Nimish Mehta, PhD, MBA; Susan L. Smith, MN, PhD Medscape, LLC, New York, NY, USA

purpose

The one constant in solid organ transplantation (SOT), regardless of the organ transplanted, is the need for lifelong maintenance immunosuppression.[1] However, the goal of preventing allograft rejection while minimizing drug toxicities has not been achieved and many SOT recipients are faced with graft loss and/or drug toxicities due to inadequate, inconsistent, or inappropriate immunosuppression regimens.[2] Transplant clinicians along the entire continuum of patient care continue to grapple with this challenge of balancing the benefits with the risks of immunosuppression therapy. A study was conducted to determine if online educational interventions could improve knowledge, competence, and performance of nephrologists with respect to management of immunosuppression in SOT recipients.

methods

Based on the identified gaps in care, a series of 3 online continuing medical education interventions were developed that included an interactive, text-based review article (approximately 5000 words) and 2 case-based video discussions between 2 faculty (approximately 15 minutes each).[3-5] All of the activities included interactive questions to engage the participants throughout the educational interventions. The effectiveness of educational interventions was evaluated with a cohort of US-practicing nephrologists who participated in 1 or more of 3 online educational interventions using 2 different methodologies:

1. The interactive questions from the online interventions were grouped into 3 distinct domains of learning goals: selection of an immunosuppressive regimen, knowledge of new developments and practice recommendations, and ability to individualize therapy. Confidentiality of survey respondents was maintained and responses were de-identified and aggregated prior to analysis. A correlation t-test was conducted on questions grouped by learning goals for the participant cohort to calculate level of significance within each goal by comparing the percentage of correct vs incorrect responses. Cohen’s D formula was calculated to measure effect size of the questions within each learning goal.

2. Surveys were fielded to participants at the completion of each educational intervention. Responses to questions were collected from the participant cohort after completing the intervention. The survey was also fielded to a demographically similar control group of nonparticipants.

• The assessment method, previously validated to measure performance, included a survey of knowledge- and case-based multiple-choice questions with each question mapped to specific educational goals.

• Participant results were compared with responses from nonparticipants in order to determine the impact of the education. Non-practicing clinicians and clinicians not involved in the care of patients with SOT were excluded from the study.

• Confidentiality of survey respondents was maintained and responses were de-identified and aggregated prior to analysis. Chi-square tests were done to detect differences between the responses of the participant and control groups.

1. The correlation analysis of the sample of nephrologist participant responses (n=612) grouped by learning goals showed a positive and significant impact of online educational interventions within each group as follows:

• Selection of appropriate immunosuppressive regimen (d=0.52; P=.05)

• Knowledge of new developments and practice recommendations (d=0.45; P=.05)

• Ability to individualize therapy (d=0.41; P=.04)

2. In addition, significant improvements were also found when a sample of participant nephrologists’ (n=141) responses to knowledge- and case-based questions was compared with a demographically matched sample of nonparticipant nephrologists (n=141). For example, participants were more likely than nonparticipants to recognize that:

• Calcineurin inhibitor (CNI)-based maintenance immunosuppression is associated with long-term nephrotoxicity, cardiovascular disease, metabolic syndrome, type 2 diabetes, infection, and malignancy (Figure 1)

• A young donor, 6 human leukocyte antigen (HLA) match is the best candidate for induction with a nondepleting monoclonal antibody vs lymphocyte-depleting agent (Figure 2)

• Screening for polyomavirus (BKV) in asymptomatic kidney recipients is crucial to early detection and prevention of BKV nephropathy (94% participants vs 80% control, P=.04)

• Cidofovir is associated with serious adverse effects, hence there should not be a low threshold for its use in the treatment of BKV infection and requires careful consideration (Figure 3)

• Chemoprophylaxis with topical therapy for a patient with a history of prior squamous cell carcinoma (SCC) who is presenting with a new skin lesion is appropriate (Figure 4)

• In addition to SCC, patients receiving immunosuppressive therapy associated with renal transplantation are at increased risk for basal cell cancer, melanoma, and Merkel’s cell cancer (85% participant vs 68% control, P=.05)

results

Conclusions

This study demonstrated the effectiveness of an online curriculum of educational interventions consisting of 2 different educational formats, text-based with interactivity and case-based video, on improving the practice patterns of nephrologists in the management of SOT recipients. Effectiveness of these interventions was particularly noted in the ability to select appropriate immunosuppressive therapy, individualizing therapy in patients with skin cancer and BKV infection, and identifying practice recommendations based on key developments in SOT. Statistically significant improvements in several domains of SOT management as a result of participation in online educational interventions specifically designed to address gaps in care may result in improvements in patient care and outcomes.

References 1. Kidney Disease: Improving Global Outcomes (KDIGO) Transplant Work Group. KDIGO clinical practice guideline for the care of

kidney transplant recipients. Am J Transplant. 2009;9:S1-155.

2. Selzner N, Grant DR, Shalev I, Levy GA. The immunosuppressive pipeline: meeting unmet needs in liver transplantation. Liver Transpl. 2010;16:1359-1372.

3. Lodhi SA. A Clinical Guide to Successfully Managing Immunosuppression in Solid Organ Transplantation. Medscape Education. June 20, 2013. http://www.medscape.org/viewarticle/806307. Accessed July 8, 2014.

4. Goral S, Hariharan S. Kidney Transplant Recipient With BK Virus Infection: Practice Points for Clinicians. Medscape Education. May 21, 2013. http://www.medscape.org/viewarticle/804262. Accessed July 8, 2014.

5. Flechner SM, Zhang A. The Kidney Transplant Recipient With Skin Cancer: Practice Points for Clinicians. Medscape Education. July 19, 2013. http://www.medscape.org/viewarticle/807767. Accessed July 8, 2014.

