Background and Purpose: Chronic kidney disease (CKD) appears to be an independent risk factor for stroke, with various purported mechanisms and treatments proposed. Low glomerular filtration rate (eGFR) is a risk factor for stroke independent of cardiovascular risk factors in epidemiological studies, but there has been no systematic assessment of the impact of more complete adjustment for blood pressure (BP) on the association. 

Methods: We did a systematic review to February 2018 (MEDLINE/EMBASE) for cohort studies or randomized controlled trials that reported stroke incidence in adults according to baseline eGFR. Study and participant characteristics and relative risks (RR) were extracted. Estimates were combined using a random effects model. Heterogeneity was assessed by x2 statistics and I2, and by subgroup strata and meta-regression.

Results: We identified 203 studies reporting data on 5,567,768 participants with 118,851 stroke outcomes. 85 studies (3,417,098 participants; 72,996 strokes) provided adequate data for meta-analysis of eGFR and stroke risk. Incident stroke risk was increased among participants with eGFR <60 ml/min/1.73m2 (RR=1.73, 95% CI 1.57-1.90; p<0.001), although there was quantitative heterogeneity between studies (x2 – p<0.0001; I2 - 78.5%). Moreover, the association was reduced after adjustment for cardiovascular risk factors, with progressive attenuation on more thorough adjustment for hypertension: single baseline BP measure (RR=1.63, 1.34-1.99; p<0.001); history or treated hypertension (RR=1.35, 1.24-1.46, p<0.001); multiple BP measurements over months to years (RR=1.10, 1.02-1.18; p=0.01).

Conclusions: The apparently independent relationship between CKD and stroke may be confounded by their shared association with long-term prior blood pressure, rendering other proposed mechanisms and related treatments unnecessary.

4 - IS THE ASSOCIATION BETWEEN CHRONIC KIDNEY DISEASE AND STROKE RISK TRULY INDEPENDENT?