Basiliximab for posterior reversible encephalopathy syndrome after lung transplantation

Abstract

INTRODUCTION

Posterior reversible encephalopathy syndrome (PRES) is a clinico-radiological disorder that includes various neurological symptoms [1]. PRES presents with various clinical conditions [1] such as hypertension, eclampsia, renal disease and immunosuppression. PRES is considered a multifactorial disease, but its underlying mechanisms are still unclear [1]. Calcineurin inhibitors (CNIs), which are widely used for immunosuppression after lung transplantation (LT), are major risk factors for PRES [1, 2]. There is no consensus yet on the best practices for immunosuppressive therapy management when PRES occurs after organ transplantation [1].

From April 2002 to September 2016, 151 patients underwent 155 LTs, including 77 living-donor lobar LTs and 78 cadaveric LTs, at Kyoto University Hospital, Japan, following which PRES occurred in 3 patients (1.9%).

CASE SUMMARY

The clinical characteristics of the 3 PRES cases are summarized in Table 1. The clinical course of Case 1 was previously reported [2]. We routinely check serum magnesium levels of LT recipients in the early postoperative period and intervene if hypomagnesemia and hypertension occur even at subclinical levels. All patients with PRES were children and presented with hypertension and hypomagnesemia at the onset of PRES. None of these patients had comorbidities. Renal functions were conserved in all cases. The CNIs administered at the onset of PRES included cyclosporine in Case 1 and tacrolimus in Cases 2 and 3. The CNI trough level exceeded the therapeutic range only in Case 1. In Case 2, the patient was diagnosed with acute rejection on postoperative Day 71; cyclosporine had been used as an initial CNI, but was changed to tacrolimus on postoperative Day 78 because of difficulties in keeping the trough in the target range. In all cases, we stopped CNIs and administered basiliximab (10 mg) upon the diagnosis of PRES. We also initiated antihypertensive treatment and magnesium replacement. We administered basiliximab (10 mg) again on Day 4. When symptoms resolved, we administered tacrolimus instead of cyclosporine in Cases 2 and 3. In Case 1, treatment with cyclosporine was resumed because the patient had a previous history of PRES upon the administration of tacrolimus. The durations of withholding CNIs were 8 days in Case 1 and 2 days in Cases 2 and 3. All patients recovered without neurological sequelae.

DISCUSSION

The incidence of PRES after LT was 1.9% in our study. The present study represents the first report of PRES incidence after LT in an Asian population. Our results are consistent with those of previous reports that PRES develops in 1.98–5.7% of LT recipients [3, 4].

Temporary cessation of CNIs and administration of basiliximab may be effective strategies for managing PRES. Modifying CNI administration is an important management approach for PRES and can include cessation, dose reduction or conversion [1]. However, these modifications include risks of decreasing immunosuppression, thereby resulting in acute rejection. Our strategy is to discontinue CNIs, administer basiliximab, followed by another CNI after symptoms improve. Basiliximab, an anti-CD25 monoclonal antibody, has been used in induction therapy after transplantation of solid organs, including lungs. Basiliximab is also used as an alternative treatment when adverse effects of CNIs occur, which may include acute renal dysfunction [5]. Basiliximab allows for discontinuation of CNIs until complications resolve, thereby enabling a CNI ‘holiday’. None of our patients exhibited new onset of acute rejection immediately after PRES. Our strategy is unique, because the use of basiliximab to enable a CNI ‘holiday’ during PRES has not been previously reported from other institutions.

CONCLUSION

The incidence of PRES after LT was 1.9% in our sample. Our findings suggest that temporary cessation of CNIs and the administration of basiliximab may be effective management strategies for PRES.

Conflicts of interest: none declared.

REFERENCES