{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T00:36:33Z","timestamp":1790382993237,"version":"4.1.0"},"reference-count":34,"publisher":"BMJ","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Clin Pathol"],"published-print":{"date-parts":[[1993,5]]},"abstract":"<jats:p>AIM--To compare the urinary excretion of beta 2-glycoprotein-1 with that of two other markers of early tubular disorder in diabetic patients without clinical proteinuria. METHODS--The urinary excretion of retinol binding protein, beta 2-glycoprotein-1, and N-acetyl-beta-D-glucosaminidase was measured in 90 known diabetic patients who had a negative reagent strip test for proteinuria. RESULTS--Among 43 patients with urinary albumin excretion within the reference range, 23 (53%) had raised urinary N-acetyl-beta-D-glucosaminidase activity, five (12%) increased excretion of beta 2-glycoprotein-1, and five (12%) increased loss of retinol binding protein. Among 47 patients with an albumin excretion of 0.9-7.9 mg\/mmol creatinine, 42 (89%) had increased urinary N-acetyl-beta-D-glucosaminidase, 23 (49%) an increased output of beta 2-glycoprotein-1, and 16 (34%) a raised excretion of retinol binding protein. The excretion of these markers of tubular defects seldom exceeded two and a half times the upper reference limit and the differences between the findings in the insulin dependent and non-insulin dependent patients with similar albumin excretion were small and insignificant. CONCLUSIONS--In diabetic patients with a negative dipstick test for proteinuria: (a) assay of urinary beta 2-glycoprotein-1 may be a more sensitive test for the detection of impaired tubular reabsorption of protein than measurement of retinol-binding protein; (b) assay of N-acetyl-beta-D-glucosaminidase can detect tubular injury at a time when protein reabsorption remains normal; and (c) impaired renal tubular function may be present in the absence of evidence of glomerular malfunction.<\/jats:p>","DOI":"10.1136\/jcp.46.5.465","type":"journal-article","created":{"date-parts":[[2007,6,9]],"date-time":"2007-06-09T00:50:46Z","timestamp":1181350246000},"page":"465-469","source":"Crossref","is-referenced-by-count":20,"title":["Beta 2-glycoprotein-1 (apolipoprotein H) excretion and renal tubular malfunction in diabetic patients without clinical proteinuria."],"prefix":"10.1136","volume":"46","author":[{"given":"M","family":"Lapsley","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F V","family":"Flynn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P A","family":"Sansom","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[1993,5,1]]},"reference":[{"key":"ref_1","first-page":"1430","article-title":"Microalbuminuria as a predictor of clinical nephropathy in insulin-dependent diabetes mellitus","volume":"i:","author":"Viberti, G.C.; Hill, R.D.; Jarrett, R.J.; Argyropoulos, A.; Mahmud, U.; Keen, H.","year":"1982","unstructured":"Viberti GC, Hill RD, Jarrett RJ, Argyropoulos A, Mahmud U, Keen H. Microalbuminuria as a predictor of clinical nephropathy in insulin-dependent diabetes mellitus. Lancet 1982;i: 1430-2.","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1056\/NEJM198402093100605","article-title":"Microalbuminuria predicts clinical proteinuria and early mortality in maturity-onset diabetes","volume":"310","author":"Mogensen, C.E.","year":"1984","unstructured":"Mogensen CE. Microalbuminuria predicts clinical proteinuria and early mortality in maturity-onset diabetes. N EngIlMed 1984;310:356-60.","journal-title":"N EngIlMed"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1056\/NEJM198407123110204","article-title":"Predicting diabetic nephropathy in insulin-dependent patients","volume":"311","author":"Mogensen, C.E.; Christensen, C.K.","year":"1984","unstructured":"Mogensen CE, Christensen CK. Predicting diabetic nephropathy in insulin-dependent patients. N Engi J Med 1984;311:89-93.","journal-title":"N Engi J Med"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1300","DOI":"10.1016\/S0140-6736(86)91433-9","article-title":"Effect of two years of strict metabolic