Glomerular type IV collagen in patients with diabetic nephropathy with and without additional glomerular disease

Background. Type IV collagen is a constituent of mesangial matrix and is increased in amount in many forms of glomerular injury. Methods. We performed renal biopsies in patients who (1) were donating a kidney to a relative (LRD, N = 6), (2) had diabetic glomerulopathy with or without nephrosclerosis (DM, N = 6), or (3) had diabetic glomerulopathy with a superimposed glomerular lesion (DM+, N = 5). Glomerular collagen α2(IV) and control glyceraldehyde- 3-phosphate dehydrogenase (GAPDH) mRNAs were measured, and the former correlated with clinical and morphological data to assess its usefulness in reflecting glomerular injury. Results. Collagen α2(IV) mRNA levels were lowest in LRD (2.9 ± 0.6 attomol/glomerulus), higher in DM (5.9 ± 1.6, P = 0.05), and highest in DM+ (12.7 ± 2.8 attm/glomerulus, P < 0.05 vs. LRD and vs. DM). Control GAPDH mRNA levels were not significantly different (P > 0.05). Levels of proteinuria, serum creatinine, and glomerular size did not correlate with collagen α2(IV) mRNA levels. The fractional mesangial area and the fractional mesangial area occupied by type IV collagen were higher in both diabetic groups than in LRD (P < 10^-6), but the intensity of type IV collagen staining in the diabetic patients was significantly less than that seen in the LRD (P < 0.01). In DM+ patients, extramesangial type IV collagen was present. Fractional mesangial area and glomerular collagen α2(IV) mRNA levels correlated (r = 0.45, P < 0.05). Conclusion. These data are consistent with a view of diabetic nephropathy as a lesion of increased α2 type IV collagen transcription, increased total amount of collagen present, but decreased mesangial density relative to other matrix molecules. These data further demonstrate that glomerular injury superimposed on diabetic nephropathy contributes to additional structural damage by inducing increased synthesis of type IV collagen at extramesangial sites.