Alpha1-microglobulin Levels Research Articles

Hemolysis scavenger proteins and renal function marker in children with sickle cell disease at steady state: A cross-sectional study.

Hemolysis is a fundamental feature of sickle cell disease (SCD) contributing to the vaso-occlusive crisis of patients. The objectives of the study were to assess the link between hemolysis proteins and hematological parameters, and to validate cystatin C(CYS C) as a potent renal marker in diagnoising SCD. Here, a cross-sectional study carried out at the pediatric SCD clinic of the Komfo Anokye Teaching Hospital comprised 90 SCDchildren (HbSC, HbSF, and HbSS). ANOVA, t-test, and Spearman's rank correlation analysis were done. Elevated proteins levels were compared to standard values; alpha-1 microglobulin (A1M) (1.8-65 µg/L), CYS C (0.1-4.5 µmol/L), and haemopexin(HPX) (500-1500 µg/mL). The mean (standard deviation) age of participants was 9.830 (±0.3217) years, and 46% of them were males. From simple descriptive analysis, we observed that all but one patient had their HPX level below the reference range (<500 µg/mL). Here, A1M levels were shown to be within the appropriate reference range for all the patients except few patients. CYS C levels were also all within the required reference values. A Spearman's rank correlation test between full blood count and HPX generally suggested a weak but positive correlation; RBC (coef. = 0.2448;p = 0.0248), HGB (coef. = 0.2310;p = 0.030), hematocrit(coef. = 0.2509; p = 0.020), and platelet(coef. = 0.1545;p = 0.160). Mean corpuscular volume(coef. = -0.5645;p = 0.610) had a stronger but negative correlation with HPX. This study depicts a positive and stronger association between CYS C and HPX levels (coef. = 0.9996;p < 0.0001), validating the use of CYS C as a useful marker of renal function in persons with SCDs. In the present study, we show that A1M levels were normal for most of the patients, hence CYS C levels are not alarming in this study. Further, there exists a correlation between hemolysis scavenger proteins and hematological parameters.

Intensive care patients with preeclampsia - Clinical risk factors and biomarkers for oxidative stress and angiogenic imbalance as discriminators for severe disease.

Approximately 180 mothers are treated in Swedish Intensive Care Units (ICU) due to preeclampsia each year. Although several clinical risk factors are known, prediction of critical disease is challenging. Two scavenger proteins, hemopexin (Hpx) and alpha-1-microglobulin (A1M) have been suggested to be associated with the oxidative stress seen in preeclampsia. The ratio of two other biomarkers, soluble fms-like tyrosine kinase (sFlt-1) to placental growth factor (PIGF), is predictive of adverse pregnancy outcomes. In total 121 women were included in this study where we compared risk factors for preeclampsia, plasma levels of Hpx and A1M in ICU-patients with preeclampsia (n = 41) compared to uncomplicated preeclampsia cases (n = 40) and normotensive pregnancies (n = 40), with the objective to identify clinical risk patterns for severe disease. The sFlt-1/PIGF ratio was investigated in early and late onset preeclampsia ICU-patients. Blood samples were collected at admission to ICU and within 27 h postpartum for all groups. Hemopexin and A1M levels were significantly lower in the preeclampsia ICU-cohort compared to uncomplicated preeclampsia patients. The sFlt-1/PIGF-ratio was elevated in the ICU-patients but there was no difference between early and late onset preeclampsia. The ICU-patients had more clinical risk factors, refractory hypertension, and an increased rate of emergency Caesarean section. Intensive care patients have more clinical risk factors and a Hpx and A1M profile suggestive of depletion and thereby a reduced capacity to respond to oxidative stress. The ratios of sFlt-1/PIGF were high in the ICU-cohort and in accordance with pre-delivery levels predictive of adverse pregnancy outcomes.

Clinical Risk Factors For Kidney Tubule Biomarker Abnormalities Among Hypertensive Adults With Reduced eGFR in the SPRINT Trial.

