NEPHROLOGY

2002; 7, S41–S42

Meeting Proceedings: Commentary

Blackwell Science, LtdOxford, UKNEPNephrology1320-53582001 Asian Pacific Society of Nephrology

7Suppl.June 2002

S12Clinical islet transplantation

J Chapman10.1046/j.1320-5358.2002.00012.x

Meeting Proceedings: CommentaryS41S42BEES SGML

Correspondence: Dr Jeremy Chapman, Department RenalMedicine, Westmead Hospital, Sydney, NSW 2145, Australia. Email:Jeremy_Chapman@wsahs.nsw.gov.au

Clinical islet transplantation: a triumph of hope over experience

Jeremy

CHAPMAN

Department Renal Medicine, Westmead Hospital, Sydney, New South Wales, Australia

The recent success of islet allotransplantation has pro-vided a solution for a selected group of patients with type1 diabetes mellitus, but it is a solution that may have lit-tle relevance to future general clinical practice formost diabetics due to the limited availability of donorpancreases.

Islet transplantation is not a new concept and despitedecades of failure, research has continued spurred onby some success stories. Recently, at the University ofAlberta, Edmonton, Canada, researchers showed aconsistent reversal of type 1 diabetes in seven patientsreceiving islet transplantation.

1

The Edmonton research was successful for a number ofreasons, but most importantly they had both a dedicatedand multidisciplinary team with funding. This allowedthem to establish methods for auto- and allo-islet isola-tion and transplantation in animal models to evaluatefunction of islet tissue, to develop new immunosuppres-sant protocols and to evaluate rejection of islet tissue.

With this in mind the success factors for islet trans-plantation could then be narrowed down to five keyareas:

1. patient selection (see Table 1)2. donor procedure3. islet separation technique4. urgent transplantation5. non-islet-toxic immunosuppression

Minimal ischaemia time in the donor procedure andrapid islet isolation procedure were quickly identifiedas important factors in success. Another vital factor inislet transplantation discovered by the Edmonton group,is that the mass of islets transplanted affects outcome.When the number of islets exceeds 8300 per kg patientsare free of insulin dependence, however, any less thanthat and no patient was insulin free post-transplant (seeFig. 1).

The immunosuppression regimen used in islet trans-plantation was no steroids, low dose tacrolimus, lowdose sirolimus and daclizumab (1 mg/kg every 14 days

×

5).As clinicians we will be faced with the question of

whether to use a donated pancreas for islet transplanta-tion, whole pancreas transplantation or even combinedtransplantations of pancreas and kidney or islet andkidney.

At Westmead, while implementing a clinical allograftislet program, we are seeking to address the lack of donororgans by developing a potential xenograft donor in theWestran pigs. While this research is in the early stages wehave shown that in the absence of a rejection mechanismwe can get foetal islets to grow and release insulin in

Fig. 1

Relationship between islet mass and insulinindependence.

0

20

40

60

80

100

4100

4300

5300

5700

6400

7200

8300

1040

0

1120

0

1240

0

1404

0

Islet equivalents/Kg

% In

sulin

inde

pend

ent

Table 1

Patient selection criteria

Metabolic instabilityHypoglycaemia not felt at < 3.0 mmol/LProgressive secondary complications despite best effortsGood cardiac functionBody mass index < 28, < 70 kgCreatinine clearance > 100 mL/minUltrasound of liver – no haemangiomas

S

42

NEPHROLOGY

J Chapman

a syngeneic model. Together with our collaborators weseek to resolve the current safety and efficacy barriers toxenotransplantation of islets such that we will be able tooffer a range of options including whole pancreas, humanislets and pig islets transplants in the future.

REFERENCE

1. Shapiro AM, Lakey JR, Ryan EA

et al

. Islet Transplantation in sevenpatients with type 1 diabetes mellitus using a glucocorticoid-freeimmunosuppressive regimen.

N. Engl. J. Med.

2000;

343

: 230–8.