Histology and proteinuria after renal transplantation

Proteinuria is a nonspecific sign of the troubled renal allograft. Small increases of proteinuria more than 150 mg/d are associated with poor renal allograft survival. During the 90s, it was assumed that chronic allograft nephropathy, defined as the presence of interstitial fibrosis and tubular atrophy, was the histologic lesion responsible for proteinuria and renal function deterioration in most kidneys. Thus, the interest to pursue a histologic diagnosis in patients with proteinuria or renal function deterioration faded during this period. In 2005, the criteria to diagnose chronic humoral rejection, a condition that in the previous year was not distinguished from chronic allograft nephropathy (CAN), were defined. The description of chronic humoral rejection as a major cause of proteinuria and graft loss represented a change of paradigm because it became clear that chronic humoral rejection and other conditions such as recurrence of original disease, de novo glomerulonephritis, polyomavirus infection, and others are responsible for proteinuria. These conditions can be diagnosed on histologic and clinical grounds, provided that special techniques such as C4d, immunofluorescence, immunohistochemistry, electron microscopy, and determination of donor specific antibodies are used. Thus, it became rather clear that proteinuria should be studied by means of a renal biopsy, especially if we take into consideration that there is very poor correlation between the amount of proteinuria and the disease responsible for it. Studies based on surveillance biopsies showed that histologic diagnosis precedes clinical manifestations. Despite the lack of clinical trials, series of patients have shown that different entities respond to different treatments, further reinforcing the idea that early diagnosis and early treatment may contribute to improve graft outcome.