In this study, sol-gel processing was proposed to prepare a creatinine (Cre)-imprinted molecularly imprinted polymer (MIP). The intermolecular interaction constituted by the cross-linkers, i.e., 2-acrylamido-2-methylpropane-sulfonic acid (AMPS) and aluminium ion (Al3+), was studied and compared in order to form a confined matrix that promises the effectiveness of molecular imprinting. In view of the shape recognition, the hydrogen bonded Cre-AMPS did not demonstrate good recognition of Cre, with Cre binding found only at 5.70 +/- 0.15 mg g(-1) of MIP. Whilst, MIP cross-linked using Al3+ was able to attain an excellent Cre adsorption capacity of 19.48 +/- 0.64 mg g(-1) of MIP via the stronger ionic interaction of Cre-Al3+. Based on the Scatchard analysis, a higher Cre concentration in testing solution required greater driving force to resolve the binding resistance of Cre molecules, so as to have a precise Cre binding with shape factor. The molecular recognition ability of Cre-MIP in present work was shape-specific for Cre as compared to its structural analogue, 2-pyrrolidinone (2-pyr), by an ideal selectivity coefficient of 6.57 +/- 0.10. In overall, this study has come up with a practical approach on the preparation of MIP for the detection of renal dysfunction by point-of-care Cre testing. (C) 2016 Elsevier B.V. All rights reserved.