We examined type IV collagen distribution and density in human diabetic kidneys by quantitative immunogold electron microscopy. We studied normal kidney transplant donors and 'slow-track' and 'fast-track' insulin dependent diabetic (IDDM) patients. The 'slow-track' patients had IDDM for ≥ 20 years and mesangial volume fraction (VvMes/glom) of ≤ 0.32. The 'fast-track' patients had IDDM for ≤ 20 years and VvMes/glom ≥ 0.37. Renal biopsies were embedded in Lowicryl, reacted with polyclonal anti-type IV collagen (in the distribution of the classical α1(IV) and α2(IV) collagen chains) and monoclonal anti-α4(IV) collagen chain antibody followed by gold conjugated secondary antibody. We found, by morphometric techniques, a decrease in the immunogold densities of anti-type IV collagen in the subendothelial zone of the GBM in the 'fast-track' IDDM patients. There was a trend towards a decrease in mesangial matrix (MM) particle density in the 'fast-track' (P = 0.07) but not in the 'slow-track' patients. However, because of the marked increase in MM in the 'fast-track' patients, the per glomerulus estimated quantity of these antigens in MM was increased. In contrast, the density of α4(IV) collagen chain was increased in the epithelial zone of the GBM in the 'fast-track' IDDM patients. It is not known whether these changes in glomerular type IV collagen represent markers of advanced diabetic lesions or whether these changes might be detected earlier in diabetic patients destined for the later development of serious lesions.
Bibliographical noteFunding Information:
This work was supported by grants DK-13083 and DK-43605 from the National Institutes of Health and Grant #191366 and #189946 from the Juvenile Diabetes Foundation International. Dr. Dan Zhu is a Fellow of
the Juvenile Diabetes Foundation International and was recipient of a grant from the American Diabetes Association, Minnesota Affiliate. The authors thank Drs. Alfred F. Michael and Mary Kleppel for the kind donation of monoclonal antibodies for these studies. We are grateful to Dr. Ruth sterby for her advice regarding measurements of particle density. We appreciate the secretarial assistance of Ms. Cyn-thia Dawis.