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Islet transplantation—the imperative need for continued clinical trials

Nature Clinical Practice Nephrology volume 4, pages 662–663 (2008)Cite this article

Remuzzi and colleagues have struggled to start a clinical islet transplantation program in Italy over the past 10 years, and have publicly declared that their decision to abandon the procedure is “in the best interests” of their patients.1 This decision must be seen as entirely personal, as the clinicians and researchers involved in the majority of programs do not share the pessimistic view expressed by the Italian group. Although islet transplantation is currently far from the ideal alternative to insulin replacement therapy in all patients with type 1 diabetes, now is not the time for a moratorium on clinical research trials. All new medical breakthroughs face bumps in the road, and islet transplantation is no different. The first patient to receive an insulin injection of “thick, brown muck” in 1922 developed a buttock abscess and had limited clinical response.2 Weeks later, alcoholic extraction of more-purified insulin was rightly hailed as the most important life-saving advance in diabetes care.2 Only through iterative trials and intensive collaborations between research groups will the remaining hurdles left in the way of a more-widespread application of islet transplantation be removed.

The introduction of the 'Edmonton protocol' in 2000 was seen as a key advance in islet transplantation, as all of the first seven patients treated using this approach were insulin-independent for up to 1 year.3 The Edmonton protocol built upon 30 years of intensive iterative research that began with Lacy's cure of diabetes in mice by islet transplantation, Ricordi's development of techniques for large-scale human islet isolation, and many other previous clinical attempts at rendering islet transplantation a viable alternative to insulin replacement. Eight years after the Edmonton protocol was introduced, almost 700 patients with type 1 diabetes have been treated with refined versions of the protocol worldwide (over 100 at the Edmonton site), including 36 who participated in an international trial.4 A number of concerns have emerged, but none is insurmountable. Given that achieving insulin independence can require multiple donor islet infusions, the risk of sensitization to the donor's human leukocyte antigens is of concern; however, this risk is substantial only in the small subgroup of patients (<10%) whose grafts fail completely and whose immunosuppression has been discontinued.5 Lack of sustained independence from insulin by 3–5 years after islet transplantation might be disappointing for some, but complete insulin independence is not usually the primary goal of therapy.6 A need for small amounts of supplemental insulin is a relatively minor inconvenience when continued protection from hypoglycemia is provided by a partially functioning graft.4 In any event, the challenges described above are likely to be overcome with straightforward strategies that enhance and protect the mass of the initial islet engraftment.

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Acknowledgements

The author would like to thank the following institutions for financial support: Juvenile Diabetes Research Foundation (JDRF), Clinical Center for Islet Transplantation, Clinical Islet Transplant (CIT) Consortium, National Institutes of Health, Diabetes Research Institute Foundation Canada (DRIFCan) and the Alberta Heritage Foundation for Medical Research (AHFMR).

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  1. Clinical Islet Transplant Programme, University of Alberta, 2000 College Plaza, 8215 112th Street, Edmonton, AB T6G 2C8, Canada amjs@islet.ca

Authors and Affiliations

  1. AMJ Shapiro is Professor of Surgery and Director of the Clinical Islet Transplant Programme at the University of Alberta, Edmonton, AB, Canada.,

    AM James Shapiro

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The author has declared associations with the following company: Novocell, for which he is a consultant.

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James Shapiro, A. Islet transplantation—the imperative need for continued clinical trials. Nat Rev Nephrol 4, 662–663 (2008). https://doi.org/10.1038/ncpneph0964

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