Reduction of Maintenance Immunosuppression in Kidney Transplant Recipients during Acute Complicated Urinary Tract Infection

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.