Review of early circulating biomolecules associated with diabetes nephropathy - Ideal candidates for early biomarker array test for DN

BACKGROUND: Diabetic nephropathy (DN) is one of the catastrophic complications of type 2 diabetes mellitus (T2DM). 45% of DN patients progressed to End Stage Renal Disease (ESRD) which robs casualties of the quality of live. The challenge in early diagnosis of DN is it is asymptomatic in the early phase. Current gold standard test for screening and diagnosis of DN are nonspecific and are not sensitive in detecting DN early enough and subsequently monitor renal function during management and intervention plans. Recent studies reported various biomolecules which are associated with the onset of DN in T2DM using cutting-edge technologies. These biomolecules could be potential early biomarkers for DN. This review selectively identified potential early serum biomolecules which are potential candidates for developing an Early Biomarker Array Test for DN.

METHODS: An advanced literature search was conducted on 4 online databases. Search terms used were "Diabetes Mellitus, Type 2", "Diabetic nephropathy", "pathogenesis" and "early biomarker. Filters were applied to capture articles published from 2010 to 2020, written in English, human or animal models and focused on serum biomolecules associated with DN.

RESULTS: Five serum biomolecules have been evidently described as contributing pivotal roles in the pathophysiology of DN. MiR-377, miR-99b, CYP2E1, TGF-β1 and periostin are potential candidates for designing an early biomarker array for screening and diagnosis of early stages of DN. The five shortlisted biomolecules originates from endogenous biochemical processes which are specific to the progressive pathophysiology of DN.

CONCLUSION: miR-377, miR-99b, CYP2E1, TGF-β1 and periostin are potential candidate biomolecules for diagnosing DN at the early phases and can be developed into a panel of endogenous biomarkers for early detection of DN in patients with T2DM. The outcomes of this study will be a stepping stone towards planning and developing an early biomarker array test for diabetic nephropathy. The proposed panel of early biomarkers for DN has potential of stratifying the stages of DN because each biomolecule appears at distinct stages in the pathophysiology of DN.