Urinary IgG Research Articles

小児腎疾患における尿蛋白構成成分に関する研究(第1編)―各種腎疾患における尿蛋白構成成分の特徴特に,IgA腎症と尿中IgAについて―

Urinary protein components in children with renal disease were analyzed by the Reversed-Single Radial Immunodiffusion (R-SRID) method. The results were as follows: (1) In idiopathic nephrotic syndrome, the percentage of urinary albumin excretion was very high (79.5%). Urinary IgA excretion was 0.1% and IgG excretion was 1.6%, hence the excretion of these high-molecular-weight proteins amounted to 1.7% of the total urinary protein. (2) In membranous glomerulonephritis, urinary IgA was not detected, whereas the percentage of urinary IgG excretion was high (5.4%). (3) The percentage of urinary IgA excretion was higher in IgA nephropathy (IgAN) and Henoch-Schönlein purpura nephritis (HSPN) (2.4%, 1.6% respectively) than in other diverse renal diseases. (4) The percentage of urinary IgA excretion was correlated significantly with the serum IgA concentration in IgAN and HSPN (P < 0.001), but there was no such correlation in other diverse renal diseases. (5) In IgAN, the percentage of urinary IgA excretion was significantly higher in the subgroup with a duration of less than one year from the onset (3.6%) than in the subgroup with a duration longer than one year (1.5%) (p < 0.01).

The value of IgG-uria in predicting renal failure in idiopathic glomerular diseases. A long-term follow-up study

Background. Proteinuria is the hallmark of glomerular disease and non-selective proteinuria is often associated with progression to renal failure. The predictive value of urine IgG excretion was studied comprehensively in patients with nephrotic syndrome. In the present follow-up study, we examine the predictive value of IgG-uria in patients with idiopathic glomerular diseases with a wide range of proteinuia. Methods. A total of 189 (113 males and 76 females) patients with idiopathic glomerulonephritis and serum creatinine of less than 150 μmol/L diagnosed between 1993 and 2004 were followed up to their last visit in 2009. Measurement of urine excretion of albumin, IgG, and protein HC were performed in the early morning of spot urine samples collected at the time of the diagnostic renal biopsy. Patients were stratified according to urine protein concentrations and the progression rate to end-stage renal disease (ESRD) calculated using Kaplan–Meier survival analysis. ESRD was defined as the start of renal replacement therapy. Results. During the study follow-up time of 1429 person-years; 26 (13.8%) patients reached ESRD. The overall mean kidney survival time of studied patients with serum creatinine less than 150 were 13.4 years. The incidence rate of ESRD was ∼18 per 1000 person-years. Stratified analysis identified urinary excretion of IgG, but not albuminuria, as predictor of ESRD. The progression rate to ESRD was 36 per 1000 person-years in patients with urine IgG concentration exceeding 5 mg/mmol urine creatinine, compared to a progression rate of 6/1000 person-years for patients with lower levels of urine IgG. Conclusion. The findings of the study suggest that at early stages, the level of IgG-uria is useful to be used in risk stratification of patients with proteinuric glomerular diseases.

Diagnostic value of urinary light chain detection in essential hypertension renal injury

Objective To investigate the diagnostic value of urinary light chain detection in essential hypertension renal injury. Methods According to National Prevention and Treatment Guide of Hypertension (2005 Edition) and the diagnostic criteria of essential hypertension renal injury, patients'medical history and damage of target organs, we selected 60 patients with essential hypertension and divided them into two groups: 28 patients without renal injury and 32 patients with renal injury. Meanwhile, Thirty healthy individuals were included in a control group. Urinary proteins and light chains were detected by immuonephelometry and the activity of NAG was determined by liquid kinetic rate assay with MNP as substrate. The urinary light chains concentration of each group were compared and analyzed with those of Alb and α1-MG. Results The results of lamU in renal injury group [8. 89(3.84-33. 30) mg] were higher than those of non renal injury group [3. 84(3. 84-10. 4) mg] and control group [3.84(0. 00-3.84) mg]. There was statistically significant difference ( H = 37.97, P ＜ 0. 01 ). The levels of kapU in renal injury group [26. 65 (6. 97-62. 5 ) mg] were higher than those of non renal injury group [6. 97 (6. 97-23.7 )mg] and control group [6. 97(6. 97-7. 20) mg], which also had statistical significance (H =40. 09,P ＜0. 01 ). All the other results in renal injury group ( Alb, α1-MG, IgG, TRF and NAG) were higher than those of non renal injury group and control group ( H =21.02, 32. 65, 25.50, 30. 45 and 30. 57, P ＜0. 01 ). Correlation analysis showed that Alb levels were highly correlated with urinary IgG and TRF levels [Correlation coefficient (r) =0. 911, 0. 965, P ＜ 0. 01]. The levels of urinary light chain lamU and kapU were also highly correlated with α1-MG ( r = 0. 804, 0. 827, P ＜ 0. 01 ). However, There was no correlationship between NAG and α1MG levels (r=0. 398,P＞0. 05). Conclusion The urinary light chain lamU and kapU can be used as indicators for evaluation of renal injury in essential hypertension, especially renal tubular injury. Key words: Hypertension,renovascular; Immunoglobulin λ chain; Immunoglobulin κ chain; Urinalysis

