Introduction:
32 yr old man was diagnosed with hypertension, renal dysfunction (Creatinine [Cr] 4.3 mg/dl) and small kidneys on ultrasound in April 2022. Serum creatinine worsened to 7.8 mg/dl in Jan 2023 necessitating 2 per week hemodialysis (HD) via arteriovenous fistula. He underwent ABO compatible kidney transplant in Nov 2023 with donor being his father. The CDC, flowcytometry crossmatch was negative. Patient received low dose induction regimen with Antithymocyte globulin 2mg/kg and methyl prednisolone 500mg. He was started on maintenance immunosuppression with Mycophenolate mofetil 500mg BD, Tacrolimus (Tac) 4 mg BD and tapering doses of prednisolone.
Methods:
During immediate post OP course, patients C0 Tac level was 13.9ng/ml. Repeat C0 Tac was 24.5 ng/ml. Tac dose reduced to 2.5mg BD. Post-operative period was uneventful with nadir Cr being 1.4. He presented 15 days later with Cr value of 2.45mg/dl with C0 Tac level 20.2ng/ml on 2.5 mg BD dose of Tac. Urine examination and graft artery doppler were normal. Tac dose was reduced to 1.5 mg BD and renal allograft biopsy was done which was suggestive of acute tubular injury. Inspite of this, at 6 weeks, his Cr remained in range of 2.5- 3 with C0 Tac level between 15-20 ng/ml. Reducing Tac doses further to 0.25 BD did not help and his Cr rose to 3.5 mg/dl. Repeat allograft biopsy was done and it revealed severe acute tubular injury. At 10 weeks, Patient was switched to Cyclosporine (CsA)25 BD; with this, his C0 CsA level was 200-250. Patient developed raised liver enzymes and needed switching of CsA to Sirolimus. C0 Sirolimus was 34 while on 0.5 mg BD. During follow-up visit, patient developed proteinuria of 600 mg/day with Cr 4.5 mg/dl.
Results:
Repeat renal biopsy was suggestive of chronic T cell mediated rejection. During this period, patient was admitted multiple times with fever and respiratory tract infections for which mycophenolate mofetil was temporarily stopped. He progressed to graft loss and was reinitiated on HD. His genotyping for CYP3A4/5 polymorphism is awaited. In patients with high tacrolimus levels and toxicity, such as the one described, CYP3A4/5 genotyping may reveal poor metabolizer status, necessitating lower initial doses or alternative immunosuppressive strategies (e.g., switching to cyclosporine or sirolimus). Early identification of polymorphisms could prevent adverse outcomes, such as acute tubular injury, chronic T cell-mediated rejection (TCMR), or graft loss, by allowing for tailored immunosuppressive regimens based on genetic metabolism profiles.
Conclusions:
Our case highlights the importance of testing genetic polymorphisms and grave consequence of multiple immunosuppressant drug toxicities in the form of graft dysfunction, rejection and multiple infection episodes in kidney transplant recipient. There is need of non-nephrotoxic medication like Belatacept in such patients. Equitable access to essential medicines for renal transplant patients is necessary to achieve optimum outcomes.
This abstract was also submitted for the ‘34th Annual ISOT conference.’
I have no potential conflict of interest to disclose.
I did not use generative AI and AI-assisted technologies in the writing process.