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Diagnosis:
Thrombotic microangiopathy (originated in the donor)

Thrombotic microangiopathy (TMA) is defined by the presence of thrombi in capillary and/or arterioles. TMA is also a well-recognized serious complication of renal transplantation. Clinical features of intravascular hemolysis are not always found. It may occur as de novo or recurrent and the majority of de novo cases are related to cyclosporin therapy. Viral infections, severe renal ischemia and acute vascular rejection are less frequent causes.

The presence of fibrin thrombi within the glomerular capillaries or arterioles is used to define thrombotic microangiopathy. Systemic TMA is diagnosed by the presence of thrombocytopenia and evidence of microangiopathic hemolysis. Patients with the biopsy findings compatible with thrombotic microangiopathy but without any systemic finding is considered as having localized TMA.

Two forms of post-transplant TMA may be recognized: recurrent TMA and de novo TMA. Recurrent TMA may occur in patients who developed a nondiarrhoeal form of haemolytic uraemic syndrome (HUS) being particularly frequent in patients with autosomal recessive or dominant HUS. The recurrence is almost the rule in patients with mutation in complement factor H gene. Most patients eventually lose the graft. De novo TMA is rarer. A number of factors including viral infection may be responsible of de novo TMA, but in most cases TMA is triggered by calcineurin inhibitors or mTOR inhibitors. The clinical presentation of de novo TMA may be variable with some patients showing clinical and laboratory features of HUS while others showing only a progressive renal failure (in localized forms of the disease). The prognosis is less severe than with recurrent TMA. Complete withdrawal of the offending drug may lead to improvement in many cases. The addition of plasma exchange may result in graft salvage in about 80% of cases. (Ponticelli C, Banfi G. Thrombotic microangiopathy after kidney transplantation. Transpl Int. 2006;19(10):789-94. [PubMed link])

The association between cyclosporine (CsA) and TMA was first suggested in 1981; only a minority of the patients with CsA-associated TMA has the full clinical picture of hemolytic uremic syndrome, and the diagnosis is frequently not apparent before a renal biopsy is performed. Cases of tacrolimus-induced and m-TOR-inhibitors-induced TMA have also been reported.

In our case the very early TMA develop and, mainly, the presence of TMA in both receptors of this donor permit us the diagnosis of donor-originated TMA. The other receptor, a 9-year-old girl had also a similar clinical and histologic picture, but different to our case, this patient showed mild thrombocytopenia and evidence of microangiopathic hemolysis. Both patients recovered completely the renal function and a second renal biopsy, 2 weks later to the first biopsy showed few microthrombi. Both allografts are well several month after transplantation.

An intact fibrinolytic system can dissolve microthrombi in most cases of sparse donor glomerular involvement, and in at least some cases of extensive or diffuse glomerular TMA, as evidenced in these two receptors.

Etiology in our case is probably related to final premortem events in the donor, and ischemia-reperfusion injury.

See the chapter Vascular Diseases of our Tutorial (at present only there is a Spanish version).

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Bibliography

• Goplani KR, Vanikar AV, Shah PR, Gumber M, Feroz A, Patel HV, Kasat P, Falodia J, Saboo D, Kaswaan K, Geerish MS, Pandya T, Trivedi HL. Postrenal transplant hemolytic uremic syndrome/thrombotic microangiopathy: Ahmedabad experience. Transplant Proc. 2008;40(4):1114-6. [PubMed link]
• Ardalan MR, Shoja MM, Tubbs RS, Etemadi J, Esmaili H, Khosroshahi HT. Thrombotic microangiopathy in the early post-renal transplant period. Ren Fail. 2008;30(2):199-203. [PubMed link]
• Ardalan MR. Review of thrombotic microangiopathy (TMA), and post-renal transplant TMA. Saudi J Kidney Dis Transpl. 2006;17(2):235-44. [PubMed link] [Free full text]
• Ponticelli C, Banfi G. Thrombotic microangiopathy after kidney transplantation. Transpl Int. 2006;19(10):789-94. [PubMed link]
• Jumani A, Hala K, Tahir S, Al-Ghamdi G, Al-Flaiw A, Hejaili F, Qureshi J, Raza H, Ghalib M, Khader AA. Causes of acute thrombotic microangiopathy in patients receiving kidney transplantation. Exp Clin Transplant. 2004;2(2):268-72. [PubMed link][Free full text]

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