Urine biomarkers of kidney tubule health may distinguish aspects of kidney damage that cannot be captured by current glomerular measures. Associations of clinical risk factors with specific kidney tubule biomarkers have not been evaluated in detail. We performed a cross-sectional study in the Systolic Blood Pressure Intervention Trial among 2,436 participants with a baseline estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m2. Associations between demographic and clinical characteristics with urine biomarkers of kidney tubule health were evaluated using simultaneous multivariable linear regression of selected variables. Each standard deviation higher age (9 years) was associated with 13% higher levels of chitinase-3-like protein-1 (YKL-40), indicating higher levels of tubulointerstitial inflammation and repair. Men had 31% higher levels of alpha-1 microglobulin and 16% higher levels of beta-2 microglobulin, reflecting worse tubule resorptive function. Black race was associated with significantly higher levels of neutrophil gelatinase-associated lipocalin (12%) and lower kidney injury molecule-1 (26%) and uromodulin (22%). Each standard deviation (SD) higher systolic blood pressure (SBP) (16 mmHg) was associated with 10% higher beta-2 microglobulin and 10% higher alpha-1 microglobulin, reflecting lower tubule resorptive function. Clinical and demographic characteristics, such as race, sex, and elevated SBP, are associated with unique profiles of tubular damage, which could reflect under-recognized patterns of kidney tubule disease among persons with decreased eGFR.

Urinary Alpha 1 Microglobulin in Non Alcoholic Fatty Liver Disease and its association with liver fibrosis

Background: NAFLD is the most common cause of CLD worldwide with definite diagnosis based on Liver Biopsy. Recent studies have provided a strong insight into the liver kidney cross talk between NAFLD and CKD. Alpha-1 Microglobulin (A1M) is a glycoprotein secreted by liver. Glomeruli freely filter the unbound form of A1M, then reabsorbed and broken down by proximal tubular epithelial cells. Hence elevated A1M levels in urine strongly suggest defective reabsorption capacity of proximal tubules indicating kidney function decline.

Elevated blood pressure positively associates with alpha-1 microglobulin in prepubescent children: the ExAMIN Youth SA study.

Hypertension is a growing health concern in childhood populations and individuals of African descent. As the kidneys play a significant role in blood pressure regulation, we compared alpha-1 microglobulin (A1M) as a marker of proximal tubular function between young healthy black and white children (n = 957; aged: 5-9 years) and explored its association with blood pressure. The black children had higher levels of A1M (P < 0.001) and higher DBP (P < 0.001) when compared with their white counterparts. In multiple regression analysis, SBP (adj. R2 = 0.173, β = 0.151; P < 0.001) and DBP (adj. R2 = 0.110, β = 0.179; P < 0.001) associated positively with A1M in the black children. In binary logistic regression, each standard deviation increase in A1M increased the odds of having elevated blood pressure by 28% (P = 0.002) in the black group, independent of age, sex, BMI z-score and body height. No significance was reached in the white children. Our findings highlight the importance of a marker of proximal tubular function, especially in children of black ethnicity, in the setting of elevated blood pressure. Early childhood screening for elevated blood pressure remains essential in order to promote primary prevention of hypertension and early onset kidney damage in children.

Plasma Heme Scavengers Alpha-1-Microglobulin and Hemopexin as Biomarkers in High-Risk Pregnancies.

Women with established preeclampsia (PE) have increased plasma concentration of free fetal hemoglobin. We measured two hemoglobin scavenger system proteins, hemopexin (Hpx) and alpha-1-microglobulin (A1M) in maternal plasma using enzyme-linked immunosorbent assay during the late second trimester of pregnancy in women with high and low risk of developing PE. In total 142 women were included in nested case-control study: 42 women diagnosed with PE and 100 controls (49 randomly selected high-risk and 51 low-risk controls). The concentration of plasma A1M in high-risk controls was higher compared to low-risk controls. Women with severe PE had higher plasma A1M levels compared to women with non-severe PE. In conclusion, the concentration of plasma A1M is increased in the late second trimester in high-risk controls, suggesting activation of endogenous protective system against oxidative stress.

