TMA in Kidney Transplantation

Abstract

Thrombotic microangiopathy (TMA) is a rare and devastating complication of kidney transplantation, which often leads to graft failure. Posttransplant TMA (PT-TMA) may occur either de novo or as a recurrence of the disease. De novo TMA can be triggered by immunosuppressant drugs, antibody-mediated rejection, viral infections, and ischemia/reperfusion injury in patients with no evidence of the disease before transplantation. Recurrent TMA may occur in the kidney grafts of patients with a history of atypical hemolytic uremic syndrome (aHUS) in the native kidneys. Studies have shown that some patients with aHUS carry genetic abnormalities that affect genes that code for complement regulators (CFH, MCP, CFI) and components (C3 and CFB), whereas in 10% of patients (mostly children), anti-FH autoantibodies have been reported. The incidence of aHUS recurrence is determined by the underlying genetic or acquired complement abnormality. Although treatment of the causative agents is usually the first line of treatment for de novo PT-TMA, this approach might be insufficient. Plasma exchange typically resolves hematologic abnormalities but does not improve kidney function. Targeted complement inhibition is an effective treatment for recurrent TMA and may be effective in de novo PT-TMA as well, but it is necessary to establish which patients can benefit from different therapeutic options and when and how these can be applied.

“Eculizumab First” in the Management of Posttransplant Thrombotic Microangiopathy

“…However, recent evidence have emphasized its role in the predisposition to secondary HUS under strong complement-activating conditions, such as kidney transplant, even in patients without other genetic variants. 18 , 32 , 33 Our data could confirm this hypothesis, because among patients with the haplotype MCP C.∗897 T>C (rs7144) , only the half of them had a combination of this condition with other complement risk factors (polymorphisms or risk haplotypes).…”

“…However, the lack of diagnosis awareness and the absence of clear therapeutic strategies often cause a delay that can lead to the graft loss. 18 , 19 …”

A Head-to-head Comparison of De Novo Sirolimus or Everolimus Plus Reduced-dose Tacrolimus in Kidney Transplant Recipients: A Prospective and Randomized Trial

“…mTORi and CNIs are associated with an increased risk of de novo TMA, primarily in the presence of additional risk factors for endothelial damage such as ischemia–reperfusion injury early after transplantation. 29 Perhaps the ideal strategy is to delay its introduction till full recovery of graft function after ischemia–reperfusion injury.…”

Thrombotic Microangiopathy in Solid Organ Transplantation

“…In the setting of de novo TMA post-transplantation occurring secondary to immunosuppression, the offending agent should be reduced or stopped immediately. This occurs most commonly in the setting of CNI use post-transplant and the patient is typically switched to the alternative CNI or an MTOR inhibitor once deemed clinically appropriate based on TMA resolution [76]. In cases where continuation of a CNI is desired, tacrolimus can be switched to cyclosporine and vice versa.…”