Aims/hypothesis. Type 1 diabetes is an autoimmune disorder associated with T-cell mediated injury to multiple endocrine tissues. T-cell infiltration of the juxtaglomerular apparatus could be associated with changes in local renin angiotensin system activity and, thus, with changes in the renal microenvironment. We examined the frequency of juxtaglomerular apparatus T-cell infiltration early in Type 1 diabetes and tested whether this is associated with renal structure and function. Methods. We classified 89 Type 1 diabetic patients by immunohistochemical analysis as either juxtaglomerular apparatus T-cell positive (n=37) or T-cell negative (n=38). Borderline cases (n=14) were not considered further. Results. T-cell positive patients had a shorter duration of diabetes (6.7±2.5 years) than T-cell negative patients (9.2±5.0 years, p=0.011) and lower albumin excretion rate, but they had a similar glomerular filtration rate and blood pressure. Renal biopsy morphometric analysis showed similar glomerular basement membrane width and mesangial fractional volume in these two groups. However, glomerular capillary surface density (p=0.0012) and filtration surface per glomerulus (p=0.0155) were greater in the T-cell positive patients. Conclusion/Interpretation. Increased filtration surface per glomerulus could be associated with glomerular filtration rate preservation in diabetes. Thus, juxtaglomerular apparatus immunologic injury in Type 1 diabetes patients could delay the clinical consequences of diabetic nephropathy.
Bibliographical noteFunding Information:
Acknowledgements. This work was primarily supported by
grants from the Juvenile Diabetes Foundation International. Clinical studies in Minneapolis were supported by a General Clinical Research Center (GCRC) grant (M01-RR00400) from the National Center for Research Resources and the National Institutes of Health. Support was also provided by the Emma Howe Foundation and the Robert Palmer Fund. Dr. R. Moriya was supported by a Juvenile Diabetes Foundation International (JDFI) Research Fellowship Award. Dr. S. Suissa is the recipient of a Senior Scientist Award from the Medical Research Counsel of Canada. Mr. J. Basgen and Ms. S. Sisson-Ross performed the renal morphometry studies. Ms. S. Kupcho performed the urinary albumin measurements. Ms. J. Bucksa headed the clinical research laboratory. Ms. P. L. Erickson and J. Stein prepared this manuscript. Ms. T. Strand, M. Nolander, P. Moynihan, V. Siefert, and M. Watrin performed the coordinator duties in Minnesota, while B. Maruca assisted in this capacity in Montreal, and C. Delcroix, MD and D. Simon, MD performed the coordinator duties in Paris. Ms. M. Mills coordinated the Montreal laboratory efforts. Ms. H. Beaufils and V. Beaudoin performed many of the clinical studies in Paris. We also thank the nurses at the General Clinical Research Center at Fairview-University Medical Center and at the International Diabetes Center in Minneapolis, and Ms. M. Proulx at St. Paul Children’s Hospital for their excellent patient care. We are especially grateful to Ms. R. Meerovici who performed the data cleaning and entry and Ms. S. Dell’Aniello who performed the statistical analyses for these studies.
- Diabetic nephropathy
- Juxtaglomerular apparatus
- Type 1 diabetes