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Miami Transplant Institute

Miami Transplant Institute

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Kidney and Pancreas Transplantation Projects

Project 1

The recurrence of auto-immunity in patients with type 1 diabetes and end stage renal disease who undergo a K/P transplant

PROJECT SUMMARY:

In studying the recurrence of auto-immunity in patients with type 1diabetes (T1D) and end-stage renal disease who undergo a kidney-pancreas transplant, we have noted that a small number of patients (5%) will return with hyperglycemia. This ultimately reflects a selective loss of islet cells, which is what leads to type 1diabetes in the first place. For this project, we are collaborating with the team at the Diabetes Research Institute at the University of Miami, particularly Dr. Alberto Pugliese, and also the team at the Diabetes Research Institute in Seattle (Virginia Mason Institute) and have been supported by an NIH RO1 grant since 2005, as well as a JDRF Fellowship for 2 years. We have recently applied for an ARRA Grant and are in the process of competitive renewal revision for our NIH RO1 grant. A list of our current publications over the last 2 years is included (1-5).

What is hyperglycemia?

Hyperglycemia, or high blood glucose (sugar), is a serious health problem for those with diabetes. Hyperglycemia develops when there is too much sugar in the blood. In people with diabetes, there are two specific types of hyperglycemia that occur.

Fasting hyperglycemia is defined as a blood sugar greater than 90-130 mg/dL (milligrams per deciliter) after fasting for at least 8 hours.

Postprandial or after-meal hyperglycemia is defined as a blood sugar usually greater than 180 mg/dL. In people without diabetes postprandial or post-meal sugars rarely go over 140 mg/dL but occasionally, after a large meal, a 1-2 hour post-meal glucose level can reach 180 mg/dL. Consistently elevated high post-meal glucose levels can be an indicator that a person is at high risk for developing type 2 diabetes.

When a person with diabetes has hyperglycemia frequently or for long periods of time as indicated by a high HbA1c blood test, damage to nerves, blood vessels and other body organs can occur. Hyperglycemia can also lead to more serious conditions, including ketoacidosis — mostly in people with type 1 diabetes — and hyperglycemic hyperosmolar nonketotic syndrome (HHNS) in people with type 2 diabetes or in people at risk for type 2 diabetes.

It’s important to treat the symptoms of hyperglycemia promptly to prevent complications from diabetes.

GOAL:

Ultimately, we hope that insights from treating our patients will translate to possible prevention or cure of Type 1 Diabetes in children who are newly diagnosed with the disease.

Project 2

The recurrence of proteinuria with focal segmental glomerulosclerosis in children and young adults

PROJECT SUMMARY:

We are actively investigating the recurrence of proteinuria, specifically in children and young adults with focal segmental glomerulosclerosis (FSGS). This is an unusual disease where immediately after kidney transplantation the recipient often begins to spill protein in the urine. From January 2000-December 2003, we observed a rate of recurrence of 80% (similar to published literature) in our pediatric population with FSGS subsequent to kidney transplantation. Since January 2004, we have treated these patients with a novel induction regimen, including rituximab, a monoclonal antibody. We reasoned that rituximab may play a role in stabilization of the podocyte (a key cellular element of the kidney glomerulus) at the time of transplantation. Since January 2004, we have used this protocol on approximately 25 patients and have observed a remarkable decrease in the incidence of proteinuia after transplant as well as the need for plasmapheresis after transplant. We are currently investigating the mechanisms for this and are pursuing ultimate therapies for this difficult and challenging clinical problem. We have a series of abstracts and are currently working on federal grants and publications.

What is Focal Segmental Glomerulosclerosis (FSGS)?

Hyperglycemia, or high blood glucose (sugar), is a serious health problem for those with diabetes. Hyperglycemia develops when there is too much sugar in the blood. In people with diabetes, there are two specific types of hyperglycemia that occur.

“Focal” means that some of the glomeruli become scarred, while others remain normal. “Segmental” means that only part of an individual glomerulus is damaged.

