Impact of Donor-Specific Antibodies in (Highly-) Immunized Living Donor Kidney Transplant Recipients

Study Overview
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Brief Summary
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Kidney transplantation is the preferred treatment for end-stage renal disease. Alongside limited availability of donors, rejection and premature graft loss are main barriers to kidney transplantation. Donor-specific antibodies pre-transplantation may arise due to to prior solid organ transplantation, pregnancy or blood transfusions. Their presence is considered a risk of graft failure. The impact of DSA is differently reported in literature, also according to the technique by which DSA have been measured. Techniques such as the complement-dependent cytotoxicity crossmatch, the immunofluorescence crossmatch and the Luminex Single Antigen Bead have different sensitivities for detecting DSA. Historically, our kidney transplant program has been advocating living donor transplantation and as a result the majority of transplantations are with a living donor. In this context and in the absence of a compatible living donor, pretransplant DSA have not been considered an absolute contra-indication for transplantation. The aim of the current study is to determine the effect of DSAs on rejection and death-censored graft survival in living donor kidney transplantation. Participants are adults who underwent a living donor kidney transplantation between 2010 and 2019 in the presence of DSA. Control subjects are both immunized and non-immunized kidney transplant recipients in the same period. This is a retrospective, case control study. Death-censored graft survival is analyzed for all patients and compared by presence of DSA and other predicting variables, such as immunization level, age, sex and HLA mismatches. Furthermore, biopsy proven rejection, patient survival, kidney function, length of hospital stay and proteinuria are analyzed. Also, a predefined subgroup analysis is performed in the DSA positive patients. These are compared according to amount, strength and HLA-class of DSAs.

Official Title
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Impact of Donor-Specific Antibodies in (Highly-) Immunized Living Donor Kidney Transplant Recipients

Conditions
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Renal Failure

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Pre-transplantation donor-specific antibodies in Luminex Single Antigen Bead analysis. Age 18 years or older Exclusion Criteria: Desensitization treatment for a current or historic positive CDC-crossamtch

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| DSA+<br>Patients with pre-transplantation detected donor-specific antibodies, with Luminex Single Antigen Bead analysis. | |
| PRA+<br>Immunized controls without DSAs pre-transplantation, with equal peak PRA levels and donor/recipient age as the DSA+ group. | |
| PRA-<br>Non-immunized controls without DSAs pre-transplantation, with a peak PRA of less than 6%, with equal donor/recipient age as the DSA+ group. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Death-censored graft survival | Amount of patients who were alive with a functioning graft, divided by all alive included patients at different moments in time. | 4-12 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Patient survival | Amount of patients alive, divided by total amount of included patients at different moments in time. | 4-12 years | 
| Biopsy proven rejection | Amount of patients with a pathologically confirmed rejection. | 4-12 years | 
| Hospital admission days | Number of days that the patient spent admitted to the hospital. | first year post-transplantation | 
| Renal function | Estimated Glomerular Filtration Rate (eGFR) | first year post-transplantation | 
| Proteinuria | Grams of protein per 1 liter of urine. | first year post-transplantation |