Everolimus Rescue Immunosuppression in the Treatment of Chronic Allograft Dysfunction in Renal Transplant Recipients
Condition: Chronic Allograft Dysfunction in Renal Transplantation
Study type: Interventional
Phase: Phase 4

Summary: 
      Despite the remarkable improvement in short-term patient and graft survival among the
      recipients of kidney transplants, the progressive renal dysfunction (chronic allograft
      dysfunction) accompanied by chronic interstitial fibrosis, tubular atrophy, vascular
      occlusive changes and glomerulosclerosis remains the chief cause of graft loss. As a result
      of this damage from immunologic and non-immunologic injury, the long-term survival of kidney
      transplants has changed little during the past decade. And, among the non-immunologic
      factors, calcineurin inhibitor nephrotoxicity has been shown to be the most common factor
      leading to long-term graft damage and progression to graft failure. This is further supported
      by the previous finding that long-term use of calcineurin inhibitor-based therapy leads to
      deterioration in kidney function, even in recipients of non-renal organ transplants.

      The growing interest in calcineurin inhibitor minimisation protocols to optimize renal
      transplant outcome offers a new therapeutic options in the management of patients with
      chronic allograft dysfunction. Recently, mammalian target-of-rapamycin inhibitors (mTOR
      inhibitors) including everolimus has been shown to achieve an improvement of long-term
      function through an early modulation of immunosuppressive regimen. In this aspect,
      percutaneous renal graft biopsy represents an important diagnostic tool to allow
      visualization of the lesions of chronic allograft dysfunction and therefore the ability to
      delineate the potential improvement after introduction of everolimus. Histologic and
      morphometric findings from a protocol-mandated biopsies obtained from renal transplant
      recipients who are suffering from chronic allograft dysfunction and treated with everolimus
      are needed to provide a clinical blueprint for the drug's efficacy, if confirmed.
    

Detailed description: 
      The objective of the present study is to evaluate the a priori hypothesis that calcineurin
      inhibitor and rescue immunosuppression with everolimus-based therapy would attenuate the
      renal parenchymal injury associated with long-term use of calcineurin inhibitors in renal
      transplant recipients with declining kidney function. Another objective of this study is to
      elucidate the efficacy of our approach to arrest the progression of allograft dysfunction by
      means of protocol renal allograft biopsy.
    

Intervention name(s): everolimus
Intervention type(s): Drug
Intervention description(s): everolimus at an initial daily loading dose between 1 and 4 mg dose of everolimus will be adjusted to maintain a trough everolimus level between 5 and 12 ng/mL
Other intervention name(s): Certican
Intervention MeSH terms: Everolimus
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: mammalian target-of-rapamycin inhibitors; chronic allograft dysfunction; everolimus; calcineurin inhibitors