O'Leary JG, Kaneku H, Susskind BM, Jennings LW, Davis GL, Klintmalm GB, Terasaki PI
Stegall MD, Park WD, Dean PG, Cosio FG.
In the American Journal of Transplantation, Stegall and colleagues outline a new road to improving allograft survival in renal transplant patients. They make the argument that "rather than searching for new and better de novo immunosuppressive agents, we need to focus more on improving long term follow-up." Dr Stegall suggests "a combination of serum tests (DSA levels and polyoma virus testing) and protocol biopsies" should be used to identify the patients at highest risk of allograft loss. Once these highest risk patients are identified changes in immunosuppression and monitoring may be means to do something that hasn't been done in the 40+ year history of transplantation - significantly improve the rate of allograft loss after the first year post transplant.
Amico P, Hönger G, Mayr M, Steiger J, Hopfer H, Schaub S
The cumulative incidence of AMR (clinical and subclinical) at day 200 post-transplant in patients with preformed DSA was 55%, significantly higher compared to 6% in patients without preformed DSA. Five-year graft survival was significantly worse in patients with preformed DSA who also had AMR, compared to patients without preformed DSA and patients with preformed DSA without AMR (68% vs. 89% vs. 87%, p=0.002).
Fortheringham J, Angel C, Goodwin J, Harmer AW, McKane WS
Patients with de novo DSA after renal transplantation showed significantly higher rates of acute rejection (74% vs. 41%), more graft losses (29% vs. 9%), lower glomerular filtration rate (GFR) at the time of antibody detection (31.8 ml/min/1.73m2 vs. 44.1 ml/min/1.73m2) and lower 3-year allograft survival (69.5 vs. 91.1%) than patients with NDSA. The GFR decline was -5.85 ml/min/1.73m2/year in DSA patients, which was significantly higher than the -3.21 ml/min/1.73m2/year and the -0.08 ml/min/1.73m2/year for the control patients. In regards to proteinuria, 45% of DSA positive patients had more than 3 g/L of protein in urine at the time of antibody detection compared to only 3% in NDSA positive patients.
Lefaucheur C, Suberbielle-Boissel C, Hill GS, Nochy D, Andrade J, Antoine C, Gautreau C, Charron D, Glotz D
CDC-XM negative patients with preformed DSA detected by ELISA showed a 9-fold higher incidence of AMR than patients without DSA. Eight-year graft survival is significantly lower in patients with preformed DSA compared to patients without preformed DSA (67.9% vs. 77.3%, p=0.03), and this difference was even more significant if patients with DSA and AMR were analyzed separately from patients with DSA and no AMR (43.6% vs. 78.5%). Patients with DSA and no AMR have similar graft survival compared to patients without preformed DSA.
Loupy A, Suberbielle-Boissel C, Hill GS, Lefaucheur C, Anglicheau D, Zuber J, Martinez F, Thervet E, Mejean A, Charron D, Duong van Huyen JP, BrunevalP, Legendre C, Nochy D
CDC-XM negative patients with preformed DSA have significantly higher rates of AMR compared with DSA negative patients (19% vs. 0%, p<0.001), and also exhibit significantly lower 4-year graft survival (86.2% vs. 96.2%, p=0.01)
Gupta A, Iverson V, Varagunam M, Bodger S, Sinnott P, Thuraisingham RC
The presence of preformed DSA had no impact on delayed graft function, incidence of AMR or one-year graft survival, but a tendency toward lower 5-year graft survival was seen. A multivariate analysis demonstrated a six-fold increased risk of graft failure in DSA positive patients.
Singh N, Djamali A, Lorentzen D, Pirsch JD, Leverson G, Neidlinger N, Voss B, Torrealba JR, HofmannRM, Odorico J, Fernandez LA, Sollinger HW, Samaniego M
Sixty-seven percent of negative CDC-XM had detectable DSA using single antigen beads with a low cutoff and showed lower AMR-free survival compared to DSA negative patients.
Gloor JM, Winters JL, Cornell LD, Fix LA, DeGoey SR, Knauer RM, Cosio FG, Gandhi MJ, Kremers W, Stegall MD
The strength of DSA, measured by MFI using single antigen beads, correlates with the incidence of AMR. Positive CDC-XM patients with the highest MFI displayed the highest incidence of AMR, followed by patients with FC-XM>300 and FC-XM<300. Also, lower AMR-free survival was observed in patients with preformed DSA over 10 000, compared to patients with lower MFI.
Issa N, Cosio FG, Gloor JM, Sethi S, Dean PG, Moore SB, DeGoey S, Stegall MD
Only the presence of preformed DSA against class II showed a risk association for development of transplantglomerulopathy (TG). The higher the MFI, the greater the risk. There was also an association between highMFI and C4d staining, and patients with C4d positive and TG showed the lowest graft survival.