control on progression of incipient nephropathy in insulin-dependent diabetes","volume":"ii:","author":"Feldt-Rasmussen, B.; Mathiesen, E.R.; Deckert, T.","year":"1986","unstructured":"Feldt-Rasmussen B, Mathiesen ER, Deckert T. Effect of two years of strict metabolic control on progression of incipient nephropathy in insulin-dependent diabetes. Lancet 1986;ii: 1300-4.","journal-title":"Lancet"},{"key":"ref_5","first-page":"337","article-title":"Diabetic proteinuria. Glomerular or tubular in origin?","volume":"4","author":"Abrass, C.K.","year":"1984","unstructured":"Abrass CK. Diabetic proteinuria. Glomerular or tubular in origin? Am J Nephrol 1984;4:337-46.","journal-title":"Am J Nephrol"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1136\/adc.64.1.129","article-title":"Renal tubular proteinuria and microalbuminuria in diabetic patients","volume":"64","author":"Gibb, D.M.; Tomlinson, P.A.; Dalton, N.R.; Turner, C.; Shah, V.; Barratt, T.M.","year":"1989","unstructured":"Gibb DM, Tomlinson PA, Dalton NR, Turner C, Shah V, Barratt TM. Renal tubular proteinuria and microalbuminuria in diabetic patients. Arch Dis Child 1989;64: 129-34.","journal-title":"Arch Dis Child"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1177\/000456328702400509","article-title":"Retinol binding protein as a small molecular weight marker of renal tubular function in diabetes mellitus","volume":"24","author":"Rowe, D.J.F.; Anthony, F.; Polak, A.; Shaw, K.; Ward, C.D.; Watts, G.F.","year":"1987","unstructured":"Rowe DJF, Anthony F, Polak A, Shaw K, Ward CD, Watts GF. Retinol binding protein as a small molecular weight marker of renal tubular function in diabetes mellitus. Ann Clin Biochem 1987;24:477-82.","journal-title":"Ann Clin Biochem"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/0009-8981(88)90312-9","article-title":"Relationship between the urinary excretion of albumin and retinolbinding protein in insulin-dependent diabetics","volume":"177","author":"Holm, J.; Hemmingsen, L.; Nielsen, N.V.","year":"1988","unstructured":"Holm J, Hemmingsen L, Nielsen NV. Relationship between the urinary excretion of albumin and retinolbinding protein in insulin-dependent diabetics. Clin Chim Acta 1988;177:101-6.","journal-title":"Clin Chim Acta"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"589","DOI":"10.2337\/diab.34.6.589","article-title":"Urinary excretion of plasma proteins in diabetic subjects. Increased excretion of kappa light chains in diabetic patients with and without proliferative retinopathy","volume":"34","author":"Teppo, A.-M.; Groop, L.","year":"1985","unstructured":"Teppo A-M, Groop L. Urinary excretion of plasma proteins in diabetic subjects. Increased excretion of kappa light chains in diabetic patients with and without proliferative retinopathy. Diabetes 1985;34:589-94.","journal-title":"Diabetes"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1093\/clinchem\/37.1.74","article-title":"Excretion of \/,-glycoprotein-I (apolipoprotein H) in renal tubular disease","volume":"37","author":"Norden, A.G.W.; Fulcher, L.M.; Lapsley, M.; Flynn, F.V.","year":"1991","unstructured":"Norden AGW, Fulcher LM, Lapsley M, Flynn FV. Excretion of \/,-glycoprotein-I (apolipoprotein H) in renal tubular disease. Clin Chem 1991;37:74-7.","journal-title":"Clin Chem"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"812","DOI":"10.1136\/jcp.44.10.812","article-title":"\/i2-glycoprotein-1 (apolipoprotein H) excretion in chronic renal tubular disorders: comparison with other protein markers of tubular malfunction","volume":"44","author":"Lapsley, M.; Sansom, P.A.; Marlow, C.T.; Flynn, F.V.; Norden, A.G.W.","year":"1991","unstructured":"Lapsley M, Sansom PA, Marlow CT, Flynn FV, Norden AGW. \/i2-glycoprotein-1 (apolipoprotein H) excretion in chronic renal tubular disorders: comparison with other protein markers of tubular malfunction. 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London: British Medical Journal, 1989:71-9."