Recent studies show that elevated Creatinine levels are a late indicator of damage done to a graft. In fact, subclinical acute rejection (silent rejection) is prevalent in 25% of patients histology and characterized as borderline in 80% of these cases1. Until recently, studies have ignored the prevalence of borderline rejection in protocol biopsies that could be a leading cause for renal failure.
Subclinical Acute Rejection, also referred to as "silent" rejection or "inflammation", is when a patient has a stable serum creatinine (within normal range for the patient) but without renal deterioration. It is further classified as:
Clinical Acute Rejection is the consequence of an immune response to the graft once significant damage has occurred. Some signs and symptoms of Clinical Acute Rejection are elevated serum creatinine, decreased urine output, proteinuria.
Some causes of acute kidney injury are:
Subclinical acute rejection is not easily detected and is caused by mononuclear cell infiltration of renal tubules without renal dysfunction. While clinical acute rejection is detected once enough damage to the kidney has occurred. Timely detection of subclinical acute rejection and intervention can lead to better long-term graft outcome.
Other than risky biopsies, TruGraf is the only alternative to rule out "silent" rejection in stable kidney patients.
* Am J Transplant 2010; 10(9): 2066–73; Am J Transplant 2010; 10: 324–330
No protocol is a one-size-fits-all and monitoring assays are no exception. That's why understanding what test is right for your patient is crucial. Below is a comparison of TruGraf vs dd-cfDNA and their utility.
TruGraf® is a non-invasive blood test validated to rule out "silent" subclinical acute rejection in stable kidney transplant recipients.
Donor-derived cell-free DNA (dd-cfDNA) is an non-invasive assay that monitors clinical acute rejection in transplant recipients.
Normal Kidney Biopsy
Borderline T Cell Mediated Rejection
Banff IA Acute T Cell Mediated Rejection
Banff IB Acute T Cell Mediated Rejection
dd-cfDNA assays do not rule out silent rejection in patients with stable renal function.
Study: J Am Soc Nephrol 20; 28: 2221–2232
The use of dd-cfDNA may complement the Banff classification and risk stratify patients with borderline/TCMR 1A identified on biopsy
But it's only useful AFTER a biopsy, and not for surveillance.
Study: doi: 10.1111/AJT.15822
Despite published data, dd-cfDNA can’t distinguish STA (stable) from BL (borderline), and 80% of subclinical rejection cases are BL.
The data provided either can’t be classified as “subclinical” by definition or there's a lack of data on renal function and therefore impossible to draw conclusions from the data set.