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Exp Clin Endocrinol Diabetes 2004; 112(4): 195-200
DOI: 10.1055/s-2004-817933
Article

J. A. Barth Verlag in Georg Thieme Verlag KG Stuttgart · New York

β2-Microglobulin and Cystatin C in Type 2 Diabetes: Assessment of Diabetic Nephropathy

S. Apakkan Aksun1 , D. Özmen1 , B. Özmen2 , Z. Parildar1 , I. Mutaf1 , N. Turgan1 , S. Habif1 , K. Kumanlioğluc3 , O. Bayindir1
  • 1Department of Clinical Biochemistry, Ege University Faculty of Medicine, Bornova, Izmir, Turkey
  • 2Department of Endocrinology, Celal Bayar University Faculty of Medicine, Manisa, Turkey
  • 3Department of Nuclear Medicine, Ege University Faculty of Medicine, Bornova, Izmir, Turkey
Further Information

Publication History

Received: January 9, 2003 First decision: February 24, 2003

Accepted: May 12, 2003

Publication Date:
04 May 2004 (online)

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Abstract

Background: Changes in glomerular filtration rate (GFR) provide a valuable indicator of the progression of diabetic nephropathy (DN). This study was designed to demonstrate the clinical values of serum cystatin C (Cys C) and β2-microglobulin in the assessment of renal function in type 2 diabetics by comparing them with the GFR, estimated from the uptake phase of 99 m technetium dimetiltriamino pentaacetic acid renogram (GFR-DTPA) and creatinine clearances.

Materials and Methods: 68 type 2 diabetic patients with (urinary albumin excretions (UAE) 30 - 300 mg/24 h) (n = 39) and without (UAE < 30 mg/24 h) (n = 29) microalbuminuria and 32 controls were enrolled in the study. Serum Cys C, β2-microglobulin, creatinine, urinary microalbumin levels, creatinine clearances and GFR-DTPA values were determined in all groups. Non-parametric ROC curves, using a cut-off GFR-DTPA of 60 mL/min/1.73 m2, were obtained for these markers.

Results: Serum Cys C, β2-microglobulin, glucose and HbA1c concentrations were significantly higher in the group with diabetes compared to controls. In the patients with microalbuminuria, serum Cys C and glucose concentrations increased significantly in comparison to patients with normoalbuminuria, while no differences were observed for β2-microglobulin levels. Serum creatinine concentrations, GFR-DTPA values and creatinine clearances were not different between both diabetic groups and controls.

Cys C was positively correlated with β2-microglobulin and creatinine and negatively with GFR values; β2-microglobulin was also positively correlated with serum creatinine in microalbuminurics. A significant inverse correlation was found between β2-microglobulin and GFR values in both microalbuminurics and normoalbuminurics.

Conclusions: Increased Cys C and β2-microglobulin in diabetics may be early indicators of incipient DN. The diagnostic accuracies of Cys C and β2-microglobulin are superior to that of serum creatinine in distinguishing between mild and moderately reduced GFR.