Renal parenchymal thickness and urinary protein levels in patients with ureteropelvic junction obstruction after nephrostomy placement

To assess recovery of renal parenchymal thickness and urinary protein levels in patients with severely hydronephrotic kidneys after nephrostomy placement. Fourteen patients (median age 1 year, range 6 months-7 years) who underwent nephrostomy placement for unilateral ureteropelvic junction obstruction at our hospital between May 2007 and January 2009 were included in a retrospective analysis. All patients had severe hydronephrosis, with a median parenchymal thickness of 1.8 mm (range 1-2.5 mm). Kidney morphology was examined by ultrasound before the procedure and 1, 2, 3, 4, 6 and 8 weeks after. Urinary proteins (including albumin, immunoglobulin [IgG], alpha2-macroglobulin, alpha1-microglobulin, beta2-microglobulin [beta2-MG] and kappa chain) and creatinine levels were also tested during these follow-up visits. Fifteen healthy children were assessed for urinary protein levels as well and made up the control group. Parenchymal thickness increased within 4 weeks of nephrostomy placement. Kidney volumes were significantly decreased within 2 weeks. No further changes in morphology were detected after 4 weeks. Urinary alpha1-microglobulin and beta2-MG levels decreased to baseline within 1 and 4 weeks, respectively. Urinary albumin, IgG, alpha2-macroglobulin and kappa chain levels decreased gradually after nephrostomy, but did not return to baseline within 8 weeks. After nephrostomy placement, parenchymal thickness increases within 4 weeks, tubular function returns to normal earlier than glomerular function and glomerular membrane repair is inversely correlated with the severity of damage.

The ratio between kidney volume and function increases with the progression of nephropathy in Type 2 diabetes

In Type 2 diabetes, it is not clear if renal size is constantly related to the glomerular filtration rate. In addition, it is not known if kidney volume (KV) is associated with an increased urinary albumin and IgG excretion. The relationship between kidney volume, creatinine clearance (CrCl), urinary albumin and IgG excretion in 95 Type 2 diabetic patients with different stages of nephropathy (1 - 4 Stage sec NKDF-QD) was elevated and compared to 85 non-diabetic subjects with similar degree of kidney function. In Type 2 diabetic patients the KV/CrCl ratio was increased, in comparison with the control subjects, from about 15% in Stage 1 to 53% in Stage 4. In T2D subjects, significant correlations were found between KV and urinary albumin excretion (r = 0.665, p < 0.05), and between KV and urinary IgG excretion (r = 0.800, p < 0.001). The present study finds that Type 2 diabetic subjects, are characterized by an increased ratio between KV/CrCl, throughout the different progressive stages of nephropathy. In Type 2 diabetes relationships between KV and urinary albumin and between KV and IgG excretion also were found to be significant, suggesting a role for the impaired size selectivity of proteinuria as a possible determinant of KV.

Non enzymatic glycosylation of IgG and their urinary excretion in patients with diabetic nephropathy.

