Evaluation of cystatin C and beta-2 microglobulin as markers of renal function in patients with type 2 diabetes mellitus.
BACKGROUND
Despite recent studies showing that serum cystatin C (CC) is a better marker for GFR than the ubiquitously used serum creatinine, its clinical utility remains under evaluation.


METHODS
To evaluate their usefulness in patients with type 2 diabetes mellitus (DM), serum concentrations of CC, beta-2 microglobulin (B2M) and creatinine were measured in 105 (38 males, 67 females) Kuwaiti patients with type 2 DM. The results were compared with creatinine clearance (Ccr), which was measured (mCcr) and estimated (eCcr) with the Cockroft-Gault formula, and correlated with 24-h urine protein and early morning urine albumin/creatinine excretion ratio.


RESULTS
In patients with eCcr and mCcr results (n=51), eCcr and mCcr showed significant correlation with each other (r's=.86, P<.0001) with no significant difference between the two. In all patients (n=105), CC and B2M showed significant correlation with each other (r's=.82, P<.0001) and with serum creatinine concentration (r's=.77 and.84, respectively, P<.0001). Serum CC, B2M and creatinine showed significant (P<.001) inverse correlation with eCcr (r's=-.63, -.61 and -.76, respectively). Partial correlations after correcting for age and sex improved the correlation of serum creatinine with eCcr (r=-.81, P<.0001), but there was no significant change in the correlations of CC and B2M with eCcr (r=-.65, P<.0001 and r=-.62, P<.0001, respectively). Receiver operating characteristic (ROC) plots for serum CC, B2M and creatinine for detection of changes in the eCcr showed that the area under the ROC curve+/-S.E. is 0.897+/-0.119 for CC, 0.871+/-0.091 for B2M and 0.785+/-0.087 for serum creatinine. There was no statistically significant difference between the areas under the curve (AUC) for serum creatinine and CC (P=.07) and B2M (P=.12). CC had the highest sensitivity for detection of eCcr (<60 ml/min/1.73 m(2)) at routinely used cutoff values. CC was also the best discriminator when patients with normoalbuminuria were compared with patients with microalbuminuria.


CONCLUSIONS
Although there is no significant difference in the overall diagnostic accuracies of CC, B2M and creatinine for the detection of changes in the GFR, CC is the most sensitive marker at routinely used cutoff values and would be more clinically useful than B2M or serum creatinine in diabetic patients.
Department of Pathology, Faculty of Medicine, Kuwait University, PO Box 24923, Safat code 13110, Kuwait. segunade@yahoo.com
Olusegun A
OA
Mojiminiyi
Nabila
N
Abdella
D000419:Albuminuria; D015415:Biomarkers / Q000097:blood; D001794:Blood Pressure; D015992:Body Mass Index; D001830:Body Surface Area; D003404:Creatinine / Q000097:blood / Q000652:urine; D055316:Cystatin C; D015891:Cystatins / Q000032:analysis*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000503:physiopathology; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007677:Kidney Function Tests; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D012016:Reference Values; D012680:Sensitivity and Specificity; D001613:beta 2-Microglobulin / Q000032:analysis*
D015415:Biomarkers; D003404:Creatinine; D055316:Cystatin C; D015891:Cystatins; D006442:Glycated Hemoglobin; D001613:beta 2-Microglobulin; C525030:CST3 protein, human