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Late Renal Allograft Dysfunction

Bethesda Marriott
Bethesda, MD
July 15, 2004

Summary

Over the last decade, the incidence of ESRD has increased at a faster rate than the availability of kidney donors (USRDS 2003 Annual Data Report). As a result, the rate of kidney transplants per 100 patient years on dialysis has declined steadily. Although renal allograft and recipient survivals have also increased during the last decade, over the last several years one-year graft survival and allograft half-life are largely unchanged.

Despite effective immunosuppressive strategies that have markedly reduced rates of early allograft failure over time, occurrence of late renal allograft loss remains a significant problem in the transplant patient population. The number of patients returning to dialysis therapy each year has nearly doubled in the last decade, as approximately 4,500 patients with failed transplants restarted dialysis in 2001 (USRDS). Such patients represented approximately 4.7% of the total number of patients starting or restarting dialysis in 2001.

Observations from clinical studies suggest that in addition to cellular and humorally-mediated allograft rejection, other non-immunologically-mediated factors likely contribute to progressive loss of kidney function in transplant recipients. Donor factors such as age and cadaveric status, as well as transplant characteristics such as form of preservation and vascular anatomy also contribute to progressive renal dysfunction. In addition, recipient factors such as hypertension, vascular disease, proteinuria, drug exposure, and post-transplant infections likely play a role in late allograft failure.

In view of the apparent trends for late renal allograft loss, and the increasing incidence of chronic kidney disease and ESRD in this patient population, NIDDK and NIAID are sponsoring a workshop to discuss immunologic and non-immunologic factors that influence late allograft outcome. Clinical investigators interested in late renal allograft dysfunction will discuss the current understanding of the problem, outline important questions that should be studied, and recommend strategies for future investigations.

Agenda

Draft Agenda as of April 9, 2004

	7:30am	Registration, Continental Breakfast & Introductions
		Late Renal Allograft Loss Chair: Phillip Halloran
	8:00am	Clinical Definition, Risk Factors & Rationale for a Classification Lawrence Hunsicker
	8:30am	The Pediatric Perspective on Late Renal Allograft Loss William Harmon
	9:00am	Histopathologic Lessons from Late Renal Allograft Loss Robert Colvin
	9:30am	Discussion
		Allograft Injury -Mechanisms and Renal Response Chair: Arthur Matas
	10:00am	Progression of Renal Injury after Transplant Sundaram Hariharan
	10:20am	AlloAntibody-Mediated Injury Paul Terasaki
	10:40am	Immunosuppression William Bennett
	11:00am	Renal Allograft Response to Injury Phillip Halloran
	11:20am	BK Virus and Late Allograft Function Roslyn Mannon
	11:40am	Working Lunch with Discussion
		Utilty of Databases Chair: Lawrence Hunsiker
	1:00pm	Tools for Transplant Research Bertram Kasiske
	1:20pm	The Scientific Registry of Transplant Recipients Robert Merion
	1:50pm	Lessons from Studies of CKD Joseph Coresh
	2:10pm	Discussion
		Group Discussions on Clinical Studies of Late Allograft Loss Chair: William Harmon
	2:30pm	Endpoints & Study Designs to Evaluate Renal Allograft Loss Arthur Matas
	2:40pm	Protocol Biopsies and Analyses & Sample Repositories Allan Kirk
	2:50pm	In Search of Biomarkers or Surrogate Measures of Reduced Renal Function or Rejection Microarrays Minnie Sarwal
	3:00pm	In Search of Biomarkers or Surrogate Measures of Reduced Renal Function or Rejection Small Molecules Peter Nickerson
	3:10pm	Discussion
	4:00pm	Summary (Kirk & Meyers)