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Abstract

Objectives: Thrombotic microangiopathy is a form of renal capillary injury possibly associated with calcineurin inhibitor toxicity, acute humoral rejection, infections, and recurrent diseases. Here, we examined its incidence in patients diagnosed with acute and chronic active humoral rejection, polyomavirus nephropathy, acute cellular rejection, and immunoglobulin A recurrence. Materials and Methods: In total, 272 renal allograft recipients who met the inclusion criteria were reevaluated for presence of renal thrombotic microangiopathy. Thrombotic microangiopathy diagnosis was established by clinical, laboratory, and histologic features. C4d expression in peritubular capillaries was determined. Clinical data were collected from medical records. Results: Of 272 patients (mean age of 42.8 ± 12.7 years), only 74 patients (27.2%) had de novo thrombotic microangiopathy, which was found in 30/90 patients (33.3%) with acute humoral rejection, 9/51 (17.6%) with acute cellular rejection, 22/53 (41.5%) with chronic active humoral rejection, 10/55 (18.2%) with polyomavirus nephropathy, and 3/23 (13%) with immunoglobulin A nephropathy. Significant differences were shown between therapy type and thrombotic microangiopathy development (P = .02). Patients who received cyclosporine (38.5%) tended to show higher incidence of thrombotic microangiopathy than patients who received tacrolimus (20.7%) or sirolimus (7.7%). Patients with C4d-positive acute humoral (97.6% vs 2.4%) and chronic active humoral rejection (68.2% vs 31.8%) had greater incidence of thrombotic microangiopathy versus those who were C4d-negative. Graft loss was significantly higher in C4d-positive than in C4d-negative thrombotic microangiopathy groups (P < .001). Overall 1-, 3-, and 5-year graft survival was 94%, 85%, and 85% versus 83%, 51%, and 51% in thrombotic microangiopathy-negative versus thrombotic microangiopathy-positive patients (P < .001). Conclusions: Acute humoral rejection and chronic active humoral rejection were the most common and therefore most important causes of de novo thrombotic microangiopathy in renal transplant patients. Its presence in the renal allograft biopsy should arouse suspicion for underlying acute or chronic active humoral rejection. Key words: Acute cellular rejection, Acute humoral rejection, C4d expression, Chronic active humoral rejection, IgA nephropathy, Polyomavirus nephropathy, Renal allograft biopsy IntroductionThrombotic microangiopathy (TMA) describes a pathologic lesion in which abnormalities in the vessel wall of arterioles and capillaries lead to microvascular thrombosis. The clinical features of TMA result from the obstruction of the microcirculation and ultimately depend on the distribution of involved vascular beds. Microangiopathic hemolysis is the hallmark feature of this obstructed microcirculation. Thrombotic microangiopathy is a pathologic diagnosis, but its presence is commonly inferred from observations of thrombocytopenia and microangiopathic hemolysis in the appropriate clinical setting. [1][2]...

Unveiling the Incidence and Graft Survival Rate in Kidney Transplant Recipients With De Novo Thrombotic Microangiopathy: A Systematic Review and Meta-Analysis

“…However, the 2-year graft loss rate was similar between the two groups, with nearly 40% in each group. In contrast, another study of 74 individuals with kidney allograft TMA found that those with C4d+ had a higher graft loss rate than those without C4d staining (55.6% vs. 30%) [ 46 ]. Nevertheless, C4d deposits are not uncommon in kidney allograft TMA, particularly in the glomeruli.…”

Microangiopatía trombótica en el trasplante renal, el tacrolimus como causante

“…La patogenia del MAT se centra en la activación de las células del endotelio vascular, el daño por activación leucocitaria y agregación plaquetaria [6] . Existen diferentes factores desencadenantes que incluyen bacterias, virus, toxinas y drogas (inhibidores de la calcineurina), injuria isquemia-reperfusión, RMA y activación o disregularización del complemento en la aparición del MAT [7][8][9][10] . El caso clínico planteó dos problemas diagnósticos, el primero estuvo centrado en diferenciar si se trataba de una MAT recurrente o de novo.…”

“…El caso clínico planteó dos problemas diagnósticos, el primero estuvo centrado en diferenciar si se trataba de una MAT recurrente o de novo. El SUH recurrente según la literatura se manifiesta con MAT sistémico como es el caso de la paciente y ocurre en el trasplante temprano [9][10][11] , mientras que el MAT secundario es de afectación renal preferentemente y de aparación tardía (después del año), sin embargo, la paciente no tenía ancedente de SUH como causa de su enfermedad renal crónica. Por otro lado, no se pudieron realizar estudios para determinar si se trata de una deficiencia de Dentro de las causas de MAT de novo que se consideraron en la paciente tenemos el RMA, infección por CMV y la toxicidad por tacrolimus [8][9][10][11] .…”

Thrombotic microangiopathy after kidney transplantation: Expanding etiologic and pathogenetic spectra

“…The prognosis of de novo or recurrent TMA in kidney allografts is generally guarded and varies according to underlying causes[ 60 - 68 ]. With better understanding and characterization of the disease, the patient and allograft outcomes are improving steadily.…”