Prospective Donor Specific Antibody (DSA) Monitoring Protocol

• Proportion of patients who develop DSA within the first year post-transplant [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  
• Risk factors for developing DSA [ Time Frame: 1 year ] [ Designated as safety issue: No ]

  Patient demographics and immunosuppression regimen to be collected:

  Age at transplant Date of transplant Gender Race Cause of renal failure Donor type Repeat transplant (yes/no) Transplant current panel reactive antibody (PRA) Transplant flow crossmatch Previous crossmatch Serum creatinine at baseline DSA Class I/Class II, MICA, IgG3, C1Q Induction and maintenance immunosuppressant therapy Cytomegalovirus, BK virus, and Epstein Barr virus patient and donor seropositivity

  
  

• Change in allograft function at 1 year post-transplant compared to baseline (measured by Cockcroft-Gault) [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  
• Incidence of patient survival at 1 year [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  
• Proportion of patients who are DSA negative at 1 year [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  
• Percent change of DSA from baseline to 1 year [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  
• Proportion of Class I versus Class II detectable DSA that progress to antibody mediated rejection [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  
• Incidence of allograft survival at 1 year [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  

Organ transplantation is an effective treatment for several end-stage organ diseases. Preventing rejection of transplanted organs remains the premier challenge. According to the humoral theory, donor specific antibodies (DSA) are the major cause of chronic rejection and allograft loss. Despite this, and evidence that links human leukocyte antigen (HLA) antibodies to allograft dysfunction and loss, doubt remains about the cause-and-effect relationship and confirmation of this evidence is necessary to help facilitate change in transplant practice. Prospective monitoring for de novo DSA in the serum of patients who have received a transplant may allow for earlier detection, evaluation, and characterization of factors leading to the development of antibodies prior to the development of clinical manifestations of graft dysfunction.

The contribution of the major histocompatibility complex (MHC) Class I and Class II antibodies to transplant outcomes is well documented. However, there is emerging evidence that antibody mediated rejection and the severity of outcomes may involve proteins and antibodies that go beyond HLA Class I and II. A number of assays are available for testing for these additional antibodies and proteins but they are currently not used for widespread patient monitoring in part due to lack of data justifying their commercial use. This pilot study will prospectively evaluate for the presence and/or emergence of these unique antibodies, (I.E. MICA antigen, IgG3 and C1Q) in serial samples of serum, and confirm or reject the utility of incorporating these assays into routine patient monitoring which might provide earlier evidence of emerging rejection. Serum samples will be stored indefinitely for future kidney transplant research projects.