Topic Discussion: HSCT associated TMA

Recently, we wrote an article on Bone marrow transplant or HSCT related TMA for AJKD.
Few things that we have seen in our experience and also what we learnt while writing on this topic is important for Nephrologists to understand.

1.       Diagnosis of TMA related to HSCT that effects the kidney is hard to diagnosis. It is likely the most common kidney biopsy finding post HSCT.  Besides the lab parameters of kidney injury, TRENDING the LDH, haptoglobin, platelets and hemoglobin is critical. In addition, HTN might be the first and most important sign of impending TMA. If the patient requires more than 2 meds for HTN control, one for CNI and other for steroids, it is possible that there is a smoldering TMA . Perhaps we miss some of these cases due to this. Early Nephrology referral might be key as urinalysis is not uniformly done in most centers years post HSCT.

2.       Once infections such as parvo, BK and CMV have been ruled out, a complement mediated process is the likely cause.

3.       CNIs are usually portrayed as the most likely culprit but not all allogenic HSCTS are on CNI and none of the autologous HSCT are on CNIs, yet TMA ensues. In many instances, TMA still gets worse.

4.       Based on some recent findings in the basic science world and few case reports, we propose that TMA following HSCT in many cases might be an “endothelial” variant of GVHD. Treating the underlying GVHD might be the best option in these cases. This might open certain treatment avenues that we haven’t really encountered.

5.       If the TMA is not a ADAMTS13 process, or a “antibody” being removed, TPE doesn’t really help in most cases. Rituximab can be a potential option as this might also help treat GVHD. Alternatively, in many pediatric patients, eculizumab has been used with some success to halt the activated complement  process.