Saturday, October 12, 2019

Topic Discussion: HSCT associated TMA, a renal endothelial variant of GVHD

Kidney injury post HSCT is a mystery. While the initial AKI is from multiple causes, the chronic damage we see in the survivors of HSCT is not well understood. In a recent review in AJKD, we did consider this to be mostly TMA related. But is TMA a form of GVHD ( renal limited) is what some including us have proposed. When one looks at the literature from GVHD and links to the kidney- one thinks of secondary membranous, but perhaps this is a rare finding- endothelial glomerular damage might be more common(TMA).

In a recent mice study, the authors looked at HSCT effect on kidney in various murine models of GVHD. The most common finding was glomerular with classic mesangiolysis, mesangial proliferation and edema with subendothelial widening and microthombi. These are features of HSCT- associated TMA. So, it is very possible that getting a HSCT might be a second hit to several folks who might carry a complement deficiency and perhaps there is some activation of complement system.

Some of the literature proposes that TMA and GVHD are not related but both affect the complement cascade. As clinicians we have seen several cases of TMA and concurrent GVHD and a recent reported case series confirms this. It is intriguing and possible that renal-limited TMA might be a variant of GVHD.  GVHD is usually an epithelial cell disease but having an “endothelial” target might be possible in the kidney. In most cases, when TMA is diagnosed in a patient with HSCT, the knee jerk response is to discontinue CNIs. Whether this is of potential benefit or harm is not clear.

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