The cause of focal segmental glomerulosclerosis is usually unknown. A small number of cases result from reflux nephropathy. The condition affects both children and adults. Males are affected slightly more often than females, and it also occurs more frequently in African-Americans.

Focal segmental glomerulosclerosis causes about 10 – 15% of all cases of nephrotic syndrome.

GOAL:

Ultimately, we hope that this research will translate to a cure for children with this unusual disease before they develop renal failure and need to be transplanted.

Project 3

Bariatric Surgery for patients with end-stage renal disease and a BMI > 35

PROJECT SUMMARY:

The research interest involves bariatric (weigh loss) surgery for those patients with end-stage renal disease and a BMI >35, i.e. those patients who tend to be obese and to have problems with hypertension, high cholesterol and diabetes, collectively known as the metabolic syndrome. We are in the process of putting together a multi-group research project that will include members from the Dept. of Surgery, the Diabetes Research Institute, Radiology as well as collaborations with Dr. David Cummings at the University of Washington in Seattle.

What is Bariatric Surgery?

Bariatric surgery, also known as weight loss surgery, refers to the various surgical procedures performed to treat obesity by modification of the gastrointestinal tract to reduce nutrient intake and or absorption. The term does not include procedures for surgical removal of body fat such as liposuction or abdominoplasty.

Bariatric surgery is an option for people who have a body mass index above 40. Surgery is also an option for people with a BMI between 35 and 40 who have health problems like type 2- diabetes or heart disease. This surgery may help to attain a more healthy body weight.

GOAL:

Our hope is that patients who are waiting on the kidney transplant list can undergo bariatric surgery with subsequent weight loss and improvement in their metabolic picture (in some cases including coming off insulin), in order to be better prepared for kidney transplantation in the future. This will likely translate to improved quality of life and patient survival.

Project 4

The use of the pulsatile perfusion machine in deceased donor kidney transplantation and how it contributes to improve organ preservation

PROJECT SUMMARY:

This research project is regarding the use of the pulsatile perfusion machine in deceased donor kidney transplantation. We have been using the machine for all deceased donors since 1978. We have recently made the observation that kidneys tend to perform better after longer periods of time on the machine. In fact, our group of patients who received kidneys that were on the machine for 36 to 50 hours, performed as well, if not better, than those that were on the machine for less than 36 hours. We are currently in the process of publishing these data and working on grant submissions, specifically looking at the mechanisms that may explain how machine-perfusion contributes to improved preservation. Perhaps machine perfusion results in the shedding or masking of immunologically active receptors on endothelial cells.

What is a Pulsatile Perfusion Machine?

Perfusion is the introduction of a liquid into a tissue or an organ by circulating it through blood vessels or other channels within the body.

Machine perfusion (MP) is a technique used in organ transplantation as a means of preserving the organs which are to be transplanted. To some degree, it emulates natural perfusion. So far it has mainly been used in kidney transplantation. It is an alternative to cold storage (CS).

Pulsatile perfusion is important because the quality of the organ at the time of transplant significantly influences both short & long term outcome.

GOAL:

We want to increase the number of precious kidneys available for transplantation by the use of the pulsatile perfusion machine.

Clinical Research

Clinical Research in the Miami Transplant Institute includes basic laboratory and clinical research within our three main divisions: Kidney and Pancreas, Liver and Gastrointestinal and Heart and Lungs transplant.

The overall mission of our research is to study novel immunosuppressive treatments in order for our transplanted patients to attain a better quality of live after transplantation: reducing the side effects of medications, as well as reducing the incidence of transplant rejection after cadaveric or living-related donor transplants.

Clinical trials are organized within the other two groups under the direction of Dr. George Burke for the Kidney and Pancreas Program and Dr. Andreas Tzakis for the Liver and GI program.

Our research is funded under different sources; institutional, government/agency and industry.

Miami Transplant Institute
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