Kidney Function, Albuminuria, and Risk of Incident Atrial Fibrillation: A Systematic Review and Meta-Analysis

Rationale & Objective

Atrial fibrillation (AF) and chronic kidney disease (CKD) often coexist. However, it is not known whether CKD is an independent risk factor for incident AF. Therefore, we evaluated the association between markers of CKD—estimated glomerular filtration rate (eGFR) and albuminuria—and incident AF.

Study Design

Systematic review and meta-analysis of cohort studies and randomized controlled trials.

Setting & Study Populations

Participants with measurement of eGFR and/or albuminuria who were not receiving dialysis.Selection Criteria for Studies: Cohort studies and randomized controlled trials were included that reported incident AF risk in adults according to eGFR and/or albuminuria.

Analytical Approach

Age- or multivariate-adjusted risk ratios (RRs) for incident AF were extracted from cohort studies, and RRs for each trial were derived from event data. RRs for incident AF were pooled using random-effects models.

Results

38 studies involving 28,470,249 participants with 530,041 incident AF cases were included. Adjusted risk of incident AF was greater among participants with lower eGFR than those with higher eGFR (eGFR<60 vs≥60mL/min/1.73m²: RR, 1.43; 95% CI, 1.30-1.57; and eGFR<90 vs≥90mL/min/1.73m²: RR, 1.42; 95% CI, 1.26-1.60). Adjusted incident AF risk was greater among participants with albuminuria (any albuminuria vs no albuminuria: RR, 1.43; 95% CI, 1.25-1.63; and moderately to severely increased albuminuria vs normal to mildly increased albuminuria: RR, 1.64; 95% CI, 1.31-2.06). Subgroup analyses showed an exposure-dependent association between CKD and incident AF, with the risk increasing progressively at lower eGFR and higher albuminuria categories.

Limitations

Lack of patient-level data, interaction between eGFR and albuminuria could not be evaluated, possible ascertainment bias due to variation in the methods of AF detection.

Conclusions

Lower eGFR and greater albuminuria were independently associated with increased risk of incident AF. CKD should be regarded as an independent risk factor for incident AF.

Plain-Language Summary

Irregular heartbeat, or atrial fibrillation (AF), is the commonest abnormal heart rhythm. AF occurs commonly in people with chronic kidney disease (CKD), and CKD is also common in people with AF. However, CKD in not widely recognized as a risk factor for new-onset or incident AF. In this research, we combined data on more than 28 million participants in 38 studies to determine whether CKD itself increases the chances of incident AF. We found that both commonly used markers of kidney disease (estimated glomerular filtration rate and albuminuria, ie, protein in the urine) were independently associated with a greater risk of incident AF. This finding suggests that CKD should be recognized as an independent risk factor for incident AF.