Glycoxidative modification of AA amyloid deposits in renal tissue

Background. N-epsilon-carboxymethyllysine (CML) is a product of the oxidati ve modification of glycated proteins, which damages proteins with ageing, d iabetes, uraemia and Alzheimer's disease. In contrast, pyrraline is one of the advanced glycation end products, which is independent of oxidative proc esses. CML has been identified in beta-amyloid of Alzheimer's disease and b eta(2)-microglobulin-associated amyloid. We investigated whether CML and py rraline are formed in AA and AL amyloid of the kidney. Method. Renal specimens from 19 cases of AA amyloidosis and 14 cases of AL amyloidosis were investigated for immunolocalization of CML, pyrraline, col lagen type IV and laminin in amyloid deposits. Renal biopsies of 10 age-mat ched cases with thin basement membrane disease and normal renal function we re used as controls. The fractional areas of amyloid, CML, laminin and coll agen IV in glomeruli and interstitium (%amyloid, %CML, %laminin and %collag en, respectively) were calculated using the point counting method. The corr elation between these parameters was evaluated using Spearman's rank correl ation test. Results. CML colocalized with AA amyloid, but not AL amyloid, except in two cases of the latter with a long history of nephropathy exceeding 14 years. In contrast, pyrraline was not observed in either type of amyloid. Mean %C ML in AA amyloid was significantly higher than %collagen and %laminin in gl omeruli and interstitium, indicating that AA amyloid is modified by CML ind ependent of colocalized extracellular matrix. %CML significantly correlated with %amyloid both in glomeruli and interstitium in AA amyloidosis. AL amy loid cases with a long history of nephropathy showed positive staining for CML in glomeruli and interstitium but no staining for collagen IV and lamin in in amyloid deposits. Conclusion. CML modification may occur in amyloid deposits of AA amyloidosi s, independent of extracellular matrix components. Glycoxidative modificati on may have a functional link to AA amyloid deposition in renal tissues.