Study Shows Renal Dysfunction in Cardiac Transplant Recipients Caused by Cyclosporine A, Not Everolimus: Presented at ATC

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Title: Study Shows Renal Dysfunction in Cardiac Transplant Recipients Caused by Cyclosporine A, Not Everolimus: Presented at ATC
URL: http://www.pslgroup.com/dg/222F46.htm
Doctor's Guide
June 4, 2008

By Thomas S. May

TORONTO -- June 4, 2008 -- Exposure to cyclosporine A (CsA), not to everolimus, is associated with impaired renal function in de novo heart transplant recipients, according to a multicentre, randomised, open-label trial presented here at the 2008 American Transplant Congress (ATC).

The study, presented on May 31, investigated the relationship between trough levels of everolimus and CsA and renal dysfunction events in de novo heart transplant recipients.

Shaida Varnous, MD, Hôpital Pitié Salpétrière, Paris, France, and colleagues enrolled 176 heart transplant recipients. Within 72 hours after transplantation, 92 patients were randomised to everolimus at an initial dose of 0.75 mg BID adjusted to a target trough level of 3 to 8 ng/mL with reduced exposure CsA and 84 patients received mycophenolate mofetil (MMF) 1500 mg BID with standard exposure CsA. Both groups also received corticosteroids.

Primary endpoints included renal function and efficacy, defined on biopsy-proven acute rejection (BPAR) as grade 3A or greater at 6 and 12 months using International Society for Heart & Lung Transplantation criteria. Renal dysfunction events were defined as >30% decrease in creatinine clearance from day 30.

Trough values were available for analysis for 91 everolimus patients. During post-transplant days 30 to 225, CsA exposure exerted a strong influence on renal dysfunction events (P = .015), but everolimus exposure showed no significant effect (P = .512).

An even stronger influence for CsA exposure was observed up to day 450 (P = .002), but everolimus exposure exerted no significant effect (P = .634). From days 30 to 450, renal dysfunction events occurred in 3.1% of 32 patients with CsA trough <150 ng/mL, increasing to 25.0% of 32 patients and 47.4% of 19 patients with trough levels of 150 to 200 ng/mL and >= 200 ng/mL, respectively.

Achievement of everolimus target trough levels of 3 to 8 ng/mL was strongly correlated with low BPAR rates, the investigators found. Furthermore, renal dysfunction was associated with CsA levels but not everolimus exposure.

The researchers concluded that, in heart transplant recipients, the use of everolimus-based immunosuppressive therapy may facilitate further reductions in calcineurin inhibitor exposure and renal dysfunction events, while preserving efficacy.

Funding for this study was provided by Novartis Pharma AG.

[Presentation title: Exposure to CsA, and Not to Everolimus, Is Associated With Impaired Renal Function in De Novo Heart Transplant Recipients. Abstract 624]

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