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Thrombotic microangiopathy (TMA) after kidney transplantation is a rare but severe complication, significantly affecting long-term patient and graft survival. The reasons for the development of TMA in a transplant are varied, and patient management depends on its nature. Kidney biopsy allows to suspect TMA, in many cases. However, it is not always possible to unambiguously verify TMA and clarify its cause based on biopsy data. The aim of this study was to evaluate the incidence of TMA in a kidney transplant based on biopsy data and to analyze the sensitivity and specificity of this method to verify the diagnosis of TMA and clarify its nature.
A single center non-interventional retrospective study using electronic database of 1780 index graft biopsies (2012 to 2022y), identified 89 biopsies with signs of TMA (5.1%). None of of these patients had TMA diagnosed prior to transplantation. The mean time between transplantation and kidney biopsy was 36.5 ± 48.3 months (range 1 day to 152 months). A genetic screening in genes encoding complement-regulatory proteins and hereditary thrombophilia was performed in 18 patients. Mean follow-up – 17,8 ± 23,1 months.
According to the histological picture, 2 groups of patients were identified. The first group consisted of 38 cases with a picture definitely indicating TMA, the second group included 51 patients with findingы suspicious for TMA and requiring differential diagnosis with other conditions, such as chronic humoral rejection, glomerulonephritis and chronic CNI-nephrotoxicity. The most common findings in this group were C4d-/DSA- transplant glomerulopathy and/or vasculopathy (n=24), MPGN pattern negative for immunoglobulins and complement (n=4), ischemic nephropathy and/or focal cortical necrosis without signs of large vessels pathology ( n=5). In 18 patients, only minimal vascular lesions were noted.
Three-years graft survival was low in both groups: 22% and 36%, respectively (p = 0.38). After additional examination, the cause of TMA was established in 42% of patients in group 1 and 35% - in group 2 (p>0.05). The most common specified cause of TMA was aHUS, diagnosed in 17 patients (11/38 in group 1, and 6/51 in group 2). In most cases (13 out of 17), genetic study revealed characteristic mutations. In the remaining cases, the diagnosis was revised based on recurrence of TMA during retransplantation, after excluding other possible causes. Besides aHUS, TMA was considered as a donor pathology (in 5 cases), 6 patients were diagnosed with antiphospholipid syndrome, another 5 - with multigenic thrombophilia.
Nine patients with aHUS started Eculizumab, which prevented progression (in 2 cases) or ensured stable function during subsequent transplantation in 4 patients. In the absence of complement blocking therapy, 5 out of 6 patients with retranslation, had an early recurrence of TMA, leading to the ESRD in 4 of them.
Histological examination of a renal graft is a sensitive but poorly specific method for diagnosing thrombotic microangiopathy. Genetic testing should be performed in all cases of suspected TMA in the graft, for early detection of aHUS and quick initiation of complement blocking therapy.