Alfalfa-Induced Acute Cellular Rejection in a Kidney Allograft

Introduction: Tacrolimus is an immunosuppressant used in solid organ transplants. Tacrolimus has known drug-drug interactions with a variety of prescripation medications, as well as foods, food extracts, and over the counter supplements. These interactions can cause subtherapeutic or supratherapeutic levels of tacrolimus resulting in suboptimal immunosuppression or nephrotoxicity. We present a case of acute cellular rejection in a renal allograft caused by a drug-drug interaction between tacrolimus and an alfalfa supplement. Case Description: 56 year old female with history of ESKD secondary to IgA nephropathy, s/p LDKT 1997, DDKT 2015 who presented with subacute cough, poor appetite, and fatigue. She recently returned from a four week trip to Mexico, prior to this she started taking an alfalfa supplement. She denied missing doses of her immunosuppressants tacrolimus and mycophenolic acid. Physical exam was unremarkable. Labs notable for Cr 3.09mg/dL (baseline 0.70-0.80mg/dL), CK normal, UA with bland sediment, UPCR 0.45g/g, Ur Na 29mmol/L, FENA 3.4%. Retroperitoneal US showed increased cortical thickness and mild hydronephrosis of left renal allograft. CT abdomen/pelvis showed perinephric inflammation and mild collecting system dilatation of left renal allograft. She was started on IV fluids but no change in Cr after 24 hours. Further studies showed a tacrolimus level < 1.5 ng/mL, negative CMV DNA, and negative BK DNA. Foley catheter was placed, repeat renal allograft US showed improved hydrouerteronephrosis but no change in Cr. Renal allograft biopsy showed Banff 1B acute cellular rejection, C4D staining negative. Patient was treated with a 3 day course of pulse-dose steroids followed by prednisone taper. She was resumed on her tacrolimus and mycophenolic acid. The alfalfa supplement was discontinued. She was counseled to avoid OTC supplements in the future. Discussion: Adverse interactions between tacrolimus and other medications have been previously reported, as well as interactions between tacrolimus and foods including grapefruit juice, clementine, tumeric, and cranberry extract. To our knowledge, this is the first reported case of an alfalfa supplement interfering with the metabolism of tacrolimus, resulting in subtherapeutic levels and acute cellular rejection in a kidney allograft. This case demonstrates the importance of counseling patients on the potential harms of over the counter supplements.