Renal Involvement in Chronic Graft-Versus-Host Disease

Graft versus host disease (GvHD) is a common complication of allogeneic hematopoietic stem cell transplantation (HSCT). While the skin, eyes, mouth, and liver are the most commonly affected organs in chronic GvHD, there is increasing recognition of less typical sites of involvement. Emerging evidence suggests that the kidney may also be affected; however, current data remain limited and largely derived from small retrospective studies or case series. We examined a cohort of 1441 patients transplanted and identified 12 patients (0.8%) presenting with nephrotic syndrome that had renal biopsies consistent with membranous nephropathy (MN). None of the patients had pre-existing renal disease. All patients had nephrotic range proteinuria (median 6.6 g/24 h, range 4.1-17.8) at presentation. The median time to diagnosis of glomerular disease was 1.8 years (range 0.6-4.3 years) after HSCT. The median time to diagnosis of nephrotic syndrome was 407 days (range 95-1415 days) after an initial diagnosis of chronic GvHD. Three patients had features of renal vein thrombosis at presentation. All patients showed typical pathologic features of MN with additional mild microangiopathic features on ultrastructural examination, and nine tested were PLA2R negative. All patients received immunosuppressive therapy. Seven had a complete response to treatment, four achieved a partial response, and one did not respond. Herein, we describe their clinical characteristics, disease course, and clinical outcomes. None of our patients developed irreversible renal impairment, outlining the importance of rapid intervention with appropriate immunosuppression. In the absence of effective biomarkers, the management of suspected renal GvHD presenting with proteinuria should include renal biopsy to identify and appropriately classify the lesion.