The FRAILMar Study Protocol: Frailty in Patients With Advanced Chronic Kidney Disease Awaiting Kidney Transplantation. A Randomized Clinical Trial of Multimodal Prehabilitation

Abstract

Introduction: Frailty is very frequent among patients with chronic kidney disease (CKD) who are awaiting deceased donor kidney transplantation (KT), and transplant outcomes are worsened in those frail recipients. Frailty and poor fitness powerfully predict mortality, kidney graft survival, and healthcare utilization after KT. Intervention is essential to improve survival and quality of life for frail CKD patients, regardless of their age. Studies of post-transplant physical therapy intervention have been met with limited success, in large part due to high dropout rates. A pre-transplant clinical framework for multimodal prehabilitation interventions including physical therapy, nutritional measures, and psychological support scheduled during the KT waiting list period may improve patient retention and compliance, better mitigate the effects of frailty and poor fitness after KT, and improve main outcomes in frail CKD patients.Main Objective: To study the effectiveness, feasibility, and safety of multimodal prehabilitation (exercise, nutritional plans, psychological advice) in KT candidates.Methods: Randomized controlled clinical trial in 38 frail and 76 non-frail KT candidates. The prehabilitation program will consist of physical exercise (24 sessions, 8 weeks), nutritional supplementation, and psychological advice. The primary endpoint will be a composite achievement of clinical and functional main outcomes in frail and non-frail KT candidates at 90 days post-transplantation. Secondary outcomes include changes in exercise capacity, physical activity, gait speed, respiratory and peripheral muscle strength, muscle size, body composition, performance in activities of daily living (basic and instrumental), anxiety and depression symptoms, and health-related quality of life. Feasibility of the intervention will be also analyzed.Expected Results: Multimodal prehabilitation is a feasible and effective intervention to decrease bad outcomes at 90 days post-KT by 25 and 12.5% in frail and non-frail patients, respectively.Clinical Trial Registration:clinicaltrials.gov (NCT04701398), date: 2021, January 8th (Protocol version: Frailmar_vers2).

Increased mortality after kidney transplantation in mildly frail recipients

“…Giving the large number of frailty scales, it is important to validate them in the renal population, clarifying their predictive value for bad outcomes [ 20 ] or analyzing the clinical significance of their definition for frailty. In addition, identifying pre-frail or frail patients may allow clinicians to establish proper strategies to revert the situation [ 21 ].…”

Targeted Non-Pharmacological Interventions for People Living with Frailty and Chronic Kidney Disease

“…Existing prehabilitation studies have predominantly focused on those awaiting transplant or approaching dialysis, concluding that prehabilitation has a positive influence on physical activity, frailty status, function, and strength [95][96][97]. Further definitive trials are required; an ongoing study by Perez-Saez et al will provide additional information on the role of prehabilitation, specifically in frail kidney transplant candidates [98]. Interestingly, no research has been conducted for those opting for conservative care.…”

“…Evidence from systematic reviews have suggested that although nutritional interventions delivered in isolation may not show a beneficial effect [110], when used as part of multi-component interventions incorporating physical exercise, they may provide an additive effect, yielding greater improvement in frailty status and physical functioning [111]. For people with frailty and CKD, several such trials are currently underway and will begin to shed light on the impact of multi-component interventions on frailty in people with CKD stage 3-5 [51], those receiving haemodialysis [112], and in kidney transplant recipients [98].…”

“…Future research is needed to develop and test multi-component interventions, which include elements designed to help support the management of both depression and frailty and the impact these symptoms have on HRQoL. At present, there are three multi-component research trials underway, which will go some way to addressing this gap [51,98,112].…”

“…Beetham et al [147] recently demonstrated the benefits of a multi-component lifestyle intervention, which also included an exercise component, for people with CKD. There are three ongoing studies utilising exercise programmes in conjunction with nutrition and psychological components that will provide further evidence for the frail CKD population [51,98,112].…”