Are people with CKD more likely to die of heart disease or of kidney failure?

Across most of the CKD spectrum, the risk of dying from cardiovascular disease exceeds the risk of progressing to kidney failure, which is why CKD is regarded as a major cardiovascular risk state.

Why is cardiovascular risk in CKD not explained by the usual risk factors alone?

In addition to common factors like hypertension and diabetes, CKD adds non-traditional contributors such as inflammation, volume overload, vascular calcification, and anemia, which promote heart failure and non-atherosclerotic disease as well as atherosclerosis.

Cardiovascular Risk in CKD

Chronic kidney disease is one of the strongest known amplifiers of cardiovascular risk. People with reduced kidney function and increased albuminuria face markedly higher rates of death, heart failure, and atherosclerotic events, and most people with CKD are in fact more likely to die of cardiovascular disease than to reach kidney failure, making the heart-kidney relationship central to the prognosis of the condition.

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Definition

Cardiovascular risk in CKD refers to the elevated and graded probability of cardiovascular events and cardiovascular death associated with reduced glomerular filtration rate and increased albuminuria, mediated by both traditional and CKD-specific (non-traditional) risk factors.

Scope

This topic covers the graded relationship between kidney function, albuminuria, and cardiovascular outcomes; the mechanisms that link CKD to both atherosclerotic and non-atherosclerotic cardiovascular disease; and the evidence, including recent SGLT2-inhibitor trials, on reducing cardiovascular and kidney events together. It is a reference account of the risk relationship and its evidence base, not individualized treatment guidance.

Core questions

How strongly does CKD raise cardiovascular risk, and in what graded pattern?
Which traditional and CKD-specific factors drive this excess risk?
Why are heart failure and non-atherosclerotic disease so prominent in CKD?
What evidence supports reducing cardiovascular and kidney risk together?

Key concepts

Graded eGFR-albuminuria risk relationship
Traditional cardiovascular risk factors
Non-traditional (uremic) risk factors
Vascular calcification and arterial stiffness
Left ventricular hypertrophy and heart failure
Competing risk of death versus kidney failure
Cardiorenal benefit of SGLT2 inhibition

Mechanisms

The excess cardiovascular risk in CKD arises from the convergence of traditional risk factors, which are highly prevalent in this population (hypertension, diabetes, dyslipidemia), with CKD-specific or non-traditional factors such as volume overload, inflammation, oxidative stress, mineral-bone disturbances promoting vascular calcification, anemia, and activation of the renin-angiotensin and sympathetic systems. These processes favour arterial stiffening, endothelial dysfunction, and left ventricular hypertrophy, so the cardiovascular burden in CKD includes a large share of heart failure, arrhythmia, and sudden death alongside atherosclerotic events. The graded relationship between lower GFR, higher albuminuria, and cardiovascular mortality has been shown across pooled cohorts, and trials of SGLT2 inhibitors such as CREDENCE and EMPA-KIDNEY demonstrated reductions in combined cardiovascular and kidney outcomes.

Clinical relevance

Because cardiovascular disease dominates the outcomes of CKD, the condition is treated as a major cardiovascular risk state and the two organ systems are considered together in prognosis. This entry explains that relationship and summarizes the trial evidence; it characterizes risk and the evidence base and does not provide individualized risk scores, targets, or treatment recommendations.

Epidemiology

Cardiovascular event rates rise steeply as GFR falls and albuminuria increases, and across most of the CKD spectrum the risk of cardiovascular death exceeds the risk of progressing to kidney failure. Large cohort and pooled analyses established the independent, graded contribution of both kidney measures to cardiovascular and all-cause mortality.

History

Although clinicians long recognised that dialysis patients had very high cardiovascular mortality, the broader insight that even mild-to-moderate reductions in kidney function carry graded cardiovascular risk was crystallised by large cohort analyses in the 2000s, notably Go and colleagues in 2004, and by pooled meta-analyses linking GFR and albuminuria to mortality. The subsequent demonstration that SGLT2 inhibitors reduce cardiovascular and kidney events together marked a major shift in how cardiorenal risk is approached.

Debates

Why do some cardiovascular interventions underperform in advanced CKD?: Treatments that reduce atherosclerotic events in the general population have shown attenuated benefit in advanced CKD, likely because a large share of cardiovascular disease in this group is non-atherosclerotic (heart failure, arrhythmia, sudden death); how best to address this distinct risk profile remains an open question.

Key figures

Alan S. Go
Ron T. Gansevoort
Vlado Perkovic

Seminal works

go-2004
levey-2010
gansevoort-2013

Frequently asked questions

Are people with CKD more likely to die of heart disease or of kidney failure?: Across most of the CKD spectrum, the risk of dying from cardiovascular disease exceeds the risk of progressing to kidney failure, which is why CKD is regarded as a major cardiovascular risk state.
Why is cardiovascular risk in CKD not explained by the usual risk factors alone?: In addition to common factors like hypertension and diabetes, CKD adds non-traditional contributors such as inflammation, volume overload, vascular calcification, and anemia, which promote heart failure and non-atherosclerotic disease as well as atherosclerosis.