Early alteration of kidney function in nonuremic type 1 diabetic islet transplant recipients under tacrolimus-mycophenolate therapy.
BACKGROUND
Transplant patients on tacrolimus therapy exhibit a reduced glomerular filtration rate (GFR). The type of graft and immune treatment protocol may influence the extent and reversibility of this side effect.


METHODS
The present single-center study is conducted in 48 nonuremic type 1 diabetic recipients of an intraportal islet-cell graft under maintenance immunosuppression (IS) with tacrolimus and mycophenolate mofetil. Estimated GFR (eGFR) and albuminuria were followed up to 5 years posttransplantation.


RESULTS
Mean eGFR values decreased by 19 mL/min/1.73 m after 1 to 2 weeks of IS (P<0.0001) and then remained stable throughout the complete treatment period. The decrease was related to predose trough tacrolimus concentrations or doses and disappeared upon its discontinuation; it was also associated with the presence of albuminuria at the time of transplantation. Tacrolimus treatment resulted in a reduction of albuminuria; its discontinuation restored albuminuria to the initial levels.


CONCLUSIONS
The use of tacrolimus in our islet-cell transplant protocol caused an initial 20% reduction in eGFR, which was reversible following its discontinuation, at least within the 5-year follow-up period. The associated reduction in albuminuria was also reversible, compatible with a tacrolimus-induced preglomerular vasoconstriction. These observations support further use of our tacrolimus regimen in this patient population.
1 Department of Clinical and Experimental Medicine, University of Leuven-KUL and Department of Endocrinology, University Hospitals Leuven, Leuven, Belgium. 2 Diabetes Research Center, Brussels Free University-VUB and University Hospital Brussels, Brussels, Belgium. 3 I-Biostat, Biostatistical Centre, University of Leuven-KUL, Leuven, Belgium. 4 Study Program of Statistics, Universitas Brawijaya, Indonesia. 5 Department of Nephrology and Renal Transplantation, University Hospitals Leuven, Leuven, Belgium. 6 Department of Clinical Chemistry, University Hospital Brussels, Brussels, Belgium. 7 Address correspondence to: Pieter Gillard, M.D., Ph.D., Department of Endocrinology, University Hospitals Leuven, Herestraat 49, 3000 Leuven, Belgium.
Pieter
P
Gillard
Maria
M
Rustandi
Achmad
A
Efendi
Da Hae
DH
Lee
Zhidong
Z
Ling
Robert
R
Hilbrands
Dirk
D
Kuypers
Chantal
C
Mathieu
Daniel
D
Jacobs-Tulleneers-Thevissen
Frans
F
Gorus
Daniel
D
Pipeleers
Bart
B
Keymeulen
D000328:Adult; D000419:Albuminuria / Q000188:drug therapy; D003922:Diabetes Mellitus, Type 1 / Q000503:physiopathology / Q000601:surgery*; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects*; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D016381:Islets of Langerhans Transplantation; D007668:Kidney / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives*; D016559:Tacrolimus / Q000008:administration & dosage*
D007166:Immunosuppressive Agents; D009173:Mycophenolic Acid; D016559:Tacrolimus