Steroid withdrawal in kidney allograft recipients

Abstract

This review highlights the aggregate of knowledge obtained from the temporal trend of kidney transplant immune suppression. We will discuss the burden of steroid side effects and their impact on quality of life in kidney allograft recipients, which have led to minimizing steroid exposure. Issues arising since the inception of the concept of steroid withdrawal will be discussed, along with how they have continually led to a shift in research focus on this subject matter. The usefulness of surveillance biopsies and how further elucidation of the pathophysiology of interstitial fibrosis and tubular atrophy could contribute to improving long-term allograft outcomes will also be discussed. We will elaborate on the role of calcineurin inhibitor minimization alongside steroid withdrawal in improving long-term graft survival. Future expectations of subsequent studies with a view to improving overall kidney allograft outcomes by eliminating attendant problems associated with steroids will also be covered.

Keywords::

• acute rejection
• allograft
• calcineurin
• cyclosporine
• glomerulonephritis
• immunosuppression
• interstitial fibrosis and tubular atrophy
• mycophenolate mofetil
• new onset diabetes after transplantation
• surveillance biopsy

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Steroid use post-kidney transplantation is clearly not without its attendant metabolic side effects, which have limited the success of long-term allograft outcomes.

• The current evidence is more in favor of steroid avoidance (withdrawal of corticosteroid ≤1 week post transplant), because it has better acute rejection rates than withdrawing steroid later post-transplant.

• Although acute rejection episodes were higher in the steroid avoidance patients compared to patients on chronic steroid maintenance, these rejection episodes are unlikely to be severe enough to adversely affect long-term allograft outcomes.

• Most of the data about steroid withdrawal or avoidance is limited to patients with ‘low immunologic risk’ and receiving thymoglobulin induction.

• Induction with Thymoglobulin and maintenance with both tacrolimus and mycophenolate mofetil are currently the preferred regimen for steroid avoidance protocols.

• Validity of generalizing current study results (cohorts with low-risk factors) to high-risk categories is in question, and this highlights the importance of more studies that incorporate cohorts with high-risk factors.

• Elucidation of the pathophysiology of interstitial fibrosis and tubular atrophy makes strong arguments for minimizing exposure to calcineurin inhibitors and utilizing surveillance biopsies.

• Achieving immune tolerance via immune modulation rather than immune suppression might be the key to unlocking the limitations to achieving more successful long-term allograft results.

• Despite the achievements made possible by recent immunosuppressive drugs, there remains a role for even newer therapeutic agents in helping to further maximize the outcomes of steroid minimization.