Effect of Pravastatin in People with Diabetes and Chronic Kidney Disease

Abstract

Although diabetes is a major cause of chronic kidney disease (CKD), limited data describe the cardiovascular benefit of hydroxymethyl glutaryl CoA reductase inhibitors (statins) in people with both of these conditions. This study sought to determine whether pravastatin reduced the incidence of first or recurrent cardiovascular events in people with non-dialysisdependent CKD and concomitant diabetes, using data from three randomized trials of pravastatin 40 mg daily versus placebo. CKD was defined by estimated GFR <60 or 60 to 89.9 ml/min per 1.73 m 2 with proteinuria. Of 19,737 patients, 4099 (20.8%) had CKD but not diabetes at baseline, 873 (4.4%) had diabetes but not CKD, and 571 (2.9%) had both conditions. The primary composite outcome was time to myocardial infarction, coronary death, or percutaneous/surgical coronary revascularization. Median follow-up was 64 mo. After adjustment for trial and random treatment assignment, the incidence of the primary outcome was lowest in individuals with neither CKD nor diabetes (15.2%), intermediate in individuals with only CKD (18.6%) or only diabetes (21.3%), and highest in individuals with both characteristics (27.0%). Pravastatin reduced the relative likelihood of the primary outcome to a similar extent in subgroups defined by the presence or absence of CKD and diabetes. For example, pravastatin was associated with a significant reduction in the relative risk of the primary outcome by 25% in patients with CKD and concomitant diabetes and by 24% in individuals with neither characteristic. However, the absolute reduction in the risk of the primary outcome as a result of pravastatin use was highest in patients with both CKD and diabetes (6.4%) and lowest in individuals with neither characteristic (3.5%). In conclusion, stage 2 or early stage 3 CKD and diabetes both are associated with higher cardiovascular risk, and pravastatin reduces cardiovascular event rates in people with neither, one, or both characteristics. Given the high absolute benefit of pravastatin in patient with diabetes and stage 2 or early stage 3 CKD, this population in particular should be targeted for widespread use of statins. Additional studies are needed to determine whether these benefits apply to patients with more severe CKD, and recruitment to such studies should be given high priority.

The Challenge of Sudden Death in Dialysis Patients

“…This alternative is further supported by the recent observation that in patients with advanced CKD 4 or 5, intensified multiple risk factor intervention for 2 yr compared with conventional care failed to modify significantly vascular abnormalities (carotid intima media thickness and endothelial function as evaluated by brachial artery reactivity); it also failed to affect cardiovascular events (80). It remains sensible, however, to start intervention with statins in early stages of CKD, when they are still effective (81).…”

Targeting of RhoA/ROCK Signaling Ameliorates Progression of Diabetic Nephropathy Independent of Glucose Control

“…A recent review of the effect of statins on renal function suggested that statins reduced the rate of kidney function loss by ϳ75% and reduced albuminuria by 47% in people with baseline albuminuria of Յ300 mg/dl (20 -22). Although the benefits of statins had initially been attributed to their lipidlowering effects (21,23,24), recent studies have proposed that statins have direct modulatory effects on the Rho GTPase signaling pathways (25,26). These pleiotropic, or lipid-independent, effects of statins primarily involve inhibition of the mevalonate pathway with subsequent inactivation of several signaling proteins including .…”

A Cluster Randomized Trial of an Enhanced eGFR Prompt in Chronic Kidney Disease

“…Patients with CKD often do not receive optimal therapy (5-7), perhaps because physicians do not recognize earlier stages of CKD or are unaware that CKD confers elevated cardiovascular risk. This is particularly important given that treatments have been shown to delay or prevent ESRD and improve cardiovascular outcomes (8)(9)(10)(11)(12)(13).…”