Statins for Renal Patients: A Fiddler on the Roof?

Table 1

Overview of major statin studies.

Study		Patient population	Followup	Treatment	Outcome	Results
Overview of renal outcomes
GREACE	Post hoc subgroup analysis	1,600 patients with dyslipidemia and CAD	3 years	Atorvastatin 10–80 mg/day or usual medical care	Rate of kidney function decline	CrCl had a 12% increase in atorvastatin group (𝑃<0.0001); CrCl had a 5.2% decrease in patients not treated with statins (𝑃<0.0001); CrCl had a 4.9% increase in the usual care group on various statins
ALLIANCE	Post hoc subgroup analysis	2,442 patients with dyslipidemia	4 years	Atorvastatin 10–80 mg/day or usual medical care	Rate of kidney function decline	CrCl did not change in the atorvastatin group versus baseline; CrCl declined by 4.4% in the usual care group (𝑃=0.0001 versus baseline)
CARE	Post hoc subgroup analysis	3,384 individuals of whom 690 (20.4%) had GFR < 60 mL/min per 1.73 m^2	4 years	Pravastatin 40 mg/day versus placebo	Change in GFR	The decline in the pravastatin group versus placebo was nonsignificant; In patients with GFR < 40 mL/min per 1.73 m^2, the rate of change in the pravastatin versus placebo group was 2.5 mL/min per 1.73 m^2/year slower (95% CI: 1.4–3.6; 𝑃=0.0001)
SHARP	Randomized double blind, multicenter trial	9,270 participants, including 3000 receiving hemodialysis	4.9 years	Ezetimibe 10 mg/day + simvastatin 20 mg/day versus placebo versus simvastatin 20 mg/day	ESRD, major atherosclerotic events	17% reduction in major atherosclerotic events; No difference of progression to ESRD
PLANET I	Randomized double blind, multicenter trial	325 patients with diabetes who had proteinuria and hypercholesterolemia	1 year	Rosuvastatin 10 mg/day or rosuvastatin 40 mg/day versus atorvastatin 80 mg/day	Change in urinary protein excretion (urinary protein/; creatinine ratio)	Atorvastatin significantly reduced proteinuria by about 15% rosuvastatin had no significant effect on proteinuria; Patients on atorvastatin lost 1 to 2 mL/min per 1.73 m^2, those on rosuvastatin 10 mg/day lost 4 mL/min per 1.73 m^2, and those on rosuvastatin 40 mg/day lost 8 mL/min per 1.73 m^2 over 52 weeks
PLANET II	Randomized double-blind, multicenter trial	220 patients without diabetes who had proteinuria and hypercholesterolemia	1 year	Rosuvastatin 10 mg/day or rosuvastatin 40 mg/day versus atorvastatin 80 mg/day	Change in urinary protein excretion (urinary protein/; creatinine ratio)	Atorvastatin reduced proteinuria by 23.8% (𝑃=0.0056); Significant decline in GFR with rosuvastatin; No significant difference in the amount of lipid lowering was reported among the treatment groups
Strippoli et al.; [23]	Meta-analysis	11 studies, 548 patients		Different statins	Change in GFR	Statins did not improve GFR
Sandhu et al.; [21]	Metaanalysis	27 studies (21 with data for GFR), 39,704 participants		Different statins	Change in GFR	Statins slowed the loss of GFR by a mean of 1.22 mL/min/year; 95% CI: 0.44–2.00; In studies of CVD, patients were slower than controls (0.93 mL/min/year, 95% CI: 0.10–1.76), with statistical significance
Douglas et al.; [22]	Metaanalysis	15 studies, 1,384 patients		Different statins	Change in urinary protein excretion	Statins reduced albuminuria and proteinuria in 13 studies; The reduction of excretion was greater among studies with greater baseline albuminuria or proteinuria
Overview of cardiovascular outcomes in patients with kidney disease
Pravastatin Pooling Project (WOSCOPS, CARE and LIPID)	Randomized double-blind, multicenter trial	4,491 patients with or without CAD and with moderate CKD (GFR, 30–60 mL/min/1.73 m^2)		Pravastatin 40 mg/day versus placebo	Time to MI, coronary death, or PCR	Significant reduction in primary outcome in statin-treated patients, with moderate CKD (HR: 0.77, 95% CI: 0.68–0.86); reduction in total mortality in treated patients
4D Study	Randomized double blind, multicenter trial	1,255 hemodialysis patients, with type 2 diabetes	4 years	Atorvastatin 20 mg/day versus placebo	Composite of cardiac death, nonfatal MI, and stroke	No significant difference in primary endpoint with statin treatment, but increased risk for fatal stroke (𝑃=0.04)
AURORA	Randomized double blind, multicenter trial	2,776 patients receiving long-term hemodialysis	3.2 years	Rosuvastatin 10 mg/day versus placebo	Composite of cardiac death, nonfatal MI, and stroke	Rosuvastatin lowered the LDL level (𝑃<0.0001) but had no significant effect on primary endpoint

GREACE: Greek Atorvastatin and Coronary Heart Disease Evaluation; ALLIANCE: Aggressive Lipid-Lowering Initiation Abates New Cardiac Events; CARE: Cholesterol And Recurrent Events; SHARP: Study of Heart and Renal Protection; PLANET: Prospective Evaluation of Proteinuria and Renal Function in Diabetic Patients; WOSCOPS: West of Scotland Coronary Prevention Study; LIPID: Long-Term Intervention with Pravastatin in Ischaemic Disease; 4D Study: Die Deutsche Diabetes Dialyse Studie; AURORA: A Study to Evaluate the Use of Rosuvastatin in Subjects on Regular Hemodialysis; CAD: coronary artery disease; CrCl: creatinine clearance; GFR: glomerular filtration rate; ESRD: end-stage renal disease; CVD: cardiovascular disease; CKD: chronic kidney disease; PCR: percutaneous coronary revascularization.