Risk of End-Stage Renal Disease and Death After Cardiovascular Events in Chronic Kidney Disease

Study Questions:

What is the effect of cardiovascular (CV) events on subsequent risk of progression to end-stage renal disease (ESRD) or all-cause mortality (ACM) prior to ESRD?


This retrospective cohort study involved 2,964 CKD subjects, referred between January 2001 and December 2008, to the nephrology clinic at Sunnybrook Health Sciences Centre, Toronto, Ontario. Interim CV events (heart failure, myocardial infarction, and stroke), ESRD, and ACM were ascertained from administrative data. A stratified, cause-specific Cox proportional hazard model for the outcomes of ESRD and ACM prior to ESRD was developed.


Over a median follow-up time of 2.76 years (interquartile range, 1.45-4.62), 447 (15%) subjects had a CV event. In the same time period, 318 (11%) developed ESRD, and 446 (15%) suffered ACM prior to ESRD (156 [5%] from a CV and 290 [10%] from a non-CV-related cause). When analyzed as a time-dependent variable, an interim CV event was associated with a higher risk of subsequent ESRD (hazard ratio [HR], 5.33; 95% confidence interval [CI], 3.74-7.58) and ACM prior to ESRD (HR, 4.15; 95% CI, 3.30-5.23). The HR for CV-related death versus non-CV-related death prior to ESRD was 12.38 (95% CI, 8.30-18.45) versus 2.13 (95% CI, 1.57-2.87).


The authors concluded that CV events are common in patients with CKD stages 3-5, and are associated with a substantial increase in the risk of ESRD and all-cause mortality prior to ESRD.


This study reports that after adjustment for baseline factors, a CV event was associated with a four- to five-fold higher relative risk of both subsequent progression to ESRD and ACM prior to ESRD. The risk was higher for CV-related mortality than for non-CV-related mortality. The magnitude of the relative risks did vary somewhat among subgroups of patients, but overall suggested a consistent qualitative conclusion regarding the clinical importance of interim CV events. Additional investigations in this high-risk population are indicated to determine if primary and secondary preventative measures may attenuate the risk of these competing outcomes.

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