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Changes in renal function after clinical islet transplantation: four-year observational study.

AbstractTight glycemic control can reduce progression of diabetic nephropathy (DN) while the histological changes may regress after pancreas transplantation. Clinical islet transplantation (CIT) can restore euglycemia but the effects of CIT and concomitant immunosuppression on renal function are not known. Renal function (modification of diet in renal disease estimated glomerular filtration rate [GFR]) is reported in 41 type 1 diabetes subjects followed for 29.8 (6-57) months after CIT who received sirolimus and tacrolimus. HbA(1c) improved by 3 months (6.1 +/- 0.5 vs. 8.1 +/- 1.3%, p < 0.001) and was sustained. Over 4 years estimated GFR (eGFR) declined (repeated measures ANOVA: p = 0.0011). The median rate of change in eGFR was -0.39 mL/min/1.73 m(2)/month but was highly variable (range: +1.62 to -2.79 mL/min/1.73 m(2)/month). Progression of albuminuria was observed in ten individuals while regression of microalbuminuria was observed in only one (chi square = 22.51, df = 4, p = 0.0002). Despite improved glycemia, CIT and concomitant immunosuppression, was associated with a fall in eGFR and progression of albuminuria over 4 years of observation. The rate of decline in eGFR was extremely variable and difficult to predict. The risk of progressive nephrotoxicity with decline in eGFR should be discussed with prospective CIT candidates and the risk: benefit ratio carefully considered in individuals with pre-existing renal impairment.
AuthorsP A Senior, M Zeman, B W Paty, E A Ryan, A M James Shapiro (Affiliation: Clinical Islet Transplant Program, University of Alberta, Edmonton AB, Canada. petersonsenior at ualberta.ca)
JournalAmerican journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons (Am J Transplant) Vol. 7 Issue 1 Pg. 91-8 (Jan 2007) ISSN: 1600-6135 Denmark
PMID17227560 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Chemical References
  • Hemoglobin A, Glycosylated
  • Tacrolimus
  • Sirolimus
Topics
  • Adult
  • Albuminuria (etiology)
  • Diabetes Mellitus, Type 1 (complications, therapy)
  • Female
  • Follow-Up Studies
  • Glomerular Filtration Rate
  • Hemoglobin A, Glycosylated (analysis)
  • Humans
  • Immunosuppression
  • Islets of Langerhans Transplantation (adverse effects)
  • Kidney (physiology)
  • Male
  • Middle Aged
  • Sirolimus (therapeutic use)
  • Tacrolimus (therapeutic use)