Studies of Organ Transplantation in Animals and Man

NCT00156364 | Completed DMC

• 2 other identifiers: 8107M00116NIH 2P01-DK13083-38
• Study Type: observational
• Target: 655
• Locations: 1 country
• Sites: 1

Brief Summary

A. To study the effects of pancreas transplantation (PT) on the structural abnormalities of diabetic nephropathy (DN) in patients with type 1 (insulin-dependent) diabetes mellitus (type 1 D). These studies will address the influence of long-term normoglycemia on two stages of diabetic renal disease. Due to the difficulties encountered for recruitment of patients to agree to undergo a GFR and a native kidney biopsy in conjunction with their clinical evaluation visit for transplant, we are now focusing efforts on obtaining skin biopsies previous to transplant, and then at regular intervals (3, 6, and 9 months, and yearly) following a successful transplantation.

• Pancreas Transplantation Alone (PTA). To determine, at 5, 10, and 15 years after PTA, the effects of normoglycemia on the established lesions of DN in the long-term type 1 D patients' own kidneys.
• Islet Transplantation Alone (ITA). To determine, at 5 years after ITA, the effects of normoglycemia on the early lesions of DN in type 1 D patients' own kidneys.
• Pancreas Transplantation after Kidney Transplantation (PAK). To determine at 5-10 years the effects of normoglycemia on the early structural lesions of DN in kidneys transplanted some years earlier into type 1 D recipients. Hypothesis: The benefits of PT on the early glomerular lesions of DN will be demonstrable after 5 years in kidneys exposed to diabetes for a short duration, while in patients with long-standing type 1 D and more advanced glomerular DN lesions, longer exposure to euglycemia is necessary to demonstrate arrest or regression of the lesions.

Conditions

Diabetes Mellitus

Keywords

Diabetic Nephropathy; Kidney Transplant; Pancreas Transplant; Renal Interstitium; Diabetes Mellitus; Cyclosporine; Tacrolimus

Outcome Measures

Primary Outcomes (1)

• Structural-functional relationships in diabetic nephropathy through detailed quantitative studies of Podocytes.

  structural-functional relationships in diabetic nephropathy through detailed quantitative studies of podocytes, including cell number, shape and attachment using innovative approaches including quantitative immunoelectron microscopy and 3-dimensional high resolution electron microscopy. We will also study relationship between podocyte and glomerulotubular junction abnormalities.

  baseline through follow-up biopsy

Secondary Outcomes (1)

• We will continue our study the natural history of diabetic nephropathy.

  Baseline through follow up visits

Other Outcomes (1)

• We have compared the development of calcineurin lesions in the native kidneys of 14 tacrolimus- and 12 calcineurin-treated pancreas transplant alone recipients cured of type 1 diabetes.

  Baseline through follow-up

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)
• Sampling Method: Probability Sample

Study Population

This is not a study that recruits from the general population. This study is selectively offered to eligible patients who are scheduled for a Pre-pancreas Transplant evaluation visit at the University of Minnesota Medical Center, Fairview Transplant Center. If interested in learning more, contact the Transplant Center for more information.

You may qualify if:

• Pancreas Transplantation. The patients considered for recruitment are those being evaluated for pancreas transplant alone or pancreas transplant after kidney transplantation in IDDM patients at the University of Minnesota (U of M). The consent forms have been approved by the Institutional Review Board at the University of Minnesota and the transplant coordinators responsible for interacting with patients have continuously utilized these consent forms in the recruitment process.
• Long-Term Post Kidney Transplant IDDM Patients. These patients are recruited by a study coordinator working directly with the PI and also use consent forms approved by the Institutional Review Board at the University of Minnesota.

You may not qualify if:

• Pancreas Transplantation Alone
• Serum creatinine \>1.5 mg/dl or CCr \<50 ml/min/1.73M2, as kidneys in such IDDM patients are approaching end stage renal disease and are not readily amenable to morphometric analysis.
• Solitary kidneys or evidence of unilateral renal disease, based upon significant discrepancies in renal size by ultrasound.
• Evidence of other important kidney disease by history, ultrasound, or baseline biopsy.
• Other chronic diseases or conditions, in addition to IDDM, such as cystic fibrosis, serious mental illness, severe mental retardation, etc.
• Pregnancy. Pregnancy tests will be performed on all eligible females of child-bearing age, and pregnant women will be excluded. Patients will again be eligible 3 months after completion of pregnancy.
• Pancreas Transplantation After Kidney Transplantation
• Serum creatinine \>2 mg/dl; a higher value is accepted than for native kidney patients since patients have a single kidney and are receiving CSA or FK506.
• Moderate to severe chronic rejection on baseline biopsy.
• Evidence of other important kidney disease by history, ultrasound, or baseline biopsy.
• Other chronic diseases or conditions, in addition to IDDM, such as cystic fibrosis, serious mental illness, severe mental retardation, etc.
• Pregnancy. Pregnancy tests will be performed on all eligible females of child-bearing age, and pregnant women will be excluded. Patients will again be eligible 3 months after completion of pregnancy.

