Urinary Low Molecular Proteins Research Articles

ESTABLISHMENT OF NOVEL URINARY KIDNEY DISEASE NEW BIOMARKERS AND THERAPEUTIC EFFECT OF METHANOL FRACTION OF TERMINALIA ARJUNA ON ACETAMINOPHEN INDUCED KIDNEY DISEASE IN RATS

Objective: There were main two objectives, first was the identification of best biomarkers for early screening of kidney diseases whether plasma urea and creatinine or novel urinary low molecular weight protein biomarkers Interleukin-18 (IL-18), kidney injury molecule-1 (KIM-1), and cystatin-C. Second was the therapeutic efficacy of methanol fraction of Terminalia arjuna (MFTA) on urinary novel biomarkers.
 Methods: A total of 35 adult male rats were divided into three Groups (n=5), Group 1 was fed normal food, Group 2, normal food with administration of acetaminophen (APAP) for 5 days, 10 days, and 15 days, and Group 3, normal food with administration of APAP and coadministration of MFTA for 5 days, 10 days, and 15 days. All rats were sacrificed at 15th day of the experiment.
 Results: Results showed 5 days, 10 days, and 15 days administrations of APAP increased novel urinary biomarkers as IL-18, KIM-1 near two-folds and cystatin-C near six-folds increased than old biomarkers plasma urea and plasma creatinine. Administration of APAP with coadministration of MFTA represented the protective effect by decreasing old and new novel biomarkers with superoxide dismutase and catalase but malondialdehyde level increased. Sodium dodecyle sulphate-polyacrylamide gel electrophoresis showed new low molecular weight urinary protein bands in APAP administration rats, the protective effect of MFTA presents no band at this molecular level as normal rats.
 Conclusion: MFTA is the most potent nephroprotective agent, and urinary low molecular proteins are the best thing diagnostic tools for early detection of kidney disease over common plasma urea and creatinine.

Treatment with low-dose angiotensin-converting enzyme inhibitor (ACEI) plus angiotensin II receptor blocker (ARB) in pediatric patients with IgA nephropathy

IgA nephropathy associated with heavy proteinuria is considered a more progressive form of this disease. In this report, we describe the favorable clinical effect of combination therapy with low doses of an angiotensin-converting enzyme inhibitor (ACEI) and angiotensin II receptor blocker (ARB) in the chronic stage of pediatric IgA nephropathy associated with heavy proteinuria. We initially used ACEI for seven children with IgA nephropathy and heavy proteinuria who did not achieve remission with the routine treatment including steroids. With ACEI therapy alone, only three patients showed an antiproteinuric response. In one of the three patients, the proteinuria decreased by half, but was still over 1 g/day. In the other four patients, the proteinuria did not decrease. In these five patients, of whom one partial was a responder and four were non-responders for ACEI, ARB was added, and in marked contrast to ACEI therapy alone, the antiproteinuric effect was significantly augmented (p < 0.01). The antiproteinuric response induced by combination therapy was not accompanied by blood pressure changes. Urinary low-molecular protein and N-acetyl-beta-D-glucosaminidase (NAG) levels tended to decrease after both ACEI alone and combination therapy. These data indicate that inhibition therapy of the angiotensin system not only decreases proteinuria levels but also protects renal tubular cells. Moreover, there were no obvious side effects associated with this therapy during the follow-up period of our clinical trial. In conclusion, this report shows that the combination of low doses of ACEI and ARB might provide marked antiproteinuric and long-term renoprotective effects in pediatric IgA nephropathy, with this approach appearing to be both well-tolerated and safe.

第18回日本総合健診医学会学術大会講演抄録集 総合健診受診の高尿酸血症症例における尿中微量物質の測定・検討

第18回日本総合健診医学会学術大会講演抄録集 総合健診受診の高尿酸血症症例における尿中微量物質の測定・検討

尿中低分子量蛋白に関する研究

正常尿を100-1000倍に濃縮すると, アルブミン, α1-抗トリプシン, トランスフェリン, γ-グロブリンなどが出現する. 腎疾患の患者尿中には上記の蛋白が正常人に比較し多量に出現するが, 腎臓の障害の部位によりその出現する蛋白の種類や量が異なる. 腎糸球体の障害により起こる糸球体性蛋白尿では中分子量 (60,000-160,000) のアルブミン, トランスフェリン, IgGなどの蛋白が主体となり, 疾患としてはネフローゼ症候群, 腎炎, 高血圧性腎症, 糖尿病性腎症などがある. これに対し近位尿細管障害による尿細管性蛋白尿では低分子量 (10,000-50,000) のL鎖, β2-ミクログロブリン, 血清酵素などが出現し, 疾患としては慢性カドミウム中毒, Fanconi症候群, ウイルソン病などがある. この他糸球体と尿細管がともに障害されることによって起こる尿毒症性蛋白尿では低および中分子量蛋白が同時に出現し, 尿毒症の時にみられる. 著者は糸球体性蛋白尿をきたした慢性腎疾患患者尿中の低分子量γ-グロブリンとアルブミンについて物理化学的および免疫学的検索をした. 尿中低分子量γ-グロブリンの分子量は約12,000でIgGのH鎖フラグメントであるFcとFabおよびL鎖を含んでいた. 尿中低分子量アルブミンは分子量約10,000のminialbuminが出現し, 免疫原性を有した.

Studies on urinary low molecular albumin

Low molecular proteins contained in the urine of the patients of multiple myeloma and diabetes mellitus were studied physicochemically and immunologically. Urinary low molecular proteins, approximately 10, 000 to 50, 000 in molecular weight, were concentrated about 100 times by ultrafiltration.Immunoelectrophoresis of these low molecular proteins revealed fractions common in antigenic properties with albumin, α1-antitrypsin, ceruloplasmin, transferrin, IgG and Bence-Jones protein. The low molecular weight albumin was separated and purified by chromatography on Sephadex G-75 and DEAE-cellulose. Purity of this albumin was checked by double immunodiffusion and polyacrylamide gel disc electrophoresis. The approximate molecular weight of this albumin was measured as 10, 000 by ultracentrifugal and light scattering analysis. The ability of the low molecular fraction to induce formation of antibody was confirmed with experimental inoculation to rabbits.