BackgroundRabbit antithymocyte globulin (rATG) is the most widely used kidney transplant induction immunotherapy in the United States. It was recently Food and Drug Administration approved for this indication with typical dose recommendations of 1.5 mg/kg for up to 7 days given via a central line.MethodsWe theorized that reduced rATG dosing when compared with conventional dosing (6-10.5 mg/kg) is safe and effective, leading to development of a risk-stratified treatment protocol. Five-year data from a retrospective cohort of 224 adult kidney transplants (2008-2013) with follow-up through 2015 is presented. Cumulative rATG doses of 3 mg/kg were administered peripherally to nonsensitized living donor recipients, 4.5 mg/kg to nonsensitized deceased donor recipients. A subset of higher immunologic risk recipients (defined as history of prior transplant, panel reactive antibody greater than 20%, or flow cytometry crossmatch positivity) received 6 mg/kg.ResultsThere were no differences in patient or graft survival between the 3 groups. One-year rejection rates in the first 2 groups were 8.3% and 8.8%, respectively, comparable to contemporaneous rates reported to the Scientific Registry of Transplant Recipients. Dose tailoring permitted substantial cost savings estimated at US $1 091 502. Mean length of stay fell by almost 3 days as the protocol was refined. There were no episodes of phlebitis. Infection rates were comparable with those reported to the Scientific Registry of Transplant Recipients.ConclusionsThe novel findings of the current study include peripheral administration, reduced dosing, favorable safety, excellent allograft outcomes, and clear associative data regarding reduced costs and length of stay.
Bivalirudin dosing requirements increased with increasing Clcr values. The high degree of variability suggests that dosing in individual patients will require careful titration to achieve adequate anticoagulation.
Tacrolimus (TAC) is subject to many drug interactions as a result of its metabolism primarily via CYP450 isoenzyme 3A4. Numerous case reports of TAC and CYP3A4 inducers and inhibitors have been described including antimicrobials, calcium channel antagonists, and antiepileptic drugs. We present the case of a 13-year-old patient with cystic fibrosis and a history of liver transplantation, where subtherapeutic TAC concentrations were suspected to be a result of concomitant TAC and nafcillin (NAF) therapy. The observed drug interaction occurred on two separate hospital admissions, during both of which the patient exhibited therapeutic TAC concentrations prior to exposure to NAF, a CYP3A4 inducer. Upon discontinuation of NAF, TAC concentrations recovered in both instances. This case represents a drug-drug interaction between TAC and NAF that has not previously been reported to our knowledge. Despite the lack of existing reports of interaction between these two agents, this case highlights the importance of therapeutic drug monitoring and assessing for any potential drug-drug or drug-food interactions in patients receiving TAC therapy.
Postpartum atypical hemolytic uremic syndrome (aHUS) is a rare disorder associated with poor maternal and fetal outcomes. We describe a case of severe postpartum aHUS with recurrence in a kidney allograft after a second pregnancy. The patient had initially presented age 28 years with aHUS that developed after her first delivery. In spite of treatment with plasma exchange, she developed end-stage renal disease (ESRD) requiring years of hemodialysis before receiving a kidney transplant from a living unrelated donor. Two years later, she became pregnant again and at 26 weeks gestation she presented to our hospital with hypertension and proteinuria. Within 48 hours of delivery she developed hemolytic anemia, thrombocytopenia, and oliguric acute kidney injury (AKI) culminating in the need for dialysis. There was no response to therapeutic plasma exchange (TPE). However, treatment with eculizumab led to prompt, successful resolution of hemolysis, thrombocytopenia, and AKI. Three months after therapy was stopped, her disease relapsed causing renal failure again requiring dialysis. At that time, an allograft biopsy revealed severe thrombotic microangiopathy (TMA). Eculizumab was resumed without plasma exchange leading to resolution of aHUS and return of kidney function. Now, her baby is nearly 2 years old. She remains on maintenance eculizumab therapy 1,200 mg every 2 weeks without dialysis. She has excellent renal function with creatinine of 1.2 mg/dL, eGFR 52 mL/min/1.73 m, and proteinuria 0.35 g/day. She will likely be on eculizumab for the remainder of her life.
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