How should microemulsified Cyclosporine A (Neoral®) therapy in patients with nephrotic syndrome be monitored?

Abstract

Cyclosporine A (CyA) has been used empirically for almost two decades in the treatment of severe forms of idiopathic nephrotic syndrome (NS), in both children and adults [1]. The mechanism of CyA’s action remains unclear. It may be related to immunosuppressive or haemodynamic properties, or have an effect on heparan sulfate, the main component of the glomerular charge barrier [2]. Initially, the therapy was performed with ‘classic’ Cyclosporine (Sandimmune ). Because of substantial interand intra-patient variability and a narrow therapeutic window, therapeutic drug monitoring of Cyclosporine therapy is mandatory [3,4]. With ‘classic’ CyA, trough level monitoring was recommended. In the mid-1990s a microemulsified (ME) formulation of Cyclosporine (Neoral ) became available and many patients were converted because of more predictable pharmacokinetics—not always without problems [5]. Similar to renal transplant patients, patients with NS were often converted from the classic Cyclosporine to the microemulsified formulation (CyA ME). There is growing evidence that CyA ME should be monitored using the 2 h post-intake concentration (C2) rather than the preor post-dose trough level. This has been studied extensively in patients receiving a solid organ transplant, both in adults [6] and in children [7]. Targeting of C2 concentration as part of a post-transplantation treatment strategy is leading to excellent outcomes in adult transplantation with the ME Cyclosporine [8]. As CyA ME is used increasingly in patients with NS, the question arises whether C2 monitoring is also beneficial in patients with NS. However, even recent studies have not addressed this question in detail [9].