BK Viremia After Renal Transplantation

BK Viremia After Renal Transplantation: Screening, Early Diagnosis, Early Reduction in Immunosuppression and Treatment With Leflunomide (Arava)

Hypothesis: Early detection, and treatment, of BK virus infection after kidney transplantation will prevent BK virus associated kidney transplant injury.

BK virus associated nephropathy (BKVN) is estimated to cause a progressive kidney transplant injury in 1-10% of renal transplant recipients. Diagnostic and monitoring strategies for BKVN is still being developed. Detectable virus in the blood by polymerase change reaction-test (PCR) is predictive of BKVN. Additionally, PCR provides a objective estimate of the degree of infection.

If early detection and treatment of BK virus infection is effective in preventing subsequent kidney transplant injury has not been studied. However, renal injury and dysfunction develops late in the natural course of BKVN and it seems likely that screening in combination with early treatment would be beneficial for long-term transplant survival.

There is no established treatment for BK virus infection. Nevertheless, in kidney transplanted patients diagnosed with BK virus infection, immunosuppression is reduced to allow the patients own immune system to handle the virus. However, reduction of immunosuppression has not been associated with rejection. This indicate that these patients were over-immunosuppressed, predisposing them to BKVN. Therefore, to compare the degree of immunosuppression in BKVN patients (over-immunosuppressed) to other patients (not over-immunosuppressed) could yield interesting information. One possibility would be to quantify these patients specific cellular immune response to BK virus but also to other viruses (T cell reactivity).

Leflunomide (Arava) is an immunosuppressive drug, approved for the treatment of rheumatoid arthritis, and has been used in more than 300,000 patients worldwide. Furthermore, leflunomide has been used safely in humans after clinical kidney and liver transplantation for more than 300 days. In addition to leflunomide's value in preventing rejection, it has been shown to exert inhibitory effects on different viruses. Recently published pilot studies suggest that leflunomide treatment of patients with BKVN significantly reduces the amount of BK virus in blood and prevents recurrence of kidney transplant injury. At Karolinska University Hospital, leflunomide has been used for treatment of BKVN and, in some of the patients, renal function has stabilized and BK virus load has decreased significantly.

Study Overview

• Status: Unknown
• Conditions: BK Virus Infection; Terminal Renal Failure
• Intervention / Treatment: Drug: leflunomide

• Study Type: Interventional
• Enrollment (Anticipated): 100
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Sweden
  • Stockholm, Sweden, 14186
    • Karolinska University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• All adult patients undergoing kidney transplantation at Karolinska University Hospital

Exclusion Criteria:

• Absence of informed consent
• Allergy to leflunomide
• Pregnancy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: SINGLE_GROUP
• Masking: NONE

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Renal function (serum creatinine)	1 year after diagnosis of BK viremia

Secondary Outcome Measures

Outcome Measure	Time Frame
Incidence of BK virus associated nephropathy	1 year after diagnosis of BK viremia

Collaborators and Investigators

• Sponsor: Karolinska University Hospital
• Collaborators: Uppsala University Hospital

Study record dates

Study Major Dates

• Study Start: May 1, 2007
• Primary Completion (ANTICIPATED): May 1, 2009
• Study Completion (ANTICIPATED): May 1, 2009

Study Registration Dates

• First Submitted: May 21, 2008
• First Submitted That Met QC Criteria: May 23, 2008
• First Posted (ESTIMATE): May 26, 2008

Study Record Updates

• Last Update Posted (ESTIMATE): February 6, 2009
• Last Update Submitted That Met QC Criteria: February 5, 2009
• Last Verified: February 1, 2009

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Virus Diseases; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Sepsis; Viremia; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Immunosuppressive Agents; Immunologic Factors; Leflunomide
• Other Study ID Numbers: BK study