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 (IoCI) 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 IoCl. 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 anti-rejection 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% (42/42 episodes of AR in 29 patients) complete reversal whereas only 32 % (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 % (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 IoCl. AR is not invariably deleterious to long-term renal graft function if each episode of AR can be completely reversed.

Reduced-dose Cyclosporine with Mycophenolate Mofetil and Prednisone Significantly Improves the Long-term Glomerular Filtration Rate and Graft Survival

“…The number of rejection episodes after reduction of CSA was only slightly increased in the patients treated with MMF and steroids, as observed in other reports (17,18). A further analysis showed that the reversible rate of acute rejection was 72.7% (8/11) in the RCMP group vs. 62.5% (5/8) in the CMP group (p=1.0), indicating that acute rejection in the RCMP group was easy to control, although with a slightly increased acute rejection rate, while completely reversible acute rejection had no effect on long-term graft survival (19,20).…”

Steroid Sparing with Tacrolimus and Mycophenolate Mofetil in Renal Transplantation

“…Furthermore, an elevated serum creatinine at 1 year is predictive of cardiovascular death (32), and so it is reassuring that attempts to limit patient morbidity and mortality with this steroid-sparing regime have not been accompanied by exacerbation of other risk factors for poor patient outcome (i.e., compromised graft function). There was no significant difference in graft function between recipients experiencing and not experiencing rejection episodes, which may be due to the reduction in the severity of rejection in Tacrolimus and MMF-based regimes (25) and a consequent reversal of the rejection episode with treatment (33). It should however be noted that one of the graft losses was due to a repeated rejection episode.…”

Fibrosis-associated gene expression in renal transplant glomeruli after acute renal allograft rejection

“…Similarly, a lower dose of tacrolimus (0·1 mg per kg per day) was used. All NHBD kidney recipients received azathioprine 1 mg per kg per day unless the total white blood cell count fell below 4000 per mm 3 . All patients received prednisolone 20 mg per kg per day for 3 months, subsequently reduced to 10 mg per kg per day on alternate days by 6 months.…”

“…In the short term, acute renal allograft rejection remains one of the commonest causes of graft loss, although graft loss due to acute rejection is now less frequently encountered owing to improvements in immunosuppression. Despite its relatively common occurrence, the detrimental effect of acute rejection on long-term graft survival and the later development of CAN is debatable 2,3 . Although disputed by some 2,4 , it is generally believed that a successfully treated isolated episode of acute rejection in the early postoperative period has little impact on the later development of CAN or late graft loss 5,6 .…”