Drug repositioning in Alzheimer rsquo s disease

Hemoglobin released from damaged erythrocytes is a major pro-oxidant, generator of free radicals and inflammatory mediator. Huntington's disease is an inherited neurodegenerative disorder characterized by both neurological and systemic abnormalities, in which oxidative stress has been suggested as a possible pathogenic mechanism. In the present work we have investigated levels of hemoglobin and markers of oxidative damage, including the heme- and radical-scavenger alpha1-microglobulin, in plasma and urine samples from two separate sample cohorts, including controls, premanifest gene carriers and subjects at different stages of Huntington's disease. The results show statistically significant increased levels of hemoglobin and alpha1-microglobulin in Huntington's disease urine samples. Interestingly, urine hemoglobin levels correlate with clinical severity. The results suggest that hemolysis may be linked to the pathogenesis of Huntington's disease and that assay of hemoglobin and alpha1-microglobulin may provide biomarkers that are linked to biologically relevant processes.

Urinary Retinol Binding Protein Is a Marker of the Extent of Interstitial Kidney Fibrosis

Currently, a non-invasive method to estimate the degree of interstitial fibrosis (IF) in chronic kidney disease is not available in routine. The aim of our study was to evaluate the diagnostic performance of the measurement of urinary low molecular weight (LMW) protein concentrations as a method to determine the extent of IF. The urines specimen from 162 consecutive patients who underwent renal biopsy were used in the analysis. Numerical quantification software based on the colorimetric analysis of fibrous areas was used to assess the percentage IF. Total proteinuria, albuminuria, and the urinary levels of retinol binding protein (RBP), alpha1-microglobulin (α1MG), beta 2-microglobulin (β2MG), transferrin, and IgG immunoglobulins were measured. There was a significant correlation between the degree of IF and the RBP/creatinine (creat) ratio (R2: 0.11, p<0.0001). IF was associated to a lesser extent with urinary β2MG and α1MG; however, there was no association with total proteinuria or high molecular weight (HMW) proteinuria. The correlation between IF and RBP/creat remained significant after adjustment to the estimated glomerular filtration rate, age, body mass index, α1MG, and β2MG. The specificity of the test for diagnosing a fibrosis score of >25% of the parenchyma was 95% when using a threshold of 20 mg/g creat. In conclusion, RBP appears to be a quantitative and non-invasive marker for the independent prediction of the extent of kidney IF. Because methods for the measurement of urinary RBP are available in most clinical chemistry departments, RBP measurement is appealing for implementation in the routine care of patients with chronic kidney disease.

Urinary Biomarkers for Kidney Disease in ATTR Amyloidosis

Aim: The detection and prognosis of nephropathy in transthyretin amyloidosis depends on albuminuria and renal function. Knowing that urinary levels of alpha-1 microglobulin and beta-2 microglobulin reflect tubular dysfunction while urinary alpha-2 macroglobulin implies glomerular damage, we decide investigate the diagnostic value of these markers in the patients with transthyretin amyloidosis. Methods: Serum and urinary samples collected from 30 patients and 11 asymptomatic carriers were tested for alpha-1 microglobulin, beta-2 microglobulin, alpha-2 macroglobulin, albumin, creatinine and cystatin C. Results: Pathological urinary alpha-1 microglobulin was detected in 17 patients, beta-2 microglobulin in 6 and alpha-2 macroglobulin in 5; 5 patients had albuminuria (mg/g creatinine) 30-300 and in 20 patients values >300 were present. Asymptomatic carriers did not present pathological excretion of these biomarkers and albuminuria was >30 in 1 individual. The excretion rates of alpha-1 microglobulin and beta-2 microglobulin were positively correlated with albuminuria (P<0.001), serum creatinine (P<0.05) and cystatin C (P<0.001). Urinary alpha-2 macroglobulin was almost exclusively found in the presence of albuminuria, although their levels do not correlate. Conclusion: Urinary biomarkers emerge as a potential approach to detect renal disease but unexpectedly, urinary alpha-2 macroglobulin was not a marker of the severity of albuminuria

