Completely reversed acute rejection is not a significant risk factor for the development of chronic rejection in renal allograft recipients

Abstract

Although acute rejection (AR) has been shown to correlate with decreased long-term renal allograft survival, we have noted AR in recipients who subsequently had stable function for more than 5 years. We reviewed 109 renal graft recipients with a minimum of 1 year graft survival and follow-up of 5-8 years. Post-transplant sodium iothalamate clearances (IoC1) measured at 3 months and yearly thereafter were used to separate recipients into 2 groups. In 61 patients (stable group), there was no significant decrease ( > 20% reduction in IoCl over 2 consecutive years) in IoC1. Forty-eight patients had significant declines in IoCl (decline group). Groups were compared for incidence, severity, timing, and completeness of reversal of AR. Rejection was considered completely reversed if the post-AR serum creatinine (Scr) returned to or below the pre-AR nadir Scr after antirejection therapy. The incidence of AR was not significantly different between groups (47 % vs 52 %). A trend toward a lower mean number of AR episodes per patient was noted in the stable group (0.69 vs 1.04, P = 0.096), but the timing of AR was not different. Steroid-resistant AR occurred in approximately 25 % of both groups. A striking difference was seen in complete reversal of AR, with the stable group having 100 YO (42/42 episodes of AR in 29 patients) complete reversal whereas only 32 YO (8/25) of the patients in the decline group had complete reversal ( P < < 0.001). Of 8 declining patients with complete reversal, graft loss was due to chronic rejection (CR) in only 3. Seventeen declining patients had incomplete reversal of AR, and 82 '30 (14/17) lost their grafts to CR. Overall, only 8 % (3/37) of the recipients with complete reversal of AR developed CR. No patients with incompletely reversed AR had stable long-term function as measured by IoCI. AR is not invariably deleterious to longterm renal graft function if each episode of AR can be completely reversed.

C4d deposition in allograft renal biopsies is an independent risk factor for graft failure

“…In our centre, we discovered that early completely reversed AR had no significant effect on the long‐term outcome 11 . Another study had a similar result, 12 and showed that later AR had poor clinical outcome and was often refractory to anti‐rejection therapy. In this retrospective study, we found that grafts without capillary C4d deposition in early (<6 months) biopsies had a markedly higher survival rate as compared to grafts with capillary C4d deposition.…”

How Should Acute T-cell Mediated Rejection of Kidney Transplants Be Treated: Importance of Follow-up Biopsy

“…18,19 A higher grade of Banff rejection on the kidney biopsy is associated with inadequate response to the treatment and inferior graft survival. 20,21 Functional recovery after rejection treatment is an important prognostic factor for long-term outcomes 22,23 ; however, the data on the impact of histological response after the treatment on long-term graft outcome are limited. Our findings demonstrate that better histological responses as well as kidney function responses to rejection treatment are associated with better long-term graft outcomes.…”

Clinical Management of Kidney Allograft Dysfunction

“…An increase in proteinuria after rejection is associated with poor graft outcome. Early diagnosed and completely reversed rejection after treatment may not affect long-term graft survival [28]. Whenever a rejection is diagnosed and treated, it is important to address the possibility of non-compliance or inadequate immunosuppression.…”