Kidney Replacement
Conditions
Keywords
Kidney transplant, Basiliximab, RATG induction therapy
Brief summary
This trial is to compare the risk/benefit profile over six-month follow-up of two induction immunosuppressive regimens based on one or seven low-dose perioperative RATG infusions on top of the same induction therapy with basiliximab and steroid (progressively tapered post-transplant) and maintenance therapy with calcineurin inhibitors and mycophenolate mofetil/mycophenolic acid in 75 recipients (25 Patients and 50 Reference-Patients) of a single or dual first kidney transplant from an ideal or marginal donor at a single Renal Transplant Center.
Detailed description
In patients receiving a kidney transplant, it is necessary to use immunosuppressive drugs that serve to reduce or prevent the risk of rejection. Some of these drugs are infused only in the first days of the transplant to more effectively reduce the reactivity of the immune system when the risk of rejection is highest. Among these are thymoglobulins, antibodies that destroy immune system cells (lymphocytes) which can cause rejection. For this reason, in their Center the investigators have developed a protocol that provides for the infusion of thymoglobulins for seven consecutive days starting from the day of the transplant. The first infusion begins even before the transplant is performed so that the lymphocytes are destroyed before the kidney is implanted and can therefore be recognized by the immune system as a foreign organ. This first administration is therefore certainly the most important, to the point that perhaps subsequent infusions of thymoglobulins may not even be necessary. Based on this reasoning, starting from April 1st 2023 the investigators began to infuse only the first dose of thymoglobulins, always starting the infusion before the transplant was performed, avoiding subsequent administrations. The goal was to maintain the same anti-rejection efficacy, but reducing the risk of side effects. In fact, thymoglobulins reduce the number of white blood cells and platelets in the blood and can increase the risk of opportunistic infections which are facilitated by the fact that the activity of the immune system is reduced by thymoglobulins. In other words, the effects of thymoglobulins on the immune system that serve to reduce the risk of rejection are the same as those that increase the risk of infections. At this point the investigators would therefore like to verify whether actually infusing a single dose of thymoglobulin starting before the transplant can maintain the same anti-rejection effect that is obtained by administering seven doses of thymoglobulin, while reducing the risk of side effects. For this reason, in this study they want to compare the data already collected for clinical reasons in kidney transplant recipients treated with a single dose of thymoglobulin with the data, also already collected, in kidney transplant recipients who instead received all seven doses of thymoglobulin. The latter must have the same characteristics as patients who have received a single dose of thymoglobulins. In essence the investigators should compare two groups of patients who are very similar in terms of the type of transplant performed (for example single or double) and the other anti-rejection therapies administered in addition to thymoglobulins and who differ only in having received one or seven infusions. All patients will have received the transplant from the same surgical team and will have been monitored and treated by the same nephrology team based on the same standardized clinical monitoring and immunosuppressive treatment protocols (regardless of the number of thymoglobulin doses). In this way, any differences in the risk of rejection or side effects that may emerge between the two groups could only be explained by the difference in treatment with thymoglobulins (with a single dose or with seven doses).
Interventions
DRUGRATG
Thymoglobulin, Genzyme corporation, Italy.
DRUGBasiliximab
Simulect, Novartis, Italy.
Sponsors
Mario Negri Institute for Pharmacological Research
Study design
Observational model
CASE_CONTROL
Time perspective
RETROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Consecutive recipients of a single or dual kidney transplant from ideal or marginal donors who, from 01/04/2023 to 31/12/2023, were induced with one single perioperative RATG infusion * Consecutive recipients (Reference-Patients) of a single or dual kidney transplant from ideal or marginal donors who before 01/04/2023 were induced with seven perioperative RATG infusions (on top of the same induction and maintenance treatment used for patients receiving one single RATG infusion)
Exclusion criteria
* Living donor recipients, second transplant recipients or patients receiving a multiorgan transplant, and patients with a peak panel reactive antibody titer \>30% or positive B cell cross-match
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of thrombocytopenia and/or leukopenia | From day 0 post-transplant up to 10 days or patient discharge, then at 2, 3 and 4 weeks post-transplant and every 1 month up to 12 months | Incidence of thrombocytopenia and/or leukopenia requiring or not requiring down-titration or transient withdrawal of mycophenolate mofetil/ mycophenolic acid (and/or RATG) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Occurrence of viral infections | From day 0 post-transplant up to 10 days or patient discharge, then at 2, 3 and 4 weeks post-transplant and every 1 month up to 12 months | Polyomavirus BK (BKV) and/or Cytomegalovirus (CMV) infection/reactivations |
| Occurrence of pneumonia | From day 0 post-transplant up to 10 days or patient discharge, then at 2, 3 and 4 weeks post-transplant and every 1 month up to 12 months | Pneumocystis carinii pneumonia |
| Occurrence of opportunistic infections | From day 0 post-transplant up to 10 days or patient discharge, then at 2, 3 and 4 weeks post-transplant and every 1 month up to 12 months | Systemic candidiasis and any other opportunistic infection |
| Occurrence of delayed graft function | From day 0 post-transplant up to 10 days or patient discharge, then at 2, 3 and 4 weeks post-transplant and every 1 month up to 12 months | Delayed Graft Function defined as need of dialysis during the first week post-transplant |
| Occurrence of allograft rejection | From day 0 post-transplant up to 10 days or patient discharge, then at 2, 3 and 4 weeks post-transplant and every 1 month up to 12 months | Acute allograft rejection (overall, steroid-resistant and biopsy-proven rejections considered separately) |
| Occurrence of anemia | From day 0 post-transplant up to 10 days or patient discharge, then at 2, 3 and 4 weeks post-transplant and every 1 month up to 12 months | Occurrence of anemia requiring treatment with erythropoiesis stimulating agents |
| Survival | From day 0 post-transplant up to 10 days or patient discharge, then at 2, 3 and 4 weeks post-transplant and every 1 month up to 12 months | Six-month patient/graft survival |
| Platelet and WBC counts | From day 0 post-transplant up to 10 days or patient discharge, then at 2, 3 and 4 weeks post-transplant and every 1 month up to 12 months | Six-month time course of platelet and WBC counts |
| Creatinine levels | From day 0 post-transplant up to 10 days or patient discharge, then at 2, 3 and 4 weeks post-transplant and every 1 month up to 12 months | Six-month time course of serum creatinine levels |
| Adverse events | From day 0 post-transplant up to 10 days or patient discharge, then at 2, 3 and 4 weeks post-transplant and every 1 month up to 12 months | Incidence of serious and non-serious adverse events |
| Occurrence of biopsy proven rejection | From day 0 post-transplant up to 10 days or patient discharge, then at 2, 3 and 4 weeks post-transplant and every 1 month up to 12 months | Banff score for biopsy proven rejections |
Countries
Italy
Outcome results
None listed