Mesothelin Levels in Urine are Affected by Glomerular Leakage and Tubular Reabsorption

BackgroundMesothelin is a soluble biomarker of malignant mesothelioma. Levels in serum, however, are also influenced by other factors, including age and glomerular filtration rate (GFR). The measurement of mesothelin in urine has recently gained interest, but the renal handling of this protein has not been sufficiently examined. Patients and MethodsA total of 75 patients with benign kidney disease were prospectively included in the study. Mesothelin levels were measured in the serum and in the urine of all the participants by using enzyme-linked immunosorbent assay. Urinary albumin and alpha 1-microglobulin (A1M) levels, which are markers of glomerular leakage and of decreased tubular reabsorption, respectively, and the estimated GFR (eGFR) of each participant were obtained. All urine analyte levels were standardized (std) against urinary creatinine levels. ResultsAbsolute mesothelin levels in urine (median, 0.58 nmol/L; interquartile range [IQR], 0.25-1.03 nmol/L) were significantly lower than those in serum (median, 1.74 nmol/L; IQR, 1.35-2.43 nmol/L; P < .001). Urinary mesothelinstd levels positively correlated with serum mesothelin (r = 0.35, P < .01), albuminstd (r = 0.51, P < .001), and A1Mstd levels (r = 0.71, P < .001). Neither age nor eGFR were associated with urinary mesothelinstd levels. Similarly, multiple linear regression analysis indicated that only albuminstd and A1Mstd levels were significantly positively associated with the urinary mesothelinstd levels (adjusted R2 = 0.49). ConclusionMesothelin levels in urine are affected by impaired glomerular and tubular function, which can influence the interpretation of mesothelin measurements and might cause false-positive results. These effects need to be accounted for to improve the further validation and possible clinical use of urinary mesothelin.

Increased levels of hemoglobin and alpha1-microglobulin in Huntington s disease

Hemoglobin released from damaged erythrocytes is a major pro-oxidant, generator of free radicals and inflammatory mediator. Huntington's disease is an inherited neurodegenerative disorder characterized by both neurological and systemic abnormalities, in which oxidative stress has been suggested as a possible pathogenic mechanism. In the present work we have investigated levels of hemoglobin and markers of oxidative damage, including the heme- and radical-scavenger alpha1-microglobulin, in plasma and urine samples from two separate sample cohorts, including controls, premanifest gene carriers and subjects at different stages of Huntington's disease. The results show statistically significant increased levels of hemoglobin and alpha1-microglobulin in Huntington's disease urine samples. Interestingly, urine hemoglobin levels correlate with clinical severity. The results suggest that hemolysis may be linked to the pathogenesis of Huntington's disease and that assay of hemoglobin and alpha1-microglobulin may provide biomarkers that are linked to biologically relevant processes.

Laboratory and imaging features of kidney involvement in autoimmune pancreatitis: incidence, correlation, and steroid therapy response

Autoimmune pancreatitis (AIP) is a rare subtype of chronic pancreatitis. AIP has been suggested to be complicated by tubulointerstitial nephritis or glomerulonephritis, implying that the kidney is involved as a phenotype of IgG4-positive multi-organ lymphoproliferative syndrome; however, the clinical significance of this novel entity is not well-defined. We conducted a retrospective cohort analysis of 47 (male, 39; female, 8) AIP patients. The patients (mean age, 70.3 +/- 9.5 years) had a mean observation period of 4.1 years. Before treatment, renal dysfunction with an eGFR of 30 and 15 ml/min/1.73 m2 developed only in 10.6% (5/47) and 2.1% (1/47) of the patients, respectively. Nevertheless, urinary N-acetyl-beta-D-glucosaminidase and alpha1-microglobulin levels were elevated in 78.6% (11/14) and 30.8% (4/13) of the patients, respectively. Renal involvement in contrast-enhanced CT imaging was present in 18.2% (8/44) of the patients and was associated with proteinuria (p = 0.04) and a decrease in eGFR (p < 0.01). Furthermore, a follow-up CT study (mean, 545 days) revealed improved kidney lesions in 80.0% (4/5) of the patients after oral corticosteroid administration. In contrast, first-time kidney involvements appeared newly in 3.6% (1/28) of the patients after steroid therapy for nonrenal AIP symptoms, and in 14.3% (1/7) of the patients under no specific therapy (p = 0.02). Although severe renal failure develops rarely in AIP patients, renal abnormalities have been significantly detected by biochemical and radiological tests. Oral corticosteroid administration, even when not targeting symptomatic nephropathy, can treat and prevent kidney involvements in AIP.

