Microangiopathy in Kidney and Simultaneous Pancreas/Kidney Recipients Treated With Tacrolimus: Evidence of Endothelin and Cytokine Involvement

Abstract

These data are consistent with a mechanism of microangiopathy involving endothelial cell injury (associated with tacrolimus treatment), and accompanied by cytokines (IL-10, IL-12, tumor necrosis factor-a, interferon-gamma) that affect expression of adhesion molecules, chemokines (IL-8) that direct the influx of white blood cells and endothelins that may exacerbate underlying hypertension and increase shear force-related red blood cell destruction.

Diagnosis and treatment of transplantation-associated thrombotic microangiopathy: real progress or are we still waiting?

“…47,49,[72][73][74][75] In addition, calcineurin inhibitors used for GVHD prophylaxis have been associated with increased production of thromboxane A 2 (TXA 2 ) and decreased production of PGI 2 (CsA), 76,77 as well as direct toxicity to the endothelium (CYA and possibly tacrolimus). [78][79][80][81][82][83] The addition of sirolimus to a calcineurin inhibitor has been associated with potentiation of these effects. 22,23,84 The net effect of the changes to endothelial integrity induced by these insults may be the generation of a procoagulant endothelium, ultimately leading to a predilection for secondary TMA.…”

Effect of plasma exchange on cytokines measured by multianalyte bead array in thrombotic thrombocytopenic purpura

“…In childhood TTP/hemolytic uremic syndrome, IL-6 and TNF-a were shown to be elevated [23]. In kidney/pancreas transplant patients who developed TTP following treatment with tacrolimus, IL-8, IL-10, and IL-12 were elevated during the acute phase in all three reported patients [24]. TNF-a and IFN-g were elevated in 2 of 3 patients, whereas IL-6 was normal.…”

“…TGF-b1 upregulation has also been reported to be partially protective, suppressing microvascular endothelial cell damage via its anti-apoptotic properties [20]. Measurements of other cytokines including pro-inflammatory cytokines have produced variable results and have been limited to measurements at the disease onset and complete remission [21][22][23][24][25]. In this pilot study, we used a novel multiplexing bead array technique that allowed for simultaneous measurement of multiple cytokines in single serum samples.…”

Transplant-Associated Thrombotic Microangiopathy in Childhood

“…Cyclosporine and most probably tacrolimus show direct toxicity to endothelium (40)(41)(42)(43)(44)(45) and addition of sirolimus to calcinorin inhibitors potentializes these toxic effects (46)(47)(48).…”