Research Article: Cardiovascular disease risk factors in chronic kidney disease: A systematic review and meta-analysis

Date Published: March 21, 2018

Publisher: Public Library of Science

Author(s): Rupert W. Major, Mark R. I. Cheng, Robert A. Grant, Saran Shantikumar, Gang Xu, Issaam Oozeerally, Nigel J. Brunskill, Laura J. Gray, Gianpaolo Reboldi.


Chronic kidney disease (CKD) is a global health burden and is independently associated with increased cardiovascular disease risk. Assessment of cardiovascular risk in the general population using prognostic models based on routinely collected risk factors is embedded in clinical practice. In CKD, prognostic models may misrepresent risk due to the interplay of traditional atherosclerotic and non-traditional risk factors. This systematic review’s aim was to identify routinely collected risk factors for inclusion in a CKD-specific cardiovascular prognostic model.

Systematic review and meta-analysis of observational cohort studies and randomized controlled trials. Studies identified from MEDLINE and Embase searches using a pre-defined and registered protocol (PROSPERO ID—2016:CRD42016036187). The main inclusion criteria were individuals ≥18 years of age with non-endstage CKD. Routinely collected risk factors where multi-variable adjustment for established cardiovascular risk factors had occurred were extracted. The primary outcome was fatal and non-fatal cardiovascular events.

The review of 3,232, abstracts identified 29 routinely collected risk factors of which 20 were presented in more than 1 cohort. 21 cohorts were identified in relation to 27,465 individuals and 100,838 person-years. In addition to established traditional general population cardiovascular risk factors, left ventricular hypertrophy, serum albumin, phosphate, urate and hemoglobin were all found to be statistically significant in their association with future cardiovascular events.

These non-traditional risk factors should be assessed in the development of future cardiovascular prognostic models for use in individuals with CKD.

Partial Text

Chronic kidney disease (CKD) is a global health burden estimated to affect up to 15% of adult populations [1–3] and is independently associated with increased cardiovascular (CV) disease risk similar to the risk of diabetes mellitus or coronary heart disease [1–2]. This risk increases as CKD advances and is evidenced by worsening excretory function, usually manifest as declining glomerular filtration rate, and increasing proteinuria [3–4]. The overall cost of CKD accounts for 1.3% of healthcare budgets [5] of which 13% is related to the excess myocardial infarctions and strokes associated with CKD [5].

Ovid MEDLINE and Embase were searched using a pre-defined and registered systematic review and meta-analysis protocol [13] (PROSPERO ID—2016:CRD42016036187). Search strategies are available in the Supporting Information (Tables A and B in S1 File). Reporting of the current systematic review follows the PRISMA guidance, also available in the Supporting Information (S2 File). The inclusion criteria were observational cohort studies and secondary analyses of randomized controlled trials in adult (≥18 years of age) with either CKD stage 3a or worse (any eGFR formula <60 ml/min/1.73m2) or proteinuria based on standard definitions [14]. The search was limited to English language manuscripts. General population studies with subgroup analysis presenting results for CKD groups were also included. Studies including individuals with end-stage renal disease, either receiving maintenance dialysis or with a renal transplant, were excluded. Studies of outcomes after acute kidney injury were also excluded. The minimum follow-period was six months. A formal definition of CKD using a standardised eGFR formula was first established in 1999 [15], therefore the search range was restricted from this date until 20th October 2017. Three thousand two hundred and thirty-two abstracts were reviewed. Fig 1 shows the screening process, including the number of cohorts and risk factors identified, and reasons for any exclusion. Twenty-one cohorts were included in the systematic review [19–39]. Fourteen (66.7%) studies were observational cohort studies with recruitment from nephrology outpatient settings and the others were randomized controlled trials. Six cohorts provided additional data [19–24]. Whilst CV prognostic models are well established for the general population [6,7] it is unclear how well these models perform in patients with CKD [10]. CV prognostic models developed specifically for those with CKD exist but have poor methodology and limited clinical applicability [10]. The current systematic review, using a pre-defined and registered protocol [13], presents the association between routinely collected risk factors and CV disease events in individuals with CKD. The results confirm that most traditional atherosclerotic related risk factors confer risk in CKD populations. These include age, gender, smoking, established CV disease and diabetes mellitus, all of which were statistically significant risk factors that are incorporated in general population prognostic models and/or are established risk factors.   Source:


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