Symptom burden and health-related quality of life in chronic kidney disease: A global systematic review and meta-analysis

Abstract

Background: The importance of patient-reported outcome measurement in chronic kidney disease (CKD) populations has been established. However, there remains a lack of research that has synthesised data around CKD-specific symptom and health-related quality of life (HRQOL) burden globally, to inform focused measurement of the most relevant patient-important information in a way that minimises patient burden. The aim of this review was to synthesise symptom prevalence/severity and HRQOL data across the following CKD clinical groups globally: (1) stage 1-5 and not on renal replacement therapy (RRT), (2) receiving dialysis, or (3) in receipt of a kidney transplant.

Methods and findings: MEDLINE, PsycINFO, and CINAHL were searched for English-language cross-sectional/longitudinal studies reporting prevalence and/or severity of symptoms and/or HRQOL in CKD, published between January 2000 and September 2021, including adult patients with CKD, and measuring symptom prevalence/severity and/or HRQOL using a patient-reported outcome measure (PROM). Random effects meta-analyses were used to pool data, stratified by CKD group: not on RRT, receiving dialysis, or in receipt of a kidney transplant. Methodological quality of included studies was assessed using the Joanna Briggs Institute Critical Appraisal Checklist for Studies Reporting Prevalence Data, and an exploration of publication bias performed. The search identified 1,529 studies, of which 449, with 199,147 participants from 62 countries, were included in the analysis. Studies used 67 different symptom and HRQOL outcome measures, which provided data on 68 reported symptoms. Random effects meta-analyses highlighted the considerable symptom and HRQOL burden associated with CKD, with fatigue particularly prevalent, both in patients not on RRT (14 studies, 4,139 participants: 70%, 95% CI 60%-79%) and those receiving dialysis (21 studies, 2,943 participants: 70%, 95% CI 64%-76%). A number of symptoms were significantly (p < 0.05 after adjustment for multiple testing) less prevalent and/or less severe within the post-transplantation population, which may suggest attribution to CKD (fatigue, depression, itching, poor mobility, poor sleep, and dry mouth). Quality of life was commonly lower in patients on dialysis (36-Item Short Form Health Survey [SF-36] Mental Component Summary [MCS] 45.7 [95% CI 45.5-45.8]; SF-36 Physical Component Summary [PCS] 35.5 [95% CI 35.3-35.6]; 91 studies, 32,105 participants for MCS and PCS) than in other CKD populations (patients not on RRT: SF-36 MCS 66.6 [95% CI 66.5-66.6], p = 0.002; PCS 66.3 [95% CI 66.2-66.4], p = 0.002; 39 studies, 24,600 participants; transplant: MCS 50.0 [95% CI 49.9-50.1], p = 0.002; PCS 48.0 [95% CI 47.9-48.1], p = 0.002; 39 studies, 9,664 participants). Limitations of the analysis are the relatively few studies contributing to symptom severity estimates and inconsistent use of PROMs (different measures and time points) across the included literature, which hindered interpretation.

Conclusions: The main findings highlight the considerable symptom and HRQOL burden associated with CKD. The synthesis provides a detailed overview of the symptom/HRQOL profile across clinical groups, which may support healthcare professionals when discussing, measuring, and managing the potential treatment burden associated with CKD.

Protocol registration: PROSPERO CRD42020164737.

Conflict of interest statement

I have read the journal’s policy and the authors of this manuscript have the following competing interests: MC is Director of the Birmingham Health Partners Centre for Regulatory Science and Innovation, Director of the Centre for the Centre for Patient Reported Outcomes Research and is a National Institute for Health Research (NIHR) Senior Investigator. MC receives funding from the National Institute for Health Research (NIHR) Birmingham Biomedical Research Centre, the NIHR Surgical Reconstruction and Microbiology Research Centre and NIHR ARC West Midlands at the at the University of Birmingham and University Hospitals Birmingham NHS Foundation Trust NIHR/UKRI., Health Data Research UK, Innovate UK (part of UK Research and Innovation), Macmillan Cancer Support, UCB Pharma, Janssen, GSK and Gilead. MC has received personal fees from Astellas Aparito Ltd, CIS Oncology, Takeda, Merck, Daiichi Sankyo, Glaukos, GSK and the Patient-Centered Outcomes Research Institute (PCORI) outside the submitted work. OLA is supported by the NIHR Birmingham BRC, West Midlands, Birmingham; UKRI, Janssen, Gilead and GSK. He declares personal fees from Gilead Sciences Ltd, Merck and GSK outside the submitted work. DK reports grants from Macmillan Cancer Support, Innovate UK, the NIHR, NIHR Birmingham Biomedical Research Centre, and NIHR SRMRC at the University of Birmingham and University Hospitals Birmingham NHS Foundation Trust, and personal fees from Merck outside the submitted work.

Figures

Fig 1. PRISMA diagram.

CKD, chronic kidney disease; PROM, patient-reported outcome measure.

Fig 2. Pooled prevalence of patient-reported symptoms across included studies for patients not on renal replacement therapy (RRT).

Fig 3. Pooled prevalence of patient-reported symptoms across included studies for patients on dialysis.

Fig 4. Pooled prevalence of patient-reported symptoms across included studies for patients in receipt of a kidney transplant.

Fig 5. Pooled symptom severity across included studies for patients not on renal replacement therapy.

Scores represent mean severity scores converted to a 0–100 scale, where a higher score indicates greater severity; vertical line at 50 for reference. RRT, renal replacement therapy.

Fig 6. Pooled symptom severity across included studies for patients on dialysis.

Scores represent mean severity scores converted to a 0–100 scale, where a higher score indicates greater severity; vertical line at 50 for reference.

Fig 7. Pooled symptom severity across included studies for patients in receipt of a kidney transplant.

Scores represent mean severity scores converted to a 0–100 scale, where a higher score indicates greater severity; vertical line at 50 for reference.

Fig 8. Prevalence of fatigue in chronic kidney disease.

See S4 Appendix for full references for included studies. ES, effect size; HD, haemodialysis; PD, peritoneal dialysis; RRT, renal replacement therapy.

Fig 9. Symptom prevalence comparison across groups.

CKD, chronic kidney disease; RRT, renal replacement therapy.

Fig 10. Health-related quality of life in CKD.

CKD, chronic kidney disease; EQ5D, EuroQoL–5 Dimension; KSS, Kidney Disease Quality of Life Summary Score; MCS, Mental Component Summary; No. pops, number of populations; PCS, Physical Component Summary; SF12, 12-Item Short Form Health Survey; SF36, 36-Item Short Form Health Survey.

Fig 11. Quality of included studies.

Yes = appraised as adequate; no = appraised as not adequate.