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Increased C4d in post-reperfusion biopsies and increased donor specific antibodies at one-week post transplant are risk factors for acute rejection in mild to moderately sensitized kidney transplant recipients.

Djamali A, Muth BL, Ellis TM, Mohamed M, Fernandez LA, Miller KM, Bellingham JM, Odorico JS, Mezrich JD, Pirsch JD, D'Alessandro TM, Vidyasagar V, Hofmann RM, Torrealba JR, Kaufman DB, Foley DP - Kidney Int. (2013)

Bottom Line: The study included 146 patients transplanted with a negative flow crossmatch and a mean follow-up of 18 months with the majority (83%) followed for at least 1 year.The incidence of acute rejection (mean 1.65 months) as a combination of clinical and subclinical rejection was 32%, including 14% cellular, 12% antibody-mediated, and 6% mixed rejection.A rise in MFImax by 500 was associated with a 2.8-fold risk of rejection.

View Article: PubMed Central - PubMed

Affiliation: Department of Surgery, University of Wisconsin, Madison, Wisconsin 51703, USA. axd@medicine.wisc.edu

ABSTRACT
In order to define the intensity of immunosuppression, we examined risk factors for acute rejection in desensitization protocols that use baseline donor-specific antibody levels measured as mean fluorescence intensity (MFImax). The study included 146 patients transplanted with a negative flow crossmatch and a mean follow-up of 18 months with the majority (83%) followed for at least 1 year. At the time of transplant, mean-calculated panel-reactive antibody and MFImax ranged from 10.3-57.2% and 262-1691, respectively, between low- and high-risk protocols. Mean MFImax increased significantly from transplant to 1 week and 1 year. The incidence of acute rejection (mean 1.65 months) as a combination of clinical and subclinical rejection was 32%, including 14% cellular, 12% antibody-mediated, and 6% mixed rejection. In regression analyses, only C4d staining in post-reperfusion biopsies (hazard ratio 3.3, confidence interval 1.71-6.45) and increased specific antibodies at 1-week post transplant were significant predictors of rejection. A rise in MFImax by 500 was associated with a 2.8-fold risk of rejection. Thus, C4d staining in post-reperfusion biopsies and an early rise in donor specific antibodies after transplantation are risk factors for rejection in moderately sensitized patients.

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Changes in DSA after transplantationPanel a. The bar graph displays mean DSA levels (MFImax) early post transplant in all desensitization protocols.Panel b. The graph shows mean DSA levels in all patients throughout the first posttransplant year. DSA increased with time despite immunosuppression and desensitization. MFIsum class II was the primary cause of the rise in DSA.
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Figure 1: Changes in DSA after transplantationPanel a. The bar graph displays mean DSA levels (MFImax) early post transplant in all desensitization protocols.Panel b. The graph shows mean DSA levels in all patients throughout the first posttransplant year. DSA increased with time despite immunosuppression and desensitization. MFIsum class II was the primary cause of the rise in DSA.

Mentions: We next examined the one-year incidence of rejection, overall, and in each protocol. One hundred and twenty one patients (83% of all) were followed for at least one year at the time of these analyses. Mean follow-up time was 18±6.7 months. Mean time to acute rejection was 1.65±0.46 months. There was no graft loss or patient death during the study period. The overall incidence of acute rejection (clinical and subclinical) was 32% including 14% cellular, 12% antibody-mediated and 6% mixed rejection (Table 3). Of these, 14% were subclinical and were diagnosed by protocol biopsies. There was no difference in the incidence of rejection among protocols. At 12 months, mean eGFR and serum creatinine levels were 55±1.7 ml/min/1.73m2 and 1.5±0.1 mg/dL respectively. There was no significant difference in kidney function among the 5 groups.


Increased C4d in post-reperfusion biopsies and increased donor specific antibodies at one-week post transplant are risk factors for acute rejection in mild to moderately sensitized kidney transplant recipients.

Djamali A, Muth BL, Ellis TM, Mohamed M, Fernandez LA, Miller KM, Bellingham JM, Odorico JS, Mezrich JD, Pirsch JD, D'Alessandro TM, Vidyasagar V, Hofmann RM, Torrealba JR, Kaufman DB, Foley DP - Kidney Int. (2013)

Changes in DSA after transplantationPanel a. The bar graph displays mean DSA levels (MFImax) early post transplant in all desensitization protocols.Panel b. The graph shows mean DSA levels in all patients throughout the first posttransplant year. DSA increased with time despite immunosuppression and desensitization. MFIsum class II was the primary cause of the rise in DSA.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3672254&req=5

Figure 1: Changes in DSA after transplantationPanel a. The bar graph displays mean DSA levels (MFImax) early post transplant in all desensitization protocols.Panel b. The graph shows mean DSA levels in all patients throughout the first posttransplant year. DSA increased with time despite immunosuppression and desensitization. MFIsum class II was the primary cause of the rise in DSA.
Mentions: We next examined the one-year incidence of rejection, overall, and in each protocol. One hundred and twenty one patients (83% of all) were followed for at least one year at the time of these analyses. Mean follow-up time was 18±6.7 months. Mean time to acute rejection was 1.65±0.46 months. There was no graft loss or patient death during the study period. The overall incidence of acute rejection (clinical and subclinical) was 32% including 14% cellular, 12% antibody-mediated and 6% mixed rejection (Table 3). Of these, 14% were subclinical and were diagnosed by protocol biopsies. There was no difference in the incidence of rejection among protocols. At 12 months, mean eGFR and serum creatinine levels were 55±1.7 ml/min/1.73m2 and 1.5±0.1 mg/dL respectively. There was no significant difference in kidney function among the 5 groups.

Bottom Line: The study included 146 patients transplanted with a negative flow crossmatch and a mean follow-up of 18 months with the majority (83%) followed for at least 1 year.The incidence of acute rejection (mean 1.65 months) as a combination of clinical and subclinical rejection was 32%, including 14% cellular, 12% antibody-mediated, and 6% mixed rejection.A rise in MFImax by 500 was associated with a 2.8-fold risk of rejection.

View Article: PubMed Central - PubMed

Affiliation: Department of Surgery, University of Wisconsin, Madison, Wisconsin 51703, USA. axd@medicine.wisc.edu

ABSTRACT
In order to define the intensity of immunosuppression, we examined risk factors for acute rejection in desensitization protocols that use baseline donor-specific antibody levels measured as mean fluorescence intensity (MFImax). The study included 146 patients transplanted with a negative flow crossmatch and a mean follow-up of 18 months with the majority (83%) followed for at least 1 year. At the time of transplant, mean-calculated panel-reactive antibody and MFImax ranged from 10.3-57.2% and 262-1691, respectively, between low- and high-risk protocols. Mean MFImax increased significantly from transplant to 1 week and 1 year. The incidence of acute rejection (mean 1.65 months) as a combination of clinical and subclinical rejection was 32%, including 14% cellular, 12% antibody-mediated, and 6% mixed rejection. In regression analyses, only C4d staining in post-reperfusion biopsies (hazard ratio 3.3, confidence interval 1.71-6.45) and increased specific antibodies at 1-week post transplant were significant predictors of rejection. A rise in MFImax by 500 was associated with a 2.8-fold risk of rejection. Thus, C4d staining in post-reperfusion biopsies and an early rise in donor specific antibodies after transplantation are risk factors for rejection in moderately sensitized patients.

Show MeSH
Related in: MedlinePlus