STATINS AND CKD, dialysis patients, and renal transplant recipients

suggest good side-effect profiles with statins [35,54-56]. The

CARDIOVASCULAR safety of a statin in patients with CKD was perhaps best
OUTCOMES IN CHRONIC evaluated in the first United Kingdom Heart and Renal

KIDNEY DISEASE — Mild CKD and Protection (UK-HARP-I) study [56]. In this pilot safety trial,
448 patients with CKD (242 predialysis patients with a serum
moderately increased albuminuria (formerly called
creatinine concentration ≥1.7 mg/dL [≥150 micromol/L], 73
"microalbuminuria") are associated with an increase in
dialysis patients, and 133 patients with a renal allograft) were
susceptibility to cardiovascular disease and are now
randomly assigned in a 2x2 design
considered to be coronary artery disease equivalents. This is
to simvastatin (20mg/day) or placebo and modified-
discussed in detail separately. (See "Chronic kidney disease
release aspirin (100 mg/day) or placebo. A similar risk for
and coronary heart disease" and "Moderately increased
abnormal liver function tests or elevated creatine kinase
albuminuria (microalbuminuria) and cardiovascular disease".)
levels was reported for simvastatin and placebo.

Patients on dialysis — Several randomized trials, including

In the Study of Heart and Renal Protection (SHARP) trial,
4-D, AURORA, and Study of Heart and Renal Protection
discontinuation of therapy due to myalgias was significantly
(SHARP) have examined the effect of statin therapy on
more common with simvastatin/ezetimibe therapy (1.1
cardiovascular outcomes in patients with end-stage renal
versus 0.6 percent), but the rates of other adverse effects
disease (ESRD) requiring dialysis. Findings from these trials,
were similar between the treatment and placebo groups [51].
as well as recommendations pertaining to statin therapy in
dialysis patients, are discussed separately. (See "Secondary Results from the 4-D trial in dialysis patients, the ALERT trial
prevention of cardiovascular disease in end-stage renal in renal transplant recipients, and the secondary analysis of
disease (dialysis)", section on 'Trials of statin therapy'.) the SHARP study [52] all suggest that the general incidence
of statin-related side effects is low in this patient population
Patients not on dialysis — The SHARP trial examined the
and not demonstrably higher than that seen in non-CKD
effect of statin therapy (given with ezetimibe) in patients with
patient cohorts. As with other drugs, close attention must be
CKD not on dialysis. The effect of statin therapy on
paid to drug interactions (especially in patients on long-term
cardiovascular endpoints in CKD patients has also been
immunosuppression) and proper dosing. (See "Lipid
evaluated in post-hoc analyses of randomized trials that
abnormalities in nephrotic syndrome" and "Lipid
inadvertently enrolled patients with CKD. Detailed
abnormalities after renal transplantation".)
discussions, as well as recommendations concerning statins
and cardiovascular disease in patients with CKD not on SUMMARY AND RECOMMENDATIONS
dialysis, are presented elsewhere. (See "Indications for
statins in nondialysis chronic kidney disease", section on ●There is indirect evidence of beneficial effects of
'Evidence in support of treatment with statins'.) statins on vessel stiffening and endothelial function in
patients with chronic kidney disease (CKD).
STATINS AND SEPSIS — Observational studies in patients (See 'Physiologic effects' above.)
without CKD suggested that statin therapy may decrease the
rates of severe sepsis and mortality from sepsis. Among
●Once renal injury has occurred, the yearly decline in
1041 dialysis patients, a prospective cohort study also found
glomerular filtration rate (GFR) may be accelerated
a reduction in the risk of sepsis with statin therapy (incidence
and perpetuated by dyslipidemia. However, this effect
rate ratio 0.41, CI 0.25-0.68) [53]; the apparent protective
has been derived from post-hoc analyses, which are
effect was even larger with additional adjustment for
limited by unmeasured confounders that are closely
comorbidities or with propensity matching. However, it needs
correlated to dyslipidemia. If real, this effect is very
to be remembered that this report is a secondary analysis of
modest and would require an immense trial to
the 4-D study, and the original study was neither designed
demonstrate conclusively. (See 'Effect of dyslipidemia
nor powered for sepsis endpoints. (See "Statins: Possible
on kidney function'above.)
noncardiovascular benefits".)

ADVERSE EFFECTS OF STATINS IN CHRONIC KIDNEY ●Two meta-analyses of small, randomized trials found
DISEASE — With respect to adverse effects, studies in that statin therapy significantly reduced albuminuria.
However, patients in the trials that were included in
these meta-analyses were not uniformly taking
angiotensin blockade. In contrast, two large-scale,
randomized trials found no effect of statins on albumin
excretion in patients who received optimal therapy for
slowing CKD progression with angiotensin blockers
and good blood pressure control. (See 'Effect on
protein excretion' above.)
●There are conflicting data concerning the effect of
statins on progression of CKD. The bulk of the data
derived from large intervention studies with hard
clinical endpoints suggest that statins do not prevent
the loss of renal function. All of the trials that evaluated
the effect of statin therapy on CKD progression were
subset analyses of trials designed to evaluate the
efficacy of statin therapy on cardiovascular disease in
CKD. (See 'Effect on chronic kidney disease
progression' above.)
●Thus, statin therapy cannot be recommended solely
for renal protection. Effects on proteinuria, if any, are
likely to be limited to patients who are not already
receiving optimal therapy to slow CKD progression.
(See 'Effect on protein excretion' above.)
●However, patients with CKD may be candidates for
statin therapy for cardiovascular protection. The effect
of statin therapy on cardiovascular endpoints and
recommendations concerning the use of statins in
dialysis patients and CKD patients not on dialysis are
presented elsewhere. (See "Secondary prevention of
cardiovascular disease in end-stage renal disease
(dialysis)", section on 'Lipid
modification' and "Indications for statins in nondialysis
chronic kidney disease", section on 'Evidence in
support of treatment with statins'.)
●With respect to adverse effects, good side-effect
profiles with statins have been reported patients with
CKD, dialysis patients, and renal transplant recipients.
However, accurate estimates of the risk of adverse
events (especially myopathy) are not available in
patients with end-stage renal disease (ESRD) or
moderate to severe chronic renal insufficiency, since
the existing clinical trials with statins in these patients
have been quite small. (See'Adverse effects of statins
in chronic kidney disease' above.)