Mortality and Morbidity Following Exercise-Based Renal Rehabilitation in Patients With Chronic Kidney Disease

The Effect of Programme Completion and Change in Exercise Capacity

Sharlene A. Greenwood; Ellen Castle; Herolin Lindup; Juliet Mayes; Iain Waite; Denise Grant; Emmanuel Mangahis; Olivia Crabb; Kamer Shevket; Iain C. Macdougall; Helen L. MacLaughlin

Disclosures

Nephrol Dial Transplant. 2019;34(4):618-625. 

In This Article

Abstract and Introduction

Abstract

Background: Twelve weeks of renal rehabilitation (RR) have been shown to improve exercise capacity in patients with chronic kidney disease (CKD); however, survival following RR has not been examined.

Methods: This study included a retrospective longitudinal analysis of clinical service outcomes. Programme completion and improvement in exercise capacity, characterised as change in incremental shuttle walk test (ISWT), were analysed with Kaplan–Meier survival analyses to predict risk of a combined event including death, cerebrovascular accident, myocardial infarction and hospitalisation for heart failure in a cohort of patients with CKD. Time to combined event was examined with Kaplan–Meier plots and log rank test between 'completers' (attended >50% planned sessions) and 'non-completers'. In completers, time to combined event was examined between 'improvers' (≥50 m increase ISWT) and 'non-improvers' (<50 m increase). Differences in time to combined event were investigated with Cox proportional hazards models (adjusted for baseline kidney function, body mass index, diabetes, age, gender, ethnicity, baseline ISWT and smoking status).

Results: In all, 757 patients (male 54%) (242 haemodialysis patients, 221 kidney transplant recipients, 43 peritoneal dialysis patients, 251 non-dialysis CKD patients) were referred for RR between 2005 and 2017. There were 193 events (136 deaths) during the follow-up period (median 34 months). A total of 43% of referrals were classified as 'completers', and time to event was significantly greater when compared with 'non-completers' (P = 0.009). Responding to RR was associated with improved event-free survival time (P = 0.02) with Kaplan–Meier analyses and log rank test. On multivariate analysis, completing RR contributed significantly to the minimal explanatory model relating clinical variables to the combined event (overall χ 2 = 38.0, P < 0.001). 'Non-completers' of RR had a 1.6-fold [hazard ratio = 1.6; 95% confidence interval (CI) 1.00–2.58] greater risk of a combined event (P = 0.048). Change in ISWT of >50 m contributed significantly to the minimal explanatory model relating clinical variables to mortality and morbidity (overall χ 2 = 54.0, P < 0.001). 'Improvers' had a 40% (hazard ratio = 0.6; 95% CI 0.36–0.98) independent lower risk of a combined event (P = 0.041).

Conclusions: There is an association between completion of an RR programme, and also RR success, and a lower risk of a combined event in this observational study. RR interventions to improve exercise capacity in patients with CKD may reduce risk of morbidity and mortality, and a pragmatic randomised controlled intervention trial is warranted.

Introduction

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in patients with chronic kidney disease (CKD). Although many patients with CKD have other risk factors for CVD (e.g. diabetes, smoking, sedentary lifestyle, hypertension), and part of the increased risk is attributable to these risk factors, studies demonstrate that CKD itself is a major independent risk factor.[1] As renal function declines, the association with CVD increases, and patients with non-dialysis-requiring CKD are more likely to die from CVD than to develop end-stage renal disease. There is evidence of an increased prevalence of physical symptoms associated with declining kidney function.[2] Exercise-based rehabilitation, which promotes a more physically active lifestyle, has the potential to positively impact upon functional ability, aerobic capacity and the quality of life of patients with CKD, independent of the stage of the disease process.[3–5] Despite published recommendations calling for physical activity (PA) and exercise counselling for patients with CKD,[6,7] exercise-based renal rehabilitation (RR) for patients with CKD is not routinely offered to patients.

Cardiorespiratory capacity, as measured by the integrated index of peak oxygen uptake, has been identified as prognostically important for CVD and all-cause mortality in the general population,[8] and in patients with CKD Stage 5.[9] Habitual levels of PA, as measured using self-report questionnaires, are also linked to CV health. Physical inactivity has been shown to be a strong independent risk factor for CV morbidity and mortality in patients with CKD Stage 5[10] and in patients with CKD Stages 2–4.[11,12] Physical inactivity, physical function limitations, muscle mass and muscle function-related measures have also been identified as strong predictors of disease progression and survival in patients at all stages of CKD.[2,13,14] Self-reported physical function, as evaluated using the physical component score from the SF-36 questionnaire, has also been shown to carry a significant hospitalisation and survival prognostic value for patients on dialysis.[15,16] To our knowledge, no studies have compared the survival rates in patients with CKD who have completed a pragmatic RR exercise-based intervention. A Cochrane review,[17] and a systematic review and research evidence synthesis of studies investigating exercise therapy for patients with CKD,[18] suggest that as the studies to date have relatively short duration of interventions and follow-up periods, combined with extremely small sample sizes, there has been little opportunity thus far for any real observations with regards to the effect of exercise-based rehabilitation on morbidity and mortality rates in patients with CKD.

The King's College Hospital RR programme for patients with CKD is a complex exercise-based rehabilitation programme comparable in design to the cardiac rehabilitation (CR)[19,20] and pulmonary rehabilitation (PR)[21] programmes that are routinely offered to those patients with disease-specific long-term conditions in the UK. A systematic review and meta-analysis showed that those patients after myocardial infarction who attended CR had a lower risk of all-cause mortality than non-attendees.[22] A recent study by Houchen-Wolloff et al.[23] suggested that there was an association between the successful completion of PR and survival in patients with chronic obstructive pulmonary disease (COPD), and that PR success [>50 m change in incremental shuttle walk test (ISWT) walking distance] was associated with improved survival in patients with COPD.

In the interest of evaluating whether the RR programme, offered to patients at all stages of the CKD trajectory at King's College Hospital (KCH), was able to offer a comparable event-free survival advantage when compared with that reported for PR in the recent study by Houchen-Wolloff et al.,[23] we declared the following hypothesis for our study: the successful completion of a pragmatic RR programme (>50%) for patients with CKD and RR programme success (>50 m change in walking distance) would be associated with a longer event-free period of time in patients with CKD. Our aims, similar to those of Houchen-Wolloff et al.,[23] were to compare the long-term morbidity and mortality rates in two cohorts of patients referred to RR: those who successfully completed RR, and a comparator group constructed from patients who either did not complete RR or did not start the programme. Additionally, we compared survival between those people who were able to achieve a clinically meaningful improvement in ISWT (>50 m walking distance) following RR with those who were not.

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