In-Depth Review De Novo Glomerular Diseases after Renal Transplantation

Glomerular diseases developing in the kidney allograft aremore often recurrences of the original disease affecting the native kidneys. However, in an undefined number of cases de novo, glomerular diseases unrelated to the original disease in the native kidneys can develop in the transplanted kidney. The clinical presentation and histologic features of de novo diseases are often similar to those features observed in patients with primary or secondary GN in the native kidneys. However, in transplanted kidneys, the glomerular, vascular, and tubulointerstitial changes are often intertwined with structural abnormalities already present at the time of transplant or caused by antibodyor cell-mediated allograft rejection, immunosuppressive drugs, or superimposed infection (most often of a viral nature). The pathophysiology of de novo glomerular diseases is quite variable. In rare cases of de novo minimal change disease, circulating factors increasing the glomerular permeability likely participate. Maladaptive hemodynamic changes and tissue fibrosis caused by calcineurin inhibitors or other factors may be involved in the pathogenesis of de novo FSGS. The exposure of cryptic podocyte antigens may favor the development of de novo membranous nephropathy. Many cases of de novo membranoproliferative GN are related to hepatitis C virus infection. Patients with Alport syndrome lacking antigenic epitopes in their glomerular basement membrane may develop antibodies against these glomerular basement membrane antigens expressed in the transplanted kidney. Infection may cause acute GN to have a heterogeneous clinical presentation and outcome. De novo pauci-immune GN in renal transplant is rare. Preexisting or acquired intolerance to glucose may, in the long term, cause diabetic nephropathy. The prognosis of de novo diseases depends on the type of GN, the severity of lesions caused by the alloimmune response, or the efficacy of immunosuppressive therapy. In most cases, the management of de novo glomerular diseases is empirical or elusive. Clin J Am Soc Nephrol 9: 1479–1487, 2014. doi: 10.2215/CJN.12571213 Introduction Post-transplant glomerular diseases represent a frequent complication of kidney transplantation that may worsen the graft function and impair long-term graft survival. In a Canadian review, glomerular diseases were diagnosed in 15.7% of renal transplant patients at 15 years. Post-transplant GN occurred in 24.3% of allografted patients whose original renal disease resulted from biopsy-proven GN compared with 10.5% of those patients with other types of renal or systemic diseases. Patients who developed glomerular diseases had significantly reduced graft survival (1). Post-transplant glomerular disease is generally divided into recurrences of the same original disease that affected the native kidney of the recipient and de novo disease, in which the post-transplant disease is unrelated to the original disease. This differentiation may be difficult, because only 15%–20% of recipients have had biopsies of native kidneys before transplantation. Also, the incidence of de novo GN posttransplant is hard to assess, because immunofluorescence and electron microscopy are not routinely performed in all centers (2). Another important issue is that information on time-zero (preimplantation) biopsy and protocol biopsies was available only in rare cases. Therefore, it is possible that some patients labeled as having de novo disease actually received kidneys already affected by GN. Establishing the role of immunosuppression, hypertension, infection, rejection, genetic differences, or similarity between donor and recipient is also a difficult task. In this review, we will examine the most frequent types of de novo glomerular disease and the current knowledge about this particular complication of transplanted kidneys. Minimal Change Disease De novo minimal change disease (MCD) in the renal allograft is quite rare. Many of the cases reported as de novo MCD disease failed to meet stringent criteria for this diagnosis, and it is possible that some cases represented an early manifestation of FSGS. Markowitz et al. (3) described one case and reported eight other cases that fulfilled the criteria for MCD. Truong and colleagues (4) reported five additional cases (3,5). Other anecdotal reports of de novo MCD have been reported, including cases occurring in ABO-incompatible transplants. Nephrotic-range proteinuria usually develops immediately or shortly after transplantation, but a patient developed de novo MCD 8 years after transplantation (6). AKI occurred in three patients. On biopsy, *Division of