Tubular atrophy and interstitial fibrosis, important in progression of renal diseases, including diabetic (D) and cyclosporine-induced (CSA) nephropathy, have been considered irreversible. Normoglycemia for 10 years following pancreas transplantation alone (PTA) reversed D glomerulopathy lesions. This study quantified tubular, interstitial, and arteriolar parameters in PTA recipients. Kidney function studies and biopsies were performed in eight non-uremic type I D patients (pts) at 5 and 10 years after PTA. Renal biopsies were analyzed by morphometric analysis. All pts were normoglycemic and insulin independent and received CSA during the study. Cortical interstitial volume fraction was increased at 5 years (0.31 ± 0.07 vs normal 0.15 ± 0.02, P < 0.01) and decreased at 10 years post-PTA (0.23 ± 0.03, P < 0.02 vs 5 years). There was a reduction in the volume fraction of interstitial collagen and cells per cortical tissue, measured using electron microscopy, from 5 (0.126 ± 0.061 and 0.103 ± 0.026, respectively) to 10 years (0.079 ± 0.031, P < 0.05, and 0.074 ± 0.018, P < 0.05, respectively). The volume fraction of tubules which were atrophic (AT) was abnormal at 5 years (0.160 ± 0.090) and decreased from 5 to 10 years (0.044 ± 0.034, P < 0.02), apparently due to AT reabsorption. The index of arteriolar hyalinosis did not change during the study (1.30 ± 0.22 and 1.34 ± 0.33 at 5 and 10 years, respectively, nonsignificant). This study demonstrates, for the first time in humans, that interstitial expansion is reversible and that atrophic tubules can be reabsorbed. In contrast, there was no improvement in the arteriolar lesions. Whether this is due to long-term normoglycemia, reduction of CSA dose or other mechanisms is unclear.
Bibliographical noteFunding Information:
This work was supported by grants from the National Institutes of Health (DK13083), the National Center for Research Resources (MO1-KK00400), and by an endowment from the Kroc Research Foundation. During the initial stages of this work, Dr Fioretto was supported by Research Fellowship and Career Development Awards from the Juvenile Diabetes Foundation International. We are grateful to Ms Susan Sisson-Ross for excellent technical assistance, and Dr Maria Luiza A Caramori for help with the statistical analyses. We are indebted to the patients who generously participated in these studies.
- Diabetic nephropathy; cyclosporine nephrotoxicity
- Interstitial fibrosis
- Morphometric analysis
- Pancreas transplantation
- Tubular atrophy