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Acute-Phase Markers of Inflammation and Glomerular Structure in Patients with Type 2 Diabetes

Michele Dalla Vestra^*, Michele Mussap, Pietro Gallina^*, Marino Bruseghin^*, Anna Maria Cernigoi, Alois Saller^*, Mario Plebani and Paola Fioretto^*

^* Department of Medical and Surgical Sciences and Department of Laboratory Medicine, University of Padova Medical School, Padova, Italy; and Diabetes Clinic, Monfalcone Hospital, Monfalcone, Italy

Address correspondence to: Dr. Paola Fioretto, Department of Medical and Surgical Sciences, University of Padova, Via Giustiniani 2, 35128 Padova, Italy. Phone: +39-049-8211879; Fax: +39-049-8212151; E-mail: paola.fioretto{at}unipd.it

Type 2 diabetes is frequently associated with an inflammatory status; the relationships between low-grade inflammation and diabetic nephropathy are still unclear. The aim of this study was to evaluate the relationships between acute-phase markers of inflammation, glomerular structure, and albumin excretion rate (AER) in type 2 diabetes. In 74 patients with type 2 diabetes (23 normoalbuminuric, 30 microalbuminuric, and 21 proteinuric) fibrinogen, serum amyloid A protein (SAA), C-reactive protein (CRP), and IL-6 were determined. AER was measured on three 24-h urine collections; GFR was measured by ⁵¹Cr EDTA plasma clearance. A kidney biopsy was performed, and mesangial fractional volume [Vv(mes/glom)] and glomerular basement membrane (GBM) width were estimated by electron microscopic morphometric analysis. CRP, fibrinogen, SAA, and IL-6 differed among groups, with proteinuric patients having the highest levels. SAA and fibrinogen correlated with AER (P < 0.03 and P < 0.001, respectively). GBM width and Vv(mes/glom) increased from normoalbuminuric to proteinuric patients [P < 0.005 normoalbuminuric and microalbuminuric versus proteinuric for GBM, P < 0.01 normoalbuminuric versus proteinuric for Vv(mes/glom)]. In patients with increased GBM width (>396 nm), CRP, SAA, and IL-6 were higher than in patients with normal GBM width (P < 0.003, P < 0.004, and P < 0.0004, respectively). GBM width was directly correlated with fibrinogen (r = 0.33, P < 0.002) and IL-6 (r = 0.25 P < 0.05). In conclusion, this study demonstrates that acute-phase markers of inflammation are associated with nephropathy status and GBM thickening, suggesting a role for inflammation in the pathogenesis of diabetic glomerulopathy.

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Copyright © 2008 by the American Society of Nephrology. Online ISSN: 1533-3450 Print ISSN: 1046-6673