Serum amyloid A enrichment impairs the anti-inflammatory ability of HDL from diabetic nephropathy patients.

Aims: Impaired anti-inflammatory ability of high-density lipoprotein (HDL) has been demonstrated in patients with type-2 diabetes mellitus (T2DM). However, whether HDL from patients with diabetic nephropathy (DN) suffers additional damage remains unknown. This study compared the anti-inflammatory capacities of HDL from healthy controls, T2DM patients with normal renal function, and T2DM patients with DN.

Materials And Methods: HDL was isolated from healthy controls (n=33) and T2DM patients with normal renal function (n=21), chronic kidney disease (CKD) (n=27), and end-stage renal disease (ESRD) (n=27). Human peripheral blood mononuclear cells (PBMCs) from healthy volunteers were pretreated with HDL (100μg/mL) for 1h, then incubated with lipopolysaccharide (LPS) (50ng/mL) for 24h. The anti-inflammatory ability of HDL was measured as the secretion of TNF-α in LPS-activated monocytes.

Results: The anti-inflammatory ability of HDL was gradually impaired as kidney function declined. Serum amyloid A (SAA) concentration in HDL significantly increased and was positively correlated with the impaired anti-inflammatory ability of HDL (Pearson r=0.315, P=0.006). Furthermore, HDL supplemented with SAA significantly increased TNF-α release from PBMCs compared with that from control HDL.

Conclusions: These findings identified an impaired anti-inflammatory capacity of HDL from DN patients, which might be attributable to SAA enrichment.