DISEASE OF THE MONTH Glomerulonephritis Recurrence in the Renal Graft

Renal transplantation is a treatment, not a cure. Although transplantation may return renal function to the recipient, it does not necessarily remove the cause of the recipient’s original renal disease. Glomerulonephritis is the cause of renal failure for 20 to 40% of those who receive a transplant; for these recipients, the threat of recurrent disease is real. The transplant setting of immunosuppression, different antigenic characteristics of the graft versus the native kidney, and different chronology may attenuate or prevent recurrence of some forms of glomerulonephritis. Others will, despite these barriers, recur and may result in allograft failure. Allograft survival rates have steadily improved over the past 20 yr, largely as a result of our increasing ability to prevent and treat rejection (1). Recurrent glomerulonephritis is at present a minor contributor to allograft failure, responsible for 3% of all grafts lost in Australia and New Zealand from 1979 to 1998 (E. Briganti and S. Chadban, unpublished data) and a similar number in the United Kingdom (2). However, the propensity for glomerulonephritis to recur seems to be time dependent (3). Thus, as graft survival increases, so, too, does the likelihood of disease recurrence. As the average cadaveric graft is now projected to function for more than 13 yr and the average live-donor graft for more than 21 yr (1), we can expect to see an increased incidence of recurrent glomerulonephritis and a greater number of grafts failing as a result of recurrence. By implication, the diagnosis of recurrent glomerulonephritis requires an accurate diagnosis of both the primary renal disease and subsequent disease in the transplant kidney. In most cases, these criteria will be fulfilled only by obtaining renal biopsy material from both organs for diagnostic assessment, which may need to include electron microscopy and immunohistology (4,5). Although biopsy of native and transplant kidneys is simple, safe, and widely practiced, it is not performed in all cases of suspected glomerulonephritis in native or transplanted kidneys (6). Electron microscopy and immunohistology also are not routinely performed on transplant biopsies. Thus, the true incidence and impact of recurrent glomerulonephritis is not accurately known and is probably underestimated. This article discusses recurrent glomerulonephritis in the current era. The strength and quality of data reported in the literature are variable; where evidence is cited, its strength is considered. The epidemiology of recurrence is reviewed in a general sense, and recurrence of specific forms of glomerulonephritis is addressed individually. The incidence of recurrence and recurrence leading to graft failure is examined, and risk factors for disease recurrence are assessed. Where available, data on the pathogenesis and management of recurrent glomerulonephritis also is presented. Controversies in the area are discussed, including the diagnosis of recurrent glomerulonephritis and the implications of recurrence for retransplantation. The issues of de novo glomerulonephritis posttransplantation and recurrent metabolic diseases have been reviewed elsewhere (6–8) and are not directly addressed here.