TABLE 2.

Clinical association of hemorheological properties with diabetic nephropathy.

	Alteration of hemorheological properties
Diabetic mellitus	[Deformability] - Impaired deformability in T2DM - Hyperglycemia-induced glycation and oxidation (Resmi et al., 2005) - formation of advanced glycation end-products (AGEs) including HbA1c - increased internal fluid viscosity & reduced membrane fluidity (Watala et al., 1985; Linderkamp et al., 1999) [Aggregation] - Increased aggregation in T2DM - reduced charges in RBC membrane (sialic acid moieties of glycoproteins) - increased fibrinogen level and decreased albumin in T2DM lead to synergistic increase of RBC aggregation - (Angelkort, 1999; Vayá et al., 2011; Li et al., 2015; Mahendra et al., 2015)
Diabetic Nephropathy	[Pre-clinical studies] - No reports on sensitivity, specificity and ROC curve analysis - most reported decreased RBC deformability for human subjects: Kikuchi et al. (1982), [opetwcite]B97,B87[clotwcite]Zimmermann et al. (1996); Sotirakopoulos et al. (2004), Brown et al. (2005), Shin et al. (2007b), Saito et al. (2011) - rare report on RBC aggregation for human subjects - Lee et al. (2015): T2DM at 4 stages of CKD (n = 105), decreased RBC deformability, increased AI, CSS, fibrinogen, ACR (p < 0.05)
	[Clinical studies] (1) Lee et al. (2018) - proposed [fibrinogen × ESR/EI], as a newly proposed diagnostic index of DN - a significant difference at all stages of DN classified according to the GFR - moderate sensitivity (74.5%), specificity (63.1%) and AUC of ROC curve (0.762) - No significant difference of RBC deformability alone to the degree of DN (2) Chung et al. (2018) - significantly higher CSS in patients with DN than in those without DN (p < 0.001) - CSS cut-off value: 312.67 mPa - moderate sensitivity (60.2%), specificity (60.3%) and AUC (0.635) - No significant difference of RBC deformability alone to the degree of DN