Diabetic nephropathy is a major cause of end stage renal disease. Increased excretion of albumin has widely been recognized as an early manifestation of diabetic nephropathy particularly in subjects with diabetes mellitus. However, certain other proteins besides albumin may be excreted in high amount during early phase of diabetic nephropathy. The serum and urinary IgG, Glycosylated hemoglobin, fructosamine and glycosylated IgG were evaluated in the present study. Thirty-two patients of Type 2 Diabetes without any complications, thirty-one patients of Type 2 Diabetes with nephropathy, twenty-six patients of non-diabetic nephropathy and forty normal healthy individuals were enrolled in this study. Subjects were grouped based on their serum creatinine level. Serum IgG, glycosylation of IgG and urinary IgG excretion were increased significantly in diabetic patients compared to healthy controls, which were further increased significantly in chronic renal failure patients with respect to the clinical stage of nephropathy. A positive correlation was observed between glycosylation of IgG and IgG excretion (R(2)=0.5995, 0.7114 respectively) in diabetic patients without any complications and diabetic nephropathy patients only, suggesting a significant role of IgG glycosylation in the vascular clearances of IgG during diabetic nephropathy.

Effects of the administration of cholera toxin as a mucosal adjuvant on the immune and protective response induced by Proteus mirabilis MrpA fimbrial protein in the urinary tract

Proteus mirabilis is commonly associated with complicated UTI and expresses several virulence factors, including MR/P fimbriae. In the present study mice were immunised nasally with MrpA, the structural subunit of MR/P, with or without CT as a mucosal adjuvant. The animals were then challenged with P. mirabilis and induction of specific serum and urine IgG and IgA, IFN-gamma production and bacterial kidney and bladder colonization were assessed. MrpA-immunised mice exhibited significant induction of serum IgA and urine IgA and IgG. MrpA/CT-immunised mice showed both significant serum and urine IgA and IgG production. Only this group showed significant IFN-y production. Both groups of animals had significant decrease in bacterial colonization of kidneys but not of bladders. No correlation between specific antibody induction in serum and CFU decrease was observed in any group of animals. Our results suggest that a mucosal adjuvant (CT) in the urinary tract enhanced humoral and cytokine response although it did not influence the degree of protection against UTI provided by MrpA. Further studies are necessary to understand immune modulation in the urinary tract.

Screening for celiac disease in patients with osteoporosis

Objective Whether patients with osteoporosis should be screened for celiac disease is controversial. The objective of this study was to measure the prevalence of asymptomatic celiac disease in a cohort of patients with osteoporosis. Methods We studied 140 patients (133 postmenopausal women and 7 men) aged 40–75 years (mean age, 62.9 ± 9.4 years) with primary osteoporosis diagnosed by absorptiometry (spine or hip T-score <−2.5 SD). We routinely measured serum and urinary calcium, serum phosphate, alkaline phosphatase, 25-OH-vitamin D3, and IgG and IgA antigliadin antibodies. Patients with positive antigliadin antibody tests were tested for antitransglutaminase antibodies. Results A history of fractures were noted in 52 (37%) patients, with 57 peripheral and 54 vertebral fractures overall. Vitamin D deficiency was found in 60 (43%) patients. IgG antigliadin antibodies were positive in 11 (8%) patients, IgA antigliadin antibodies in 11 (8%) patients, and both antibodies in 4 (3%) patients. Antitransglutaminase antibodies were negative in all patients. No significant differences in laboratory test or absorptiometry results were found between patients with versus without IgA antigliadin antibodies. The T-score at the spine was nonsignificantly lower in patients with than without IgG antigliadin antibodies (−3.17 ± 0.49 and −2.82 ± 0.77, P = 0.076). Conclusion We found no excess risk of celiac disease in our cohort of patients with osteoporosis. Despite the small sample size, our results cast doubt on the need for celiac-disease screening in osteoporotic patients who have no gastrointestinal symptoms.

Megalin contributes to the early injury of proximal tubule cells during nonselective proteinuria

Megalin, a member of the LDL receptor family, is expressed on the apical membrane of proximal tubules and serves as an endocytic scavenger of filtered proteins and hence might contribute to the tubule injury as a consequence of glomerular disease. To study its role, we crossed megalin knockout mosaic mice (lacking megalin expression in 60% of proximal tubule cells) with NEP25 mice (a transgenic line expressing human CD25 in the podocyte). Treatment of this transgenic mouse with the immunotoxin causes nephrotic syndrome, focal segmental glomerulosclerosis and tubule-interstitial injury. Following this treatment, the double transgenic mice had massive non-selective proteinuria and mild glomerular and tubular injury. Comparison of megalin-containing to megalin-deficient proximal tubule cells within each kidney showed that albumin, immunoglobulin light chain, IgA and IgG were preferentially accumulated in proximal tubule cells expressing megalin. Tubule injury markers such as heme-oxygenase-1, monocyte chemoattractant protein-1 and cellular apoptosis were also preferentially found in these megalin-expressing cells. These results show that megalin plays a pivotal role in the reabsorption of small to large molecular size proteins and provides direct in vivo evidence that reabsorption of filtered proteins triggers events leading to tubule injury.

