Proximal tubular basement membrane width in insulin-dependent diabetes mellitus. Although glomerular structure has been studied, careful evaluation of tubular basement membrane (TBM) structure in diabetes in humans has not been done. We measured proximal TBM width, glomerular basement membrane (GBM) width, mesangila fractional volume [Vv(Mes/glom)], mesangial matrix fractional volume [Vv(MM/glom)], and cortical interstitial fractional volume [Vv(Int/cortex)] in 35 insulin-dependent diabetic (IDDM) patients and 20 controls. The patients' mean age was 28 ± 10 years (V̇ ± SD) and IDDM duration was 17 ± 8 years. Twenty-five patients were normoalbuminuric, four microalbuminuric, and six had overt proteinuria. Tubular basement membrane and GBM widths were measured by the orthogonal intercept method and mesangial and interstitial parameters by point counting. The TBM width was 915 ± 320 nm in IDDM patients and 558 ± 116 nm in controls (P = 0.0005); the TBM width was also increased in normoalbuminuric patients (849 ± 297 nm, P = 0.0005). The TBM width was strongly directly related to GBM width (r = 0.67, P < 0.001), Vv(Mes/glom) (r = 0.52, P < 0.01), and Vv(MM/glom) (r = 0.61, P < 0.001), but only weakly to Vv(Int/cortex) (r = 0.29, NS). The TBM width (r = 0.65, P < 0.001) and GBM width (r = 0.65, P < 0.001) were strongly related to hemoglobin A1C (HbA1C), while the Vv(Mes/glom) (r = 0.35, P < 0.05) and Vv(Int/cortex) (r = 0.30, NS) were only weakly related to HbA1C. Thus, increased proximal TBM width is an integral component of early nephropathology in IDDM patients. This study suggests that the metabolic disturbances of diabetes are strong determinants of the constellation of structural abnormalities occurring in human diabetic nephropathy.
Bibliographical noteFunding Information:
This work was supported by grants from the National Institutes of Health (#DK13083), the National Center for Research Resources (#M01-RR00400), and the Juvenile Diabetes Foundation International. Dr. Paola Fioretto is supported by a Juvenile Diabetes Foundation International Career Development Award. We thank Ms. Susan Sisson-Ross for her technical help and Ms. Grace Mwawasi for performing some of the statistical analyses and Drs. Samy Suissa and Michael Kramer for their helpful advice regarding this manuscript. We appreciate the secretarial assistance of Sandy Cragg. We greatly appreciate the willingness of the diabetic patients and the renal transplant donors to volunteer for these research kidney biopsies.
- Diabetic nephropathy
- Renal tubule
- Tubular basement membrane