| 1. |
- Haynes, Richard, et al.
(author)
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Effects of Lowering LDL Cholesterol on Progression of Kidney Disease
- 2014
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In: Journal of the American Society of Nephrology. - 1046-6673 .- 1533-3450. ; 25:8, s. 1825-1833
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Journal article (peer-reviewed)abstract
- Lowering LDL cholesterol reduces the risk of developing atherosclerotic events in CKD, but the effects of such treatment on progression of kidney disease remain uncertain. Here, 6245 participants with CKD (not on dialysis) were randomly assigned to simvastatin (20 mg) plus ezetimibe (10 mg) daily or matching placebo. The main prespecified renal outcome was ESRD (defined as the initiation of maintenance dialysis or kidney transplantation). During 4.8 years of follow-up, allocation to simvastatin plus ezetimibe resulted in an average LDL cholesterol difference (SEM) of 0.96 (0.02) mmol/L compared with placebo. There was a nonsignificant 3% reduction in the incidence of ESRD (1057 [33.9%] cases with simvastatin plus ezetimibe versus 1084 [34.6%] cases with placebo; rate ratio, 0.97; 95% confidence interval [95% CI], 0.89 to 1.05; P=0.41). Similarly, allocation to simvastatin plus ezetimibe had no significant effect on the prespecified tertiary outcomes of ESRD or death (1477 [47.4%] events with treatment versus 1513 [48.3%] events with placebo; rate ratio, 0.97; 95% CI, 0.90 to 1.04; P=0.34) or ESRD or doubling of baseline creatinine (1189 [38.2%] events with treatment versus 1257 [40.2%] events with placebo; rate ratio, 0.93; 95% CI, 0.86 to 1.01; P=0.09). Exploratory analyses also showed no significant effect on the rate of change in eGFR. Lowering LDL cholesterol by 1 mmol/L did not slow kidney disease progression within 5 years in a wide range of patients with CKD.
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| 2. |
- Herrington, William, et al.
(author)
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The effect of lowering LDL cholesterol on vascular access patency : post hoc analysis of the Study of Heart and Renal Protection
- 2014
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In: Clinical journal of the American Society of Nephrology : CJASN. - 1555-905X. ; 9:5, s. 914-919
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Journal article (peer-reviewed)abstract
- BACKGROUND AND OBJECTIVES:Reducing LDL cholesterol (LDL-C) with statin-based therapy reduces the risk of major atherosclerotic events among patients with CKD, including dialysis patients, but the effect of lowering LDL-C on vascular access patency is unclear.DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS:The Study of Heart and Renal Protection (SHARP) randomized patients with CKD to 20 mg simvastatin plus 10 mg ezetimibe daily versus matching placebo. This study aimed to explore the effects of treatment on vascular access occlusive events, defined as any access revision procedure, access thrombosis, removal of an old dialysis access, or formation of new permanent dialysis access.RESULTS:Among 2353 SHARP participants who had functioning vascular access at randomization, allocation to simvastatin plus ezetimibe resulted in a 13% proportional reduction in vascular access occlusive events (355 [29.7%] for simvastatin/ezetimibe versus 388 [33.5%] for placebo; risk ratio [RR], 0.87; 95% confidence interval [95% CI], 0.75 to 1.00; P=0.05). There was no evidence that the effects of treatment differed for any of the separate components of this outcome. To test the hypothesis raised by SHARP, comparable analyses were performed using the AURORA (A Study to Evaluate the Use of Rosuvastatin in Subjects on Regular Hemodialysis: An Assessment of Survival and Cardiovascular Events) trial cohort. AURORA did not provide independent confirmation (vascular access occlusive events: 352 [28.9%] for rosuvastatin versus 337 [27.6%] for placebo; RR, 1.06, 95% CI, 0.91 to 1.23; P=0.44). After combining the two trials, the overall effect of reducing LDL-C with a statin-based regimen on vascular access occlusive events was not statistically significant (707 [29.3%] with any LDL-C-lowering therapy versus 725 [30.5%] with placebo; RR, 0.95, 95% CI, 0.85 to 1.05; P=0.29).CONCLUSIONS:Exploratory analyses from SHARP suggest that lowering LDL-C with statin-based therapy may improve vascular access patency, but there was no evidence of benefit in AURORA. Taken together, the available evidence suggests that any benefits of lowering LDL-C on vascular access patency are likely to be modest.
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| 3. |
- Linder, Adam, et al.
(author)
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Small Acute Increases in Serum Creatinine Are Associated with Decreased Long-Term Survival in the Critically Ill
- 2014
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In: American Journal of Respiratory and Critical Care Medicine. - 1535-4970. ; 189:9, s. 1075-1081
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Journal article (peer-reviewed)abstract
- Rationale: Long-term outcomes after acute kidney injury (AKI) are poorly described. Objectives: We hypothesized that one single episode of minimal (stage 1) AKI is associated with reduced long-term survival compared with no AKI after recovery from critical illness. Methods: A prospective cohort of 2,010 intensive care unit (ICU) patients admitted to the ICU between years 2000 and 2009 at a provincial tertiary care hospital. Development of AKI was determined according to the KDIGO classification and mortality up to 10 years after ICU admission was recorded. Measurements and Main Results: Of the 1,844 eligible patients, 18.4% had AKI stage 1, 12.1% had stage 2, 26.5% had stage 3, and 43.0% had no AKI. The 28-day, 1-year, 5-year, and 10-year survival rates were 67.1%, 51.8%, 44.1%, and 36.3% in patients with mild AKI, which was significantly worse compared with the critically ill patients with no AKI at any time (P < 0.01). The unadjusted 10-year mortality hazard ratio was 1.53 (95% confidence interval, 1.2-2.0) for 28-day survivors with stage 1 AKE compared with critically ill patients with no AKI. Adjusted 10-year mortality risk was 1.26 (1.0-1.6). After propensity matching stage 1 AKI with no AKE patients, mild AKE was still significantly associated with decreased 10-year survival (P =0.036). Conclusions: Patients with one episode of mild AKI have significantly lower long-term survival rates than critically ill patients with no AKI. Close medical follow-up of these patients may be warranted and mechanistic research is required to understand how AKI influences long-term events.
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