant negative correlation was observed between levels of serum soluble interleukin-2 receptor and total DMSA uptake values (right uptake plus left uptake r= −0.678, p <0.0001). In the scarred kidneys leukocyte infiltrates were markedly increased in fibrosed spaces. The predominant cell type in these lesions was memory T cells. Conclusions These results suggest that elevated levels of serum soluble interleukin-2 receptor are likely to reflect activated T cells in the kidneys of patients with reflux nephropathy and may be a useful predictor of progression of renal injury in these children.

Massive glycation of protein HC, a low molecular weight lipocalin, in non-diabetic individuals

Human protein HC is a member of the lipocalin superfamily with unique properties since it carries a covalently bound fluorescent chromophore mediating the linkage of the major part of protein HC to several plasma proteins, with IgA as the dominating complex partner. Native protein HC displays characteristic absorption and fluorescence spectra similar to those of glycated proteins with advanced glycosylation end products (AGEs). In vitro glycation of protein HC induces the formation of fibril aggregates with a corresponding increase of absorption in the visible region of the spectrum. Boronate-affinity chromatography and a novel galactosyltransferase assay indicate that protein HC is modified with residues of glucose exposed in a terminal non-reducing position which is typical of glycated proteins. The glycation level of several isolated batches of protein HC as measured by both assays was around 35%, which represents the highest level described for human plasma-derived proteins from healthy individuals.

Study on objective parameters of Syndrome Differentiation of diabetic nephropathy

This is a study about objective parameters of Syndrome Differentiation of diabetic nephropathy (DN) using radio immunoassay (RIA) technique. The result showed that beta 2-microglobulin (beta 2-mG), alpha 1-microglobulin (alpha 1-mG) in blood rose significantly in both groups. The group of Spleen-Kidney Deficiency and Qi-Blood Deficiency as well as the group of Yang Deficiency caused edema and upward gush of turbid Yin, there was significant difference between two groups, also there was significant difference between the two groups in measuring on atrial natriuretic factor (ANP), pancreatic glucagon (PG) in blood and beta 2-mG. Immunoglobulin G (IgG), albumin (Alb), secretory immunoglobulin A(SIg A) in urine. So above-mentioned parameters offered us some objective data on Syndrome Differentiation of DN. It is vital in guiding the Syndrome Differentiation and treatment of DN.