Effect of ulinastatin in promotion of graft recovery in early stage after kidney transplantation: a clinical study

To investigate the effects of ulinastatin (UTI), a urinary trypsin inhibitor, on the promotion of the function recovery of transplanted kidney, especially for those with acute tubular necrosis (ATN). Thirty patients underwent general cadaver kidney transplantation were randomly allocated to 2 equal groups: Group A (UTI-treatment group) and Group B (control group). 40 patients whose allografts were presumed to be with acute tubular necrosis (ATN) were also divided into 2 equal groups: Group C (UTI-treatment group) and Group D (control group). Group A and C were given ulinastatin perioperatively. 1, 3, 7, and 10 days after the transplantation blood and urine samples were collected. The levels of urine and blood alpha1-microglobulin (MG) were detected by radioimmunoassay. Blood IL-8, IL-10, and serum creatine (sCr) were detected by ELISA. Within 10 days after the transplantation the urine volume of Group A significantly increased, especially the urine volumes of days 2, 6, 7, 9, and 10 were significant greater than those of Group B (all P < 0.05). The levels of blood IL-8 of Group A in days 1 and 3 were (93.75 +/- 31.5) ng/L and (41.98 +/- 24.01) ng/L respectively, significantly lower than those of Group B [(135.0 +/- 31.2) ng/L and (78.34 +/- 76.39) ng/L respectively, both P < 0.05]. The levels of urine alpha1-MG in days 1 and 3 were (69.89 +/- 32.60) mg/L and (35.33 +/- 34.54) mg/L respectively, both significantly lower than those of Group B [(91.15 +/- 28.39) mg/L and (65.84 +/- 33.38) mg/L respectively, both P < 0.05]. In group C, the levels of blood alpha1-MG in days 7 and 10 of Group C were (118.26 +/- 41.23) mg/L and (99.49 +/- 68.63) mg/L respectively, both significantly lower than those of Group D [(187.15 +/- 55.23) mg/L and (151.27 +/- 87.42) mg/L respectively, both P < 0.05]. The urine alpha1-MG in days 7 and 10 were (39.89 +/- 22.32) mg/L and (38.21 +/- 20.36) mg/L respectively, both significantly lower than those of Group D [(67.34 +/- 21.56) mg/L and (62.26 +/- 29.24) mg/L respectively, both P < 0.05]. Compared to Group D, the increasing tendency of blood IL-8 was better suppressed in Group C, and the diuretic phases appeared earlier. UTI significantly improves the microcirculation, protects the tubule of transplanted kidney, increases the volume of urine, inhibits the inflammatory response, and promotes the recovery of ATN during the perioperative period of kidney transplantation.

Prevalence of Balkan Endemic Nephropathy Has Not Changed Since 1971 in the Kolubara Region in Serbia

Background/Aims: Thirty-one years after the first cross-sectional study, the population of Vreoci, a Balkan endemic nephropathy (BEN) village, was reinvestigated in order to determine the current prevalence of BEN and the clinical and laboratory characteristics of BEN family members with detected signs of kidney disease. Methods: A total of 2,009 inhabitants (82% of the adult population) of the village were examined. Danilovic’s criteria were used for diagnosis and classification of BEN. Results: The prevalence of BEN (1.70%) was similar to that in 1971 (1.67%). Diagnosis of BEN was established in 19 BEN family members, suspected BEN in 23, proteinuria in 29, while 16 healthy members were examined as controls. Urine protein, alpha1-microglobulin levels and frequency of glucosuria were significantly higher and kidney length significantly smaller in the three patient groups than in healthy persons. Serum urea and creatinine levels were significantly higher, but creatinine clearance was lower in BEN and BEN suspected patients than in the other two groups. Conclusion: The prevalence of BEN remains stable over time in Vreoci village. Manifested disease was found in both BEN and BEN suspected patients. In persons with proteinuria but not enough criteria for BEN, tubular disorders and hypertension were frequently found.

