Research

The renal division of Maine Medical Center is entirely staffed by the physicians of Maine Nephrology Associates. Drs. Jonathan Himmelfarb and John Vella have an extensive background in both clinical and basic science research that is pertinent to kidney disease and transplantation.

Jonathan Himmelfarb, MD

Dr. Jonathan Himmelfarb is one of the country's leading researchers in the field of nephrology. His work has resulted in many publications in peer-reviewed medical journals, as well as several book chapters and editorials. Research in Dr. Himmelfarb's laboratory, located at Maine Medical Center Research Institute, is focused on improving the outcomes for patients with kidney disease. These include patients with acute kidney disease, chronic kidney disease, and end-stage renal disease requiring dialysis or transplantation for survival. They employ a translational, "bedside to bench to bedside" approach to solving problems in patients with kidney disease, using advanced biochemical and molecular cell biological approaches to the examination of blood, urine, and kidney tissue specimens from patients with kidney disease. With this patient-oriented research approach, they are attempting to develop novel therapies to improve the outcomes for patients with kidney disease based on improved understanding of the molecular, biochemical, and cellular pathogenesis of complications related to kidney disease. The long-term goals of Dr. Himmelfarb's research include:
  1. Understanding how the loss of kidney function leads to increased oxidative stress, acute phase inflammation, and endothelial dysfunction, which in turn contribute to cardiovascular disease.Studying how antioxidants administered to patients with chronic kidney disease can attenuate oxidative stress, inflammation, endothelial dysfunction, and cardiovascular risk.
  2. Understanding the metabolic effects that accompany acute renal failure and affect recovery of kidney function. These include the study of insulin-resistance pathways, as well as inflammatory, erythropoietic, and angiogenic signaling pathways.
  3. Understanding the pathogenesis of acute kidney transplant dysfunction (frequently called delayed graft function) including an understanding of ischemic, inflammatory, and metabolic conditions that lead to or are the result of delayed graft function. This approach includes detailed examination of the molecular pathology of allografts at the time of transplantation, as well as the development of plasma and urinary biomarkers that predict the development of and recovery from delayed graft function. Novel therapeutic approaches to preventing the development of delayed graft function are also being explored.
  4. Understanding the pathogenesis and consequences of chronic allograft nephropathy, a condition characterized by long-term progressive fibrosis and renal tubular atrophy after kidney transplantation. Our approach to understanding chronic allograft nephropathy involves detailed molecular characterization of kidney transplant biopsy tissue in patients with chronic allograft nephropathy, as well as plasma and urinary biomarker discovery. Long-term metabolic consequences of chronic allograft nephropathy include an increase in oxidative stress, acute phase inflammation, and endothelial dysfunction (similar to patients with chronic kidney disease without kidney transplantation). We approached this problem by studying surrogate markers of atherosclerosis and determining the extent to which novel therapies including antioxidant therapy may be beneficial.
  5. Isolation of adult human kidney progenitor cells that will aid in the development of novel renal replacement therapies including regenerative therapies.
Dr. Himmelfarb's laboratory staff includes Ellen McMonagle (research associate), Elizabeth McMenamin and Phuong Le (research assistants), and Stephanie Freedman, RN, Jane Kane, RN, and Helen Cyr-Alves, RN (research nurses).

John P. Vella, MD

Having completed his training in Ireland, Dr. Vella completed a four year fellowship in nephrology and tranplantation at Brigham and Women's Hospital in Boston. He remains active in both clinical studies as well as research into the immunologic basis of rejection post-transplantation. Publications

Clinical Research:

  1. Immunosuppression without calcineurin inhibition: Shattering the prevailing paradigm: A clinical trial sponsored by Roche laboratories and approved by the Institutional Review Board of Maine Medical Center. This pilot study is currently underway and is designed to look at a novel combination of anti-rejection medications in patients who receive kidneys from older donors.
  2. A randomized, open label, comparative evaluation of conversion from calcineurin inhibitors to sirolimus versus continued use of calcineurin inhibitors to renal allograft recipients. This trial sponsored by Wyeth laboratories will examine the impact of converting from one type of anti-rejection medication to another on long term function of kidney transplants. Recruitment will start in December.
Basic Immunology:

Currently, Dr. Vella is carrying out some immunologic studies focusing on why some people experience rejection and others do not. This work is funded through a variety of sources which include the Maine Medical Center Research Institute. A technologist, Shay Harris, is employed full time at MMCRI on these studies which involve a variety of assays including flow cytometry, PCR and cell culture. Krista Garrison is a research study coordinator based at Maine Medical Center.