Key words

Type 2 diabetes - beta 2-microglobulin - cystatin C - diabetic nephropathy

References

  • 1 Abrahamson M, Olafsson I, Palsdottir A, Ulvsback M, Lundwall A, Jensson O, Grubb A. Structure and expression of the human cystatin C gene.  Biochem J. 1990;  268 287-294
    PubMedGoogle Scholar
  • 2 Bianchi C, Donadio C, Tramonti G, Consani C, Lorusso P, Rossi G. Reappraisal of serum beta2-microglobulin as marker of GFR.  Ren Fail. 2001;  23 419-429
    CrossrefPubMedGoogle Scholar
  • 3 Bökenkamp A, Domanetzki M, Zinck R, Schumann G, Byrd D, Brodehl J. Cystatin C - A new marker of glomerular filtration rate in children independent of age and height.  Pediatrics. 1998;  101 875-881
    CrossrefPubMedGoogle Scholar
  • 4 Coll E, Botey A, Alvarez L, Poch E, Quinto L, Saurina A, Vera M, Piera C, Darnell A. Serum cystatin C as a new marker for noninvasive estimation of glomerular filtration rate and as a marker for early impairment.  Am J Kidney Dis. 2000;  36 29-34
    CrossrefPubMedGoogle Scholar
  • 5 Donadio C, Lucchesi A, Ardini L, Ardini M, Giordani R. Cystatin C, β2-microglobulin, and retinol-binding protein as indicators of glomerular filtration rate: comparison with plasma creatinine.  J Pharm Biomed Anal. 2001;  24 835-842
    CrossrefPubMedGoogle Scholar
  • 6 Finney H, Newman D J, Price C P. Adult reference ranges for serum cystatin C, creatinine and predicted creatinine clearance.  Ann Clin Biochem. 2000;  37 49-59
    CrossrefPubMedGoogle Scholar
  • 7 Grubb A, Simonsen O, Storfelt G, Truedsson L, Thysell H. Serum concentration of cystatin C, factor D and beta 2-microglobulin as a measure of glomerular filtration rate.  Acta Med Scand. 1985;  218 499-503
    PubMedGoogle Scholar
  • 8 Hallab M, Gallois Y, Chatellier G, Rohmer V, Fressinaud P, Marre M. Comparison of reduction in microalbuminuria by enalapril and hydrocholorothiazide in normotensive patients with insulin dependent diabetes.  Brit Med J. 1993;  306 175-182
    PubMedGoogle Scholar
  • 9 Harmoinen A P, Kouri T T, Wirta O R, Lehtimaki T J, Rantalaiho V, Turjanmaa V M, Pasternack A I. Evaluation of plasma cystatin C as a marker for glomerular filtration rate in patients with type 2 diabetes.  Clin Nephrol. 1999;  52 363-370
    PubMedGoogle Scholar
  • 10 Henne V, Frei P, Bürgisser P. Beta2-microglobulin - a rapid and automated determination for a broad range of clinical applications.  Anticancer Res. 1997;  17 2915-2918
    PubMedGoogle Scholar
  • 11 Henskens Y M, Veerman E C, Nieuw Amerongen A V. Cystatins in health and disease.  Biol Chem Hoppe-Seyler. 1996;  377 71-86
    PubMedGoogle Scholar
  • 12 Jacobs C, Selwood N H. Renal replacement therapy for end-stage renal failure in France: Current status and evolutive trends over the last decade.  Am J Kidney Dis. 1995;  25 188-195
    PubMedGoogle Scholar
  • 13 Keevil B G, Kilpatrick E S, Nichols S P, Maylor P W. Biological variation of cystatin C. implications for the assessment of glomerular filtration rate.  Clin Chem. 1998;  44 1535-1539
    PubMedGoogle Scholar
  • 14 Konen J C, Shihabi Z K. Microalbuminuria and diabetes mellitus.  American Family Physician. 1993;  48 421-428
    PubMedGoogle Scholar
  • 15 Kyhse-Andersen J, Schmidt C, Nordin G, Andersson B, Nilsson-Ehle P, Lindstrom V, Grubb A. Serum cystatin C, determined by a rapid, automated particle-enhanced turbidimetric method, is a better marker than serum creatinine for glomerular filtration rate.  Clin Chem. 1994;  40 1921-1926
    PubMedGoogle Scholar
  • 16 Larsen K. Creatinine assay by a reaction-kinetic approach.  Clin Chim Acta. 1972;  41 209-217
    CrossrefPubMedGoogle Scholar
  • 17 Mathiesen E R, Oxenbøll B, Johansen K, Svendsen P A, Deckert T. Incipient nephropathy in type 1 (insulin dependent) diabetes.  Diabetologia. 1984;  26 406-410
