What are the primary causes of death in patients with Chronic Kidney Disease (CKD)?

Primary Causes of Death in Chronic Kidney Disease Patients

Cardiovascular disease is overwhelmingly the leading cause of death in CKD patients, accounting for the majority of mortality across all stages, with patients 10 to 30 times more likely to die from cardiovascular causes than to progress to end-stage kidney disease. 1, 2, 3, 4

Cardiovascular Disease as the Dominant Cause

• Cardiovascular death is the primary cause of mortality in CKD patients, with most patients dying from cardiovascular complications before ever reaching kidney failure. 1, 3, 4
• The cardiovascular mortality rate in dialysis-dependent patients is 10 to 30 times higher than in the general population. 1, 2
• Even early-stage CKD (stages 1-3) confers significantly elevated cardiovascular risk compared to the general population, with risk increasing exponentially as kidney function declines. 1, 4

Specific Cardiovascular Causes

Coronary heart disease is the most common cardiovascular manifestation in CKD patients (20.20%), followed by heart failure (18.28%), stroke (14.01%), and atrial fibrillation (4.38%). 1

• The risk of death from any cause, including cardiovascular disease, rises with an adjusted hazard ratio of 1.2 to 5.1 as kidney function deteriorates, with a particularly sharp increase when GFR falls below 60 mL/min/1.73 m². 1
• Cardiovascular disease risk increases 40% with reduced GFR and up to 70% with proteinuria, even after adjusting for traditional risk factors. 1
• Heart failure and acute coronary syndromes carry particularly high mortality in CKD patients, with in-hospital mortality rates of 2.33% in 2017 and 2.13% in 2018 for hospitalized CKD patients. 1

Pathophysiological Mechanisms Driving Cardiovascular Death

CKD creates a perfect storm of traditional and non-traditional risk factors that accelerate cardiovascular disease through multiple pathways. 2, 3, 4

• Traditional risk factors (hypertension, diabetes, dyslipidemia) are highly prevalent but do not fully explain the excess cardiovascular mortality. 1, 3, 5
• Non-traditional factors unique to CKD include: 2, 3, 4
  • Intense pro-inflammatory state driving accelerated atherosclerosis
  • Mineral bone disorders causing vascular calcification and arterial stiffness
  • Uremic toxins causing direct myocardial and vascular toxicity
  • Volume overload and sodium retention
  • Anemia and oxidative stress
  • Sympathetic nervous system overactivity

In-Hospital Mortality Patterns

• In-hospital mortality rates in CKD patients show a decreasing trend but remain elevated, reaching 2.13% in 2018. 1
• Male CKD patients have higher in-hospital mortality rates than female patients, though both show improvement over time. 1
• Patients covered by free medical care had the highest in-hospital mortality rate (6.55%), followed by those with urban basic medical insurance (2.43%). 1

Dialysis-Specific Mortality

For dialysis-dependent patients, cardiovascular disease remains the overwhelming cause of death, with mortality rates of 3.4% for hemodialysis patients and 2.3% for peritoneal dialysis patients. 1

• Hemodialysis is the major treatment modality (92.12% of all dialysis patients), and these patients face particularly high cardiovascular mortality. 1
• The age- and sex-adjusted prevalence of dialysis in 2017 was 384.41 per million population for hemodialysis and 34.98 per million for peritoneal dialysis. 1

Critical Clinical Implications

CKD functions as a coronary risk equivalent, meaning even early-stage disease confers cardiovascular risk comparable to established coronary artery disease or diabetes. 1, 2

• Higher albuminuria levels and lower eGFR are independently and additively associated with increased cardiovascular and all-cause mortality. 1
• The 10-year cumulative all-cause mortality increases from 11.5% in diabetes patients without kidney disease to 31% in those with diabetes and kidney disease. 1
• Serum creatinine is one of only 8 independent predictors of death in the validated GRACE risk score for acute coronary syndromes. 1, 2

Secondary Causes of Death

While cardiovascular disease dominates, other causes include:

• Infections, which are more common due to immune dysfunction in CKD. 1
• Acute kidney injury superimposed on CKD, with 28.22% of AKI patients having underlying CKD. 1
• Complications of dialysis including vascular access issues and treatment-related complications. 1
• Malignancy, which has increased risk in CKD patients. 1

Geographic and Demographic Variations

• Regional differences exist in CKD causes and outcomes, with variations between urban and rural areas. 1
• The spectrum of CKD etiology affects cardiovascular burden, with diabetes-related kidney disease and hypertensive nephropathy showing higher percentages of cardiovascular disease compared to glomerulonephritis. 1