Anti- Leishmania IgA in urine samples from dogs with clinical leishmaniasis

Recently, anti- Leishmania IgG has been detected in urine samples from Leishmania-infected dogs and its concentrations have been correlated with impairment of renal function. The presence and relationship with other anti- Leishmania Ig isotypes in urine have not yet been investigated. The current study analyzed the concentrations of anti- Leishmania IgA and IgG in sera (Ig-S) and urine (Ig-U) samples by ELISA in 64 untreated dogs with clinical leishmaniasis. All 64 serum samples tested were positive for anti- Leishmania IgG. Fifty of them (78.1%) were also positive for anti- Leishmania IgA. The results showed the presence of anti- Leishmania IgA-U in 38% of the 50 dogs that were positive for specific IgA-S. Thirty-eight of the 64 dogs positive for Leishmania-specific IgG-S (59.4%) were also positive for Leishmania-specific IgG in urine (IgG-U). The concentrations of anti- Leishmania IgA-U were significantly correlated with urine protein/creatinine (uP/C) ratio ( ρ = 0.542; P < 0.001) and with serum biochemical parameters, such as γ-globulins, urea and creatinine. Goldmann–Witmer coefficient ( C value) indicated that detection of specific IgA in urine samples from dogs with leishmaniasis might not only be due to impairment of filtration of the glomerular barrier but also be due to local production of this isotype, which might reflect a local immunological response to the presence of the parasite in the genitourinary tract. Anti- Leishmania IgG-U concentrations were highly correlated with uP/C ratio ( ρ = 0.779; P < 0.001) and C value did not support in any case local production of this isotype. IgG isotype might be a more suitable and specific tool to evaluate renal damage due to the lower IgA-U sensitivity and correlation coefficients and evidence of IgA local production. However, dogs found positive for both Ig isotypes in urine presented significantly higher specific IgG-U concentrations and higher uP/C ratios than dogs found positive only for IgG-U, thus suggesting that the first group suffered more severe renal damage. This fact makes it necessary to evaluate the prognosis of dogs showing both anti- Leishmania IgA-U and IgG-U in future studies.

Primary myelofibrosis in a patient who developed primary biliary cirrhosis, autoimmune hemolytic anemia and fibrillary glomerulonephritis

Dear Editor, We report a patient with primary myelofibrosis (PMF) who developed primary biliary cirrhosis, autoimmune hemolytic anemia, and fibrillary glomerulonephritis (FGN). A 67-year-old woman was referred to our institution in November 1999 because of asthenia and nocturnal sweats associated to PMF, which was diagnosed in September 1996. In June 1998, high liver enzymes, circulating antimitochondrial antibodies, and a liver biopsy disclosed primary biliary cirrhosis. She had a history of arthralgia, positive latex test, xerosthalmia, and xerosthomia. On admission, she presented with hepatosplenomegaly, moderate thrombocytosis, mild anemia, elevated leukocytes and 6% circulating blasts. Leukocyte alkaline phosphatase score was very low, karyotype was normal, no bcr-abl translocation was detected, and high lactic dehydrogenase levels were found. Bone marrow (BM) aspiration yielded a dry tap and BM biopsy disclosed megakaryocyte and myeloid hyperplasia, diffuse increase in reticulin fibers with osteosclerosis. Progressive splenomegaly was noted. In January 2000, the patient was medicated with hydroxyurea except during 2002 when she received thalidomide 50 mg/day plus prednisone for only 4 months because of lack of response and development of marked basophilia and polyneuritis. She had severe anemia with low levels of erythropoietin but did not respond to erythropoietin. In November 2003, an immunophenotype showed 10% circulating blasts of myeloid lineage with monocytoid features. In February 2004, she was admitted because of classic autoimmune hemolytic anemia with positive direct Coomb’s test. Reduced total complement level, homogenous positive antinuclear factor, and Sm B, Sm D, and RNP-A antinuclear antibodies were also detected. She received red cells transfusion and prednisone with favorable response and a dramatic decrease in spleen size. Two weeks later, she presented with nephrotic syndrome characterized by non-selective proteinuria, 8 g/day, and decreased renal function. Renal biopsy disclosed Congo red-negative fibrillar deposits, characteristic of FGN, which were confirmed by electron microscopy (Fig. 1). Immunofluorescence microscopy revealed granular staining for IgG, IgM inside the glomeruli, and IgG, IgA in the tubular deposits. Urine IgG and IgA, lambda and kappa light chains were detected by immunoelectrophoresis. JAK2V617F mutation yielded negative results. In December 2005, she had 32% circulating blasts. In April 2006, an immunophenotype with 47% of blasts supported the diagnosis of acute myelogenous leukemia-M0. She died of sepsis. The presence of several immunologic disorders in this patient and partial improvement of PMF features with Ann Hematol (2008) 87:1019–1020 DOI 10.1007/s00277-008-0516-6

