Glomerular type IV collagen in patients with diabetic nephropathy with andwithout additional glomerular disease

Background. Type IV collagen is a constituent of mesangial matrix and is in creased in amount in many forms of glomerular injury. Methods. We performed renal biopsies in patients who (1) were donating a ki dney to a relative (LRD, N = 6), (2) had diabetic glomerulopathy with or wi thout nephrosclerosis (DM, N = 6), or (3) had diabetic glomerulopathy with a superimposed glomerular lesion (DM+, N = 5). Glomerular collagen alpha 2( IV) and control glyceraldehyde-3-phosphate dehydrogenase (GAPDH) mRNAs were measured, and the former correlated with clinical and morphological data t o assess its usefulness in reflecting glomerular injury. Results. Collagen alpha 2(IV) mRNA levels were lowest in LRD (2.9 +/- 0.6 a ttomol/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 GAPD H mRNA levels were not significantly different (P > 0.05). Levels of protei nuria, serum creatinine, and glomerular size did not correlate with collage n alpha 2(IV) mRNA levels. The fractional mesangial area and the fractional mesangial area occupied by type IV collagen were higher in both diabetic g roups than in LRD (P < 10(-6)), but the intensity of type IV collagen stain ing in the diabetic patients was significantly less than that seen in the L RD (P < 0.01). In DM+ patients, extramesangial type IV collagen was present . Fractional mesangial area and glomerular collagen alpha 2(IV) mRNA levels correlated (r = 0.45, P < 0.05). Conclusion. These data are consistent with a view of diabetic nephropathy a s a lesion of increased alpha 2 type IV collagen transcription, increased t otal amount of collagen present, but decreased mesangial density relative t o other matrix molecules. These data further demonstrate that glomerular in jury superimposed on diabetic nephropathy contributes to additional structu ral damage by inducing increased synthesis of type IV collagen at extramesa ngial sites.