Studies of Organ Transplantation in Animals and Man
Condition: Diabetes Mellitus
MeSH terms: Diabetes Mellitus
Study type: Observational

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.
    

Detailed description: 
      These continuation studies focus on large pancreas (PTx) and kidney (KTx) transplant
      populations of type 1 diabetic (D) patients (pts) in order to better understand diabetic
      nephropathy (DN), the leading cause of renal failure. Objectives are: (a) to determine
      whether PTx can more readily arrest or reverse the early vs. the more established lesions of
      DN; (b) to continue studies of renal structural-functional relationships in DN, with emphasis
      on the multifaceted pathologic DN lesions, including glomerular, vascular, interstitial
      lesions and glomerular-tubular connections; (c) to continue studies of DN natural history and
      the role of renal biopsy in predicting outcome; (d) to quantitate and understand the basis of
      atubular glomeruli (AG) in DN; (e) to elucidate glomerular (glom) epithelial cell
      abnormalities in DN; (f) to study the glom extracellular matrix abnormalities of DN; (g) to
      study the recurrence of DN in the KTx; (h) to study the molecular/genetic basis of DN and
      develop cellular markers of DN risk; (i) to determine the long-term (10-15 yr) structural
      consequences of cyclosporine (CSA) on the native kidneys of PTx recipients; and (j) to
      determine the shorter-term (5 yr) consequences of Prograf on the native kidneys of PTx
      recipients and compare these with those seen after 5 years of CSA treatment. Together, these
      studies will help to elucidate the pathogenesis and natural history of DN, unravel some of
      the molecular and genetic aspects of this disease, describe the dynamics of DN reversal in
      PTx pts, and recurrence in KTx pts and expand our knowledge of the nephrotoxic effects of
      calcinosis inhibitors.
    

Observational model: Cohort
Time perspective: Prospective
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.
      
Biospecimen description: 
      Skin Fibroblasts, Plasma and Serum samples, Urine samples, kidney biopsy culture samples.
    
Keywords: Diabetic Nephropathy; Kidney Transplant; Pancreas Transplant; Renal Interstitium; Diabetes Mellitus; Cyclosporine; Tacrolimus