Distribution of filarial elephantiasis and hydrocele in Matara district, Sri Lanka, as reported by local leaders, and an immunological survey in areas with relatively high clinical rates

To eliminate lymphatic filariasis by means of mass drug administration, it is essential to have reliable data on the disease distribution and prevalence in targeted areas. In Matara district, Sri Lanka, self-administered questionnaires were mailed to 2105 local leaders questioning the presence and the numbers of elephantiasis and hydrocele cases. The information provided by them revealed that elephantiasis was clearly aggregated in the southern part of the district along the coast, while hydrocele was distributed rather evenly in the whole district, including Deniyaya region where no endemic filariasis had been known. To confirm active transmission of filariasis in Deniyaya, Wuchereria bancrofti antigen and filaria-specific urinary IgG4 antibody were measured with 2436 subjects. The positive rates for antigen and antibody were 0.6% and 4.3%, respectively. The titer analysis of IgG4 according to age revealed that the youngest IgG4 positive was 3 years old, and that in 10 years old or less, there were 16 positives out of 607 children examined (2.6%). It was concluded that filarial transmission at a low level was going on in the region.

Presence and gradual disappearance of filaria-specific urinary IgG4 in babies born to antibody-positive mothers: A 2-year follow-up study

A total of 14 Sri Lankan pregnant women, who were anti- Brugia pahangi urinary IgG4 positive, and their 14 newborn babies were followed up for the urinary antibody for 2 years by enzyme-linked immunosorbent assay. Eight babies showed positive IgG4 reaction, at least once within 4 months after birth. Urinary antibody titers of mothers and their babies measured around the perinatal period showed a significant positive correlation, suggesting that baby's IgG4 was transferred from the mother through the placenta. The IgG4 decreased gradually and became negative in all positive babies by day 339.3 after birth. The present result provides a basis to judge if a positive urine ELISA test among babies is due to a new filarial infection.

Gamma heavy chain disease in a patient with diabetes and chronic renal insufficiency: diagnostic assessment of the heavy chain fragment

Heavy chain diseases are rare B-cell disorders that are characterized by an overproduction of abnormal and structurally incomplete monoclonal immunoglobulin (Ig) heavy chains and are devoid of light chains. We describe a case of a 62 year-old African-American woman with a long history of poorly controlled type 2 diabetes and subsequent probable diabetic nephropathy, hypertension, and recent onset of peripheral neuropathy involving all extremities. Routine laboratory testing revealed a distinct beta spike by urine protein electrophoresis (UPEP). No serum abnormality was noted on serum protein electrophoresis (SPEP). Serum and urine immunofixation demonstrated an IgG heavy chain protein devoid of any corresponding light chains. IgG subclasses identified IgG1 as the predominant IgG component but when we added all the subclasses, the sum, 683.4 mg/dL, failed to come close to our total IgG of 1,770 mg/dL. Therefore, a urine IgG subclass determination was performed in-house and we identified a subclass 3 gamma chain. In conclusion, we portray a patient with an underlying monoclonal gamma heavy chain disease (HCD) who presented with a complex medical history. The evaluation of IgG subclasses in the context of a HCD may be limited by the capability of the test to recognize the particular IgG fragment.

