Introduction:
Renal transplantation remains the gold standard treatment for end-stage renal disease (ESRD), significantly enhancing both quality of life and survival. However, chronic rejection and the adverse effects of long-term immunosuppression, especially with calcineurin inhibitors (CNIs), pose significant challenges. CNIs, such as Tacrolimus and Cyclosporine, are associated with nephrotoxicity, increasing the risk of graft dysfunction and loss. mTOR inhibitors (mTORi), particularly Everolimus, have emerged as alternative immunosuppressants that reduce CNI-related toxicity. This study aimed to assess the efficacy, safety, and clinical outcomes of transitioning to an mTORi-based regimen in post-renal transplant recipients.
Methods:
This single-center retrospective observational study evaluated adult patients who underwent kidney transplantation between 2015 and 2024 and transitioned to an mTORi-based regimen (Everolimus) following CNI-related complications or other clinical indications. Baseline immunosuppressive regimens included Prednisolone, Tacrolimus, Mycophenolic Acid (MPA), and, in fewer cases, Cyclosporine or Azathioprine. The primary outcome was biopsy-proven acute rejection within five years post-transplant. Secondary outcomes included graft survival, renal function (as measured by estimated glomerular filtration rate, eGFR), new-onset proteinuria, infection rates, and other adverse events. Statistical analyses were conducted using measures of central tendency, frequencies, and interquartile ranges where appropriate.
Results:
In this observational study of post-renal transplant recipients who transitioned to an mTOR inhibitor (Everolimus), the majority of patients (96%, n=48) were initially on a Prednisolone/Tacrolimus/MPA regimen, with only 2% (n=1) on Prednisolone/Cyclosporine/MPA and 2% (n=1) on Prednisolone/Cyclosporine/Azathioprine. After switching, 56% (n=28) were on Prednisolone/Tacrolimus/Everolimus, 32% (n=16) on Prednisolone/MPA/Everolimus, with smaller numbers on combinations involving Leflunomide, Azathioprine, or Cyclosporine. The most common reasons for switching to Everolimus included Tacrolimus-induced thrombotic microangiopathy (TMA) in 24% (n=12), MPA associated leucopenia in 20% (n=10), BK viremia (BKVAN) (14%, n=7), and Tacrolimus toxicity in 12% (n=6). Following the introduction of Everolimus, 28% (n=14) of patients developed new-onset proteinuria[SV1] [LV2] [SV3] [LV4] (>500mg/day), while 72% (n=36) remained proteinuria-free. Rejection episodes occurred in 4% (n=2) of patients, with 96% (n=47) not experiencing rejection among which 2% (n=1) experienced TCMR and 2% (n=1) had chronic AbMR. Regarding infections, 28% (n=14) BKV-PCR levels were on the lower side as compared to before changing with some patients having persistent negative levels post-everolimus. There were isolated cases of acute gastroenteritis, dengue, COVID-19, CMV, and graft pyelonephritis (2% each, n=1). Among the patients who had graft dysfunction, 26% (n=13), Graft loss was seen in 6% (n=3), whereas 20% (n=10) had a stable graft functions post-everolimus.[5] [SV6] [LV7]
In terms of graft outcomes,76 % (n=38) of patients maintained graft survival, while 24% (n=12) experienced graft loss[8] [LV9] . The causes of graft loss included chronic allograft nephropathy (CAN) in 12% (n=6), IgA recurrence in 8% (n=4), BKVAN in 4% (n=2), and chronic Tacrolimus toxicity in 2% (n=1). Additionally, adverse events like leucopenia, [10] [SV11] [LV12] [SV13] [LV14] proteinuria, delayed wound healing, and oral ulcers were also reported.
Conclusions:
This study demonstrates that mTOR inhibitors, specifically Everolimus, offer a viable alternative to traditional CNI-based immunosuppressive regimens in renal transplant recipients, particularly for those experiencing CNI-related complications such as TMA, nephrotoxicity. While Everolimus reduces CNI-associated toxicity, it is linked to an increased risk of proteinuria and viral infections. Graft survival rates were relatively favorable, though graft loss was significant in patients with pre-existing complications. These findings support the use of mTORi in high-risk patients, but highlight the need for ongoing monitoring to manage associated adverse events.
I have no potential conflict of interest to disclose.
I did not use generative AI and AI-assisted technologies in the writing process.