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Original research
Associations between multimorbidity and adverse clinical outcomes in patients with chronic kidney disease: a systematic review and meta-analysis
  1. Michael K. Sullivan1,
  2. Alastair J. Rankin1,
  3. Bhautesh D. Jani2,
  4. Frances S. Mair2,
  5. Patrick B. Mark1
  1. 1Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK
  2. 2General Practice and Primary Care, Institute of Health and Wellbeing, University of Glasgow, Glasgow, UK
  1. Correspondence to Dr Michael K. Sullivan; michael.sullivan{at}


Objective To systematically review the literature exploring the associations between multimorbidity (the presence of two or more long-term conditions (LTCs)) and adverse clinical outcomes in patients with chronic kidney disease (CKD).

Design Systematic review and meta-analysis.

Data sources MEDLINE, EMBASE, CINAHL, Cochrane Library and SCOPUS (1946–2019). The main search terms were ‘Chronic Kidney Failure’ and ‘Multimorbid*’.

Eligibility criteria Observational studies of adults over the age of 18 with CKD stages 3–5, that is, estimated glomerular filtration rate less than 60 mL/min/1.73 m2. The exposure was multimorbidity quantified by measures and the outcomes were all-cause mortality, renal progression, hospitalisation and cardiovascular events. We did not consider CKD as a comorbid LTC.

Data extraction and synthesis Newcastle-Ottawa Scale for quality appraisal and risk of bias assessment and fixed effects meta-analysis for data synthesis.

Results Of 1852 papers identified, 26 met the inclusion criteria. 21 papers involved patients with advanced CKD and no studies were from low or middle-income countries. All-cause mortality was an outcome in all studies. Patients with multimorbidity were at higher risk of mortality compared with patients without multimorbidity (total risk ratio 2.28 (95% CI 1.81 to 2.88)). The risk of mortality was higher with increasing multimorbidity (total HR 1.31 (95% CI 1.27 to 1.36)) and both concordant and discordant LTCs were associated with heightened risk. Multimorbidity was associated with renal progression in four studies, hospitalisation in five studies and cardiovascular events in two studies.

Limitations Meta-analysis could only include 10 of 26 papers as the methodologies of studies were heterogeneous.

Conclusions There are associations between multimorbidity and adverse clinical outcomes in patients with CKD. However, most data relate to mortality risk in patients with advanced CKD. There is limited evidence regarding patients with mild to moderate CKD, outcomes such as cardiovascular events, types of LTCs and regarding patients from low or middle-income countries.

PROSPERO registration number CRD42019147424.

  • chronic renal failure
  • dialysis
  • diabetic nephropathy & vascular disease
  • ischaemic heart disease
  • end stage renal failure

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See:

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  • Twitter @sullivanmk8, @alastairrankin1?lang=en, @BhauteshJani, @FrancesMair, @drpaddymark

  • Contributors MS, AR, BJ, FM and PM contributed to conceptualisation, appraisal of results, writing (review and editing) and manuscript approval. MS, AR and PM performed data analysis. MS and AR performed data extraction. MS prepared the original manuscript draft.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Disclaimer The results presented in this paper have not been published previously in whole or part.

  • Competing interests PM reports personal fees and non-financial support from Vifor, personal fees from AstraZeneca, grants from Boehringer Ingelheim, personal fees and non-financial support from Pharmacosmos, personal fees from Janssen, personal fees from Novartis, personal fees from Pfizer, personal fees from Bristol Myers Squibb, personal fees and non-financial support from Napp, outside the submitted work.

  • Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.

  • Patient consent for publication Not required.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement Data sharing is not applicable as no data sets were generated and/or analysed for this study. All relevant data are included in the article or uploaded as supplementary information.

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