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American Journal of Transplantation Images in Transplantation—Continuing Medical Education (CME)

Each month, the American Journal of Transplantation will feature Images in Transplantation, a journal-based CME activity, chosen to educate participants on current developments in the science and imaging of transplantation. Participants can earn 1 AMA PRA Category 1 Credit™ per article at their own pace.

This month's feature article is titled: “Mild Rise in Creatinine Six Months Post Kidney Transplant.”

Accreditation and Designation Statement

This activity has been planned and implemented in accordance with the Essential Areas and policies of the Accreditation Council for Continuing Medical Education (ACCME) through the joint sponsorship of Blackwell Futura Media Services, the American Society of Transplant Surgeons and the American Society of Transplantation. Blackwell Futura Media Services is accredited by the ACCME to provide continuing medical education for physicians.

Blackwell Futura Media Services designates this journal-based CME activity for a maximum of 1 AMA PRA Category 1 Credit™. Physicians should only claim credit commensurate with the extent of their participation in the activity.

Statement of Need

Clinicians may hesitate to biopsy an otherwise stable patient with a mild rise in creatinine after 3 months posttransplant. However, a wide range of pathological processes may involve the allograft at this time point. Many of these processes are associated with inflammation in the allograft, and may require special studies to make an accurate diagnosis to guide therapy and prevent deterioration in the allograft. In particular, polyoma virus infection must be identified at an early stage before persistent infection and extensive fibrosis ensue.

Purpose of Activity

The activity is designed to improve performance in practice and potentially improve patient outcomes.

Identification of Practice Gap

Concern about potential complications remains a barrier to the clinical decision to biopsy patients with mild or persistently elevated creatinine posttransplant. When a biopsy is performed, inflammatory processes in the allograft may be diagnosed as rejection, even in the absence of the specific diagnostic criteria for diagnosis of both cell- and antibody-mediated rejection, if features of other processes are not recognized. There is a tendency to rely on other noninvasive surveillance measures to identify processes that may be deleterious to the allograft—in the case of polyoma virus nephropathy, serum BK levels may not be informative. Despite the sometimes florid inflammatory process in the allograft, the mainstay of treatment for polyoma virus nephropathy remains reduction of immunosuppression.

Learning Objectives

Upon completion of this educational activity, participants will be able to:

  • • 
    Outline potential causes of allograft inflammation and dysfunction several months posttransplant.
  • • 
    Identify the cardinal diagnostic lesions in polyoma virus nephropathy.
  • • 
    Describe major risk factors for the development of polyoma virus nephropathy.
  • • 
    Indicate a major pitfall in noninvasive diagnosis of polyoma virus nephropathy.
  • • 
    Recognize the major therapeutic intervention in response to polyoma virus nephropathy.

Target Audience

This activity has been designed to meet the educational needs of physicians and surgeons in the field of transplantation.

Disclosures

No commercial support has been accepted related to the development or publication of this activity. Blackwell Futura Media Services has reviewed all disclosures and resolved or managed all identified conflicts of interest, as applicable. The following authors, editors, and staff reported no relevant financial relationships with respect to this activity.

Editor-in-Chief

Allan D. Kirk, MD, PhD, FACS

Editors

Sandy Feng, MD, PhD

Douglas W. Hanto, MD, PhD

Authors

Carla L. Ellis, MD, and Lorraine C. Racusen, MD

ASTS Staff

Mina Behari, Director of Education

This manuscript underwent peer review in line with the standards of editorial integrity and publication ethics maintained by the American Journal of Transplantation. The peer reviewers have no relevant financial relationships to disclose. The peer review process for the American Journal of Transplantation is blinded. As such, the identities of the reviewers are not disclosed in line with the standard accepted practices of medical journal peer review.

Instructions on Receiving CME Credit

This activity is designed to be completed within an hour. Physicians should claim only those credits that reflect the time actually spent in the activity. This activity will be available for CME credit for twelve months following its publication date. At that time, it will be reviewed and potentially updated and extended for an additional 12 months.

