Associations between multimorbidity and adverse clinical outcomes in patients with chronic kidney disease: a systematic review and meta-analysis.

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.