• Change in calcineurin inhibitor-related symptoms as measured by a change in the Calcineurin Inhibitor-Related Symptoms (CIRC) severity score. [ Time Frame: 12 months ]
  The CIRS is a questionnaire that assesses five symptoms (from the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events [PRO-CTCAE]) that have been shown to be associated with calcineurin inhibitors. These symptoms include trembling hands, muscle cramps, muscle weakness, swollen gums, and increased hair growth. Each symptom is based on symptom severity in the last 7 days scaled from 0 (none) - 4 (very severe). The cumulative score ranges from 0-20.
• Severity of calcineurin inhibitor-related symptoms [ Time Frame: 12 months ]
  Total percent of patients in each treatment group with a severe or very severe score (3 or 4) on any CIRS item
• Change in severity of calcineurin inhibitor-related symptoms [ Time Frame: From 4 to 12 months ]
  Total percent of patients with a reduction in a CIRS item score from a severe or very severe score (3 to 4) to a mild to moderate (1 or 2) score
• Change in any one calcineurin inhibitor-related symptom [ Time Frame: From 4 to 12 months. ]
  Total percent of patients with a reduction in any single CIRS item by 1 point or greater
• Change in transplant-related symptoms as measured by the difference in mean transplant-related symptoms (TRS) score. [ Time Frame: 12 months post-transplant ]
  The TRS is a multi-item questionnaire capturing 15 symptoms (from PRO-CTCAE) that have been shown to be associated with transplant and general health-related quality of life improvement. These symptoms include change in taste, constipation, diarrhea, swelling in arms or legs, palpitations, dry skin, darkening of skin, blurry vision, headache, insomnia, anxiety, sadness, discouraged, increase in appetite, and fatigue. Each symptom is based on symptom severity in the last 7 days and scaled from 0 (none) - 4 (very severe). Some symptoms also have added questions pertaining to frequency and/or interference with daily activities.
• Improvement in health-related qualify of life as measured by the PROMIS-29 health profile. [ Time Frame: 12 months post-transplant ]
  The PROMIS-29 produces individual scores for depression, anxiety, fatigue, pain interference, sleep disturbance, physical function, participation in social roles, and pain intensity. Physical and mental health summary scores will also be calculated.
• Change in individual transplant-related symptoms [ Time Frame: 12 months post-transplant ]
  Captured in the TRS questionnaire (individual TRS items will be classified as improved, worsened, unchanged)
• Change in overall tolerability or patient bother due to side effects [ Time Frame: 12 months post-transplant ]
  Measured by item GP5 ("I am bothered by side effects of treatment") from the FACT-G Questionnaire
• Change in mean taking adherence [ Time Frame: 12 months post-transplant ]
  Defined as the percentage of prescribed doses taken each day
• Change in patient medication satisfaction as assessed by question 14 of the Treatment Satisfaction Questionnaire for Medication. [ Time Frame: 12 months post-transplant ]
  Question 14 of the Treatment Satisfaction Questionnaire for Medication measures medication satisfaction on a 7 item scale ranging from "Extremely Dissatisfied" to "Extremely Satisfied."
• Correlation between de novo DSA and degree of taking and timing adherence [ Time Frame: 12 months post-transplant ]
  Proportion of patients at different adherence thresholds of taking and timing adherences between 4 months and 12 months post transplant will be correlated with the presence or absence of dnDSA by 12 months post-transplant
• Adverse events [ Time Frame: 12 months post-transplant ]
  Number of adverse events reported

Despite improvement in short-term graft outcomes in organ transplant, transplant patients still have to take on complex medication regimens to achieve current results. Adherence to these complex medications is an important problem in light of the potential risk of acute and chronic rejection and the associated burden of increased hospitalization, cost, and diminished quality of life that results from missed doses and poor overall drug taking. Part of the diminished quality of life is also tied to the bothersome symptoms patient feel after transplant. Most patients experience symptoms that relate to either the overall transplant immunosuppression or medication specific side effects. In the BENEFIT and BENEFIT-EXT trials, >60% of patients reported tiredness and lack of energy as an issue. Sleep problems, mood swings, restlessness, anxiety, depression, and concentration and memory difficulties appeared in approximately 50-60% of patients. In addition to these symptoms, >38% patients also reported numerous others side effects that have been strongly associated with calcineurin-inhibitors such as tacrolimus that include dizziness, muscle cramps, trembling hands, tingling in hands and feet, and headache.

The investigators hypothesize that the use of once-daily Envarsus XR® could decrease some transplant- and tacrolimus-related adverse symptoms and potentially lead to improvement in quality of life and medication adherence when compared to twice-daily tacrolimus. In order to assess this hypothesis, a prospective, multi-center, randomized, open-label, pilot study to investigate medication adherence and patient reported symptom occurrence and interference with daily life comparing once-daily Envarsus XR® and twice-daily immediate release tacrolimus in adult renal transplant recipients (SIMPLE) is being proposed.

• Drug: Envarsus XR
  Twice daily tacrolimus vs. Envarsus XR
• Drug: Tacrolimus twice daily
  Twice daily tacrolimus vs. Envarsus XR

• Active Comparator: Tacrolimus twice-daily
  Subjects assigned to this arm will take tacrolimus two times daily by mouth, at the clinically prescribed dose.
  Intervention: Drug: Tacrolimus twice daily
• Active Comparator: Envarsus XR
  Subjects assigned to this arm will take Envarsus XR one time daily by mouth, at the clinically prescribed dose.
  Intervention: Drug: Envarsus XR

Inclusion Criteria:

• Patient is an adult (18 years of age or older).
• Patient is a recipient of a deceased or living donor kidney transplant.
• Patient is able to comply with study procedures for the entire length of the study.
• Patient has been informed about the study survey and has signed an informed consent form.

Exclusion Criteria:

• Patient is unable or unwilling to complete study patient reported outcome questionnaires.
• Patient is currently receiving azathioprine
• Patient is currently receiving an mTOR inhibitor (sirolimus, everolimus)
• Patient is currently receiving an belatacept
• Patient has received investigational immunosuppression 1 month prior to transplant or post-transplant
• Patient is in a setting where a professional care taker is responsible for dispensing subject's medication.