Kidney function after islet transplant alone in type 1 diabetes: impact of immunosuppressive therapy on progression of diabetic nephropathy.
OBJECTIVE
Islet transplantation alone is an alternative for the replacement of pancreatic endocrine function in patients with type 1 diabetes. The aim of our study was to assess the impact of the Edmonton immunosuppressive protocol (tacrolimus-sirolimus association) on kidney function.


METHODS
Nineteen patients with type 1 diabetes and metabolic instability received islet transplantation alone and immunosuppressive therapy according to the Edmonton protocol. Serum creatinine (sCr), creatinine clearance (CrCl), and 24-h urinary protein excretion (UPE) were assessed at baseline and during a follow-up of 339 patient-months.


RESULTS
After islet transplantation we observed 1) sCr within the normal range in all but two patients in whom sCr increased immediately after islet transplantation, and despite withdrawal of immunosuppression, patients progressed to end-stage renal disease (ESRD); 2) CrCl remained within the normal range for those patients who had normal baseline values and decreased, progressing to ESRD in two patients with a decreased baseline CrCl; and 3) 24-h UPE worsened (>300 mg/24 h) in four patients. In the two patients who progressed to ESRD, the worsening of 24-h UPE occurred immediately after islet transplantation. In one patient 24-h UPE worsening occurred at 18 months, and, after withdrawal of immunosuppression, it returned to the normal range. In another patient 24-h UPE increased at 24 months and remained stable while immunosuppression was continued.


CONCLUSIONS
In type 1 diabetic patients receiving islet transplantation alone, the association of tacrolimus and sirolimus should be used only in patients with normal kidney function. Alternative options for immunosuppressive treatment should be considered for patients with even a mild decrease of kidney function.
Maffi
Paola
P
Department of Medicine, Transplant Unit, San Raffaele Scientific Institute, Via Olgettina 60, 20132 Milano, Italy. paola.maffi@hsr.it
Bertuzzi
Federico
F
De Taddeo
Francesca
F
Magistretti
Paola
P
Nano
Rita
R
Fiorina
Paolo
P
Caumo
Andrea
A
Pozzi
Paolo
P
Socci
Carlo
C
Venturini
Massimo
M
del Maschio
Alessandro
A
Secchi
Antonio
A
D000911:Antibodies, Monoclonal / Q000009:adverse effects; D061067:Antibodies, Monoclonal, Humanized; D003404:Creatinine / Q000097:blood; D000077561:Daclizumab; D003922:Diabetes Mellitus, Type 1 / Q000503:physiopathology* / Q000601:surgery*; D003928:Diabetic Nephropathies / Q000139:chemically induced* / Q000503:physiopathology*; D018450:Disease Progression; D005500:Follow-Up Studies; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D007074:Immunoglobulin G / Q000009:adverse effects; D007166:Immunosuppressive Agents / Q000009:adverse effects*; D007328:Insulin / Q000627:therapeutic use; D016381:Islets of Langerhans Transplantation / Q000502:physiology*; D007677:Kidney Function Tests; D012189:Retrospective Studies; D020123:Sirolimus / Q000009:adverse effects; D016559:Tacrolimus / Q000009:adverse effects
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D003404:Creatinine; D000077561:Daclizumab; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D007328:Insulin; D020123:Sirolimus; D016559:Tacrolimus