Mesangial accumulation of GA-pyridine, a novel glycolaldehyde-derived AGE, in human renal disease.
BACKGROUND
Advanced glycation end products (AGEs) contribute to diabetic and atherosclerotic end-organ damage, but the mechanisms of AGE-formation and AGE-induced damage are unclear. Glycolaldehyde (GA) is a Maillard-reaction intermediate and can be formed by reaction of L-serine with the myeloperoxidase-system. GA reacts with proteins to form AGEs, such as GA-pyridine, which is specific for protein modification by GA. GA-pyridine accumulates in human atherosclerotic lesions. As atherosclerosis and progressive glomerulosclerosis share many similarities, we hypothesized that GA-pyridine accumulates in renal diseases, especially those with prominent mesangial involvement.


METHODS
Paraffin-embedded renal biopsies from 55 patients with various renal diseases, as well as control tissue, obtained from the unaffected part of kidneys from 10 patients with renal cell carcinoma were immunohistochemically stained with a monoclonal antibody directed against GA-pyridine and were scored semiquantitatively. Additional sections were scored for mesangial matrix expansion (MME) and focal glomerular sclerosis (FGS).


RESULTS
In normal human kidneys, GA-pyridine was mainly localized in tubular epithelial cells, but not in the glomerular mesangium. Significant mesangial GA-pyridine accumulation was found in disorders with mesangial involvement as a common denominator. In contrast, mesangial GA-pyridine accumulation was less prominent in renal diseases without prominent mesangial involvement. Moreover, mesangial GA-pyridine accumulation was more pronounced in kidneys with higher MME and FGS scores across the different diagnoses.


CONCLUSIONS
GA-pyridine accumulates in the mesangium in human renal disease, in particular in disorders with mesangial involvement. Further studies should elucidate whether mesangial GA-pyridine plays a role in the progression of glomerular damage.
Greven
Wendela L
WL
Department of Pathology and Laboratory Medicine, and Department of Nephrology, University Medical Center Groningen, Groningen, The Netherlands.
Waanders
Femke
F
Nagai
Ryoji
R
van den Heuvel
Marius C
MC
Navis
Gerjan
G
van Goor
Harry
H
D000079:Acetaldehyde / Q000031:analogs & derivatives* / Q000378:metabolism; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001706:Biopsy; D002648:Child; D002675:Child, Preschool; D003928:Diabetic Nephropathies / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005920:Glomerular Mesangium / Q000378:metabolism / Q000473:pathology; D017127:Glycation End Products, Advanced / Q000378:metabolism*; D006801:Humans; D007684:Kidney Tubules / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009195:Peroxidase / Q000378:metabolism; D011725:Pyridines / Q000378:metabolism*
D017127:Glycation End Products, Advanced; D011725:Pyridines; D009195:Peroxidase; D000079:Acetaldehyde; C023666:pyridine; C010972:glycolaldehyde