Related Experiment Videos
Insulin resistance as putative cause of chronic renal transplant dysfunction
Aiko P J de Vries1, Stephan J L Bakker, Willem J van Son
1Division of Nephrology Department of Medicine, Groningen University Medical Center, Groningen, The Netherlands. a.p.j.de.vries@int.azg.nl
Abstract:
Transplantation is the preferred organ replacement therapy for most patients with end-stage renal disease. Despite impressive improvements over recent years in the treatment of acute rejection, approximately half of all grafts will loose function within 10 years after transplantation. Chronic renal transplant dysfunction, also known as transplant atherosclerosis, is a leading cause of late allograft loss. To date, no specific treatment for chronic renal transplant dysfunction is available. Although its precise pathophysiology remains unknown, it is believed that it involves a multifactorial process of alloantigen-dependent and alloantigen-independent risk factors. Obesity, posttransplant diabetes mellitus, dyslipidemia, hypertension, and proteinuria have all been identified as alloantigen-independent risk factors. Notably, these recipient-related risk factors are well-known risk factors for cardiovascular disease, which cluster within the insulin resistance syndrome in the general population. Insulin resistance is considered the central pathophysiologic feature of this syndrome. It is therefore tempting to speculate that it is insulin resistance that underlies the recipient-related risk factors for chronic renal transplant dysfunction. Recognition of insulin resistance as a central feature underlying many, if not all, recipient-related risk factors would not only improve our understanding of the pathophysiology of chronic renal transplant dysfunction, but also stimulate development of new treatment and prevention strategies.
Insights
Insulin resistance may underlie recipient-related risks for chronic kidney transplant dysfunction, a major cause of graft loss. Identifying this link could lead to new prevention and treatment strategies for transplant atherosclerosis.
Area of Science:
- Nephrology
- Immunology
- Endocrinology
Background:
- Kidney transplantation is the primary therapy for end-stage renal disease.
- Graft loss within 10 years affects approximately 50% of kidney transplants, with chronic dysfunction (transplant atherosclerosis) being a major cause.
- Current treatments for chronic renal transplant dysfunction are lacking.
Purpose of the Study:
- To explore the potential role of insulin resistance in recipient-related risk factors for chronic renal transplant dysfunction.
- To investigate the link between insulin resistance and factors like obesity, diabetes, dyslipidemia, hypertension, and proteinuria in transplant recipients.
Main Methods:
- Review of existing literature on risk factors for chronic renal transplant dysfunction.
- Analysis of the association between recipient-related risk factors and the insulin resistance syndrome.
- Speculative hypothesis generation based on current pathophysiological understanding.
Main Results:
- Alloantigen-independent risk factors for chronic renal transplant dysfunction (obesity, posttransplant diabetes mellitus, dyslipidemia, hypertension, proteinuria) are linked to cardiovascular disease and the insulin resistance syndrome.
- Insulin resistance is a central feature of the insulin resistance syndrome in the general population.
Conclusions:
- Insulin resistance is a plausible central pathophysiologic feature underlying recipient-related risk factors for chronic renal transplant dysfunction.
- Recognizing insulin resistance could enhance understanding and drive the development of novel therapeutic and preventive strategies for chronic kidney transplant dysfunction and transplant atherosclerosis.