Graft intolerance syndrome: risk factors, clinical and pathological features, ultrasound diagnostics

The annual increase in the number of kidney allotransplantations is associated with a delayed rise in the population of patients with nonfunctioning renal allografts. Approximately 10% of patients initiating maintenance hemodialysis have a nonfunctioning kidney transplant and continue to receive immunosuppressive therapy. As a result, a stable cohort of patients with an increased risk of infectious and hemodialysis-associated complications is being formed. Although multidisciplinary approaches to the management of patients after graft failure are actively discussed, universally accepted consensus guidelines are currently lacking.

Graft Intolerance Syndrome (GIS) is a clinical manifestation of chronic rejection activation that develops in approximately 30-40% of patients following rapid reduction or withdrawal of immunosuppressive therapy. GIS represents the most common indication for transplantectomy in patients with late allograft dysfunction, with more than one-third of nonfunctioning grafts being removed due to the development of this syndrome.

This review summarizes current literature data regarding the pathogenesis, clinical manifestations, laboratory findings, and histopathological features of GIS. Risk factors for syndrome development, clinical presentation, and the role of instrumental diagnostic methods are discussed. Particular attention is paid to the histopathological characteristics of explanted grafts, which are marked by a pronounced vascular component in combination with features of both acute and chronic rejection. Special emphasis is placed on ultrasonographic findings in renal allografts with GIS, including preserved active perfusion with disturbed angioarchitecture, Doppler patterns of collateral and stenotic blood flow, visualization of perforating vessels, the presence of perirenal collateral vascular networks, and various GIS-associated occlusive and stenotic lesions of major vessels.

Current conservative and surgical treatment strategies for patients with nonfunctioning renal allografts are also reviewed. The importance of comprehensive Doppler ultrasonography assessment for optimizing surgical management and implementing a personalized approach to patients with GIS and nonfunctioning kidney transplants in general is emphasized.

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