Everolimus treatment effective for improving renal function in lung transplant patients

1. Lung transplant patients showed improved renal function and reduced immunosuppressant dosage after twelve months of everolimus treatment.

2. Patients with chronic lung allograft dysfunction showed either sustained or worsened lung function depending on phenotype.

Evidence Rating Level: 2 (Good)

Following a lung transplant, two factors which reduce survival are graft failure and chronic lung allograft dysfunction (CLAD). CLAD is a substantial (> 20%) and persistent decline from baseline in measured forced expiratory volume in the first second (FEV₁). CLAD can present as two phenotypes, bronchiolitis obliterans syndrome (BOS) or restrictive allograft syndrome (RAS). Everolimus is a maintenance immunosuppressant recently introduced to lung transplant patients to prevent CLAD with its antiproliferative properties. Due to its antifibrotic effects, everolimus has been shown to slow progression of both BOS and RAS. However, use of everolimus and its impact on renal and pulmonary function as well as mortality in both CLAD and non-CLAD patients has yet to be compared beyond 6 months. In this retrospective trial, renal and lung function of 26 patients with lung transplants treated with and/or switched to everolimus were monitored for 12 months. 17 patients had CLAD (10 BOS, 7 RAS), and in all patients, reduction in immunosuppressant dosage (ISD) and all-cause mortality rate were tracked. Overall, patients experienced improvement in renal function (serum creatinine -17%, estimated glomerular filtration rate +24%) and stabilization in pulmonary function (FEV₁ -0.5%, forced vital capacity (FVC) +0.05%). While RAS patients, which typically have a worse prognosis, underwent progressive functional loss, BOS patients experienced a gradual increase in FEV₁ and FVC stability. When comparing functional trends between CLAD and nonCLAD patients, the only significant difference occurred in the 12th month; FEV₁ and FVC increased progressively. This resulting significant FVC% change is most likely due to the ameliorative effects of everolimus on renal function as opposed to direct pulmonary benefit. Finally, with the introduction of everolimus, all patients also experienced a significant and persistent ISD reduction (mean 37.7% reduction from baseline). While by design, this observational study cannot determine causation,  these results demonstrated the functional trends of improving renal function and reduced ISD in both CAD and non-CAD patients with lung transplants after treatment with everolimus. Despite everolimus introduction, CLAD patients continued to show declining pulmonary function, with the worst trend in RAS and with BOS identified as an “early everolimus responsive phenotype.” Ultimately, further study through conducting randomized, controlled trials with larger sample sizes are needed to support these trends.

Click to read the study Therapeutic Advances in Chronic Diseases

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