ISLET ALLO TRANSPLANTATION
 IN PATIENTS WITH KIDNEY GRAFT
 

OPEN ENROLLMENT

Pancreatic Islet Allo Transplantation

in Patients with Stable Kidney Graft Function

Funded Internally

Brief Description for Transplant Centers 

 

 

 

Collaborating Centers

University of Chicago, Chicago, IL- Dr. Piotr Witkowski

DMC Harper University Hospital, Detroit MI- Dr. Shakir Hussain, Dr. Jason Rolls

 

 

What do we  offer?

Patients with poorly controlled type 1 diabetes end up with ESRD. Simultaneous kidney and pancreas transplantation remains the best therapeutic option for them. Those, who received kidney alone from a live or decease donor, may benefit from Pancreas after Kidney Transplantation (PAK). 

However, there is still a group of patients with kidney transplant alone, who are compliant with immunosuppression therapy but suffering from progressive complications driven by poorly controlled diabetes, who are not candidate for a whole pancreas transplant. 

 

We have already found islet transplantation safe and beneficial for patients with brittle T1DM and good kidney function (see patient stories) and now, in current clinical, we offer islet transplantation to patients who already received kidney transplantation. 

Screening criteria:​

Subjects who meet all of the following criteria are eligible for a further screening and enrollment:

1. Male and female in age of 18 to 68 years.

2. Subjects who are able to provide written informed consent and to comply with the procedures of the study protocol.

3. Clinical history compatible with T1D with disease onset < 40 years of age and insulin-dependence for ≥ 5 years at the time of enrollment.

4. Subjects who are ≥ 3 months post-renal transplant who are taking appropriate calcineurin inhibitor (CNI) based maintenance immunosuppression (tacrolimus alone or in conjunction with sirolimus, mycophenolate mofetil, myfortic, or azathioprine; or cyclosporine in conjunction with sirolimus, mycophenolate mofetil, or myfortic) ± Prednisone ≤ 10 mg/day).

6. Stable renal function as defined by a creatinine of no more than one third greater than the average creatinine determination performed in the 3 previous months prior to islet transplantation after exclusion.

Selected exclusion criteria:​

1. Any active chronic infection (BK, HBV, HCV, HIV, TB etc)

2. Positive screen for BK virus by polymerase chain reaction (PCR)

3. Uncontrolled psychiatric disorder

 

4. Other (non kidney) organ transplants except prior failed pancreatic graft with the pancreas transplant occurring more than 6 months prior to enrollment.

5. Untreated or unstable proliferative diabetic retinopathy.

6. Proteinuria (albumin/creatinine ratio or ACr > 300 mg/g) of new onset since kidney transplantation.

7. Invasive aspergillus, histoplasmosis, and coccidoidomycosis infection within one year prior to study                      enrollment.

 

8. Any history of malignancy or PTLD except for completely resected squamous or basal cell carcinoma of the skin.

9. Known active alcohol or substance abuse. 

10. Severe co-existing cardiac disease, characterized by any one of these conditions: 

 

a. Recent MI (within 6 months);

b. Evidence of ischemia on functional cardiac exam within the last year;

c. Left ventricular ejection fraction < 30%; or

d. Valvular disease requiring replacement with prosthetic valve.

11. Active peptic ulcer disease, symptomatic gallstones, or portal hypertension.

12. A previous islet transplant.

 

Logistics Overview

  • Compliant patients are identified at the Local Transplant Center and pre-screened for the participation in the study. Patient results will be sent to the Univ of Chicago Islet Transplant Center (Islet Tx Center). 

  • Pre-approved patient are invited to come for one time evaluation to the Islet Tx Center in Chicago at own cost.

  • Once approved, patient will be listed for the islet transplantation at the University of Chicago Islet Transplant Center.

  • If interested, patient may be listed also for a pancreas transplant at the local Tx Center 

  • Once sufficient islets are isolated, patient comes to the Islet Tx Center in Chicago and islets are infused within 48 hours. Patient is usually discharge after day or 2 , but it is recommended to stay in the hotel for next 3 days before goes home and trasition under care of the local Transplant Center. 

  • The procedure is experimental and not reimbursed by the insurance. 

  • Patient may drop the study at any time.

  • if eligible, patient may proceed with the standard of care pancreas transplantation (if eligible) at any time).

Preliminary results

  • We have performed over 50 islet transplants in patients with T1DM with good kidney function but suffering from hypoglycemia unawareness and  severe hypoglycemic episodes despite optimal insulin treatment ->. 

  • Now, we would like to test whether islet transplantation can be beneficial also for those patients with T1DM who has already received kidney transplant.

  • Up-to-date reports from other centers indicate beneficial effect  of islet in terms of the glucose control without increased risk for kidney graft function. 

  • So far, we performed islet transplants in 2 kidney recipients in our center. One has been off insulin for last 4 years (Keith- in patient stories), second one dropped being relief from severe hypoglycemic episodes after first islet transplant. We have published already preliminary report in Polish language in order to introduce this new procedure  to physicians and patients in Poland. Version in English translation is available here:   Pancreatic Islet After Kidney Transplantation. Two Case Report. Forum Nephrologiczne. 2018. 11, 1, 43-49. 

  • Subsequently, we helped to open a new islet transplant Center in Gdansk, Poland, where first 3 patients with stable kidney graft function received islet transplant the end of  October of 2018 and in March and May of this year. Over last 6 months the first patient lowered his daily  insulin requirements in 50%..  More importantly he improved his overall glucose control significantly-A1c declined from 8.0 to 6.6. However, as he main benefit, patient stopped having severe hypoglycemic episodes and stop fearing of sudden death caused by that. His and his family quality of life improved substantially, patient now seeks to be active in his community running for a public office in his neighborhood. 

  • See below his CGM records before and after the islet transplant. 

Blood glucose control after to islet Tx:

  • blood glucose levels in normal range of 80-180mg/ml)                                                      A1c= 6.6

  • no more spikes over 200mg/ml,

  • no life- threatening drops below 54mg/ml

Blood glucose control prior to islet Tx: 

Each colored line represents blood glucose changes during 24 hours on a different day of the week.

  • Blood glucose spikes over 400mg/ml on several occasions as well as                  A1c=8.8

  • life- threatening drops below 54mg/ml

CONTACT:

 

 

 

 

 

 

 

 

Transplantation Institute

Clinical  Research Center

 

Islet and Kidney Transplantation

Manager, Lindsay Basto RN MSN 

Lindsay.Basto@uchospitals.edu

tel. (773) 702-2504

fax (773) 926-0671

 

Islet and Cell Processing and Research

Manager, Karolina Golab, PhD

kgolab@surgery.bsd.uchicago.edu


Transplantation Institute

University of Chicago Medicine

5841 S. Maryland Avenue

MC 5026, J-517

Chicago IL 60637

Polish-American Transplant Center

Clinical Coordinator

Patrycja Ulijaszyk RN 

Patrycja.Ulijaszyk@uchospitals.edu

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© 2018 by Kajetan Witkowski