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1863","DOI":"10.1093\/clinchem\/32.10.1863","article-title":"Measurement of urinary retinol-binding protein by enzyme-linked immunosorbent assay, and its application to detection of tubular proteinuria","volume":"32","author":"Topping, M.D.; Forster, H.W.; Dolman, C.; Luczynska, C.M.; Bernard, A.M.","year":"1986","unstructured":"Topping MD, Forster HW, Dolman C, Luczynska CM, Bernard AM. Measurement of urinary retinol-binding protein by enzyme-linked immunosorbent assay, and its application to detection of tubular proteinuria. Clin Chem 1986;32:1863-6.","journal-title":"Clin Chem"},{"key":"ref_16","first-page":"283","article-title":"A sandwich enzyme-linked immunosorbent assay for fi,-glycoprotein 1","volume":"28","author":"Sansom, P.A.; Marlow, C.T.; Lapsley, M.; Flynn, F.V.","year":"1991","unstructured":"Sansom PA, Marlow CT, Lapsley M, Flynn FV. A sandwich enzyme-linked immunosorbent assay for fi,-glycoprotein 1. Ann Clin Biochem 1991;28:283-9."},{"key":"ref_17","first-page":"295","article-title":"Colorimetric assay for N-acetyl-fl-D-glucosaminidase (NAG) in pathological urine using the w-nitrostyryl substrate: the development of a kit and the comparison of manual procedure with the automated fluorimetric method","volume":"21","author":"Yuen, C.T.; Kind, P.R.N.; Price, R.G.; Praill, P.F.G.; Richardson, A.C.","year":"1984","unstructured":"Yuen CT, Kind PRN, Price RG, Praill PFG, Richardson AC. Colorimetric assay for N-acetyl-fl-D-glucosaminidase (NAG) in pathological urine using the w-nitrostyryl substrate: the development of a kit and the comparison of manual procedure with the automated fluorimetric method. Ann Clin Biochem 1984;21:295-300."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"686","DOI":"10.2337\/diab.33.7.686","article-title":"The patterns of proteinuria in diabetes mellitus. 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Lowmolecular-weight proteinuria in insulin-dependent diabetes mellitus: a study of the urinary excretion of,B2- microglobulin and retinol-binding protein in alkalinized patients with and without microalbuminuria. Diabetes Res 1989;12:31-6.","journal-title":"Diabetes Res"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1016\/0009-8981(90)90178-U","article-title":"Urinary proteins and red cell membrane negative charges in diabetes mellitus","volume":"190","author":"Bemard, A.; Amor, O.A.; Goemare-Vanneste, J.","year":"1990","unstructured":"Bemard A, Amor OA, Goemare-Vanneste J, et al. Urinary proteins and red cell membrane negative charges in diabetes mellitus. Clin Chim Acta 1990;190:249-62.","journal-title":"Clin Chim Acta"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1111\/j.1464-5491.1990.tb01304.x","article-title":"Increased urinary excretion of transferrin in children with type 1 diabetes mellitus","volume":"7","author":"Martin, P.; Walton, C.; Chapman, C.; Bodansky, H.J.; Stickland, M.H.","year":"1990","unstructured":"Martin P, Walton C, Chapman C, Bodansky HJ, Stickland MH. Increased urinary excretion of transferrin in children with type 1 diabetes mellitus. Diabetic Med 1990;7:35-40.","journal-title":"Diabetic Med"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1818","DOI":"10.1093\/clinchem\/32.10.1818","article-title":"Determination of urinary lysozyme for potential detection of tubular dysfunction in diabetic nephropathy","volume":"32","author":"Shima, K.; Hirota, M.; Fukuda, M.; Tanaka, A.","year":"1986","unstructured":"Shima K, Hirota M, Fukuda M, Tanaka A. Determination of urinary lysozyme for potential detection of tubular dysfunction in diabetic nephropathy. Clin Chem 1986;32:1818-22.","journal-title":"Clin Chem"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"544","DOI":"10.1093\/clinchem\/34.3.544","article-title":"Urinary enzymes and low-molecular-mass proteins as indicators of diabetic nephropathy","volume":"34","author":"Jung, K.; Pergande, M.; Schimke, E.; Ratzmann, K.P.; Llius, A.","year":"1988","unstructured":"Jung K, Pergande M, Schimke E, Ratzmann KP, Llius A. Urinary enzymes and low-molecular-mass proteins as indicators of diabetic nephropathy. Clin Chem 1988;34: 544-7.","journal-title":"Clin Chem"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1120","DOI":"10.1038\/ki.1990.94","article-title":"Urinary excretion of kappa light chains in patients with diabetes mellitus","volume":"37","author":"Groop, L.; Makipernaa, A.; Stenman, S.; DeFronzo, R.A.; Teppo, A.