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Optimizing early de novo immunosuppression with sirolimus
1Division of Nephrology, Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA. mweir@medicine.umaryland.edu
Abstract:
In the past, renal transplant deterioration was approached as a problem of "chronic rejection," which implied that deterioration of kidney function occurred because of past injuries that programmed the kidney for loss of function. New evidence suggests that deterioration occurs because of a new or recent source of injury. If a graft is losing function, the cause of deterioration needs to be identified. Some causes are treatable; those that are not should be diagnosed and further studied. To this end, we need to approach deterioration (loss of function or proteinuria) of renal transplant function by identifying distinct entities or components of the problem. Early and late kidney graft survival has improved considerably, owing to advances in clinical care, particularly immunosuppression. Many of the kidney transplants functioning today should serve their new owners for their life expectancy. The main cause of late kidney function deterioration remains allograft nephropathy. Often this reflects a failure of the immunosuppressive prescription. Subclinical rejection, chronic nephrotoxicity, recurrent disease, infections, or diabetes may contribute to this process. Optimal early and late immunosuppression is required to provide efficacy without attendant risk for graft dysfunction owing to nephrotoxicity. Because 1-year serum creatinine levels often provide an indication of long-term graft function, early evaluation of subtle degrees of graft dysfunction should prompt a graft biopsy to identify treatable causes.
Insights
Kidney transplant deterioration is now viewed as a result of new injury, not just past damage. Identifying and treating recent causes is crucial for preserving long-term kidney graft function.
Area of Science:
- Nephrology
- Transplantation Immunology
Background:
- Renal transplant deterioration was historically attributed to chronic rejection, implying irreversible damage from past insults.
- Recent evidence indicates that graft dysfunction often stems from new or ongoing injury, necessitating a re-evaluation of its causes.
Purpose of the Study:
- To shift the paradigm of understanding renal transplant deterioration from chronic rejection to identifying distinct, potentially treatable, recent causes of graft dysfunction.
- To emphasize the importance of early detection and intervention for suboptimal graft function.
Main Methods:
- Review of current evidence and clinical understanding of renal transplant graft deterioration.
- Emphasis on clinical evaluation, including proteinuria and serum creatinine levels, as indicators of graft health.
- Highlighting the diagnostic value of graft biopsy in identifying treatable causes of dysfunction.
Main Results:
- Kidney graft survival has significantly improved due to advancements in immunosuppression and clinical care.
- Allograft nephropathy remains a primary cause of late graft function loss, often linked to suboptimal immunosuppression.
- Factors like subclinical rejection, nephrotoxicity, infections, and recurrent diseases contribute to graft deterioration.
Conclusions:
- Renal transplant deterioration requires a proactive approach focused on identifying and addressing new or recent sources of injury.
- Optimal immunosuppression is critical to balance efficacy and minimize nephrotoxicity.
- Early assessment of subtle graft dysfunction, including prompt biopsy, is essential for timely diagnosis and treatment, improving long-term outcomes.
