Reduction of Maintenance Immunosuppression in Kidney Transplant Recipients during Acute Complicated Urinary Tract Infection
Rates of Clinical Cure and Microbiological Eradication following Reduction of Maintenance Immunosuppression in Kidney Transplant Recipients during Acute Complicated Urinary Tract Infection
prof. Tomas Reischig, MD, PhD - Faculty of Medicine in Pilsen, Charles University, and Teaching Hospital
112 participants
Jun 25, 2025
Interventional
Conditions
Summary
Reduction of maintenance immunosuppression during acute bacterial infection is a common part of management in kidney transplant recipients. However, data from randomized trials evaluating the effect of reducing or maintaining immunosuppression are not available. The aim of this study is to compare the efficacy and safety of reducing maintenance immunosuppression (discontinuation of antimetabolite) during acute complicated urinary tract infection (cUTI) in hospitalized kidney transplant recipients compared to maintaining immunosuppression with respect to short-term clinical, microbiological and renal outcomes. In eligible patients we completely withdraw the antimetabolite (mycophenolate mofetil or mycophenolate sodium) dose from maintenance immunosuppression. Patients randomized to the group (control group) with no reduction of maintenance immunosuppression will continue to receive the antimetabolite at the full dose during infection corresponding to the mycophenolic acid (MPA) area under the curve (AUC) of 30-60 mg*h/L investigated in the past. In particular, the study should answer the question of whether a reduction in immunosuppression during cUTI leads to significantly higher rates of clinical cure and microbiological eradication (overall treatment success) and whether it poses a risk for the development of graft dysfunction, including the incidence of rejection.
Eligibility
Inclusion Criteria3
- Adult (18 years and over with no upper age limit) renal transplant patients, male or female.
- Acute complicated urinary tract infection requiring hospitalization.
- Ability to signed informed consent.
Exclusion Criteria10
- Patients presenting with clinical signs of sepsis or septic shock at baseline who require an intensive care unit (ICU).
- Note: The timing of enrollment and randomization (the time period between hospital admission and randomization) will be decided by an experienced investigator based on the evolution of the patient’s clinical condition.
- Patients who do not meet the signs or symptoms of complicated urinary tract infection.
- Suspected or confirmed acute bacterial prostatitis, orchitis, epididymitis or chronic bacterial prostatitis.
- Suspected or confirmed cyst infection in polycystic kidney disease, renal corticomedullary or perinephric abscess.
- Presence or treatment of any infection within the past 14 days and at the time of enrollment (will include patients requiring preemptive treatment with valganciclovir for significant CMV DNAemia or modulation of immunosuppression for significant BK polyomavirus viremia).
- Treatment of biopsy-proven acute/active graft rejection 1 month or less before inclusion.
- Patients not treated with antimetabolite at baseline.
- Severe leukopenia or thrombocytopenia or gastrointestinal symptoms at baseline requiring antimetabolite withdrawal.
- Inability to sign informed consent.
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Interventions
Reduction of maintenance immunosuppression In eligible patients with cUTI requiring hospitalization, we completely withdraw the antimetabolite (mycophenolate mofetil or mycophenolate sodium) dose from maintenance immunosuppression. Antimetabolite will be discontinued within 24 hours (calculated to the first missed dose) after admission to the hospital. Treatment with full-dose antimetabolite will be reinitiated on the first day after clinical cure and microbiological eradication (overall treatment success). The vast majority of patients from our transplant center (Charles University Teaching Hospital in Pilsen) use a standard maintenance immunosuppressive protocol based on tacrolimus (rarely cyclosporine A) and mycophenolate mofetil (or mycophenolate sodium) with corticosteroid (prednisone). For clinical and study purpose, tacrolimus (or cyclosporine A) levels will be monitored at baseline and then at predefined checkpoints (days 3, 5, 7 and 14). In case of progression of the clinical condition to sepsis/septic shock after randomization requiring admission to the ICU, patients will be considered for modulation (complete discontinuation or lower target levels) of tacrolimus (or cyclosporine A) dose and steroid stress dose (e.g. hydrocortisone 50mg every 6 hours) in addition to antimetabolite withdrawal for safety reasons. Otherwise, if target levels are measured and the patient is stable, we will not adjust the dose of tacrolimus (or cyclosporine A) a priori. Calcineurin inhibitor dose adjustments will be made at the baseline and during the infection only if the level is measured outside the target range. Target trough levels of tacrolimus will be 5-12 ng/mL over the first 3 months after transplantation and subsequently 5-8 ng/mL. Similarly, we will not increase the maintenance dose of steroids (mostly prednisone 5 mg daily) in clinically stable patients. The transplant nephrologist, possibly in collaboration with the intensive care unit physician, will be responsible for any change in medication, including immunosuppressive and other therapy. In particular, an electronic database of medical and patient records will be used to monitor adherence to the intervention and related issues.
Locations(1)
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ACTRN12624001408572