The ELISA-based detection of anti-Opisthorchis viverriniIgG and IgG4in samples of human urine and serum from an endemic area of north–eastern Thailand

The levels of correlation between the number of Opisthorchis viverrini eggs excreted in the faeces and levels of anti-Opisthorchis IgG and IgG(4) in the serum and urine (as indicated by absorbances in ELISA) have recently been evaluated in north-eastern Thailand. The 225 subjects investigated in detail, all of whom came from an endemic village in Chaiyaphum province, were selected on the basis of the numbers of O. viverrini eggs that they were excreting. ELISA based on a crude antigen extract of the trematode were then used to determine the levels of specific IgG and IgG(4) in serum and urine samples. Compared with the egg-negative, the villagers who were found to be egg-positive for O. viverrini had significantly higher levels of specific IgG in their urine and serum and significantly higher levels of specific IgG(4) in their serum. The serum levels of specific IgG and IgG(4) and the urine levels of specific IgG all correlated with the numbers of O. viverrini eggs/g faeces [with correlation coefficients (r) of 0.251, 0.121 and 0.142, respectively]. Although the serum levels of IgG were positively correlated with the urine levels of IgG (r=0.098), there was no significant relationship between the serum and urine levels of specific IgG(4) (r=0.051). When the 225 subjects investigated in the ELISA were divided according to whether they had no detectable Opisthorchis eggs in their faeces (N=57), or 1-100 (N=154), 101-1000 (N=5), 1001-1500 (N=5) or >1501 (N=4) eggs/g faeces, the serum and urine levels of specific IgG and the serum (but not urine) levels of specific IgG4 were also found to correlate significantly with the infection-intensity categories (with r-values of 0.550, 0.146 and 0.578, respectively). When the results of the faecal examinations were treated as the 'gold standard', the ELISA for the detection of (Opisthorchis-specific) serum IgG, serum IgG(4), urine IgG and urine IgG(4) had sensitivities of 99.2%, 23.1%, 43.0% and 45.9% and specificities of 93.0%, 29.6%, 45.9% and 67.2%, respectively. Although the study was limited by the small number of subjects with intense infections, it appears worth investigating urine samples for subclasses of specific IgG other than IgG(4).

To Study the Relationship between the IgG in Urine and Recurrence of Anaphylactoid Purpura in Children

目的 探讨小儿过敏性紫癜首次住院时尿IgG与1年内复发的关系.方法 用免疫比浊法测定28例出院后1年内出现复发的和38例出院后1年内无复发的过敏性紫癜患儿首次住院时急性期和恢复期的尿IgG,并加以比较分析.结果 出院后1年内出现复发的患儿其首次住院急性期尿IgG的水平为(1.766±0.752)g/L,与出院后1年内无复发者相若,而恢复期尿IgG的水平为(0.245±0.061)g/L,明显高于无复发者的(0.113±0.055)g/L,其差异有非常显著性意义(P＜0.01).结论 大部分过敏性紫癜患儿在急性期均有一定程度的肾损害,1年内复发的过敏性紫癜患儿其首次发病临床症状虽然基本消失,而肾损害仍存在,小血管炎没有完全消失,其病理改变仍持续存在,致紫癜易于复发.尿IgG在判断小儿过敏性紫癜的活动方面和复发的预后方面均有一定的意义。

The Clinic Significance of Urinary IgG was assayed in Henoch-Schonlein Purpura Nephritis

目的 探讨小儿过敏性紫癜肾炎尿IgG测定的临床意义.方法 应用免疫比浊法测定82例过敏性紫癜肾炎患儿分别在急性期和恢复期的尿IgG,比较两者尿IgG的平均值及阳性率.同时应用LOGISTIC多元回归方程分析急性期尿IgG与血IgG下降、皮肤紫癜、血尿、24小时尿蛋白总量、浮肿、高血压、BUN及年龄的相关关系.结果 急性期尿IgG的阳性率83%,比恢复期40%明显增高,P＜0.005.急性期尿IgG与血IgG下降、皮肤紫癜、血尿、24小时尿蛋白总量密切相关,与浮肿、高血压、BUN有一定关系,与年龄无关.结论 过敏性紫癜肾炎患儿尿IgG阳性反映肾小球滤过膜通透性的明显增加,可考虑作为活动的指标之一,且在一定程度上反映病情的轻重。