Acknowledgements

The educational interventions and outcomes measurement were funded through an independent educational grant from Novartis. Help with statistical analysis of participant only cohort was provided by Jayashri Desai of Medscape Education. Outcomes study of participants and non-participant control groups was developed by CE Outcomes. Poster layout was provided by Christopher Clarke and Irina Kogan of Medscape Education.

For more information, contact Nimish Mehta, PhD, MBA, Senior Director, Educational Strategy, Medscape, LLC, nmehta@medscape.net.

figure 1 Knowledge of long-term, multi-organ toxicity of CNI-based immunosuppression.

CNI-based immunosuppression is fraught with long-term nephrotoxicity,

cardiovascular disease, metabolic syndrome, type 2

diabetes, infection, and malignancy*

Kidney transplant recipients who

receive CNI-based immunosuppression

have histologic evidence of kidney injury by 15 years after transplant,

with a median time of onset of 2 years;

this is mirrored by gradual and

progressive renal dysfunction

Chronic allograft nephropathy from CNIs is the leading

cause of late kidney allograft failure

Nephrology nonparticipants (n=44) Nephrology participants (n=44)

100%

80%

60%

40%

20%

0%

20%30% 27%

61%

11% 14%

P <.001

A 58- year old woman with end-stage renal disease (ESRD) from type 2 diabetes and a 3-year history of peritoneal dialysis undergoes living related kidney transplat from her daughter. She receives IL-2R blocker induction immunosuppression. She receives maintenance immunosuppression with CNI and mycophenolate mofetil (MMF). The serum creatinine nadirs at 0.9 mg/dL and then starts to rise and by one year post-transplantation is 2.1 mg/dL.

figure 2 Criteria for selection of candidates for induction therapy.

An African-American recipient with elevated panel reactive

antibody (PRA) level

Presence of donor-specific antibody and long cold ischemia

time

An older recipient and expected delayed graft

function

A young donor six human leukocyte antigen (HLA) match*

25% 20%27% 27%

16% 14% 11%

59%

figure 3

Which of the following statements regarding long-term toxicity (particularly nephrotoxicity) is accurate?

2% 2%

20%11%

Only when combined with other risk factors, post-

transplant renal dysfunction manifest by serum creatinine levels >1.5mg/dL contributes to an increased risk for

cardiovascular death

Kidney transplant recipients are at a greater than 3-fold increased risk for

cardiovascular death compared with age-matched controls, and cardiovascular disease accounts for 20% of deaths

among patients with a functioning allograft

Recognition of serious adverse effects, such as nephrotoxicity and vision loss, and the need for careful consideration of cidofovir use to treat BKV infection.

figure 4 Managing SCC while maintaining immunosuppression therapy.

Systemic chemotherapy Chemoprophylaxis with topical therapy*

Radiation treatment Decrease doses of all immunosuppressants

2%

23%11%

64%

6%

45%

4%

45%

Nephrology nonparticipants (n=47) Nephrology participants (n=47)

100%

80%

60%

40%

20%

0%

P =.03

A 62-year-old man presents to your office because he recently noticed some lesions on his ear and forehead, which have been getting larger. He is status post his second cadaveric kidney transplant 4 years ago and is currently on triple immunosuppression with tacrolimus, MMF, and prednisone. He has done well except for an early episode of rejection at 3 months post-transplantation, which was treated with a biologic agent for 3 months. His renal function has been stable for the past 3 years. The patient has no history of skin malignancy prior to transplant. A biopsy was performed on his skin lesions. Final pathology is pending. You refer the patient to a dermatologist for futher evaluation and treatment. The patient undergoes resection of all his lesions and pathologies SCC with 2 cm invasion. Six months later, he is seen by his dermatologist for follow-up and has a new SCC scalp lesion 2 mm in depth on biopsy and separate from the region of an old scar.

How would you treat this patient?

Success of Online Educational Interventions on Management of Immunosuppression in Solid Organ Transplantation Success of Online Educational Interventions on Management of Immunosuppression in Solid Organ Transplantation

*denotes the correct answer

*denotes the correct answer

*denotes the correct answer

*denotes the correct answerNephrology nonparticipants (n=44) Nephrology participants (n=44)

100%

80%

60%

40%

20%

0%

P =.003

A 48-year-old man with ESRD from chronic hypertension and a 4-year history of hemodialysis undergoes kidney transplant from a standard criteria deceased donor.

Which of the following clinical scenarios would provide the best candidate for induction with a nondepleting mAb such as the il-2r blocking agent basiliximab, rather than a lymphocyte-depleting agent such as rATG??

Treatment of BKV should continue until there is resolution of

infection

If the creatinine rises during BKV treatment, biopsy should

be repeated to exclude rejection

There should be a low threshold for introducing

cidofovir because it is effective against BKV*

Leflunomide alone has not been shown to be effective at treating

BKV

10%

40%32%

18%6%

22%

60%

12%

Nephrology nonparticipants (n=50) Nephrology participants (n=50)

100%

80%

60%

40%

20%

0%

P =.001

A 62-year-old man with ESRD from diabetes and hypertension undergoes kidney transplant from a 48-year-old standard criteria deceased donor. He receives induction immunosuppression with rabbit antithymocyte globulin (rATG) and maintenance therapy with tacrolimus (TAC), mycophenolic acid (MPA) and prednisone. One month later, his serum creatinine level is 1.1 mg/dL. Between 3 and 4 months post-transplantation, his serum creatinine rises from normal to 2.1 mg/dL. The patient’s serum BKV viral load and his allograft biopsy are consistent with BKV nephropathy. The patient’s creatinine temporarily improves after changing his immunosuppressive regimen but then increases again after a month.

Which one of the following is false regarding proper treatment of his allograft dysfunction?