Glomerular crescents are responsible for chronic graft dysfunction in post‐transplant IgA nephropathy

Abstract

Information is limited regarding the histological features related to chronic graft dysfunction and failure in patients with IgA nephropathy developing after renal transplantation. The prevalence and significance of glomerular crescents in post-transplant IgAN including recurrent, de novo and transmitted forms (TxIgAN), were studied. Renal morphology was evaluated in 71 patients of TxIgAN, obtained at more than 6 months post-transplant, and compared with regard to the presence (C-TxIgAN) or absence (N-TxIgAN) of glomerular crescents. Crescents were demonstrated in 12 samples of 10 patients (14.1%). The percentages of crescents were from 4.8% to 83.3% (median, 28.6%) in each sample. Ten samples of C-TxIgAN had cellular to fibrocellular crescents, and four of these were associated with diffuse mesangial proliferation. Serum creatinine levels and the frequency of nephrotic range proteinuria at the time of biopsy and the degree of interstitial inflammation were significantly different in the two groups. Graft survival after allograft biopsies was significantly lower in C-TxIgAN (P = 0.0017). Chronic rejection was a major cause of graft loss in N-TxIgAN (31.8%), whereas TxIgAN was the major cause in C-TxIgAN (66.7%). In conclusion, the current study suggests that glomerular crescents are not rare and that they are responsible for chronic graft dysfunction in TxIgAN patients.

A primer on recurrent and de novo glomerulonephritis in renal allografts

“…52 Transmitted IgA deposition seems to encourage recurrence of IgA nephropathy, 4,53 and when associated with the formation of crescents it leads to graft loss in two-thirds of cases. 53 High levels of aberrantly glycosylated IgA 1 do not seem to predict recurrence. 54 Patients with certain polymorphisms of the genes for tumor necrosis factor and interleukin 10, which are downregulators of type 2 T-helper lymphocytes, have a reduced likelihood of experiencing recurrence.…”

Progression of renal allograft histology after renal transplantation in recurrent and nonrecurrent immunoglobulin A nephropathy

“…In the histological assessment, 7 parameters were evaluated (Table 2): glomerular crescent formation, mesangial proliferation, glomerulosclerosis, tubular atrophy, interstitial fibrosis, interstitial inflammation, and arteriolar hyalinosis. Glomerular crescents and mesangial proliferation represent active glomerular injury, which are related to the progression of IgAN in both native kidneys [19] and allografts [10,12]. Mesangial proliferation was examined in 2-to 3-μm-thick PAS-stained sections and defined as the presence of 3 or more cells in 1 mesangial area away from the vascular hilum.…”

“…In patients with recurrent or posttransplant IgAN, the formation of glomerular crescents is associated with a poor outcome [10][11][12]. The presence of segmental sclerosis in hypertrophied glomeruli is related to proteinuria in patients with posttransplant IgAN [10]. However, development of microscopic hematuria is not a characteristic feature of recurrent IgAN [13,14].…”

Predicting Post-Transplant Recurrence of IgA Nephropathy: The Importance of Crescents

“…However, recent retrospective studies with longer duration of follow-up suggest that recurrent disease contributes substantially to allograft damage 6,10,11 . Risk factors for recurrence include presence of specific HLA genotypes, zero mismatch kidneys, high serum IgA levels, choice of induction therapy, choice of maintenance immunosuppression, and duration of follow-up post-transplant 12–16 Post-transplant crescentic IgAN confers poorer allograft outcomes compared to post-transplant recurrence of non-crescentic IgAN 17,18 . Most studies assessing the predictors of recurrent IgAN have focused on post-transplant clinical features.…”