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.

The application of carbon (C) substrates has been viewed as a promising tool for lowering soil nitrogen (N) availability in grassland restoration. However, experimental evidence shows that C additions can enhance, suppress, or have no effect on native species productivity, making it difficult to predict the effects of C-additions on plant communities. We used a community assembly approach to test the roles of environmental filtering and competition on community structure after C-additions. We applied 3 recalcitrant C-additions (wood chips, shavings, mixed chips + shavings), monitored temporal changes in soil N and P availability and species' abundances, and used phylogenetic tools to examine changes in community structure. All 3 soil C-additions produced significant reductions in soil N and P fertility that, in turn, were correlated with increases in taxonomic species richness, diversity, and evenness, as well as shifts in community structure. In control and C-amended plots, however, communities were composed of taxa that were more closely related than expected by chance (phylogenetically clustered); this pattern occurred across all C-additions and years, and in both plot level and species pair-wise metrics. In nonamended plots, phylogenetic clustering was correlated with soil N availability, consistent with environmental filtering. In C-addition plots, biotic (clade specialization in different C additions) and abiotic factors (soil P variability) were important in structuring the community. These findings suggest that C-additions create a different set of environmental filters and that variations in ecological traits among phylogenetically close species may be important in understanding and predicting the effects of C-additions.

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.

Since the introduction of cylcosporine into clinical use, a major area of concern within the transplant community has been the fear of chronic nephrotoxicity. Although progressive renal damage does appear to occur in native kidneys of heart and liver transplant patients receiving cyclosporine, it has been our contention that its use is not a major cause of deterioration in renal allografts. We therefore undertook a study of 91 consecutive renal transplants performed over a three-year period with a minimum graft survival of 1 year and a follow-up of 7-9 years. Serial serum creatinine values, iothalamate clearances and cyclosporine levels were obtained at 3 months after transplantation and yearly thereafter. Biopsies were performed on all grafts that had failed as well as on the majority of patients with deteriorating renal function, and were interpreted by two nephropathologists. As measured by iothalamate clearances, 65 % of the patients in this series exhibited absolutely stable renal function despite the maintenance of cyclosporine levels of more than 200 ng/ml for 7-9 years. Since these stable patients did not reveal any decline in renal function, it therefore follows that they did not experience chronic cyclosporine nephrotoxicity. Furthermore, none of the patients with declining renal function or with failed grafts showed any evidence of nephrotoxicity on biopsy. Chronic cyclosporine nephrotoxicity may be a cause of declining function or graft loss with renal transplant recipients, but if so, it is exceedingly rare.