Rosuvastatin Increases α‐1 Microglobulin Urinary Excretion in Patients With Primary Dyslipidemia

The renoprotective effect of statins has been recently disputed because of observations of proteinuria associated with rosuvastatin treatment, the newest drug of the class. Statin-induced proteinuria findings were mainly based on crudely quantitative dipstick assays. The authors quantitatively evaluated the effect of rosuvastatin at the recommended starting dose of 10 mg/d, on urine protein excretion in patients with primary dyslipidemia. Serum lipid and nonlipid parameters as well as urinary electrolyte, creatinine, and protein (total, albumin, immunoglobulin G, and alpha-1 microglobulin) levels were measured in 40 patients treated with rosuvastatin and 30 controls at baseline and after 12 weeks. The protein-to-creatinine ratios were used to assess urinary protein excretion. Rosuvastatin improved the lipid profile, produced no deterioration of kidney function, but induced a small but significant increase in the excretion of alpha-1 microglobulin (by 16%, P < .05) indicating that statin-related proteinuria involves low-molecular-weight proteins and is of proximal tubular origin.

Renal function and cardiac angiography

To study the effect of non-ionic contrast medium on renal function in children with cardiovascular disease. Analysis of renal function in 98 children with cardiovascular disease before and after the use of Iopamidol, Iohexol, and Ioversol was done for angiography. Serum creatinine (s-Cre), urinary N-acetyl-beta-D-glucosaminase (u-NAG), urinary beta 2-microglobulin (u-BMG), and urinary alpha 1-microglobulin (u-AMG) levels were evaluated. Although s-Cre levels remained unchanged, u-NAG/Cre, u-AMG/Cre and u-BMG/Cre significantly increased 12 hours after angiography. Levels of u-NAG/Cre, u-BMG/Cre, and u-AMG/Cre after angiography were significantly higher in neonates and infants (age< 12-months, n=32) than in children (age>1-year, n=61), in patients with more than 5 ml/kg of contrast medium (n=25) than in those with less than 5 ml/kg (n=70) and in cyanotic patients (n=13) than in non-cyanotic (n=80) patients. Transient renal tubular dysfunction occurred in all of these three non-ionic contrast mediums. Although renal tubular function was intact on a long-term basis, one should be careful of contrast medium-induced nephropathy, especially in neonates and infants, in patients receiving more than 5 ml/kg of contrast mediums in total, and in patients with cyanotic heart disease in using non-ionic contrast mediums.

Evaluation of Renal Glomerular and Tubular Functional and Structural Integrity in Neonates

Renal cells are not fully differentiated at birth, representing a major risk in preterm infants. We evaluated glomerular and tubular functional integrity as well as structural integrity of renal tubules among healthy full-term and preterm infants as well as diseased preterm infants. A total of 50 newborns (10 healthy full-term, 10 healthy preterm, and 30 diseased preterm, at 38.9 +/- 1.10, 34.2 +/- 0.92, and 32 +/- 2.47 weeks gestational age, respectively) were included in the present study. Glomerular function was assessed by measuring urinary levels of both microalbumin and immunoglobulin G as well as serum creatinine levels, whereas the proximal tubular function was investigated by measuring the urinary levels of both alpha1-microglobulin and beta2-microglobulin as well as retinol-binding protein. Also, distal tubular reabsorption capacity was investigated by assessing fractional excretion of sodium. Moreover, the structural integrity of renal proximal tubules was studied by measuring the urinary activities of both the brush-border membrane enzyme leucine-aminopeptidase (LAP) and the lysosomal enzyme N-acetyl-beta-D-glucosaminidase. The preceding investigations were done on both the first and third days of life of all 50 newborns. Glomerular and tubular function and structure was relatively impaired at birth among both healthy and diseased preterm as well as healthy full-term neonates and improved rapidly thereafter. The diseased preterm neonates showed worse renal function and structure with minimal improvement regardless of the underlying sickness. Renal insufficiency and renal immaturity could be evaluated using enzymuria and low- and high-molecular-weight proteinuria as noninvasive methods.

