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Diagnosis: Thrombotic microangiopathy

In the present case there is not histologic features of rejection. Interstitium, tubules and vessels do not present alterations. However in glomeruli there are capillary thrombi, some with cellular fragmentation (Figure 4). The microphotographies of sections stained with H&E are very characteristics and permit the diagnosis in this case. Trichrome stain and staining for fibrin help in questionable cases.

The patient continued with worse renal function, and three post-biopsy days she developed thrombocitopenia, without evidence of other organs afectation. Cyclosporin was discontinuated and sirolimus was introduced. Fifteen days after, renal function started to improve and platelet count was on the rise. A year later renal function is well: serum creatinine 1.2 mg/dL.

Thrombotic microangiopathy (TMA) includes syndromes of microangiopathic hemolytic anemia, thrombocytopenia, renal dysfunction, fever, and associated organ impairments. Development of TMA has been documented also in organ transplant recipients, the majority of which presumably are associated with calcineurin inhibitors (CNI). In pathogenesis of TMA, vascular endothelial injury and platelet aggregation seem to play a pivotal role. Furthermore, several viruses, including CMV, HIV, and parvovirus B19, also have been implicated. Acute humoral rejection (antobodies mediated) can be other TMA cause, although inusual, in kidney allografts.

TMA can involve small vessels and is characterized by intravascular thrombi of aggregated platelets leading to thrombocytopenia and variable degrees of organ ischemia and anemia, which is due to erythrocyte fragmentation in microcirculation. Recent discovery of the von Willebrand Factor cleaving protease (ADAMTS 13) has offered new insight into the pathogenesis of TMA. In TMA of renal allografts 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. Recurrence is negligible in diarrhea-associated HUS in childhood, but non-diarrheal HUS recurs in majority of adults following renal transplantation.

In the majority of posttransplantation TMA induction, the association of cyclosporine or tacrolimus has been inferred because the agents can be directly toxic to endothelial cells and can induce vasoconstriction of the microvasculature and platelet aggregation. Many cases of posttransplant TMA respond to reduction of CNI.

Treatment of posttransplantation TMA relies on removal of any precipitating factors, relief of symptoms, and plasmapheresis or plasma infusion. TMA can be life-threatening in recipients after heart or lung transplantation. In post kidney transplantation TMA have a better prognosis, and if limited to the allograft, resolution is reported around to 80%.

Patients with systemic TMA are more likely to be treated with plasma exchange, more often require dialysis therapy, and have a greater rate of graft loss. Patients with localized TMA often respond to reduction, conversion, or temporary discontinuation of CNI-based immunosuppression therapy and does not routinely require plasma exchange for graft salvage. Classifying patients with post-renal transplantation TMA into those with localized and systemic disease is clinically useful because each group has distinct characteristics and clinical courses.

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Bibliography

• Nishi H, Hanafusa N, Kondo Y, Nangaku M, Sugawara Y, Makuuchi M, Noiri N, Fujita T. Clinical Outcome of Thrombotic Microangiopathy after Living-Donor Liver Transplantation Treated with Plasma Exchange Therapy. Clin J Am Soc Nephrol 2006; 1: 811-819. [Full text link]
• Manzoor K, Ahmed E, Akhtar F, Kazi JI, Naqvi SA, Rizvi SA. Cyclosporine withdrawal in post-renal transplant thrombotic microangiopathy. Clin Transplant. 2006; 20:43-7. [PubMed link]
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