-M.","year":"1990","unstructured":"Groop L, Makipernaa A, Stenman S, DeFronzo RA, Teppo A-M. Urinary excretion of kappa light chains in patients with diabetes mellitus. Kidney Int 1990;37: 1120-5.","journal-title":"Kidney Int"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1016\/0009-8981(79)90227-4","article-title":"Serum and urine N- acetyl-fl-D-glucosaminidase in diabetics on diagnosis and subsequent treatment, and stable insulin dependent diabetics","volume":"92","author":"Whiting, P.H.; Ross, I.S.; Borthwick, L.","year":"1979","unstructured":"Whiting PH, Ross IS, Borthwick L. Serum and urine N- acetyl-fl-D-glucosaminidase in diabetics on diagnosis and subsequent treatment, and stable insulin dependent diabetics. Clin Chim Acta 1979;92:459-63.","journal-title":"Clin Chim Acta"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/0009-8981(90)90153-J","article-title":"Urinary excretion of brush-border antigen and plasma proteins in early stages of diabetic nephropathy","volume":"188","author":"Mutti, A.; Alinovi, R.; Ghiggeri, G.M.","year":"1990","unstructured":"Mutti A, Alinovi R, Ghiggeri GM, et al. Urinary excretion of brush-border antigen and plasma proteins in early stages of diabetic nephropathy. Clin Chim Acta 1990; 188:93-100.","journal-title":"Clin Chim Acta"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"347","DOI":"10.3109\/00365517509095751","article-title":"The 24-hour excretion of plasma proteins in the urine of apparently healthy subjects","volume":"35","author":"Hemmingsen, L.; Skaarup, P.","year":"1975","unstructured":"Hemmingsen L, Skaarup P. The 24-hour excretion of plasma proteins in the urine of apparently healthy subjects. ScandJ Clin Lab Invest 1975;35:347-53.","journal-title":"ScandJ Clin Lab Invest"},{"key":"ref_30","first-page":"212","article-title":"Immunochemical quantitation of 42-glycoprotein 1 in various diseases","volume":"75","author":"Cohnen, G.","year":"1970","unstructured":"Cohnen G. Immunochemical quantitation of 42-glycoprotein 1 in various diseases. I Lab Clin Med 1970;75: 212-6.","journal-title":"I Lab Clin Med"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1136\/jcp.45.7.561","article-title":"Urinary excretion of 8,-glycoprotein-1 (apolipoprotein H) and other markers of tubular malfunction in \"non-tubular\" renal disease","volume":"45","author":"Flynn, F.V.; Lapsley, M.; Sansom, P.A.; Cohen, S.L.","year":"1992","unstructured":"Flynn FV, Lapsley M, Sansom PA, Cohen SL. Urinary excretion of 8,-glycoprotein-1 (apolipoprotein H) and other markers of tubular malfunction in \"non-tubular\" renal disease. J Clin Pathol 1992;45:561-7.","journal-title":"J Clin Pathol"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1111\/j.1464-5491.1990.tb01396.x","article-title":"Microproteinuria in Type 2 diabetes mellitus from diagnosis","volume":"7","author":"Martin, P.; Hampton, K.K.; Walton, C.; Tindall, H.; Davies, J.A.","year":"1990","unstructured":"Martin P, Hampton KK, Walton C, Tindall H, Davies JA. Microproteinuria in Type 2 diabetes mellitus from diagnosis. Diabetic Med 1990;7:315-8.","journal-title":"Diabetic Med"},{"key":"ref_33","first-page":"436","article-title":"Renal tubular uptake of protein: effect of molecular charge","volume":"244","author":"Christensen, E.I.; Rennke, H.G.; Carone, F.A.","year":"1983","unstructured":"Christensen EI, Rennke HG, Carone FA. Renal tubular uptake of protein: effect of molecular charge. Am J Physiol 1983;244:F436-41.","journal-title":"Am J Physiol"},{"key":"ref_34","first-page":"327","article-title":"Angiotensin converting enzyme inhibitors and diabetic nephropathy","volume":"304","author":"Mogensen, C.E.","year":"1992","unstructured":"Mogensen CE. Angiotensin converting enzyme inhibitors and diabetic nephropathy. 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