Statin Therapy in CKD Patients on Dialysis
Statins should not be initiated in patients with dialysis-dependent CKD, but should be continued in patients who were already receiving them at the time of dialysis initiation. 1
Recommendations for Statin Use in CKD Patients on Dialysis
Do Not Initiate Statins in Dialysis Patients
- Three large randomized trials (SHARP, 4D study, and AURORA) have failed to demonstrate conclusive cardiovascular benefit when statins are initiated in prevalent dialysis patients 1
- The Kidney Disease: Improving Global Outcomes (KDIGO) guidelines provide a Grade 2A recommendation against initiating statins or statin/ezetimibe combinations in adults with dialysis-dependent CKD 1
- The relative decrease in cardiovascular risk with statins diminishes as renal function declines, even after accounting for smaller reductions in LDL-C concentration in advanced CKD 1
Continue Statins in Patients Already on Them
- For patients already receiving statins or statin/ezetimibe combination at the time of dialysis initiation, KDIGO guidelines suggest continuing these agents (Grade 2C recommendation) 1
- This recommendation is supported by data from the SHARP trial, where 34% of patients (2,141 individuals) without kidney failure at baseline commenced dialysis during the trial and were analyzed in the non-dialysis group, which showed overall benefit 1
- The clinical rationale is that initiating statin regimens in patients without kidney failure and continuing treatment if kidney failure occurs appears beneficial, whereas starting statins in prevalent dialysis patients shows uncertain benefit 1
Pathophysiological Considerations
- Several mechanisms may explain "statin resistance" in dialysis patients 1:
- Poor association between LDL-C and cardiovascular risk in dialysis patients
- Predomination of non-traditional risk factors (mineral and bone abnormalities, uremia)
- Altered lipid abnormalities (lipoproteins rendered highly atherogenic by oxidation or carbamylation)
- Intracellular cholesterol synthesis activated by inflammatory stress
- Pro-calcifying effects in the vascular system
Special Considerations
- Physicians should periodically review the clinical status of dialysis patients receiving statins and reassess the decision to continue therapy 1
- Factors that might influence the decision to continue statins in dialysis patients include 1:
- Recent cardiovascular events (favoring continued treatment)
- Higher LDL-C levels (may increase likelihood of benefit)
- Longer life expectancy (favoring continued treatment)
- More severe comorbidities (favoring discontinuation)
- Higher current pill burden (favoring discontinuation)
Clinical Caveats
- The KDOQI US Commentary on KDIGO guidelines notes that patients with recent acute coronary events were typically excluded from clinical trials and may be considered for statin therapy despite being on dialysis 1
- Young patients on kidney transplant waiting lists with long life expectancy should be considered for statin use 1
- Most trials focused on hemodialysis patients, with limited data specific to peritoneal dialysis patients 1
- The guidelines create a potential inconsistency in clinical care: recommending statin therapy during CKD, not recommending initiation during dialysis, then recommending it again after kidney transplantation 1
Mortality and Cardiovascular Outcomes
- While statins significantly reduce all-cause and cardiovascular mortality in non-dialysis CKD patients 2, this benefit does not extend to patients who initiate statins while on dialysis 3, 4
- The CVD risk reduction by statins appears to decline as patients progress from early to later stages of CKD 4
- Statins have been associated with a higher incidence of stroke in ESKD patients in some studies 4
By following these evidence-based recommendations, clinicians can optimize statin therapy in CKD patients on dialysis to potentially improve cardiovascular outcomes while avoiding unnecessary medication burden.