Overt proteinuria is a hallmark of diabetic nephropathy while microalbuminuria is thought to be a predictor of later onset of diabetic nephropathy. Yet the mechanisms for abnormal urinary protein leak in diabetes have not been defined. We studied 28 patients with type I diabetes for 7 to 33 years. Creatinine clearance, urinary albumin excretion rate (UAE), and multiple blood pressures were obtained in each patient. A renal biopsy was performed in each patient and in 28 normal subjects. Quantitative stereology was used to determine foot process (FP) width, filtration slit length density (FSL(V)) and filtration slit length/glomerulus (FSL(G)). FP width was slightly wider than normal in diabetic patients with UAE <250 mg/24 hr while FP was significantly wider than both of these groups in diabetic with UAE >250 mg/24 hr. FSL(V) and FSL(G) were similar in normals and diabetics with UAE <250 mg/24 hr but both were reduced in diabetics with UAE >250 mg/24 hr. UEA correlated with FP width (P < 0.05), FSL(G) (P < 0.01) and most precisely and FSL(V) (P < 0.001). Diabetics with microalbuminuria had values for all the structural parameters measured here not different from diabetics with UAE in the normal range. Perturbations of epithelial cell structure are present in diabetes mellitus especially in patients with nephropathy. The exact relationships between albuminuria and epithelial cell structure remains to be elucidated.
Bibliographical noteFunding Information:
grants AM07087 and AMO1OI4 and the Viking Children's Fund. The authors thank Thomas Groppoli and Frank Strgar for expert technical assistance, Rai Smith for preparation of the manuscript, and Marshall
Acknowledgments This work was supported in part by National Institutes of Health