Sponsors & Collaborators

• Michael Mauer, MD: lead
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator
• National Institutes of Health (NIH): collaborator

Study Sites (1)

Universtity of Minnesota, Department of Pediatric Nephrology

Minneapolis, Minnesota, 55455, United States

Location

Related Publications (9)

• Moriya T, Groppoli TJ, Kim Y, Mauer M. Quantitative immunoelectron microscopy of type VI collagen in glomeruli in type I diabetic patients. Kidney Int. 2001 Jan;59(1):317-23. doi: 10.1046/j.1523-1755.2001.00493.x.

  PMID: 11135085 BACKGROUND

• Sutherland DE, Gruessner RW, Dunn DL, Matas AJ, Humar A, Kandaswamy R, Mauer SM, Kennedy WR, Goetz FC, Robertson RP, Gruessner AC, Najarian JS. Lessons learned from more than 1,000 pancreas transplants at a single institution. Ann Surg. 2001 Apr;233(4):463-501. doi: 10.1097/00000658-200104000-00003.

  PMID: 11303130 BACKGROUND

• Caramori ML, Kim Y, Huang C, Fish AJ, Rich SS, Miller ME, Russell G, Mauer M. Cellular basis of diabetic nephropathy: 1. Study design and renal structural-functional relationships in patients with long-standing type 1 diabetes. Diabetes. 2002 Feb;51(2):506-13. doi: 10.2337/diabetes.51.2.506.

  PMID: 11812762 BACKGROUND

• Katz A, Caramori ML, Sisson-Ross S, Groppoli T, Basgen JM, Mauer M. An increase in the cell component of the cortical interstitium antedates interstitial fibrosis in type 1 diabetic patients. Kidney Int. 2002 Jun;61(6):2058-66. doi: 10.1046/j.1523-1755.2002.00370.x.

  PMID: 12028446 BACKGROUND

• Suzuki D, Yagame M, Kim Y, Sakai H, Mauer M. Renal in situ hybridization studies of extracellular matrix related molecules in type 1 diabetes mellitus. Nephron. 2002;92(3):564-72. doi: 10.1159/000064110.

  PMID: 12372938 BACKGROUND

• Huang C, Kim Y, Caramori ML, Fish AJ, Rich SS, Miller ME, Russell GB, Mauer M. Cellular basis of diabetic nephropathy: II. The transforming growth factor-beta system and diabetic nephropathy lesions in type 1 diabetes. Diabetes. 2002 Dec;51(12):3577-81. doi: 10.2337/diabetes.51.12.3577.

  PMID: 12453917 BACKGROUND

• Najafian B, Kim Y, Crosson JT, Mauer M. Atubular glomeruli and glomerulotubular junction abnormalities in diabetic nephropathy. J Am Soc Nephrol. 2003 Apr;14(4):908-17. doi: 10.1097/01.asn.0000057854.32413.81.

  PMID: 12660325 BACKGROUND

• Caramori ML, Fioretto P, Mauer M. Low glomerular filtration rate in normoalbuminuric type 1 diabetic patients: an indicator of more advanced glomerular lesions. Diabetes. 2003 Apr;52(4):1036-40. doi: 10.2337/diabetes.52.4.1036.

  PMID: 12663477 BACKGROUND

• Huang C, Kim Y, Caramori ML, Fish AJ, Rich SS, Miller ME, Russell GB, Mauer M. Cellular basis of diabetic nephropathy: III. In vitro GLUT1 mRNA expression and risk of diabetic nephropathy in type 1 diabetic patients. Diabetologia. 2004 Oct;47(10):1789-94. doi: 10.1007/s00125-004-1533-1. Epub 2004 Oct 22.

  PMID: 15502921 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

Skin Fibroblasts, Plasma and Serum samples, Urine samples, kidney biopsy culture samples.

MeSH Terms

Conditions

Diabetes Mellitus; Diabetic Nephropathies

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Diabetes Complications

Study Officials

• Michael S Mauer, MD

  Pediatric Nephrology, University of Minnesota

  PRINCIPAL INVESTIGATOR

• Arthur J Matas, MD

  University of MN, School of Medicine, Dept of Surgery

  STUDY DIRECTOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: INDIV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 7, 2005
• First Posted: September 12, 2005
• Study Start: January 1, 1981
• Primary Completion: August 1, 2014
• Study Completion: August 1, 2014
• Last Updated: December 11, 2014

Record last verified: 2014-12

Locations

US (1)