NOTE: This article was first published in Nov 2020 in Issue 11 of our Kidney Matters magazine
"Type 1 diabetes mellitus (T1DM) is increasing in Europe, and provides challenges to patients and doctors due to its complications. These include damage to the heart, circulation, vision (retinopathy) and nerves (neuropathy). In addition, some patients can have the dangerous side effect of low blood sugar levels without any warning signs (called hypoglycaemic unawareness). This can be life threatening as patients need someone else to help them to control their dangerously low blood sugar levels. However, one of the most significant complications is kidney damage (nephropathy), which means that patients ultimately need dialysis or a kidney transplant.
T1DM occurs due to non-function of the islet cells, which control insulin release and are located in the pancreas. This has resulted in an interest in transplantation to control or remove this diabetic burden.
Pancreas transplantation has proven to be very successful (usually in conjunction with a kidney transplant – simultaneous pancreas kidney transplant or SPK) and provides durable and robust treatment of both T1DM and kidney failure, with success rates of over 85% at one year. However, a pancreas transplant involves major surgery, and does have significant side effects particularly due to the risks of bleeding and infection from the organ, which can sometimes result in death.
Some patients with T1DM and kidney failure may also choose to have a live or deceased-donor kidney transplant alone. They would then continue optimal treatment of their T1DM with their diabetologist.
However, in the long term T1DM is likely to provide ongoing damage to the transplant and may result in failure of the kidney in the intermediate to long term.
Islet cell transplantation
The potential risks of pancreas transplantation led to interest in the possibility of Islet cell transplantation (ICT). This would provide the opportunity to improve diabetic control and minimise the side effects that result from transplantation of the whole pancreas, as only the relevant islet cells would be transplanted to the recipient. Since 2009, this procedure has been nationally available in a select number of UK centres.
It has been agreed that ICT will be reserved for patients with preserved kidney function (because of the risks of immunosuppression) with hypoglycaemic unawareness, or those with very brittle and poorly controlled T1DM following a successful kidney transplant.
The process is far less invasive than a pancreas transplant (which requires major surgery) as it involves passing a thin tube or cannula into a vein in the liver, and the patient needs only sedation or a light general anaesthetic. The islet cells are infused into the patient’s body via this cannula after they have been separated from a single deceased-donor pancreas in a special islet facility. Patients needing a ‘topup’ of islet cells return to the UK transplant waiting list, where they have priority listing for six months so that
The associated risks of ICT are considerably lower than for pancreas transplantation, and include bleeding and infection. Patients need to take immunosuppression after the transplant, as with kidney and pancreas transplantation, to minimise the risks of rejection of the cells. This in turn may increase the risk of infection and certain cancers and, importantly, requires close, long-term monitoring of kidney function.
Outcomes of islet transplantation
In contrast to a pancreas transplant, where the recipient will no longer require Insulin, the patient may require reduced doses of Insulin following an ICT, but is likely to have far better diabetic control. Patients are also likely to regain awareness of hypoglycaemia. However, long-term success and survival of the islet cells is less than with a pancreas transplant. After five years, 7 in 10 pancreas transplants are functioning so that the patient does not need insulin. In contrast, although three quarters of islet patients are still making some insulin five years after their transplant, only 1 in 10 are insulin treatment-free in early international studies.
Diabetic complications are thought likely to be stabilised after ICT, reducing the severity of diabetic damage to the eyes, circulation and nerves. However, further studies are needed to definitively prove this as the data have some limitations.
Simultaneous islet-kidney transplant
Since 2016, NHS Blood & Transplant have allowed simultaneous islet kidney transplantation as a further treatment option for diabetic treatment for individuals with T1DM and kidney failure. To be eligible for this transplant patients must have kidney failure and T1DM, with at least one diabetic complication. However, unlike islet transplantation alone, hypoglycaemic unawareness is not required.
This procedure gives the opportunity to receive a kidney transplant, with islets available from the same donor, once they have been prepared, about 48 hours later. It appears to provide a valid alternative to SPK for patients who may not be able to have a whole-organ pancreas, either due to previous transplants making surgery difficult or not being fit enough. Early results across the country appear promising, although longer term follow-up will be necessary to examine how beneficial this is to patients.
Islet cell transplant provides an opportunity to improve diabetic control and keep patients with type 1 diabetes safe from further complications
Further research in islet transplantation
There is a large amount of international research at present, examining improved techniques to understand donation, preparation and clinical transplantation to improve the condition and survival of ICT. In addition, there are exciting developments in the production of islets from stem cells or encasing (‘encapsulation’) of islet cells to minimise the risk of the recipient rejecting the cells. All of these developments may improve the success of ICT in the future.
ICT provides an opportunity to improve diabetic control and keep patients with T1DM safe from further complications and importantly remove hypoglycaemic unawareness, which can be life threatening. Its advantages lie in the reduced risks of the procedure in selected individuals, compared to whole-organ pancreas transplant, with some risks associated with immunosuppression, particularly to kidney function in the long term. Simultaneous islet kidney transplantation is an exciting new option that may provide a valid and successful treatment for patients with kidney failure and T1DM, and offers hope for this group of patients who have historically been difficult to treat."