Steroid Withdrawal and Donor-specific Anti-HLA Antibodies in Renal Transplant Patients

Study Overview
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Brief Summary
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Steroids are one of the pillars of immunosuppression for kidney transplant patients but their use is associated with a high rate of complications. Withdrawal of steroids reduces some metabolic and cardiovascular complications, but it may increase the risk of acute rejection. However, little is known about whether steroid withdrawal is associated with the generation of anti-HLA donor-specific antibodies (DSA) and the relation between DSA and clinical and histological data. The aim of this study is to compare the incidence of de novo anti-HLA DSA in stable kidney transplant patients after withdrawing the steroids 3 months after the transplantation as compared with patients who continue with steroids. The hypothesis is that steroid withdrawal will increase the presence of de novo anti-HLA DSA in stable kidney transplant patients

Official Title
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Steroid Withdrawal and Novo Donor-specific Anti-HLA Antibodies in Renal Transplant Patients: a Prospective, Randomized and Controlled Study in Parallel Groups

Conditions
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Other Complication of Kidney Transplant, Renal Transplant Rejection

Intervention / Treatment
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* Drug: Prednisone withdrawal
* Drug: Prednisone continuation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female patients aged over 18 years with no immunological risk (PRA <25% and no DSA) who are receiving their first cadaveric or living kidney transplant. Patients who, three months after the transplantation, are receiving tacrolimus in combination with mycophenolic acid (MPA) or mycophenolate mofetil (MMF) plus steroids, with stable plasma levels of tacrolimus. No clinical or histological immunological dysfunction before randomization No de novo anti-HLA DSA at the time of randomization. Patients who wish to and are able to give written informed consent to participate in the study. For women, agreeing to use efficient contraception during the study. Exclusion Criteria: Patients who receive a multiorgan transplant. Retransplants. Presence of DSA before the transplant or at the time of randomization. Cold ischemia time >30 hours Patients with serum creatinine >2 mg/dL or proteinuria >1g/day at the time of randomization Prior episode of severe rejection (II-B-III in the Banff/13 classification) prior to randomization. Presence of subclinical rejection on the protocol biopsy prior to randomization Patients with BK-polyomavirus nephropathy at the time of randomization. Patients with recurrent or de novo glomerulonephritis. Patients who are being treated with immunosuppressive drugs other than those in the randomized clinical trial in question. Patients who are positive for the human immunodeficiency virus (HIV) or those who have a severe systemic infection that, in the investigator's judgment, will require continued treatment. Patients with any present or prior (during the previous 5 years) malignant disease, except basal or squamous cell carcinoma that has been excised.

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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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Steroids, tacrolimus and mycophenolate<br>Normal treatment arm | Drug: Prednisone continuation<br>* Continuation of steroids<br>|
| Experimental: Tacrolimus and mycophenolate<br>Normal treatment for first 90 days, then steroid withdrawal carrying on with the other drugs | Drug: Prednisone withdrawal<br>* Withdrawal of steroids<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cases of Kidney Transplant Patients With DSA | Measurements of DSA at baseline, and at 3, 6, 12, 18 and 24 months | 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Score on the Protocol Biopsies in the Two Treatment Groups | Measurement at 24 months according to the Banff classification. The Banff Classification of Allograft Pathology is an international consensus classification for the reporting of biopsies from solid organ transplant. The scale ranges from 0 to 3, 3 being the worst. | 24 months | 
| Number of Participants With Acute Rejection Lesions | Patients with acute rejection lesions (including subclinical rejection) at 24 months according to Banff classification | 24 months | 
| Incidence of Diabetes Mellitus | Incidence of diabetes mellitus after kidney transplant in both groups at 1, 2, 3, 4, 6, 9, 12, 18 and 24 months | 24 months | 
| Lipid Profile | Lipid profile after kidney transplant in both groups at 24 months | 24 months | 
| Blood Pressure | Blood pressure after kidney transplant in both groups at 24 months | 24 months | 
| Renal Function | Renal function after kidney transplant in both groups at 24 months measured according to the creatinine (mg/dL) concentrations | 24 months | 
| Assess the Adherence to Immunosuppressive Therapy in the Two Treatment Groups | The Basle scale was used to assess adherence (BAASIS questionnaire) to immunosuppressive therapy. | At 24 months | 
| Patient Survival | Patient survival after kidney transplant in both groups | 24 months | 
| Graft Survival | Graft survival after kidney transplant in both groups | 24 months | 
| Renal Function | Renal function after kidney transplant in both groups at 24 months measured according to the proteinuria (mg/24 h) concentrations | 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Kidney transplant, Immunosuppression, Steroid withdrawal, Donor specific antibodies