Urinary transforming growth factor-beta1 and alpha1-microglobulin in children and adolescents with type 1 diabetes.

Transforming growth factor (TGF)-beta1 is an important mediator in the pathogenesis of diabetic nephropathy. Urinary TGF-beta1 reflects TGF-beta1 production in the kidney, and alpha1-microglobulin tubular dysfunction. These 2 markers were studied in the early phases of type 1 diabetes. There were 113 type 1 diabetic children and adolescents (mean +/- SD: age 14.1 +/- 2.9 years, and diabetes duration 7.4 +/- 2.9 years, HbA1c 9.3 +/- 1.5%) and 39 healthy subjects (age 13.8 +/- 2.8 years) who participated in the study. Of the diabetic patients, 105 were normoalbuminuric (2-3 consecutive overnight urinary albumin excretion rates [AERs] <20 microg/min) and 8 had microalbuminuria (at least 2 AERs 20-200 microg/min). Overnight urinary TGF-beta1 and alpha1-microglobulin levels were measured and the results expressed as the ratio to urinary creatinine concentration. Data are medians (range). Diabetic patients had higher urinary TGF-beta1 levels than those of control subjects: 0.9 ng/mg (0.05-122.3) vs. 0.3 ng/mg (0.05-2.2) creatinine, respectively (P = 0.003). Urinary TGF-beta1 levels correlated with urinary glucose (r = 0.2, P = 0.03) and alpha1-microglobulin (r = 0.2, P = 0.02) levels, but not with HbA1c, AER, age, or duration of diabetes. In 43 patients with urinary TGF-beta1 above the control levels, urinary TGF-beta1 levels correlated with urinary glucose (r = 0.6, P < 0.001) and alpha1-microglobulin (r = 0.6, P < 0.001) levels. Diabetic patients had higher urinary alpha1-microglobulin levels than those of control subjects: 4.8 microg/mg (0.6-48.8) vs. 2.7 microg/mg (0.8-11.6) creatinine, respectively (P < 0.001). Alpha1-microglobulin levels correlated with AER (r = 0.2, P = 0.02), HbA1c (r = 0.3, P = 0.001), urinary glucose (r = 0.5, P < 0.001), and urinary TGF-beta1 levels. An early rise in urinary TGF-beta1 levels was observed in young type 1 diabetic patients. Urinary TGF-beta1 is associated with 2 interrelated tubular markers, alpha1-microglobulin and urinary glucose.

Evaluation of the fetal kidney maturation by assessment of amniotic fluid alpha-1 microglobulin levels

Objective: To evaluate the fetal renal maturation by assessment of amniotic fluid microproteins and to show these proteins originate from fetal urine. Study design: Amniotic fluid proteins (total protein, albumin, high molecular weight protein-HMWP, low molecular weight protein-LMWP, α 1-microglobulin and β 2-microglobulin) were determined in 39 pregnant women at delivery and by amniocentesis in 30 pregnant women. These values were compared with first urine values of neonates with the same gestational age. Results: Albumin was the largest protein component in the amniotic fluid. LMWP showed an increase in the amniotic fluid until the end of the second trimester; and as pregnancy advanced a progressive decrease occurred in parallel to fetal renal maturation. After 26 weeks’ gestation, a strong correlation was identified between LMWP levels and α 1-microglobulin, and between LMWP and β 2-microglobulin. No significant difference was detected between LMWP levels in the first urine of the neonates and in amniotic fluids. Conclusion: Microproteins in the fetal urine are of fetal origin. Fetal renal maturation can be evaluated by measuring microproteins in the amniotic fluid. Fetal renal maturation is best reflected by α 1-microglobulin.

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.