Impact of immunosuppressive therapy on pulmonary perfusion in kidney transplant recipients after COVID-19 illness

Abstract

Introduction: Patients who have received kidney transplants (KTR) are considered to be more susceptible to the severity of COVID-19-related illness. The transplanted patient's respiratory outcome worsened because of the ventilation-perfusion mismatch that occurs during the infection, which has been linked to endothelial damage. In this context, a reduction in immunosuppressive therapy is advisable to improve patient outcomes. However, the prognosis and suggested treatment for these types of patients are still debated.

Methods: We retrospectively analyzed 48 KTRs with stable graft function on calcineurin inhibitor therapy who underwent transient modification of the maintenance immunosuppressive regimen with withdrawal of mycophenolic acid/mycophenolate mofetil or mTOR inhibitor (mTORi) during COVID-19 infection and their reintroduction after healing. Pulmonary functional tests (EGA and spirometry) and DECT (Dual-energy CT) scans were performed 1 month following the negative nasopharyngeal swab (T0) and then after 6 months (T6).

Results: The presence an mTOR inhibitor in immunosuppressive therapy was associated with a significant increase in lung perfusion for the entire lung parenchyma of the mTORi-treated group, both in each lung segment considered separately and all of them together.

Conclusion: Our findings are consistent with the observation that the use of mTORi could play a potentially beneficial role in improving pulmonary perfusion.

Keywords: COVID-19; immunosuppression; kidney transplantation; mTOR inhibitors; pulmonary perfusion.

Figure 1

Algorhythm of the Study. KTR, kidney transplant recipients; MMF, mycophenolate mofetil; mTOR, mTOR inhibitors; Pred, prednisolon; PSM, propensity score matching; Tac, tacrolimus.

Figure 2

Dual-energy CT (DECT) angiography in kidney transplant recipients. Dual-Energy CT angiography obtained before (T0, left images) and after (T6, right images) 6 months follow up of immunosuppressive therapy with Tac/MMF/Pred (A,B) or Tac/mTORi/Pred (C,D) in kidney transplant recipients.

Figure 3

Analysis of dual-energy CT (DECT) angiography in (A) analysis of DECT angiography in kidney transplant recipients 1 month after COVID-19 recovery, showing no significant differences of lung perfusion between Group A (MMF-based) and Group B (mTORi-based) at baseline. In detail, no significant differences in the lung perfusion were observed if the analysis were performed in the entire lung parenchyma (3.44 [IQR 2.46–4.96] vs. 3.46 [IQR 2.83–4.41] DECTPA [mg/dl] for MMF/MYF-treated group and mTORi-based group respectively, p = 0.238; boxplots in the right box), as well as at each lung segment (p = not significant for each segment for MMF/MYF-treated group vs. mTORi-based group; left box). (B) Analysis of DECT angiography in kidney transplant recipients receiving MMF/MYF-treatment before (T0) and after 6-months follow-up (T6). In detail, a significant reduction of lung perfusion was observed if the analysis were performed in the entire lung parenchyma (3.44 [IQR 2.46–4.96] vs. 2.59 [IQR 1.78–3.52] DECTPA mg/dl for MMF/MYF-treated group at T0 and T6 respectively, p = 0.001; boxplots in the right box), as well as at each lung segment (p < 0.05 for each segment for MMF/MYF-treated group at T0 vs. T6 respectively; left box). (C) Analysis of DECT angiography in kidney transplant recipients receiving mTORi-treatment before (T0) and after 6-months follow-up (T6). In detail, a significant increase of lung perfusion was observed if the analysis were performed in the entire lung parenchyma (3.46 [IQR 2.83–4.41] vs. 4.43 [IQR 3.53–5.79] DECTPA mg/dl for mTORi-treated group at T0 and T6 respectively, p = 0.013; boxplots in the right box), as well as at each lung segment (p < 0.05 for each segment for mTORi-treated group at T0 vs. T6 respectively; left box). ^#p = not significant; *p < 0.05; ^§each boxplot in the right panels represents the median ± IQR of the DECT values, assessed for each patient for each lung segment examined, cumulatively, while whiskers represent 5th and 95th percentiles. RSL(a), right superior lobe – anterior area; RSL(p), right superior lobe – posterior area; ML(a), middle lobe – anterior area; ML(p), middle lobe – posterior area; RIL(a), right inferior lobe – anterior area; RIL(p), right inferior lobe – posterior area; LSL(a), left superior lobe – anterior area; LSL(p), left superior lobe – posterior area; LIL(a), left inferior lobe – anterior area; LIL(p), left inferior lobe – posterior area.