    PubMedGoogle Scholar
  • 18 Mogensen C E, Schimitz O. The diabetic kidney: from hyperfiltration and microalbuminuria to end-stage renal failure.  Medicine Clinicals of North America. 1988;  72 1465-1492
    PubMedGoogle Scholar
  • 19 Mojiminiyi O A, Abdella N, George S. Evaluation of serum cystatin C and chromogranin A as markers of nephropathy in patients with type 2 diabetes mellitus.  Scand J Clin Lab Invest. 2000;  60 483-489
    PubMedGoogle Scholar
  • 20 Mussap M, Dalla Vestra M, Fioretto P, Saller A, Varagnolo M, Nosadini R, Plebani M. Cystatin C is a more sensitive marker than creatinine for the estimation of GFR in type 2 diabetic patients.  Kidney Int. 2002;  61 1453-1461
    CrossrefPubMedGoogle Scholar
  • 21 Newman D J, Thakkar H, Edwards R G, Wilkie M, White T, Grubb A O, Price C P. Serum cystatin C measured by automated immunoassay: A more sensitive marker of changes in GFR than serum creatinine.  Kidney Int. 1995;  47 312-318
    PubMedGoogle Scholar
  • 22 Nolte S, Mueller B, Pringsheim W. Serum α1-microglobulin and beta2-microglobulin for the estimation of fetal glomerular renal function.  Pediatr Nephrol. 1991;  5 573-577
    CrossrefPubMedGoogle Scholar
  • 23 Oberbauer R, Nenov V, Weidekamm C, Haas M, Szekeres T, Mayer G. Reduction in mean glomerular pore size coincides with the development of large shunt pores in patients with diabetic nephropathy.  Exp Nephrol. 2001;  9 49-53
    CrossrefPubMedGoogle Scholar
  • 24 Oddoze C, Morange S, Portugal H, Berland Y, Dussol B. Cystatin C is not more sensitive than creatinine for detecting early renal impairment in patients with diabetes.  Am J Kidney Dis. 2001;  38 310-316
    PubMedGoogle Scholar
  • 25 Payne R B. Creatinine clearance: a redundant clinical investigation.  Ann Clin Biochem. 1986;  23 243-250
    PubMedGoogle Scholar
  • 26 Perrone R D, Madias N E, Levey A S. Serum creatinine as an index of renal function: new insights into old concepts.  Clin Chem. 1992;  38 1933-1953
    PubMedGoogle Scholar
  • 27 Piwowar A, Knapik-Kordecka M, Buczynska H, Warwas M. Plasma cystatin C concentration in non-insulin-dependent diabetes mellitus: relation with nephropathy.  Arch Immunol Ther Exp (Warsz). 1999;  47 327-331
    PubMedGoogle Scholar
  • 28 Reddi A S. Glomerular and urinary glycosaminoglycans in diabetic rats.  Clin Chim Acta. 1990;  189 211-220
    CrossrefPubMedGoogle Scholar
  • 29 Schardijn G HC, Statius van Eps L W. Beta 2-microglobulin: its significance in the evaluation of renal function.  Kidney Int. 1987;  32 635-641
    PubMedGoogle Scholar
  • 30 Schimitz A, Vaeth M, Mogensen C E. Systolic blood pressure relates to the rate of progression of albuminuria in NIDDM.  Diabetologia. 1994;  37 1251-1258
    PubMedGoogle Scholar
  • 31 Spencer K. Analytical reviews of clinical biochemistry: the estimation of creatinine.  Ann Clin Biochem. 1986;  23 1-25
    PubMedGoogle Scholar
  • 32 Swan S K. The search continues - an ideal marker of GFR.  Clin Chem. 1997;  43 913-914
    PubMedGoogle Scholar
  • 33 The Expert Committee on the Diagnosis and Classification of Diabetes Mellitus . Report of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus.  Diabetes Care. 1997;  20 1183-1197
    PubMedGoogle Scholar
  • 34 Vernier R L, Steffes M W, Sisson R S, Mauer S M. Heparan sulfate proteoglycan in the glomerular basement membrane in type I diabetes mellitus.  Kidney Int. 1992;  41 1070-1080
    PubMedGoogle Scholar

M. D. Zuhal Parildar

Department of Clinical Biochemistry
Ege University Faculty of Medicine

35100 Bornova · Izmir

Turkey

Email: zuhalp@med.ege.edu.tr

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