Follow these steps to participate, answer the questions and claim your CME credit:

  • • 
  • • 
    Read the learning objectives, target audience, and activity disclosures.
  • • 
    Read the article in print or online format.
  • • 
    Reflect on the article.
  • • 
    Access the CME Exam, and choose the best answer to each question.
  • • 
    Complete the required evaluation and print your CME certificate.

The patient is a 45-year-old obese female with end-stage renal disease due to diabetes mellitus. After 5 years on dialysis, she received a deceased donor kidney transplant from a standard criteria donor, with placement of a ureteral stent. Cold ischemia time was 27 hours. Postoperatively, creatinine improved slowly, without need for dialysis, and was 1.9 mg/dL posttransplant. She was discharged on tacrolimus, CellCept and low-dose prednisone. At a 1-month follow-up visit, the ureteral stent was removed. Her creatinine was 2.0 mg/dL at that time; tacrolimus level was 4 ng/mL, serum BK virus levels were negative by PCR studies, urine culture was negative, urinalysis revealed only a few white blood cells and donor-specific antibody to HLA antigens was negative. A renal biopsy was performed. The biopsy revealed acute cellular rejection (Banff score 1A – g0, i2, t2, v0, cg0, ci0, ct0, cv1, mm0, ptc0, ah0, C4d0, ti2), and she was treated with pulse steroids. At a follow-up visit 2 weeks later, her creatinine had returned to a baseline of 1.5 m/dL, and urine cultures were negative. At a 6-month follow-up visit, her creatinine was noted to be 1.8 mg/dL, tacrolimus level was 6 ng/mL, serum BK virus was negative by PCR, urine cultures were negative, urinalysis revealed only rare WBC and donor-specific anti-HLA antibody was negative. A renal biopsy was performed (see Figures 1 and 2). Creatinine has slowly returned to baseline after appropriate treatment.

image

Figure 1. Hematoxylin and eosin (H & E) stained section of the renal biopsy, low and high (inset) magnification.

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image

Figure 2. H & E-stained section, focusing on renal tubules. Inset: Immunoperoxidase stain.

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Questions

  1. Top of page
  2. Questions
  • 1 .   
    Based on Figure 1 from the 6-month renal biopsy, the differential diagnosis includes all except:
    • a.   
      Bacterial infection
    • b.   
      Cell-mediated rejection
    • c.   
      Viral infection
    • d.   
      Calcineurin inhibitor toxicity
    • e.   
      Drug reaction
  • 2 .   
    Based on the 6-month biopsy (Figure 2), what is the cause of the renal dysfunction at 6 months?
    • a.   
      Acute rejection, vascular type, Banff type 2A
    • b.   
      Pyelonephritis
    • c.   
      Calcineurin inhibitor toxicity
    • d.   
      Polyoma virus nephropathy
    • e.   
      Antibody-mediated rejection
  • 3 .   
    Why did the clinical testing fail to reveal the diagnosis found on biopsy?
    • a.   
      The infecting organism was anaerobic
    • b.   
      The causative organism was JC virus
    • c.   
      The patient is African American, and more sensitive to calcineurin inhibitors
    • d.   
      The process was due to an antibody to non-HLA antigen
  • 4 .   
    Possible risk factors for the cause of renal dysfunction at 6 months include all of the following except:
    • a.   
      The immunosuppressive regimen
    • b.   
      Ureteral stenting
    • c.   
      Cold ischemia time
    • d.   
      Occurrence of previous rejection
    • e.   
      Obesity
  • 5 .   
    The most important therapeutic approach at this point is:
    • a.   
      Reduction of immunosuppression
    • b.   
      Treatment with rituximab
    • c.   
      Better control of diabetes
    • d.   
      Treatment with a broad-spectrum antibiotic
    • e.   
      Increase in immunosuppression

To complete this activity and earn credit, please go to https://www.wileyhealthlearning.com/ajt.aspx