Serum amyloid A and C-reactive protein levels may predict microalbuminuria and macroalbuminuria in newly diagnosed type 1 diabetic patients

Abstract

Background: In this study we evaluated the association of baseline levels of six different candidate proteins for the development of microalbuminuria and macroalbuminuria in type 1 diabetic patients, who were followed for approximately 30 years. Two of the proteins are markers of inflammation: serum amyloid A (SAA) and C-reactive protein (CRP), three are involved in lipid metabolism: apolipoprotein A1, apolipoprotein E and adiponectin and the last protein, fibronectin, is related to structural changes.

Methods: A nested case control study population of 60 patients from an inception cohort of type 1 diabetic patients where 20 developed microalbuminuria followed by macroalbuminuria and 40 stayed normoalbuminuric during approximately 30 years of follow-up time was used to evaluate baseline levels of the six candidate biomarkers. The proteins were quantified by multiplexed immunoassays.

Results: Log SAA levels were borderline predictor of microalbuminuria, HR 2.31 (1-5.4) p=0.053 in a univariate Cox regression model and predicted the development of macroalbuminuria HR 2.432 (1-6) p=0.049, also univariate. When adjusting for covariates, log SAA predicted the development of microalbuminuria with an HR 4.131 (1.1-15) p=0.03. Log CRP predicted the development of microalbuminuria, HR 2.928 (1.4-6.1) p=0.004, and macroalbuminuria, HR 2.785 (1.3-5.8) p=0.007 in univariate models. When adjusting for covariates, log CRP predicted the development of microalbuminuria with an HR 5.882 (1.7-20.9) p=0.006 and macroalbuminuria with an HR 3.233 (1.1-9.8) p=0.038. Apolipoprotein A1, apolipoprotein E, fibronectin and adiponectin were not associated with development of elevated albumin excretion rate.

Conclusions: SAA and CRP baseline levels predicted development of micro- and macroalbuminuria during 30 years of follow up, supporting the theory that inflammation is involved in the progression of diabetic nephropathy. Further studies are needed to fully establish the two proteins' potential as additional biomarkers for the development of diabetic nephropathy.