Absence of Increased α1-Microglobulin in IgA Nephropathy Proteinuria

To search for biomarkers of IgA nephropathy, protein profiles of urine samples from patients with IgA nephropathy and normal volunteers were compared using two-dimensional DIGE. Most of the 172 spots identified in the urine were serum proteins, and their amounts in IgA nephropathy urine were much higher than those in normal urine; this can be explained as proteinuria caused by glomerular dysfunction. However, only alpha(1)-microglobulin, also one of the major serum proteins, in IgA nephropathy urine was not higher in amount than that in normal urine. We confirmed using ELISA analysis that the amounts of transferrin and albumin in IgA nephropathy and diabetic nephropathy urine were much higher than those in normal urine, whereas the amount of alpha(1)-microglobulin in IgA nephropathy urine was not higher than that in normal urine and was much lower than that in diabetic nephropathy urine. Approximately 50% of alpha(1)-microglobulin forms a complex with IgA in serum. These results suggest that alpha(1)-microglobulin in IgA nephropathy urine is a characteristic protein and might be a biomarker for IgA nephropathy and that alpha(1)-microglobulin might have a relationship with IgA nephropathy pathology.

Rapid and Simultaneous Quantification of 4 Urinary Proteins by Piezoelectric Quartz Crystal Microbalance Immunosensor Array

Urinary proteins are predictive and prognostic markers for diabetes nephropathy. Conventional methods for the quantification of urinary proteins, however, are time-consuming, and most require radioactive labeling. We designed a label-free piezoelectric quartz crystal microbalance (QCM) immunosensor array to simultaneously quantify 4 urinary proteins. We constructed a 2 x 5 model piezoelectric immunosensor array fabricated with disposable quartz crystals for quantification of microalbumin, alpha1-microglobulin, beta2-microglobulin, and IgG in urine. We made calibration curves after immobilization of antibodies at an optimal concentration and then evaluated the performance characteristics of the immunosensor with a series of tests. In addition, we measured 124 urine samples with both QCM immunosensor array and immunonephelometry to assess the correlation between the 2 methods. With the QCM immunosensor array, we were able to quantify 4 urinary proteins within 15 min. This method had an analytical interval of 0.01-60 mg/L. The intraassay and interassay imprecisions (CVs) were <10%, and the relative recovery rates were 90.3%-109.1%. Nonspecificity of the immunosensor was insignificant (frequency shifts <20 Hz). ROC analyses indicated sensitivities were > or =95.8% and, specificities were > or =76.3%. Bland-Altman difference plots showed the immunosensor array to be highly comparable to immunonephelometry. The QCM system we designed has the advantages of being rapid, label free, and highly sensitive and thus can be a useful supplement to commercial assay methods in clinical chemistry.

Relationship Between Clinical Predictors and Tubulointerstitial Damage in Adult-onset Primary Nephrotic Syndrome

Tubulointerstitial damage (TID) is an important mediator in the progression of chronic proteinuric nephropathies. Our aim in this study was to evaluate the relationship between several clinical predictors and TID in adult-onset primary nephrotic syndrome in China. One hundred ninety-five adult inpatients who were diagnosed with primary nephrotic syndrome based on clinical presentation and biopsy results were enrolled in this study from March 2003 to September 2005. The degree of TID was graded by a semiquantitative method including <2 score and >or=2 score. In all patients, the rate of glomerulosclerosis was correlated with the severity of TID. Serum creatinine and uric acid (r = 0.183, p = 0.012 and r = 0.377, p = 0.00001, respectively) but not serum lipid or total 24-h urinary protein were related with TID. In 64 patients, urinary excretion of IgG (r = 0.443, p = 0.00001) but not of albumin, transferrin, retinal-binding protein, or alpha1-microglobulin were significantly associated with the extent of TID. Proteinuria selectivity index based upon IgG also correlated significantly with the extent of TID (p = 0.0001) (score 0-1 vs. score >or=2). These results showed that serum creatinine and uric acid, the excretion of urinary IgG and proteinuria selectivity index based upon IgG, were highly correlated with the severity of TID in adult-onset primary nephrotic syndrome. These clinical parameters might be useful for predicting the development and progression of proteinuric nephropathy as independent risk factors.