Blog entry by Meguid El Nahas
Mohan and colleagues in the December issue of JASN report on the prognostic value of pre-transplant DSA (Donor Specific Antibodies) measured by solid phase assays (SPA) in relation to renal allografts outcomes. Mohan et al. JASN 2012;23:2061-2071.
They undertook a systematic review of cohort studies comprising a total of 1119 patients inclduing 145 with isolated DSA-SPA.
They noted that in the presence of negative Complemenet dependent cytotoxicity (CDC) crossmatch, a positive DSA-SPA (such a Luminex) doubles the risk of antibody-mediated rejection (AMR) and increases the risk of long term graft failure. This suggests that recipients should be checked for DSA regardless of a negative cross match. Of interest, the negative impact of a positive DSA-SPA test at transplantation on outcomes was noted regardless of the SPA titre (mean fluorescence index: MFI, low 1000).
This observation is in agreement with previous publications:
For instance, Lefaucheur and colleagues in 2010 showed that patients with MFI >6000 had >100-fold higher risk for AMR compared to those with MFI <465. The presence of HLA-DSA did not affect patients survival. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2938596/
Gary Hill and colleagues in Paris showed that DSA+ recipients have a three fold increase incidence of renal arteriosclerosis. Such accelerated arteriosclerosis was noted early within teh course of the allograft (3-12 months after transplantation). http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3083319/
My comments are:
1. Interesting observation consistent with the literature on the topic.
2. How would routine DSA-SPA screening affect outcomes?
This may stratify patients into higher risk warranting stronger initial/induction immunosuppression with ATG/Alemtuzumab.
It may also trigger closer monitoring of DSAs after transplantation and lead to related maintenance immunosuppression related strategies.
Alternatively, DSA screening would be undertaken if and when AMR is suspected; onset of albuminuria for instance!
3. Is routine DSA-SPA of all transplant recipients cost effective?
4. Are all DSAs harmful?
5. Is detection of DSA-SPA antibodies of unknown significance create unecessary investigations, excessive testing and unecessary patients' anxiety?
Is this a luxury few renal transplantation centres can afford or is it a game changer in renal transplantation?