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Abstract: SA-OR17

Reversal of Diabetic Nephropathy After 10 Years of Pancreas Transplantation Occurs Despite Parallel Podocyte Loss

Session Information

Category: Diabetic Kidney Disease

  • 602 Diabetic Kidney Disease: Clinical

Authors

  • Najafian, Behzad, University of Washinton, Seattle, Washington, United States
  • Mauer, Michael, University of Minnesota, Minneapolis, Minnesota, United States
  • Fioretto, Paola, University of Padova, Padova, Italy
Background

Diabetic nephropathy (DN) is associated with podocyte (PC) injury and loss. PC injury is believed to play important role in DN progression. DN reversal following 10 years (10Y) of euglycemia after pancreas transplantation (PTx) is documented (N Engl J Med 1998; 339:69-75). We hypothesized that if PC loss is crucial for DN development, DN reversal would be associated with PC regeneration and improvement in PC structure

Methods

Paired kidney biopsies prior to PTx (BL) and 10Y after PTx were compared for classical DN lesions, PC number and foot process width (FPW) using electron microscopy morphometry in 10 type 1 diabetic (T1D) patients with age 33 (30-54) years [median (range)], diabetes duration 23 (16-33) years and albumin excretion rate (AER) 134 (0-951)µg/min at BL. The results were compared with biopsies from 10 age matched living donor biopsies [controls (C)].

Results

Glomerular basement membrane (GBM) width, fractional volume of mesangium/glomerulus [Vv(Mes/glom)] and fractional volume of mesangial matrix/glomerulus [Vv(MM/glom)] and FPW were all increased at BL compared to C (data not shown). There were significant reductions in GBM width (30%; p=0.0002), Vv(Mes/glom) (21%; p=0.001), Vv(MM/glom) (30%; p=0.002), and glomerular volume (27%; p=0.02) at 10Y compared to BL. However, while PC number density did not change from BL to 10Y, there was a significant decrease in PC number/glomerulus (31%; p=0.049). FPW in T1D patients at BL (p=0.0008) or 10Y (p=0.002) was greater than C with no significant change from BL to 10Y. No relationship was found between change in GBM width, Vv(Mes/glom) or Vv(MM/glom) and PC number density, PC number per glomerulus or FPW. Creatinine clearance was reduced by 25% from BL to 5y post PTx in these calcineurin treated patients, and remained stable between 5 and 10Y. AER did not change significantly.

Conclusion

Substantial reversal of GBM and mesangial extracellular matrix (ECM) accumulation in T1D occurs following long term PTx despite decrease in PC number, persistence of foot process widening and no change in PC density. This study does not support PC loss to be an important mediator of glomerular extracellular dynamics in DN in T1D. Moreover, despite long-term normoglycemia, PC do not regenerate and PC injury does not regress in T1D patients.

Funding

  • Private Foundation Support