Assessment of the diagnostic value of different biomarkers in relation to various stages of diabetic nephropathy in type 2 diabetic patients

Abstract

Albuminuria is widely used to indicate early phases of diabetic nephropathy although it is limited by the fact that structural damage might precede albumin excretion. This necessitates identifying better biomarkers that diagnose or predict diabetic nephropathy. This is a cross-sectional hospital based study recruiting type 2 diabetic patients cohort aged 35–75 years with diabetes duration of ≥10 years. Out of total eligible 467 patients, 200 patients were with normal albumin excretion, 184 patients with microalbuminuria and 83 patients with macroalbuminuria. All the patients were tested for the 22 selected biomarkers including serum, plasma and urinary markers. Sensitivity, specificity, and area under the curve (AUC) were calculated as measures of diagnostic accuracy. Out of the tested biomarkers, urinary transferrin, urinary Retinol binding protein (RBP) and serum osteopontin had the best diagnostic value for diabetic nephropathy presence based on the AUC value. The rest of the biomarkers had comparatively less or even no discriminative power. The urinary transferrin and RBP and serum osteopontin, had the best diagnostic value in type 2 diabetic patients at different stages of diabetic nephropathy. Further longitudinal prospective studies are needed to evaluate the predictive power of those markers for detecting diabetic nephropathy before any structural damage occurs.

The association between thyroid dysfunction (TD) and diabetic kidney disease (DKD) in type 2 diabetes mellitus (T2DM)

“…Therefore, RBP is a useful biomarker for tracking proximal tubular dysfunction in early DKD. 28,33,34 In this study, non-parametric tests showed that urinary UACR and TRF (glomerular injury markers) were higher and urinary THP (tubular damage marker) was lower in T2DM patients with hypothyroidism compared with other groups. Both urinary IgG and RBP levels were increased in the hypothyroidism group, but no significant differences in urinary IgG and RBP were observed among different thyroid function groups.…”

“…RBP is a carrier protein with low molecular weight (21 kDa) that binds to retinol and can be freely filtered through the glomerular barrier and almost completely reabsorbed in the proximal tubule. Therefore, RBP is a useful biomarker for tracking proximal tubular dysfunction in early DKD . In this study, non‐parametric tests showed that urinary UACR and TRF (glomerular injury markers) were higher and urinary THP (tubular damage marker) was lower in T2DM patients with hypothyroidism compared with other groups.…”

“…Urinary TRF is significantly increased in T2DM patients, as demonstrated based on biopsy‐proven glomerular diffuse lesions, which can be observed even before the detection of microalbuminuria . Urinary TRF is also a robust diagnostic biomarker for renal damage at different stages of DKD in T2DM patients . IgG is another marker for assessing glomerular damage.…”

“…26,27 Urinary TRF is also a robust diagnostic biomarker for renal damage at different stages of DKD in T2DM patients. 28 IgG is another marker for assessing glomerular damage. Because of its large size (molecular weight: 150 kDa), IgG only crosses the glomerular barrier with difficulty.…”

Diabetic nephropathy in type 2 diabetes – from pathological mechanisms to clinical occupational medicine practice

“…Other tests included in the yearly T2D evaluation are the lipid profile, liver tests, vitamin B12 in metformin treated patients, serum potassium in patients treated with ACE inhibitors, angiotensin receptor II blockers and diuretics [26]. It is foreseen that one or several more subtle parameters for glomerular filtration (urine transferrin, fibronectin, laminin, ceruloplasmin), podocyte injury (nephrin, podocalyxin, podocin), glomerulo-endothelial injury (glycoaminoglycan), tubular reabsorption, (cubilin, megalin, β2microglobulin, α1 microglobulin, retinol binding protein, cystatin C), tubular integrity (urine alkaline phosphatase, N-acetylglucosaminidase, alanin aminopeptidase, kidney injury molecule, type IV and type I collagen, matrix metalloproteinase 9), inflammation (PGE2 or PGF2α, TNFα, Interleukin 6, resistin, interleukin 1α, MCP-1 among others), oxidative stress (8-oxo-7,8-dihydro-2-deoxyguanosine), growth factors (transforming growth factor β1, vascular endothelial growth factor A, connective tissue growth factor) [24,28,29,30] will replace the current screening tests, as they are able to detect the kidney disease in earlier stages. Transferrin excretion is another candidate, as it was proven to proceed albuminuria in a larger cohort [31].…”