CKD: Cardiovascular health

Cardiovascular disease is the leading cause of mortality in children with ESKD

• 1000x greater risk than in the general population

Cardiovascular injury:

• Traditional risk factors: hypertension, dyslipidemia, glucose/insulin abnormalities, obesity, physical inactivity

• Uremia related risk factors: anemia, Ca-P metabolism abnormalities, volume overload, inflammation, malnutrition

• Risk factors lead to:

  • Atherosclerosis, arteriosclerosis

    • Measure with: Flow mediated dilation, carotid IMT, pulse wave velocity, coronary artery calcification

  • LVH, diastolic dysfunction, systolic dysfunction

    • Measure with: LVMI, cardiac geometry [***]

• Ultimately leading to: [***]

BP control in children with CKD

• Graphs: Schaefer et al cjasn 2017

• Patients often have poorly controlled blood pressure before they enter ESKD

• About 1/2 of HD and 1/3 of PD patients

  • 1/5 of transplant patients will be hypertensive

• Greater risk of HTN if:

  • older

  • more years on dialysis

    • Preemptive transplantation can improve certain cardiovascular endpoints (e.g., pulsewave velocity)

  • if decreased urine output

    • Optimize urine output with use of loop diuretics (e.g., furosemide)

  • lower ultrafiltration efficacy

LVH prevalence increases with CKD:

• CK3a: ~10%

• CK3b: 25-30%

• CKD4: 35-40%

• CKD5: 45-50%

• This is an important endpoint (sign of end organ damage from HTN) but is also a risk factor for other cardiovascular complications

Risk factors for LVH:

• Systolic HTN

  • Adequate treatment of HTN can reverse LVH

• Obesity***

  • BMI adds independently to CV risk burden

  • Incidence of obesity increases after transplantation

    • May be related to steroid use and/or improved appetite

• PTH >200 pg/mL

• Congenital kidney malformation

• Urine output (L/m²/day)

Coronary Artery Calcifications in Childhood-Onset ESKD

• Very common in young adults who have had ESKD onset in childhood

• Prevalence increases with age

• Other predictors: mean CRP, mean PTH, mean Ca*Phos product, homocysteine levels

Calcium load from phosphate binders may increase risk of calcifying vasculopathy

• Limit the dose when Ca is at high-normal or elevated range

• Use of calcium-free binder (sevelamer) can decrease coronary artery calcium scaling (CACS) score

Serum fetuin-A

• Circulating anti-Ca precipitant

• Produced in the liver

• Negative acute phase reactant

• Inflammation in ESKD lowers fetuin-A levels, favoring calcification in the arterial tree

Potentially modifiable conditions associated with early cardiovascular morbidity in children with CKD

• Obesity

• Hypertension

• Hypercholesterolemia

• Passive and active smoking

• Lack of physical activity

• Uremia

• Hyperphosphatemia, hyperparathyroidism, hypercalcemia

• Co-existing inflammatory conditions

• Vitamin D deficiency

  • Supplementation of vitamin D in predialysis population can improve intermedial thickness and pulsewave velocity (a measure of arterial stiffness)

Risk factors for cardiac calcifications: [*** stump]

• Ca, phos, PTH, and FGF23 levels are independently associated with cardiovascular events

• Prolonged history on dialysis

• Chronic inflammatory state, malnutrition

• Hypertension

• Anemia

• While medical management to modify risk factors is the goal, it has not been shown to lead to regression of the calcifications, which can persist for years after transplantation

Heart block

• Hyperkalemia

• Calcific vasculopathy

• QTc prolongation

• Myocardial ischemia

• Cardiomyopathy

• Autoimmune: lupus, Sjogren's, ankylosing spondylitis

• Infectious: myocarditis, endocarditis with abscess formation

• Deposition abnormalities: hyperparathyroidism (uncontrolled CKD-MBD), dialysis-related amyloidosis